From the Department of Medicine, Infectious Disease Practice and Innovations, The Medical City, Pasig City, Philippines (Dr. Abad), the Division of Emergency Medicine, University of Wisconsin Medical School, Madison, WI (Dr. Pulia), University of Wisconsin Hospital and Clinics, Madison, WI (Ms. Krupp), and the Willam S. Middleton Memorial Veterans Affairs Hospital, Madison, WI (Dr. Safdar).

Patients in intensive care units (ICUs) are at greatly increased risk of developing health care-associated infections (HAIs) [1]. More than 70% of the bacteria that cause HAIs are resistant to at least one of the antimicrobials commonly used to treat these infections [2]. Two such pathogens, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are responsible for a considerable proportion of ICU infections that are associated with increased morbidity, mortality, and costs [3–5]. In this review, we discuss the epidemiology of colonization and infection by MRSA and VRE and provide an update on practices for prevention of transmission and infection by MRSA and VRE in the ICU.

EPIDEMIOLOGY AND MECHANISMS OF RESISTANCE

MRSA is the major cause of HAIs worldwide [6]. Among ICUs in the United States, the proportion of methicillin resistance among S. aureus isolates increased from 35.9% in 1992 to 64.4% in 2003 [4]. Approximately 8% of patients are colonized with MRSA upon admission, and an average of 5% will acquire MRSA colonization in the ICU [7,8]. A comparison study of academic tertiary care facilities found medical ICUs had higher MRSA admission prevalence rates than surgical ICUs, whereas surgical ICUs had a higher incidence rate [7]. Enteroccoccus is the third most common pathogen associated with HAIs, with 33% resistant to vancomycin [9]. VRE infection is associated with increased ICU cost and increased length of stay [10]. Incidence of ICU-acquired VRE varies among regions and countries. For example, in the United States, Warren et al [11] reported a VRE incidence of 27 cases per 1000 patient ICU days, whereas Kohlenberg et al [12] reported a mean incidence of 0.29 cases per 1000 patient ICU days in Germany.

Understanding the mechanisms that allow development of resistant strains of S. aureus and Enterococcus species is important to devise preventive strategies. Methicillin resistance in MRSA is determined by the staphylococcal cassette chromosome mec (SCCmec), a mobile genetic element that carries the mecA gene. The mecA gene codes for an additional penicillin-binding protein (PBP) that has a reduced affinity towards methicillin (PBP2a/PBP2'). This results in a reduced ability to bind to the bacterial cell wall and inhibit synthesis [13,14]. Study of molecular epidemiology has identified MRSA as originating from 8 major variants of the mecA gene [15]. The majority of MRSA infections are caused by strains belonging to a few internationally disseminated clones [14]. The first identified strains were associated with infections in hospitalized patients (hospital-associated MRSA), but community-associated MRSA strains have since emerged and have become established globally, including in health care institutions [16].

Community-acquired MRSA can cause severe infections in health hosts [17]; possible explanations include increased CA-MRSA virulence due to the acquisition of mobile genetic elements, namely those containing Panton-Valentine leukocidin (PVL) [18] or increased expression of core genome-encoded virulence genes, such as phenol-soluble modulin (PSM) cytolysins, α-toxin, and other virulence determinants [19].

Enterococcus is intrinsically resistant to several antimicrobial drugs, with resistance to vancomycin encoded by several clusters of genes known as vancomycin resistance gene clusters (eg, vanA, vanB). The gene clusters generate resistance through multiple pathways which encode enzymes to determine the structure of peptidoglycan precursors [20,21]. Genetically diverse, hospital-associated VRE outbreaks have been associated with single clones, multiple clones, and changing molecular epidemiology over time [21]. While up to 25% of the VRE genome includes acquired elements, the majority of hospital-associated infections are traced to a few clonal complexes, which differ from community-associated VRE strains [22].

The evolution of these efficient mechanisms that promote drug resistance has made it extremely challenging to eradicate organisms such as MRSA and VRE. However, advances in recent years have furthered our understanding of the epidemiology, pathogenesis, and methods of prevention and containment.

RISK FACTORS FOR COLONIZATION AND INFECTION

MRSA

The risk factors underlying MRSA colonization and infection in the ICU setting can be categorized as either patient/host or environmental factors. A wide range of patient-level factors is associated with MRSA colonization upon admission. General principles regarding the transmission of MRSA in the community include close contact with colonized or infected individuals, breaks in the skin, crowded living conditions and poor hygiene. These factors, alone or in combination, are thought to underlie observed outbreaks among sports teams, military personnel, correction facilities, American Indian communities, and daycare centers [23–34].

Two recently published systematic reviews have summarized important patient-level factors associated with MRSA colonization at the time of hospital admission. Forster et al [35] examined 27 studies and identified previous admission to hospital, transfer from nursing home or long-term care facility, and previous antibiotic use as the top 3 factors associated with MRSA colonization. A similar review conducted by McKinnell and colleagues [36] found that prior hospitalization, nursing home contact, recent antibiotic use, and exposure to health care-associated pathogens (MRSA carriage, VRE carriage, or Clostridium difficile infection) were found to portend the highest risk. Specific comorbid conditions also conveyed an increased risk, including congestive heart failure, chronic wounds/bedsores, diabetes mellitus, pulmonary disease, immunosuppression, urinary catheter, and renal failure/dialysis. It is clear that health care contacts, especially recent hospitalization, residence in a long-term care facility, and antibiotic use, are significant risk factors for MRSA colonization [37–39].

In contrast to those already colonized with MRSA, some patients acquire MRSA during hospitalization. In these cases, transmission via hands of health care workers is likely the most common mechanism for spread of MRSA [6,40–42]. An understaffed ICU has also been cited as a potential risk factor for ICU MRSA transmission, perhaps due to sacrifices in hand hygiene practices by overextended staff [6]. Additional factors associated with increased risk of nosocomial MRSA acquisition include duration of antibiotic therapy, exposure to quinolone or macrolide antibiotics, length of hospital stay, enteral feeding, post-surgical status, insertion of central line or urinary catheter during admission, ICU admission, and proximity to another patient with MRSA infection or colonization [43–45]. A summary of risk factors for MRSA acquisition is shown in Table 1.

Regardless of whether MRSA colonization precedes admission or occurs due to nosocomial spread, it is associated with increased risk of developing a HAI [46–49]. In 2 large prospective observational cohort studies, the hazard ratios of MRSA colonization developing into S. aureus infections during the ICU stay were 3.84 and 4.70, respectively [50,51]. High levels of concordance between MRSA colonization strains and HAI strains have also been reported [52]. Nasal colonization with S. aureus has also been identified as an independent risk factor for developing ventilator-associated pneumonia (VAP) and bacteremia [53,54]. A case series of ICU patients with S. aureus nasal colonization who developed lower respiratory tract infections demonstrated genetically identical nasal and bronchial strains in 15/16 cases [55]. This finding strongly suggests that nasopharyngeal colonization with S. aureus contaminates oral secretions that are aspirated by critically ill patients, resulting in subsequent pneumonia. In a long-term outcomes study among a matched cohort of veterans, MRSA colonization was associated with an increased risk of infection-related readmission and mortality [56]. These findings reflect the critically important nature of measures designed to curb nosocomial transmission and acquisition of MRSA, especially among the vulnerable ICU population.

VRE

As with MRSA, risk factors associated with VRE colonization include both patient-level and ICU-level (or environmental) factors [57]. Examples of patient-level factors include previous antimicrobial exposure [58–62], underlying medical illnesses such as chronic renal failure requiring hemodialysis [11,63], length of hospital or ICU stay [11,59,64,65], and recent exposure to health care facilities. ICU-level factors of relevance are the prevalence of VRE in the unit, with high levels of endemicity leading to higher risk of colonization and transmission.

Antibiotic use is a major risk factor for VRE acquisition, although the type and class of antibiotic varies considerably across studies; the most frequently identified antibiotics are broad-spectrum cephalosporins, vancomycin, and anti-anaerobic agents [58,62,64]. Patients with chronic liver disease and post-transplantation are at exceedingly high risk for VRE acquisition [59]. In a recent study by Pan [66], for example, the authors found that the incidence of newly acquired VRE was 21.9 per 1000 patient-days in an ICU setting. On multivariate analysis, the authors found that, similar to other reports [11,59,67], length of stay in the ICU was associated with increased risk of VRE acquisition, with each additional day of stay increasing risk of VRE by 1.03 times. Warren et al undertook a prospective cohort study involving 519 patients admitted to the ICU for more than 48 hours [11]. Seventy-four (21%) of 352 patients were subsequently colonized with VRE. The median time to development of a positive VRE culture after ICU admission was 6 days. Increased mean APACHE II score on ICU admission (P = 0.002), sucralfate use (P = 0.003), vasopressor use (P = 0.01), tracheostomy in the ICU (P = 0.02), and C. difficile diarrhea (P = 0.002) appeared to be associated with VRE acquisition.

It appears that VRE acquisition is often associated with the sick subgroup of patients, and risk factors generally associated with VRE colonization and infection co-relate with disease chronicity and severity of illness. Length of hospitalization, ICU stay, hemodialysis, or transplantation may all be markers of disease severity. A summary of risk factors for VRE acquisition is shown in Table 2.

REDUCING TRANSMISSION—MRSA AND VRE PREVENTION STRATEGIES

Evidence-based guidelines developed by the Centers for Disease Control (CDC) Hospital Infection Control Practices Advisory Committee (HICPAC) for prevention of MRSA and VRE are available [68]. Several recently conducted well-designed clinical trials also provide additional insight that may be particularly helpful in the ICU setting [69]. A summary of the MRSA prevention guidelines issued by the CDC and included in its “MRSA toolkit” is provided in Table 3. A similar guideline on prevention of VRE [70], published more than a decade ago, has similar elements. Table 3 shows a side-by-side comparison of these elements. Unfortunately, despite these guidelines and extensive research regarding prevention and control, considerable controversy exists as to the most effective approaches. As such, these recommendations should be tailored to meet the needs of the specific ICU setting.

Antimicrobial Stewardship

Antibiotic use is a major driver of antibiotic resistance. A meta-analysis by de Bruin and Riley [71] studied the effect of vancomycin usage on VRE colonization and infection. A total of 12 articles describing 13 studies were included; none were randomized controlled trials. All studies were quasi-experimental and lacked control groups. Among all studies, less than half (46%) implemented vancomycin reduction measures as the sole type of intervention [72–76]. The remaining studies implemented other infection control modalities and or restricted the use of other antimicrobials [77–83]. Although all studies that implemented vancomycin restriction alone as a single strategy showed a decline in vancomycin usage, only 2 of these [74,75] showed a relative risk reduction in VRE acquisition post-intervention. Also, studies that restricted vancomycin alone revealed a trend towards lower efficacy in reducing VRE colonization and infection (33%) when compared with those that used additional measures (71%). While judicious antibiotic use should always be practiced, the evidence for vancomycin restriction as a sole intervention to control VRE is scant. It may be that other antibiotics are as big or bigger drivers of resistance in enterococci than vancomycin. For example, a growing body of literature supports antibiotic restriction, especially fluoroquinolones, for reducing MRSA. In several time-series quasi-experimental studies, restriction of fluorquinolones was associated with reduced trends in MRSA infections in the acute care setting, and consideration should be given to monitor and optimize fluoroquinolone use in the ICU setting [84,85].

Antimicrobial stewardship programs are fundamental to optimizing antibiotic use in the ICU and the authors strongly recommend that all ICUs should have such a program in place.

Educational Interventions

Infection control and multidrug-resistant organism (MDRO)–specific education programs for health care workers is a core principle of the CDC’s prevention guidelines. The HICPAC VRE guideline also explicitly states “continuing education programs for hospital staff (including attending and consulting physicians, medical residents, and students; pharmacy, nursing, and laboratory personnel; and other direct patient-care providers) should include information concerning the epidemiology of VRE and the potential impact of this pathogen on the cost and outcome of patient care [70].” A systematic review published in 2008 [86] that included 26 studies showed that such interventions to prevent HCAIs are usually successful; in this review, 20 of 26 studies showed a statistically significant decrease in infection rates, with risk ratios ranging from 0 to 1.6. Education was usually part of a broader array of infection control interventions. While clearly essential, education alone is unlikely to have a sustained impact on reducing MRSA and VRE infections.

Infection Control Measures

Major infection control interventions include hand hygiene, the use of personal protective equipment (PPE), and cohorting. These measures can be grouped into “horizontal” (or global) vs. “vertical” (or targeted) strategies. Although not mutually exclusive, horizontal approaches are designed to have an impact on multiple pathogens (pathogen nonspecific), whereas vertical approaches are designed to reduce the impact of specific pathogens (such as VRE). For the purposes of this review, we will discuss both strategies for containment of MRSA and VRE. Horizontal strategies include hand hygiene, universal gloving and/or gowning, environmental cleaning, and daily bathing with chlorhexidine. Vertical strategies include screening for either MRSA or VRE followed by placement in contact precautions and decolonization with mupirocin.

Hand Hygiene

Hand washing is fundamental to reducing transmission of MDROs in health care institutions; however, optimal compliance is hard to achieve and sustain. Barriers to adherence may include unavailability of sinks or hand hygiene materials (eg, alcohol-based gels, gloves) time constraints, forgetfulness, or lack of knowledge [87–95]. Several monitoring strategies have been evaluated to increase compliance with hand hygiene. Most involve direct observation followed by performance assessment and feedback.

Trials examining the impact of improvements in hand hygiene compliance on HAIs in the ICU setting have largely found benefit, although not all studies showed a decline in HAI. In a prospective crossover trial, Rupp et al [96] found dramatic improvements in compliance with hand gel availability, but this did not translate to decreased nosocomial MRSA infections. Venkatesh et al [97] carried out a before-and-after interventional prospective study in a hematology unit in a tertiary level hospital to evaluate the use of an electronic method of surveillance to determine compliance with hand hygiene. The authors also used rates of horizontal transmission of VRE as a secondary end-point. Results of the study showed that hand hygiene compliance improved from 36.3% at baseline to 70.1%. This represented an OR of 4.1 (95% confidence interval, 3.7–4.5), which the authors attributed to the use of automated alerts. VRE transmission rates before and during intervention were not statistically different, but the rates of infection were lower at 1.0 per month in comparison with 4.7 infections per month in the preceding 6 months (P = 0.096).

While improved hand hygiene may result in significant reductions in HAIs [40], research indicates hand hygiene alone influences about 40% of infections in the ICU setting [98]. As such, hand hygiene should be viewed as a necessary component of a comprehensive infection control program [99]. Despite the success of hand hygiene in reducing HAIs in the ICU, effective strategies to improve compliance remain elusive even under study conditions and further research is needed in this area [100].

Personal Protective Equipment

Tenorio et al [101] conducted a study to assess the effectiveness of gloving in the prevention of hand carriage of VRE by health care workers. The study showed that among 50 health care workers who had contact with patients colonized with VRE, 6 carried a similar patient strain even prior to known contact, and 17 of 44 (69%) had a patient-related VRE strain on their gloves after contact. This suggests a relatively high rate of colonization after usual patient-care contact. Factors associated with acquisition of VRE on gloves included duration of contact, contact with a patient’s body fluids, presence of diarrhea in a patient, mean VRE colony counts on a patient’s skin, and number of body sites colonized with VRE. Although gloves reduced the risk of VRE acquisition of VRE by 71% (ie, 12/17 did not have VRE on their hands after de-gloving) the protection afforded by gloves was incomplete. As such, hand hygiene after glove removal is recommended.

Slaughter et al [102] compared the use of personal protective equipment in the acquisition of VRE. During this study, 93 patients in glove-and-gown rooms and 88 patients in glove-only rooms had similar rates of VRE at baseline entry into the ICU and after the intervention. Mean times to colonization among the patients who became colonized were 8.0 days in the glove-and-gown group and 7.1 days in the glove-only group. None of these comparisons were statistically significant and the authors concluded that the universal use of gown and gloves was no better than the use of gloves alone in preventing VRE colonization.

A recent cluster randomized trial compared the effect of universal PPE (ie, gowning and gloving) with usual care for reducing acquisition of MRSA or VRE as a composite outcome [103]. The study did not find that universal gowning and gloving reduced VRE or MRSA acquisition but found a 40% decline in MRSA acquisition in the intervention ICUs compared with baseline rates of MRSA. No major adverse effects of universal gowning and gloving were noted in this study. A thoughtful editorial commenting on this article proposes that several aspects of the study deserve consideration, including the possibility of false-negative screening tests for VRE, which may have partially accounted for the negative primary outcome [69].

Based on these studies, it appears that the use of barrier precautions may be of value more for MRSA than VRE but further studies are needed to examine its impact on other types of pathogens, including new and emerging MDROs. Until further evidence becomes available, routine gowning and gloving may be of value in units with a high prevalence of MRSA.

Environmental Cleaning

Accumulating data suggests that the environment may play a major role in transmission of pathogens. MRSA has the ability to survive for days to weeks on inanimate objects [104–107]. Environmental contamination results in contamination of staff clothing and gloves [107,108] and is highly correlated with colonization strains among inpatients [109]. Although some studies of enhanced cleaning techniques and increased environmental services staff time have demonstrated reductions in MRSA outbreaks [110–112], the results are not universally favorable [113,114] and further studies are needed to examine the impact of environmental cleaning on rates of MRSA colonization or infection.

Several studies have implicated contaminated equipment as vectors for transmission of VRE during outbreaks [115–117], but the direction of fomite transfer from patient to environment has been difficult to ascertain. VRE have been found frequently on a variety of inanimate objects and surfaces in different health care environments [118–123], including gloved or ungloved hands of health care workers [101,124,125]. Hayden et al [126] determined the effect of improved environmental cleaning on VRE acquisition rates. This study was a pre-and-post intervention study carried out in a 21-bed medical intensive care unit (MICU) in a tertiary hospital over several phases. The intervention included the creation of a unique and improved cleaning program, as well as in-services to housekeeper services, education of the MICU staff, and a hand hygiene campaign. The results of the study showed decreased acquisition of VRE from 33.47 cases per 1000 patient days at risk in period 1 to 10.40 cases per 1000 patient-days at risk by period 4 of the study. Increased environmental cleaning was also associated with reduced growth of VRE from environmental cultures. At baseline, weekly contamination rates were 0.15 and 0.1 for samples obtained before and after cleaning, respectively. Culture positivity decreased to 0.07 and 0.04 for before and after cleaning in period 2 and then remained at low levels during the remainder of the study. It is important to note that the method for disinfecting used in this study was the “bucket method” as promoted by Byers [127]. This study provides further support for the importance of an environmental reservoir and of environmental decontamination to prevent endemic cross-transmission of VRE [126].

Goodman et al [128] used similar interventions but added a feedback tool using a black-light monitoring system (ie, use of an invisible, nontoxic marker to delineate areas that are adequately or inadequately cleaned) to reduce the likelihood of isolating either MRSA or VRE from an ICU environment. This study also showed favorable results, and notably, the use of the black-light monitoring system identified specific areas that were typically inadequately disinfected. Results showed that flat, horizontal surfaces (eg, countertops, bedside tray tables, and hamper tops) were adequately cleaned more often than small, vertical surfaces (eg, doorknobs, toilet handles, light switches, and electronics).

Part of the controversy surrounding the impact of environmental cleaning is the difficulty in determining its individual value as part of an overall infection control bundle [129]. A proposed area of demonstrable impact for environmental cleaning are frequently touched sites which are more likely to be contaminated with pathogens. Focusing on these “hot-bed” areas of the care environment may offer a useful adjunct to other infection control measures [129].

Active Surveillance

Active surveillance refers to periodic screening for asymp-tomatic carriers followed by placement of colonized patients in contact isolation. This practice is highly variable across institutions, as the evidence supporting this practice is conflicting and there are concerns about the cost of implementing this approach without solid evidence [70,130,131]. Despite lack of randomized controlled trials to guide this practice for MRSA prevention, many hospitals utilize MRSA surveillance and it is mandated by law in 9 states [132,133].

A prospective, interventional cohort study of universal MRSA screening on admission to surgical wards failed to reduce nosocomial MRSA infections [134]. Most recently, a pragmatic, cluster-randomized ICU trial reported that universal decolonization with chlorhexidine wipes and mupirocin use was more effective than screening and isolation in reducing rates of MRSA clinical isolates [65]. However, concerns regarding the risk of mupirocin resistance have been expressed [135,136]. The only randomized trial that compared active surveillance for MRSA and VRE followed by contact precautions to usual care did not find a benefit to active surveillance.

Huskins et al [137], in a large, cluster-randomized trial of 19 ICUs from different hospitals, determined the utility of using a culture-based active surveillance and contact isolation, compared with usual care (contact isolation for patients colonized with MRSA or VRE) as identified by existing hospital protocols, to reduce the incidence of colonization or infection with MRSA or VRE. In this trial, which spanned 6 months and involved 3488 participants, the authors found no significant difference between the intervention and control ICUs in terms of MRSA and VRE colonization or infection rates.

Conflicting with these findings is an observational study comparing MRSA infection rates before and after institution of a universal screening protocol, which demonstrated a 69.6% (CI, –89.2% to –19.6%]; P = 0.03) reduction in hospital wide MRSA prevalence density with screening [138]. The “MRSA bundle” implemented in 2007 at VA hospitals nationwide, which included universal screening, produced a 62% (P < 0.001) reduction in MRSA ICU infections; the relative contribution of the various bundle components is uncertain [139,140].

A proposed cost-saving alternative to universal screening is selective screening based on risk factor assessment [141]. The effectiveness of this type of program depends on creating a clinical decision-making tool capable of accurately identifying high-risk individuals while also accounting for the different risk factor profiles between HA-MRSA and CA-MRSA [142]. It has been proposed that targeted screening protocols may be more cost-effective in settings with < 5% prevalence of MRSA colonization on admission [143].

Many studies [61,144–149] have shown that active surveillance against VRE is cost-effective. For example, Calfee et al [144] showed that an established active surveillance program results in control of endemic VRE in high-risk patients. The infection control program was established in response to a hospital-wide VRE outbreak, and was sustained after the outbreak was controlled. The study by Calfee et al spanned 5 years and was performed at a tertiary-level university hospital, where cultures from perirectal areas were used to identify high-risk patients who were asymptomatically colonized with VRE. During the latter 2 years, 768 new cases of VRE colonization were detected among 69,672 admissions (1.1% of admissions), of which 730 (95.1%) were identified by active surveillance methods. This implies that routine clinical cultures would probably have missed the majority of colonized patients. During this period, the incidence of VRE infection was likewise extremely low at 0.12/1000 patient days (ie, 90 nosocomial VRE infections were identified in 83 patients during 743,956 days of patient care). Sixty-nine of the 83 patients (83%) who developed nosocomial VRE infections were found to be colonized with VRE by surveillance culture before the onset of infection.

Patient Decolonization

Chlorhexidine gluconate has been used in several settings to control outbreaks and infections related to MRSA and VRE due to its broad-spectrum activity against these pathogens. Chlorhexidine-based solutions reduce the density of skin colonization with pathogens such as MRSA and VRE (skin asepsis), thus lowering the risk for horizontal transmission between health care workers and patients.

Decolonization with chlorhexidine as an MRSA infection reduction technique has demonstrated benefit in the ICU setting [150]. The previously mentioned large, cluster-randomized ICU trial by Huang and colleagues found universal decolonization with twice-daily intranasal mupirocin for 5 days and daily bathing with chlorhexidine-impregnated cloths for the entire ICU stay was superior to targeted decolonization of known MRSA carriers in preventing overall MRSA isolates. However, universal decolonization failed to show a reduction in MRSA bacteremia [151], and concerns about mupirocin resistance may limit the applicability of this approach.

There are now several studies [152–154] that show decreased acquisition of VRE with use of daily chlorhexidine bathing. In a study including 1787 ICU patients, Vernon et al found [154] that the reducing microbial density of VRE on patient’s skin by using chlorhexidine led to decreased transmission. In another study by Climo et al [153] that involved 6 ICUs at 4 academic centers and measured the incidence of MRSA and VRE colonization and blood stream infections (BSI) during a period of bathing with routine soap for 6 months compared with a 6-month period where all admitted patients received daily bathing with a chlorhexidine solution, results found decreased acquisition of VRE by 50% (4.35 vs. 2.19 cases/1000 patient days, P < 0.008) following the introduction of daily chlorhexidine bathing. Furthermore, compared with 16 of 270 patients colonized with VRE who subsequently developed VRE bacteremia at baseline, only 4 of 226 VRE-colonized patients bathed with chlorhexidine in the intervention period developed a BSI, translating into a relative risk reduction of 3.35 (95% CI, 1.13–9.87; P < 0.035). Patients colonized with VRE were 3 times less likely to develop VRE bacteremia when bathed with chlorhexidine compared with regular bathing.  Despite the success of this protocol for VRE, when analyzed by individual organism no significant reductions in MRSA acquisition or BSI were reported. This finding is similarly corroborated by a trial conducted in the pediatric ICU setting which found an overall reduction in bacteremia with daily chlorhexidine washes but no significant decrease in cases due to S. aureus [155].

The results of these studies suggest that daily bathing with chlorhexidine should be part of routine practice in health care, especially in ICUs where endemic MRSA or VRE rates are high. Whether there is benefit in other settings needs to be studied.

In addition to chlorhexidine washes, other decolonization techniques have been proposed to reduce colonization and the spread of HAIs in the ICU setting. A randomized controlled trial of daily 5% tea tree oil body washes for the prevention of MRSA colonization failed to significantly reduce rates compared to standard soap body washes [156]. Another proposed decolonization intervention that has not been widely adopted in the United States due to concerns related to development of resistant organisms is selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) with antimicrobial agents [157,158]. In terms of clinical benefit, SDD/SOD have been found to decrease MDRO infection rate [159] and mortality [160].

Cohorting

There is insufficient evidence to conclude that cohorting isolated patients is of benefit for routine use in the endemic ICU setting. A few studies, mainly in the outbreak setting, have examined this approach and the results are conflicting [161,162]. Pending further studies in this area, it is reasonable to cohort patients colonized with the same microorganisms, especially if patients cannot be placed in single rooms.

CONCLUSION

The emergence of MRSA and VRE has led to a resurgence of interest and emphasis on infection control practices and prevention. CDC guidelines to help health care practitioners manage these MDROs in the hospital and ICU-setting exist; however, many questions remain regarding best practice.

Prevention of MRSA and VRE needs to be a 2-pronged approach—antimicrobial stewardship [163] and infection control. A robust antimicrobial stewardship program to optimize and minimize inappropriate antibiotic use is necessary in every institution. From the infection prevention standpoint, it is unclear if systematic identification of MRSA and VRE colonization followed by contact precautions is useful in reducing transmission. It is clear that a strong institutional climate of promoting patient safety and a culture of infection prevention will help in reducing MRSA and VRE facility-wide. It also appears that universal gowning and gloving may be useful for reducing MRSA, but not VRE, transmission. While universal decolonization with mupirocin is efficacious in reducing MRSA, this strategy is not recommended because of promoting mupirocin resistance. However, the use of daily bathing with chlorhexidine represents a relatively low-cost, high-yield intervention that should be adopted. Pending further data, patients known to be colonized or infected with MRSA should be placed in contact precuations as is current practice in most institutions. Finally, in this era of MDROs, hand hygiene remains our best defense against the spread of pathogens in the health care environment.

Note: This article does not represent the views of the Department of Veterans Affairs.

Corresponding author: Nasia Safdar, MD, Willam S. Middleton Memorial Veterans Affairs Hospital, 2500 Overlook Terrace, Madison, WI 53705, [email protected].

Funding/support: This work is funded by a MERIT award from the Department of Veterans Affairs to Nasia Safdar.

Financial disclosures: None.

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From the Department of Medicine, Infectious Disease Practice and Innovations, The Medical City, Pasig City, Philippines (Dr. Abad), the Division of Emergency Medicine, University of Wisconsin Medical School, Madison, WI (Dr. Pulia), University of Wisconsin Hospital and Clinics, Madison, WI (Ms. Krupp), and the Willam S. Middleton Memorial Veterans Affairs Hospital, Madison, WI (Dr. Safdar).

Patients in intensive care units (ICUs) are at greatly increased risk of developing health care-associated infections (HAIs) [1]. More than 70% of the bacteria that cause HAIs are resistant to at least one of the antimicrobials commonly used to treat these infections [2]. Two such pathogens, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are responsible for a considerable proportion of ICU infections that are associated with increased morbidity, mortality, and costs [3–5]. In this review, we discuss the epidemiology of colonization and infection by MRSA and VRE and provide an update on practices for prevention of transmission and infection by MRSA and VRE in the ICU.

EPIDEMIOLOGY AND MECHANISMS OF RESISTANCE

MRSA is the major cause of HAIs worldwide [6]. Among ICUs in the United States, the proportion of methicillin resistance among S. aureus isolates increased from 35.9% in 1992 to 64.4% in 2003 [4]. Approximately 8% of patients are colonized with MRSA upon admission, and an average of 5% will acquire MRSA colonization in the ICU [7,8]. A comparison study of academic tertiary care facilities found medical ICUs had higher MRSA admission prevalence rates than surgical ICUs, whereas surgical ICUs had a higher incidence rate [7]. Enteroccoccus is the third most common pathogen associated with HAIs, with 33% resistant to vancomycin [9]. VRE infection is associated with increased ICU cost and increased length of stay [10]. Incidence of ICU-acquired VRE varies among regions and countries. For example, in the United States, Warren et al [11] reported a VRE incidence of 27 cases per 1000 patient ICU days, whereas Kohlenberg et al [12] reported a mean incidence of 0.29 cases per 1000 patient ICU days in Germany.

Understanding the mechanisms that allow development of resistant strains of S. aureus and Enterococcus species is important to devise preventive strategies. Methicillin resistance in MRSA is determined by the staphylococcal cassette chromosome mec (SCCmec), a mobile genetic element that carries the mecA gene. The mecA gene codes for an additional penicillin-binding protein (PBP) that has a reduced affinity towards methicillin (PBP2a/PBP2'). This results in a reduced ability to bind to the bacterial cell wall and inhibit synthesis [13,14]. Study of molecular epidemiology has identified MRSA as originating from 8 major variants of the mecA gene [15]. The majority of MRSA infections are caused by strains belonging to a few internationally disseminated clones [14]. The first identified strains were associated with infections in hospitalized patients (hospital-associated MRSA), but community-associated MRSA strains have since emerged and have become established globally, including in health care institutions [16].

Community-acquired MRSA can cause severe infections in health hosts [17]; possible explanations include increased CA-MRSA virulence due to the acquisition of mobile genetic elements, namely those containing Panton-Valentine leukocidin (PVL) [18] or increased expression of core genome-encoded virulence genes, such as phenol-soluble modulin (PSM) cytolysins, α-toxin, and other virulence determinants [19].

Enterococcus is intrinsically resistant to several antimicrobial drugs, with resistance to vancomycin encoded by several clusters of genes known as vancomycin resistance gene clusters (eg, vanA, vanB). The gene clusters generate resistance through multiple pathways which encode enzymes to determine the structure of peptidoglycan precursors [20,21]. Genetically diverse, hospital-associated VRE outbreaks have been associated with single clones, multiple clones, and changing molecular epidemiology over time [21]. While up to 25% of the VRE genome includes acquired elements, the majority of hospital-associated infections are traced to a few clonal complexes, which differ from community-associated VRE strains [22].

The evolution of these efficient mechanisms that promote drug resistance has made it extremely challenging to eradicate organisms such as MRSA and VRE. However, advances in recent years have furthered our understanding of the epidemiology, pathogenesis, and methods of prevention and containment.

RISK FACTORS FOR COLONIZATION AND INFECTION

MRSA

The risk factors underlying MRSA colonization and infection in the ICU setting can be categorized as either patient/host or environmental factors. A wide range of patient-level factors is associated with MRSA colonization upon admission. General principles regarding the transmission of MRSA in the community include close contact with colonized or infected individuals, breaks in the skin, crowded living conditions and poor hygiene. These factors, alone or in combination, are thought to underlie observed outbreaks among sports teams, military personnel, correction facilities, American Indian communities, and daycare centers [23–34].

Two recently published systematic reviews have summarized important patient-level factors associated with MRSA colonization at the time of hospital admission. Forster et al [35] examined 27 studies and identified previous admission to hospital, transfer from nursing home or long-term care facility, and previous antibiotic use as the top 3 factors associated with MRSA colonization. A similar review conducted by McKinnell and colleagues [36] found that prior hospitalization, nursing home contact, recent antibiotic use, and exposure to health care-associated pathogens (MRSA carriage, VRE carriage, or Clostridium difficile infection) were found to portend the highest risk. Specific comorbid conditions also conveyed an increased risk, including congestive heart failure, chronic wounds/bedsores, diabetes mellitus, pulmonary disease, immunosuppression, urinary catheter, and renal failure/dialysis. It is clear that health care contacts, especially recent hospitalization, residence in a long-term care facility, and antibiotic use, are significant risk factors for MRSA colonization [37–39].

In contrast to those already colonized with MRSA, some patients acquire MRSA during hospitalization. In these cases, transmission via hands of health care workers is likely the most common mechanism for spread of MRSA [6,40–42]. An understaffed ICU has also been cited as a potential risk factor for ICU MRSA transmission, perhaps due to sacrifices in hand hygiene practices by overextended staff [6]. Additional factors associated with increased risk of nosocomial MRSA acquisition include duration of antibiotic therapy, exposure to quinolone or macrolide antibiotics, length of hospital stay, enteral feeding, post-surgical status, insertion of central line or urinary catheter during admission, ICU admission, and proximity to another patient with MRSA infection or colonization [43–45]. A summary of risk factors for MRSA acquisition is shown in Table 1.

Regardless of whether MRSA colonization precedes admission or occurs due to nosocomial spread, it is associated with increased risk of developing a HAI [46–49]. In 2 large prospective observational cohort studies, the hazard ratios of MRSA colonization developing into S. aureus infections during the ICU stay were 3.84 and 4.70, respectively [50,51]. High levels of concordance between MRSA colonization strains and HAI strains have also been reported [52]. Nasal colonization with S. aureus has also been identified as an independent risk factor for developing ventilator-associated pneumonia (VAP) and bacteremia [53,54]. A case series of ICU patients with S. aureus nasal colonization who developed lower respiratory tract infections demonstrated genetically identical nasal and bronchial strains in 15/16 cases [55]. This finding strongly suggests that nasopharyngeal colonization with S. aureus contaminates oral secretions that are aspirated by critically ill patients, resulting in subsequent pneumonia. In a long-term outcomes study among a matched cohort of veterans, MRSA colonization was associated with an increased risk of infection-related readmission and mortality [56]. These findings reflect the critically important nature of measures designed to curb nosocomial transmission and acquisition of MRSA, especially among the vulnerable ICU population.

VRE

As with MRSA, risk factors associated with VRE colonization include both patient-level and ICU-level (or environmental) factors [57]. Examples of patient-level factors include previous antimicrobial exposure [58–62], underlying medical illnesses such as chronic renal failure requiring hemodialysis [11,63], length of hospital or ICU stay [11,59,64,65], and recent exposure to health care facilities. ICU-level factors of relevance are the prevalence of VRE in the unit, with high levels of endemicity leading to higher risk of colonization and transmission.

Antibiotic use is a major risk factor for VRE acquisition, although the type and class of antibiotic varies considerably across studies; the most frequently identified antibiotics are broad-spectrum cephalosporins, vancomycin, and anti-anaerobic agents [58,62,64]. Patients with chronic liver disease and post-transplantation are at exceedingly high risk for VRE acquisition [59]. In a recent study by Pan [66], for example, the authors found that the incidence of newly acquired VRE was 21.9 per 1000 patient-days in an ICU setting. On multivariate analysis, the authors found that, similar to other reports [11,59,67], length of stay in the ICU was associated with increased risk of VRE acquisition, with each additional day of stay increasing risk of VRE by 1.03 times. Warren et al undertook a prospective cohort study involving 519 patients admitted to the ICU for more than 48 hours [11]. Seventy-four (21%) of 352 patients were subsequently colonized with VRE. The median time to development of a positive VRE culture after ICU admission was 6 days. Increased mean APACHE II score on ICU admission (P = 0.002), sucralfate use (P = 0.003), vasopressor use (P = 0.01), tracheostomy in the ICU (P = 0.02), and C. difficile diarrhea (P = 0.002) appeared to be associated with VRE acquisition.

It appears that VRE acquisition is often associated with the sick subgroup of patients, and risk factors generally associated with VRE colonization and infection co-relate with disease chronicity and severity of illness. Length of hospitalization, ICU stay, hemodialysis, or transplantation may all be markers of disease severity. A summary of risk factors for VRE acquisition is shown in Table 2.

REDUCING TRANSMISSION—MRSA AND VRE PREVENTION STRATEGIES

Evidence-based guidelines developed by the Centers for Disease Control (CDC) Hospital Infection Control Practices Advisory Committee (HICPAC) for prevention of MRSA and VRE are available [68]. Several recently conducted well-designed clinical trials also provide additional insight that may be particularly helpful in the ICU setting [69]. A summary of the MRSA prevention guidelines issued by the CDC and included in its “MRSA toolkit” is provided in Table 3. A similar guideline on prevention of VRE [70], published more than a decade ago, has similar elements. Table 3 shows a side-by-side comparison of these elements. Unfortunately, despite these guidelines and extensive research regarding prevention and control, considerable controversy exists as to the most effective approaches. As such, these recommendations should be tailored to meet the needs of the specific ICU setting.

Antimicrobial Stewardship

Antibiotic use is a major driver of antibiotic resistance. A meta-analysis by de Bruin and Riley [71] studied the effect of vancomycin usage on VRE colonization and infection. A total of 12 articles describing 13 studies were included; none were randomized controlled trials. All studies were quasi-experimental and lacked control groups. Among all studies, less than half (46%) implemented vancomycin reduction measures as the sole type of intervention [72–76]. The remaining studies implemented other infection control modalities and or restricted the use of other antimicrobials [77–83]. Although all studies that implemented vancomycin restriction alone as a single strategy showed a decline in vancomycin usage, only 2 of these [74,75] showed a relative risk reduction in VRE acquisition post-intervention. Also, studies that restricted vancomycin alone revealed a trend towards lower efficacy in reducing VRE colonization and infection (33%) when compared with those that used additional measures (71%). While judicious antibiotic use should always be practiced, the evidence for vancomycin restriction as a sole intervention to control VRE is scant. It may be that other antibiotics are as big or bigger drivers of resistance in enterococci than vancomycin. For example, a growing body of literature supports antibiotic restriction, especially fluoroquinolones, for reducing MRSA. In several time-series quasi-experimental studies, restriction of fluorquinolones was associated with reduced trends in MRSA infections in the acute care setting, and consideration should be given to monitor and optimize fluoroquinolone use in the ICU setting [84,85].

Antimicrobial stewardship programs are fundamental to optimizing antibiotic use in the ICU and the authors strongly recommend that all ICUs should have such a program in place.

Educational Interventions

Infection control and multidrug-resistant organism (MDRO)–specific education programs for health care workers is a core principle of the CDC’s prevention guidelines. The HICPAC VRE guideline also explicitly states “continuing education programs for hospital staff (including attending and consulting physicians, medical residents, and students; pharmacy, nursing, and laboratory personnel; and other direct patient-care providers) should include information concerning the epidemiology of VRE and the potential impact of this pathogen on the cost and outcome of patient care [70].” A systematic review published in 2008 [86] that included 26 studies showed that such interventions to prevent HCAIs are usually successful; in this review, 20 of 26 studies showed a statistically significant decrease in infection rates, with risk ratios ranging from 0 to 1.6. Education was usually part of a broader array of infection control interventions. While clearly essential, education alone is unlikely to have a sustained impact on reducing MRSA and VRE infections.

Infection Control Measures

Major infection control interventions include hand hygiene, the use of personal protective equipment (PPE), and cohorting. These measures can be grouped into “horizontal” (or global) vs. “vertical” (or targeted) strategies. Although not mutually exclusive, horizontal approaches are designed to have an impact on multiple pathogens (pathogen nonspecific), whereas vertical approaches are designed to reduce the impact of specific pathogens (such as VRE). For the purposes of this review, we will discuss both strategies for containment of MRSA and VRE. Horizontal strategies include hand hygiene, universal gloving and/or gowning, environmental cleaning, and daily bathing with chlorhexidine. Vertical strategies include screening for either MRSA or VRE followed by placement in contact precautions and decolonization with mupirocin.

Hand Hygiene

Hand washing is fundamental to reducing transmission of MDROs in health care institutions; however, optimal compliance is hard to achieve and sustain. Barriers to adherence may include unavailability of sinks or hand hygiene materials (eg, alcohol-based gels, gloves) time constraints, forgetfulness, or lack of knowledge [87–95]. Several monitoring strategies have been evaluated to increase compliance with hand hygiene. Most involve direct observation followed by performance assessment and feedback.

Trials examining the impact of improvements in hand hygiene compliance on HAIs in the ICU setting have largely found benefit, although not all studies showed a decline in HAI. In a prospective crossover trial, Rupp et al [96] found dramatic improvements in compliance with hand gel availability, but this did not translate to decreased nosocomial MRSA infections. Venkatesh et al [97] carried out a before-and-after interventional prospective study in a hematology unit in a tertiary level hospital to evaluate the use of an electronic method of surveillance to determine compliance with hand hygiene. The authors also used rates of horizontal transmission of VRE as a secondary end-point. Results of the study showed that hand hygiene compliance improved from 36.3% at baseline to 70.1%. This represented an OR of 4.1 (95% confidence interval, 3.7–4.5), which the authors attributed to the use of automated alerts. VRE transmission rates before and during intervention were not statistically different, but the rates of infection were lower at 1.0 per month in comparison with 4.7 infections per month in the preceding 6 months (P = 0.096).

While improved hand hygiene may result in significant reductions in HAIs [40], research indicates hand hygiene alone influences about 40% of infections in the ICU setting [98]. As such, hand hygiene should be viewed as a necessary component of a comprehensive infection control program [99]. Despite the success of hand hygiene in reducing HAIs in the ICU, effective strategies to improve compliance remain elusive even under study conditions and further research is needed in this area [100].

Personal Protective Equipment

Tenorio et al [101] conducted a study to assess the effectiveness of gloving in the prevention of hand carriage of VRE by health care workers. The study showed that among 50 health care workers who had contact with patients colonized with VRE, 6 carried a similar patient strain even prior to known contact, and 17 of 44 (69%) had a patient-related VRE strain on their gloves after contact. This suggests a relatively high rate of colonization after usual patient-care contact. Factors associated with acquisition of VRE on gloves included duration of contact, contact with a patient’s body fluids, presence of diarrhea in a patient, mean VRE colony counts on a patient’s skin, and number of body sites colonized with VRE. Although gloves reduced the risk of VRE acquisition of VRE by 71% (ie, 12/17 did not have VRE on their hands after de-gloving) the protection afforded by gloves was incomplete. As such, hand hygiene after glove removal is recommended.

Slaughter et al [102] compared the use of personal protective equipment in the acquisition of VRE. During this study, 93 patients in glove-and-gown rooms and 88 patients in glove-only rooms had similar rates of VRE at baseline entry into the ICU and after the intervention. Mean times to colonization among the patients who became colonized were 8.0 days in the glove-and-gown group and 7.1 days in the glove-only group. None of these comparisons were statistically significant and the authors concluded that the universal use of gown and gloves was no better than the use of gloves alone in preventing VRE colonization.

A recent cluster randomized trial compared the effect of universal PPE (ie, gowning and gloving) with usual care for reducing acquisition of MRSA or VRE as a composite outcome [103]. The study did not find that universal gowning and gloving reduced VRE or MRSA acquisition but found a 40% decline in MRSA acquisition in the intervention ICUs compared with baseline rates of MRSA. No major adverse effects of universal gowning and gloving were noted in this study. A thoughtful editorial commenting on this article proposes that several aspects of the study deserve consideration, including the possibility of false-negative screening tests for VRE, which may have partially accounted for the negative primary outcome [69].

Based on these studies, it appears that the use of barrier precautions may be of value more for MRSA than VRE but further studies are needed to examine its impact on other types of pathogens, including new and emerging MDROs. Until further evidence becomes available, routine gowning and gloving may be of value in units with a high prevalence of MRSA.

Environmental Cleaning

Accumulating data suggests that the environment may play a major role in transmission of pathogens. MRSA has the ability to survive for days to weeks on inanimate objects [104–107]. Environmental contamination results in contamination of staff clothing and gloves [107,108] and is highly correlated with colonization strains among inpatients [109]. Although some studies of enhanced cleaning techniques and increased environmental services staff time have demonstrated reductions in MRSA outbreaks [110–112], the results are not universally favorable [113,114] and further studies are needed to examine the impact of environmental cleaning on rates of MRSA colonization or infection.

Several studies have implicated contaminated equipment as vectors for transmission of VRE during outbreaks [115–117], but the direction of fomite transfer from patient to environment has been difficult to ascertain. VRE have been found frequently on a variety of inanimate objects and surfaces in different health care environments [118–123], including gloved or ungloved hands of health care workers [101,124,125]. Hayden et al [126] determined the effect of improved environmental cleaning on VRE acquisition rates. This study was a pre-and-post intervention study carried out in a 21-bed medical intensive care unit (MICU) in a tertiary hospital over several phases. The intervention included the creation of a unique and improved cleaning program, as well as in-services to housekeeper services, education of the MICU staff, and a hand hygiene campaign. The results of the study showed decreased acquisition of VRE from 33.47 cases per 1000 patient days at risk in period 1 to 10.40 cases per 1000 patient-days at risk by period 4 of the study. Increased environmental cleaning was also associated with reduced growth of VRE from environmental cultures. At baseline, weekly contamination rates were 0.15 and 0.1 for samples obtained before and after cleaning, respectively. Culture positivity decreased to 0.07 and 0.04 for before and after cleaning in period 2 and then remained at low levels during the remainder of the study. It is important to note that the method for disinfecting used in this study was the “bucket method” as promoted by Byers [127]. This study provides further support for the importance of an environmental reservoir and of environmental decontamination to prevent endemic cross-transmission of VRE [126].

Goodman et al [128] used similar interventions but added a feedback tool using a black-light monitoring system (ie, use of an invisible, nontoxic marker to delineate areas that are adequately or inadequately cleaned) to reduce the likelihood of isolating either MRSA or VRE from an ICU environment. This study also showed favorable results, and notably, the use of the black-light monitoring system identified specific areas that were typically inadequately disinfected. Results showed that flat, horizontal surfaces (eg, countertops, bedside tray tables, and hamper tops) were adequately cleaned more often than small, vertical surfaces (eg, doorknobs, toilet handles, light switches, and electronics).

Part of the controversy surrounding the impact of environmental cleaning is the difficulty in determining its individual value as part of an overall infection control bundle [129]. A proposed area of demonstrable impact for environmental cleaning are frequently touched sites which are more likely to be contaminated with pathogens. Focusing on these “hot-bed” areas of the care environment may offer a useful adjunct to other infection control measures [129].

Active Surveillance

Active surveillance refers to periodic screening for asymp-tomatic carriers followed by placement of colonized patients in contact isolation. This practice is highly variable across institutions, as the evidence supporting this practice is conflicting and there are concerns about the cost of implementing this approach without solid evidence [70,130,131]. Despite lack of randomized controlled trials to guide this practice for MRSA prevention, many hospitals utilize MRSA surveillance and it is mandated by law in 9 states [132,133].

A prospective, interventional cohort study of universal MRSA screening on admission to surgical wards failed to reduce nosocomial MRSA infections [134]. Most recently, a pragmatic, cluster-randomized ICU trial reported that universal decolonization with chlorhexidine wipes and mupirocin use was more effective than screening and isolation in reducing rates of MRSA clinical isolates [65]. However, concerns regarding the risk of mupirocin resistance have been expressed [135,136]. The only randomized trial that compared active surveillance for MRSA and VRE followed by contact precautions to usual care did not find a benefit to active surveillance.

Huskins et al [137], in a large, cluster-randomized trial of 19 ICUs from different hospitals, determined the utility of using a culture-based active surveillance and contact isolation, compared with usual care (contact isolation for patients colonized with MRSA or VRE) as identified by existing hospital protocols, to reduce the incidence of colonization or infection with MRSA or VRE. In this trial, which spanned 6 months and involved 3488 participants, the authors found no significant difference between the intervention and control ICUs in terms of MRSA and VRE colonization or infection rates.

Conflicting with these findings is an observational study comparing MRSA infection rates before and after institution of a universal screening protocol, which demonstrated a 69.6% (CI, –89.2% to –19.6%]; P = 0.03) reduction in hospital wide MRSA prevalence density with screening [138]. The “MRSA bundle” implemented in 2007 at VA hospitals nationwide, which included universal screening, produced a 62% (P < 0.001) reduction in MRSA ICU infections; the relative contribution of the various bundle components is uncertain [139,140].

A proposed cost-saving alternative to universal screening is selective screening based on risk factor assessment [141]. The effectiveness of this type of program depends on creating a clinical decision-making tool capable of accurately identifying high-risk individuals while also accounting for the different risk factor profiles between HA-MRSA and CA-MRSA [142]. It has been proposed that targeted screening protocols may be more cost-effective in settings with < 5% prevalence of MRSA colonization on admission [143].

Many studies [61,144–149] have shown that active surveillance against VRE is cost-effective. For example, Calfee et al [144] showed that an established active surveillance program results in control of endemic VRE in high-risk patients. The infection control program was established in response to a hospital-wide VRE outbreak, and was sustained after the outbreak was controlled. The study by Calfee et al spanned 5 years and was performed at a tertiary-level university hospital, where cultures from perirectal areas were used to identify high-risk patients who were asymptomatically colonized with VRE. During the latter 2 years, 768 new cases of VRE colonization were detected among 69,672 admissions (1.1% of admissions), of which 730 (95.1%) were identified by active surveillance methods. This implies that routine clinical cultures would probably have missed the majority of colonized patients. During this period, the incidence of VRE infection was likewise extremely low at 0.12/1000 patient days (ie, 90 nosocomial VRE infections were identified in 83 patients during 743,956 days of patient care). Sixty-nine of the 83 patients (83%) who developed nosocomial VRE infections were found to be colonized with VRE by surveillance culture before the onset of infection.

Patient Decolonization

Chlorhexidine gluconate has been used in several settings to control outbreaks and infections related to MRSA and VRE due to its broad-spectrum activity against these pathogens. Chlorhexidine-based solutions reduce the density of skin colonization with pathogens such as MRSA and VRE (skin asepsis), thus lowering the risk for horizontal transmission between health care workers and patients.

Decolonization with chlorhexidine as an MRSA infection reduction technique has demonstrated benefit in the ICU setting [150]. The previously mentioned large, cluster-randomized ICU trial by Huang and colleagues found universal decolonization with twice-daily intranasal mupirocin for 5 days and daily bathing with chlorhexidine-impregnated cloths for the entire ICU stay was superior to targeted decolonization of known MRSA carriers in preventing overall MRSA isolates. However, universal decolonization failed to show a reduction in MRSA bacteremia [151], and concerns about mupirocin resistance may limit the applicability of this approach.

There are now several studies [152–154] that show decreased acquisition of VRE with use of daily chlorhexidine bathing. In a study including 1787 ICU patients, Vernon et al found [154] that the reducing microbial density of VRE on patient’s skin by using chlorhexidine led to decreased transmission. In another study by Climo et al [153] that involved 6 ICUs at 4 academic centers and measured the incidence of MRSA and VRE colonization and blood stream infections (BSI) during a period of bathing with routine soap for 6 months compared with a 6-month period where all admitted patients received daily bathing with a chlorhexidine solution, results found decreased acquisition of VRE by 50% (4.35 vs. 2.19 cases/1000 patient days, P < 0.008) following the introduction of daily chlorhexidine bathing. Furthermore, compared with 16 of 270 patients colonized with VRE who subsequently developed VRE bacteremia at baseline, only 4 of 226 VRE-colonized patients bathed with chlorhexidine in the intervention period developed a BSI, translating into a relative risk reduction of 3.35 (95% CI, 1.13–9.87; P < 0.035). Patients colonized with VRE were 3 times less likely to develop VRE bacteremia when bathed with chlorhexidine compared with regular bathing.  Despite the success of this protocol for VRE, when analyzed by individual organism no significant reductions in MRSA acquisition or BSI were reported. This finding is similarly corroborated by a trial conducted in the pediatric ICU setting which found an overall reduction in bacteremia with daily chlorhexidine washes but no significant decrease in cases due to S. aureus [155].

The results of these studies suggest that daily bathing with chlorhexidine should be part of routine practice in health care, especially in ICUs where endemic MRSA or VRE rates are high. Whether there is benefit in other settings needs to be studied.

In addition to chlorhexidine washes, other decolonization techniques have been proposed to reduce colonization and the spread of HAIs in the ICU setting. A randomized controlled trial of daily 5% tea tree oil body washes for the prevention of MRSA colonization failed to significantly reduce rates compared to standard soap body washes [156]. Another proposed decolonization intervention that has not been widely adopted in the United States due to concerns related to development of resistant organisms is selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) with antimicrobial agents [157,158]. In terms of clinical benefit, SDD/SOD have been found to decrease MDRO infection rate [159] and mortality [160].

Cohorting

There is insufficient evidence to conclude that cohorting isolated patients is of benefit for routine use in the endemic ICU setting. A few studies, mainly in the outbreak setting, have examined this approach and the results are conflicting [161,162]. Pending further studies in this area, it is reasonable to cohort patients colonized with the same microorganisms, especially if patients cannot be placed in single rooms.

CONCLUSION

The emergence of MRSA and VRE has led to a resurgence of interest and emphasis on infection control practices and prevention. CDC guidelines to help health care practitioners manage these MDROs in the hospital and ICU-setting exist; however, many questions remain regarding best practice.

Prevention of MRSA and VRE needs to be a 2-pronged approach—antimicrobial stewardship [163] and infection control. A robust antimicrobial stewardship program to optimize and minimize inappropriate antibiotic use is necessary in every institution. From the infection prevention standpoint, it is unclear if systematic identification of MRSA and VRE colonization followed by contact precautions is useful in reducing transmission. It is clear that a strong institutional climate of promoting patient safety and a culture of infection prevention will help in reducing MRSA and VRE facility-wide. It also appears that universal gowning and gloving may be useful for reducing MRSA, but not VRE, transmission. While universal decolonization with mupirocin is efficacious in reducing MRSA, this strategy is not recommended because of promoting mupirocin resistance. However, the use of daily bathing with chlorhexidine represents a relatively low-cost, high-yield intervention that should be adopted. Pending further data, patients known to be colonized or infected with MRSA should be placed in contact precuations as is current practice in most institutions. Finally, in this era of MDROs, hand hygiene remains our best defense against the spread of pathogens in the health care environment.

Note: This article does not represent the views of the Department of Veterans Affairs.

Corresponding author: Nasia Safdar, MD, Willam S. Middleton Memorial Veterans Affairs Hospital, 2500 Overlook Terrace, Madison, WI 53705, [email protected].

Funding/support: This work is funded by a MERIT award from the Department of Veterans Affairs to Nasia Safdar.

Financial disclosures: None.

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From the Department of Medicine, Infectious Disease Practice and Innovations, The Medical City, Pasig City, Philippines (Dr. Abad), the Division of Emergency Medicine, University of Wisconsin Medical School, Madison, WI (Dr. Pulia), University of Wisconsin Hospital and Clinics, Madison, WI (Ms. Krupp), and the Willam S. Middleton Memorial Veterans Affairs Hospital, Madison, WI (Dr. Safdar).

Patients in intensive care units (ICUs) are at greatly increased risk of developing health care-associated infections (HAIs) [1]. More than 70% of the bacteria that cause HAIs are resistant to at least one of the antimicrobials commonly used to treat these infections [2]. Two such pathogens, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are responsible for a considerable proportion of ICU infections that are associated with increased morbidity, mortality, and costs [3–5]. In this review, we discuss the epidemiology of colonization and infection by MRSA and VRE and provide an update on practices for prevention of transmission and infection by MRSA and VRE in the ICU.

EPIDEMIOLOGY AND MECHANISMS OF RESISTANCE

MRSA is the major cause of HAIs worldwide [6]. Among ICUs in the United States, the proportion of methicillin resistance among S. aureus isolates increased from 35.9% in 1992 to 64.4% in 2003 [4]. Approximately 8% of patients are colonized with MRSA upon admission, and an average of 5% will acquire MRSA colonization in the ICU [7,8]. A comparison study of academic tertiary care facilities found medical ICUs had higher MRSA admission prevalence rates than surgical ICUs, whereas surgical ICUs had a higher incidence rate [7]. Enteroccoccus is the third most common pathogen associated with HAIs, with 33% resistant to vancomycin [9]. VRE infection is associated with increased ICU cost and increased length of stay [10]. Incidence of ICU-acquired VRE varies among regions and countries. For example, in the United States, Warren et al [11] reported a VRE incidence of 27 cases per 1000 patient ICU days, whereas Kohlenberg et al [12] reported a mean incidence of 0.29 cases per 1000 patient ICU days in Germany.

Understanding the mechanisms that allow development of resistant strains of S. aureus and Enterococcus species is important to devise preventive strategies. Methicillin resistance in MRSA is determined by the staphylococcal cassette chromosome mec (SCCmec), a mobile genetic element that carries the mecA gene. The mecA gene codes for an additional penicillin-binding protein (PBP) that has a reduced affinity towards methicillin (PBP2a/PBP2'). This results in a reduced ability to bind to the bacterial cell wall and inhibit synthesis [13,14]. Study of molecular epidemiology has identified MRSA as originating from 8 major variants of the mecA gene [15]. The majority of MRSA infections are caused by strains belonging to a few internationally disseminated clones [14]. The first identified strains were associated with infections in hospitalized patients (hospital-associated MRSA), but community-associated MRSA strains have since emerged and have become established globally, including in health care institutions [16].

Community-acquired MRSA can cause severe infections in health hosts [17]; possible explanations include increased CA-MRSA virulence due to the acquisition of mobile genetic elements, namely those containing Panton-Valentine leukocidin (PVL) [18] or increased expression of core genome-encoded virulence genes, such as phenol-soluble modulin (PSM) cytolysins, α-toxin, and other virulence determinants [19].

Enterococcus is intrinsically resistant to several antimicrobial drugs, with resistance to vancomycin encoded by several clusters of genes known as vancomycin resistance gene clusters (eg, vanA, vanB). The gene clusters generate resistance through multiple pathways which encode enzymes to determine the structure of peptidoglycan precursors [20,21]. Genetically diverse, hospital-associated VRE outbreaks have been associated with single clones, multiple clones, and changing molecular epidemiology over time [21]. While up to 25% of the VRE genome includes acquired elements, the majority of hospital-associated infections are traced to a few clonal complexes, which differ from community-associated VRE strains [22].

The evolution of these efficient mechanisms that promote drug resistance has made it extremely challenging to eradicate organisms such as MRSA and VRE. However, advances in recent years have furthered our understanding of the epidemiology, pathogenesis, and methods of prevention and containment.

RISK FACTORS FOR COLONIZATION AND INFECTION

MRSA

The risk factors underlying MRSA colonization and infection in the ICU setting can be categorized as either patient/host or environmental factors. A wide range of patient-level factors is associated with MRSA colonization upon admission. General principles regarding the transmission of MRSA in the community include close contact with colonized or infected individuals, breaks in the skin, crowded living conditions and poor hygiene. These factors, alone or in combination, are thought to underlie observed outbreaks among sports teams, military personnel, correction facilities, American Indian communities, and daycare centers [23–34].

Two recently published systematic reviews have summarized important patient-level factors associated with MRSA colonization at the time of hospital admission. Forster et al [35] examined 27 studies and identified previous admission to hospital, transfer from nursing home or long-term care facility, and previous antibiotic use as the top 3 factors associated with MRSA colonization. A similar review conducted by McKinnell and colleagues [36] found that prior hospitalization, nursing home contact, recent antibiotic use, and exposure to health care-associated pathogens (MRSA carriage, VRE carriage, or Clostridium difficile infection) were found to portend the highest risk. Specific comorbid conditions also conveyed an increased risk, including congestive heart failure, chronic wounds/bedsores, diabetes mellitus, pulmonary disease, immunosuppression, urinary catheter, and renal failure/dialysis. It is clear that health care contacts, especially recent hospitalization, residence in a long-term care facility, and antibiotic use, are significant risk factors for MRSA colonization [37–39].

In contrast to those already colonized with MRSA, some patients acquire MRSA during hospitalization. In these cases, transmission via hands of health care workers is likely the most common mechanism for spread of MRSA [6,40–42]. An understaffed ICU has also been cited as a potential risk factor for ICU MRSA transmission, perhaps due to sacrifices in hand hygiene practices by overextended staff [6]. Additional factors associated with increased risk of nosocomial MRSA acquisition include duration of antibiotic therapy, exposure to quinolone or macrolide antibiotics, length of hospital stay, enteral feeding, post-surgical status, insertion of central line or urinary catheter during admission, ICU admission, and proximity to another patient with MRSA infection or colonization [43–45]. A summary of risk factors for MRSA acquisition is shown in Table 1.

Regardless of whether MRSA colonization precedes admission or occurs due to nosocomial spread, it is associated with increased risk of developing a HAI [46–49]. In 2 large prospective observational cohort studies, the hazard ratios of MRSA colonization developing into S. aureus infections during the ICU stay were 3.84 and 4.70, respectively [50,51]. High levels of concordance between MRSA colonization strains and HAI strains have also been reported [52]. Nasal colonization with S. aureus has also been identified as an independent risk factor for developing ventilator-associated pneumonia (VAP) and bacteremia [53,54]. A case series of ICU patients with S. aureus nasal colonization who developed lower respiratory tract infections demonstrated genetically identical nasal and bronchial strains in 15/16 cases [55]. This finding strongly suggests that nasopharyngeal colonization with S. aureus contaminates oral secretions that are aspirated by critically ill patients, resulting in subsequent pneumonia. In a long-term outcomes study among a matched cohort of veterans, MRSA colonization was associated with an increased risk of infection-related readmission and mortality [56]. These findings reflect the critically important nature of measures designed to curb nosocomial transmission and acquisition of MRSA, especially among the vulnerable ICU population.

VRE

As with MRSA, risk factors associated with VRE colonization include both patient-level and ICU-level (or environmental) factors [57]. Examples of patient-level factors include previous antimicrobial exposure [58–62], underlying medical illnesses such as chronic renal failure requiring hemodialysis [11,63], length of hospital or ICU stay [11,59,64,65], and recent exposure to health care facilities. ICU-level factors of relevance are the prevalence of VRE in the unit, with high levels of endemicity leading to higher risk of colonization and transmission.

Antibiotic use is a major risk factor for VRE acquisition, although the type and class of antibiotic varies considerably across studies; the most frequently identified antibiotics are broad-spectrum cephalosporins, vancomycin, and anti-anaerobic agents [58,62,64]. Patients with chronic liver disease and post-transplantation are at exceedingly high risk for VRE acquisition [59]. In a recent study by Pan [66], for example, the authors found that the incidence of newly acquired VRE was 21.9 per 1000 patient-days in an ICU setting. On multivariate analysis, the authors found that, similar to other reports [11,59,67], length of stay in the ICU was associated with increased risk of VRE acquisition, with each additional day of stay increasing risk of VRE by 1.03 times. Warren et al undertook a prospective cohort study involving 519 patients admitted to the ICU for more than 48 hours [11]. Seventy-four (21%) of 352 patients were subsequently colonized with VRE. The median time to development of a positive VRE culture after ICU admission was 6 days. Increased mean APACHE II score on ICU admission (P = 0.002), sucralfate use (P = 0.003), vasopressor use (P = 0.01), tracheostomy in the ICU (P = 0.02), and C. difficile diarrhea (P = 0.002) appeared to be associated with VRE acquisition.

It appears that VRE acquisition is often associated with the sick subgroup of patients, and risk factors generally associated with VRE colonization and infection co-relate with disease chronicity and severity of illness. Length of hospitalization, ICU stay, hemodialysis, or transplantation may all be markers of disease severity. A summary of risk factors for VRE acquisition is shown in Table 2.

REDUCING TRANSMISSION—MRSA AND VRE PREVENTION STRATEGIES

Evidence-based guidelines developed by the Centers for Disease Control (CDC) Hospital Infection Control Practices Advisory Committee (HICPAC) for prevention of MRSA and VRE are available [68]. Several recently conducted well-designed clinical trials also provide additional insight that may be particularly helpful in the ICU setting [69]. A summary of the MRSA prevention guidelines issued by the CDC and included in its “MRSA toolkit” is provided in Table 3. A similar guideline on prevention of VRE [70], published more than a decade ago, has similar elements. Table 3 shows a side-by-side comparison of these elements. Unfortunately, despite these guidelines and extensive research regarding prevention and control, considerable controversy exists as to the most effective approaches. As such, these recommendations should be tailored to meet the needs of the specific ICU setting.

Antimicrobial Stewardship

Antibiotic use is a major driver of antibiotic resistance. A meta-analysis by de Bruin and Riley [71] studied the effect of vancomycin usage on VRE colonization and infection. A total of 12 articles describing 13 studies were included; none were randomized controlled trials. All studies were quasi-experimental and lacked control groups. Among all studies, less than half (46%) implemented vancomycin reduction measures as the sole type of intervention [72–76]. The remaining studies implemented other infection control modalities and or restricted the use of other antimicrobials [77–83]. Although all studies that implemented vancomycin restriction alone as a single strategy showed a decline in vancomycin usage, only 2 of these [74,75] showed a relative risk reduction in VRE acquisition post-intervention. Also, studies that restricted vancomycin alone revealed a trend towards lower efficacy in reducing VRE colonization and infection (33%) when compared with those that used additional measures (71%). While judicious antibiotic use should always be practiced, the evidence for vancomycin restriction as a sole intervention to control VRE is scant. It may be that other antibiotics are as big or bigger drivers of resistance in enterococci than vancomycin. For example, a growing body of literature supports antibiotic restriction, especially fluoroquinolones, for reducing MRSA. In several time-series quasi-experimental studies, restriction of fluorquinolones was associated with reduced trends in MRSA infections in the acute care setting, and consideration should be given to monitor and optimize fluoroquinolone use in the ICU setting [84,85].

Antimicrobial stewardship programs are fundamental to optimizing antibiotic use in the ICU and the authors strongly recommend that all ICUs should have such a program in place.

Educational Interventions

Infection control and multidrug-resistant organism (MDRO)–specific education programs for health care workers is a core principle of the CDC’s prevention guidelines. The HICPAC VRE guideline also explicitly states “continuing education programs for hospital staff (including attending and consulting physicians, medical residents, and students; pharmacy, nursing, and laboratory personnel; and other direct patient-care providers) should include information concerning the epidemiology of VRE and the potential impact of this pathogen on the cost and outcome of patient care [70].” A systematic review published in 2008 [86] that included 26 studies showed that such interventions to prevent HCAIs are usually successful; in this review, 20 of 26 studies showed a statistically significant decrease in infection rates, with risk ratios ranging from 0 to 1.6. Education was usually part of a broader array of infection control interventions. While clearly essential, education alone is unlikely to have a sustained impact on reducing MRSA and VRE infections.

Infection Control Measures

Major infection control interventions include hand hygiene, the use of personal protective equipment (PPE), and cohorting. These measures can be grouped into “horizontal” (or global) vs. “vertical” (or targeted) strategies. Although not mutually exclusive, horizontal approaches are designed to have an impact on multiple pathogens (pathogen nonspecific), whereas vertical approaches are designed to reduce the impact of specific pathogens (such as VRE). For the purposes of this review, we will discuss both strategies for containment of MRSA and VRE. Horizontal strategies include hand hygiene, universal gloving and/or gowning, environmental cleaning, and daily bathing with chlorhexidine. Vertical strategies include screening for either MRSA or VRE followed by placement in contact precautions and decolonization with mupirocin.

Hand Hygiene

Hand washing is fundamental to reducing transmission of MDROs in health care institutions; however, optimal compliance is hard to achieve and sustain. Barriers to adherence may include unavailability of sinks or hand hygiene materials (eg, alcohol-based gels, gloves) time constraints, forgetfulness, or lack of knowledge [87–95]. Several monitoring strategies have been evaluated to increase compliance with hand hygiene. Most involve direct observation followed by performance assessment and feedback.

Trials examining the impact of improvements in hand hygiene compliance on HAIs in the ICU setting have largely found benefit, although not all studies showed a decline in HAI. In a prospective crossover trial, Rupp et al [96] found dramatic improvements in compliance with hand gel availability, but this did not translate to decreased nosocomial MRSA infections. Venkatesh et al [97] carried out a before-and-after interventional prospective study in a hematology unit in a tertiary level hospital to evaluate the use of an electronic method of surveillance to determine compliance with hand hygiene. The authors also used rates of horizontal transmission of VRE as a secondary end-point. Results of the study showed that hand hygiene compliance improved from 36.3% at baseline to 70.1%. This represented an OR of 4.1 (95% confidence interval, 3.7–4.5), which the authors attributed to the use of automated alerts. VRE transmission rates before and during intervention were not statistically different, but the rates of infection were lower at 1.0 per month in comparison with 4.7 infections per month in the preceding 6 months (P = 0.096).

While improved hand hygiene may result in significant reductions in HAIs [40], research indicates hand hygiene alone influences about 40% of infections in the ICU setting [98]. As such, hand hygiene should be viewed as a necessary component of a comprehensive infection control program [99]. Despite the success of hand hygiene in reducing HAIs in the ICU, effective strategies to improve compliance remain elusive even under study conditions and further research is needed in this area [100].

Personal Protective Equipment

Tenorio et al [101] conducted a study to assess the effectiveness of gloving in the prevention of hand carriage of VRE by health care workers. The study showed that among 50 health care workers who had contact with patients colonized with VRE, 6 carried a similar patient strain even prior to known contact, and 17 of 44 (69%) had a patient-related VRE strain on their gloves after contact. This suggests a relatively high rate of colonization after usual patient-care contact. Factors associated with acquisition of VRE on gloves included duration of contact, contact with a patient’s body fluids, presence of diarrhea in a patient, mean VRE colony counts on a patient’s skin, and number of body sites colonized with VRE. Although gloves reduced the risk of VRE acquisition of VRE by 71% (ie, 12/17 did not have VRE on their hands after de-gloving) the protection afforded by gloves was incomplete. As such, hand hygiene after glove removal is recommended.

Slaughter et al [102] compared the use of personal protective equipment in the acquisition of VRE. During this study, 93 patients in glove-and-gown rooms and 88 patients in glove-only rooms had similar rates of VRE at baseline entry into the ICU and after the intervention. Mean times to colonization among the patients who became colonized were 8.0 days in the glove-and-gown group and 7.1 days in the glove-only group. None of these comparisons were statistically significant and the authors concluded that the universal use of gown and gloves was no better than the use of gloves alone in preventing VRE colonization.

A recent cluster randomized trial compared the effect of universal PPE (ie, gowning and gloving) with usual care for reducing acquisition of MRSA or VRE as a composite outcome [103]. The study did not find that universal gowning and gloving reduced VRE or MRSA acquisition but found a 40% decline in MRSA acquisition in the intervention ICUs compared with baseline rates of MRSA. No major adverse effects of universal gowning and gloving were noted in this study. A thoughtful editorial commenting on this article proposes that several aspects of the study deserve consideration, including the possibility of false-negative screening tests for VRE, which may have partially accounted for the negative primary outcome [69].

Based on these studies, it appears that the use of barrier precautions may be of value more for MRSA than VRE but further studies are needed to examine its impact on other types of pathogens, including new and emerging MDROs. Until further evidence becomes available, routine gowning and gloving may be of value in units with a high prevalence of MRSA.

Environmental Cleaning

Accumulating data suggests that the environment may play a major role in transmission of pathogens. MRSA has the ability to survive for days to weeks on inanimate objects [104–107]. Environmental contamination results in contamination of staff clothing and gloves [107,108] and is highly correlated with colonization strains among inpatients [109]. Although some studies of enhanced cleaning techniques and increased environmental services staff time have demonstrated reductions in MRSA outbreaks [110–112], the results are not universally favorable [113,114] and further studies are needed to examine the impact of environmental cleaning on rates of MRSA colonization or infection.

Several studies have implicated contaminated equipment as vectors for transmission of VRE during outbreaks [115–117], but the direction of fomite transfer from patient to environment has been difficult to ascertain. VRE have been found frequently on a variety of inanimate objects and surfaces in different health care environments [118–123], including gloved or ungloved hands of health care workers [101,124,125]. Hayden et al [126] determined the effect of improved environmental cleaning on VRE acquisition rates. This study was a pre-and-post intervention study carried out in a 21-bed medical intensive care unit (MICU) in a tertiary hospital over several phases. The intervention included the creation of a unique and improved cleaning program, as well as in-services to housekeeper services, education of the MICU staff, and a hand hygiene campaign. The results of the study showed decreased acquisition of VRE from 33.47 cases per 1000 patient days at risk in period 1 to 10.40 cases per 1000 patient-days at risk by period 4 of the study. Increased environmental cleaning was also associated with reduced growth of VRE from environmental cultures. At baseline, weekly contamination rates were 0.15 and 0.1 for samples obtained before and after cleaning, respectively. Culture positivity decreased to 0.07 and 0.04 for before and after cleaning in period 2 and then remained at low levels during the remainder of the study. It is important to note that the method for disinfecting used in this study was the “bucket method” as promoted by Byers [127]. This study provides further support for the importance of an environmental reservoir and of environmental decontamination to prevent endemic cross-transmission of VRE [126].

Goodman et al [128] used similar interventions but added a feedback tool using a black-light monitoring system (ie, use of an invisible, nontoxic marker to delineate areas that are adequately or inadequately cleaned) to reduce the likelihood of isolating either MRSA or VRE from an ICU environment. This study also showed favorable results, and notably, the use of the black-light monitoring system identified specific areas that were typically inadequately disinfected. Results showed that flat, horizontal surfaces (eg, countertops, bedside tray tables, and hamper tops) were adequately cleaned more often than small, vertical surfaces (eg, doorknobs, toilet handles, light switches, and electronics).

Part of the controversy surrounding the impact of environmental cleaning is the difficulty in determining its individual value as part of an overall infection control bundle [129]. A proposed area of demonstrable impact for environmental cleaning are frequently touched sites which are more likely to be contaminated with pathogens. Focusing on these “hot-bed” areas of the care environment may offer a useful adjunct to other infection control measures [129].

Active Surveillance

Active surveillance refers to periodic screening for asymp-tomatic carriers followed by placement of colonized patients in contact isolation. This practice is highly variable across institutions, as the evidence supporting this practice is conflicting and there are concerns about the cost of implementing this approach without solid evidence [70,130,131]. Despite lack of randomized controlled trials to guide this practice for MRSA prevention, many hospitals utilize MRSA surveillance and it is mandated by law in 9 states [132,133].

A prospective, interventional cohort study of universal MRSA screening on admission to surgical wards failed to reduce nosocomial MRSA infections [134]. Most recently, a pragmatic, cluster-randomized ICU trial reported that universal decolonization with chlorhexidine wipes and mupirocin use was more effective than screening and isolation in reducing rates of MRSA clinical isolates [65]. However, concerns regarding the risk of mupirocin resistance have been expressed [135,136]. The only randomized trial that compared active surveillance for MRSA and VRE followed by contact precautions to usual care did not find a benefit to active surveillance.

Huskins et al [137], in a large, cluster-randomized trial of 19 ICUs from different hospitals, determined the utility of using a culture-based active surveillance and contact isolation, compared with usual care (contact isolation for patients colonized with MRSA or VRE) as identified by existing hospital protocols, to reduce the incidence of colonization or infection with MRSA or VRE. In this trial, which spanned 6 months and involved 3488 participants, the authors found no significant difference between the intervention and control ICUs in terms of MRSA and VRE colonization or infection rates.

Conflicting with these findings is an observational study comparing MRSA infection rates before and after institution of a universal screening protocol, which demonstrated a 69.6% (CI, –89.2% to –19.6%]; P = 0.03) reduction in hospital wide MRSA prevalence density with screening [138]. The “MRSA bundle” implemented in 2007 at VA hospitals nationwide, which included universal screening, produced a 62% (P < 0.001) reduction in MRSA ICU infections; the relative contribution of the various bundle components is uncertain [139,140].

A proposed cost-saving alternative to universal screening is selective screening based on risk factor assessment [141]. The effectiveness of this type of program depends on creating a clinical decision-making tool capable of accurately identifying high-risk individuals while also accounting for the different risk factor profiles between HA-MRSA and CA-MRSA [142]. It has been proposed that targeted screening protocols may be more cost-effective in settings with < 5% prevalence of MRSA colonization on admission [143].

Many studies [61,144–149] have shown that active surveillance against VRE is cost-effective. For example, Calfee et al [144] showed that an established active surveillance program results in control of endemic VRE in high-risk patients. The infection control program was established in response to a hospital-wide VRE outbreak, and was sustained after the outbreak was controlled. The study by Calfee et al spanned 5 years and was performed at a tertiary-level university hospital, where cultures from perirectal areas were used to identify high-risk patients who were asymptomatically colonized with VRE. During the latter 2 years, 768 new cases of VRE colonization were detected among 69,672 admissions (1.1% of admissions), of which 730 (95.1%) were identified by active surveillance methods. This implies that routine clinical cultures would probably have missed the majority of colonized patients. During this period, the incidence of VRE infection was likewise extremely low at 0.12/1000 patient days (ie, 90 nosocomial VRE infections were identified in 83 patients during 743,956 days of patient care). Sixty-nine of the 83 patients (83%) who developed nosocomial VRE infections were found to be colonized with VRE by surveillance culture before the onset of infection.

Patient Decolonization

Chlorhexidine gluconate has been used in several settings to control outbreaks and infections related to MRSA and VRE due to its broad-spectrum activity against these pathogens. Chlorhexidine-based solutions reduce the density of skin colonization with pathogens such as MRSA and VRE (skin asepsis), thus lowering the risk for horizontal transmission between health care workers and patients.

Decolonization with chlorhexidine as an MRSA infection reduction technique has demonstrated benefit in the ICU setting [150]. The previously mentioned large, cluster-randomized ICU trial by Huang and colleagues found universal decolonization with twice-daily intranasal mupirocin for 5 days and daily bathing with chlorhexidine-impregnated cloths for the entire ICU stay was superior to targeted decolonization of known MRSA carriers in preventing overall MRSA isolates. However, universal decolonization failed to show a reduction in MRSA bacteremia [151], and concerns about mupirocin resistance may limit the applicability of this approach.

There are now several studies [152–154] that show decreased acquisition of VRE with use of daily chlorhexidine bathing. In a study including 1787 ICU patients, Vernon et al found [154] that the reducing microbial density of VRE on patient’s skin by using chlorhexidine led to decreased transmission. In another study by Climo et al [153] that involved 6 ICUs at 4 academic centers and measured the incidence of MRSA and VRE colonization and blood stream infections (BSI) during a period of bathing with routine soap for 6 months compared with a 6-month period where all admitted patients received daily bathing with a chlorhexidine solution, results found decreased acquisition of VRE by 50% (4.35 vs. 2.19 cases/1000 patient days, P < 0.008) following the introduction of daily chlorhexidine bathing. Furthermore, compared with 16 of 270 patients colonized with VRE who subsequently developed VRE bacteremia at baseline, only 4 of 226 VRE-colonized patients bathed with chlorhexidine in the intervention period developed a BSI, translating into a relative risk reduction of 3.35 (95% CI, 1.13–9.87; P < 0.035). Patients colonized with VRE were 3 times less likely to develop VRE bacteremia when bathed with chlorhexidine compared with regular bathing.  Despite the success of this protocol for VRE, when analyzed by individual organism no significant reductions in MRSA acquisition or BSI were reported. This finding is similarly corroborated by a trial conducted in the pediatric ICU setting which found an overall reduction in bacteremia with daily chlorhexidine washes but no significant decrease in cases due to S. aureus [155].

The results of these studies suggest that daily bathing with chlorhexidine should be part of routine practice in health care, especially in ICUs where endemic MRSA or VRE rates are high. Whether there is benefit in other settings needs to be studied.

In addition to chlorhexidine washes, other decolonization techniques have been proposed to reduce colonization and the spread of HAIs in the ICU setting. A randomized controlled trial of daily 5% tea tree oil body washes for the prevention of MRSA colonization failed to significantly reduce rates compared to standard soap body washes [156]. Another proposed decolonization intervention that has not been widely adopted in the United States due to concerns related to development of resistant organisms is selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) with antimicrobial agents [157,158]. In terms of clinical benefit, SDD/SOD have been found to decrease MDRO infection rate [159] and mortality [160].

Cohorting

There is insufficient evidence to conclude that cohorting isolated patients is of benefit for routine use in the endemic ICU setting. A few studies, mainly in the outbreak setting, have examined this approach and the results are conflicting [161,162]. Pending further studies in this area, it is reasonable to cohort patients colonized with the same microorganisms, especially if patients cannot be placed in single rooms.

CONCLUSION

The emergence of MRSA and VRE has led to a resurgence of interest and emphasis on infection control practices and prevention. CDC guidelines to help health care practitioners manage these MDROs in the hospital and ICU-setting exist; however, many questions remain regarding best practice.

Prevention of MRSA and VRE needs to be a 2-pronged approach—antimicrobial stewardship [163] and infection control. A robust antimicrobial stewardship program to optimize and minimize inappropriate antibiotic use is necessary in every institution. From the infection prevention standpoint, it is unclear if systematic identification of MRSA and VRE colonization followed by contact precautions is useful in reducing transmission. It is clear that a strong institutional climate of promoting patient safety and a culture of infection prevention will help in reducing MRSA and VRE facility-wide. It also appears that universal gowning and gloving may be useful for reducing MRSA, but not VRE, transmission. While universal decolonization with mupirocin is efficacious in reducing MRSA, this strategy is not recommended because of promoting mupirocin resistance. However, the use of daily bathing with chlorhexidine represents a relatively low-cost, high-yield intervention that should be adopted. Pending further data, patients known to be colonized or infected with MRSA should be placed in contact precuations as is current practice in most institutions. Finally, in this era of MDROs, hand hygiene remains our best defense against the spread of pathogens in the health care environment.

Note: This article does not represent the views of the Department of Veterans Affairs.

Corresponding author: Nasia Safdar, MD, Willam S. Middleton Memorial Veterans Affairs Hospital, 2500 Overlook Terrace, Madison, WI 53705, [email protected].

Funding/support: This work is funded by a MERIT award from the Department of Veterans Affairs to Nasia Safdar.

Financial disclosures: None.

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In 1987, the chief of staff of the Lexington VAMC and the staff attorney for the VA Regional Counsel Office in Lexington, Kentucky, discovered that a recent patient death was due to a mistake made in the medical care provided at their facility. They decided to disclose what happened to the family who had no knowledge of this mistake in care because “it was the right thing to do.”

The Lexington Model for disclosure, as it became known worldwide, continued to flourish under the leadership of Kraman and Hamm.^1,2 The VA National Center for Ethics in Health Care adopted these principles of disclosure in drafting a national VHA policy directive in 2008, which was updated in 2012.³ However, despite the ethical and professional imperatives, disclosing adverse events (AEs) to patients and family members has continued to be one of the most difficult challenges in the practice of medicine.

VHA policy has made a distinction between clinical disclosure, conducted by a clinician with a patient as a routine professional practice, and institutional disclosure, conducted by institutional leadership for an AE rising above a threshold of serious patient harm. According to VHA Director of Risk Management Yuri Walker in a 2013 personal communication, the frequency of institutional disclosure reports from VAMCs since 2011 have reflected significant variation in disclosure practice among facilities of similar size and complexity.

In this report, the authors share their experience developing and delivering a simulation-based disclosure training program in the VHA intended to close the gap between policy expectations and practical challenges for providers and institutions when facing the task of disclosing an AE to patients and families.

Medical Error Disclosure

It is not difficult to understand why health care providers (HCPs) are uncomfortable about disclosing AEs to patients. The study by Delbanco and Bell describes physicians experiencing guilt, shame, and fear of retribution after a patient experiences an AE. The resulting silence and avoidance of the patient only compounds patient harm.⁴ Many HCPs believe disclosure will lead to tort claims, provide evidence against their defense, encourage reporting to the National Practitioners’ Databank, and damage their reputations with a potentially negative impact on their careers.^5-7

In a 2009 survey of 1,891 practicing physicians in the U.S., one-third did not agree with disclosing serious medical errors to patients.⁸ Another survey of physicians reported wide variations in responses about whether they would offer an apology after making a medical mistake.⁹ Therefore, a gap between patient expectations and HCP communication when a medical mistake occurs should be expected.¹⁰

Few HCPs receive training in empathic communication skills for effective disclosure of AEs to patients and families.¹¹ In a survey of 3,171 physicians in the U.S. and Canada, Waterman and colleagues found that only 10% of physicians believed they had adequate support from their health care organizations (HCOs) after an AE occurred, even though 86% expressed significant interest in receiving training on the disclosure of AEs.¹² Despite this gap, some medical educators, such as Katie Watson at Northwestern University, are successfully demonstrating the power of teaching medical students improvisational acting skills to enhance professionalism and communication in future physician–patient interaction.¹³

Disclosure Training Program

In 2010, the Lexington VAMC was awarded a 3-year VA Systems Improvement Capability Grant, which funded the development of a Disclosure Training Program (DTP). A team of investigators designed a 2-day workshop based on principles of experiential learning. Each workshop incorporated interactive teaching techniques using filmed clinical vignettes to provide a context for facilitated small-group disclosure simulations with professional actors.¹⁴ A total of 14 workshops were conducted for 346 participants from December 2011 to September 2012.

The DTP workshop integrates focused didactic sessions with interactive audience-workshop facilitator discussion, debriefing of teaching films, and disclosure simulations, with the majority of time spent the conducting and debriefing of simulations. Core content addressed during workshop activities included the following:

  1. Historical origins of disclosure policy at the VHA

  2. Ethical obligation, professional duty, and legal mandates for disclosure

  3. Empathic communication–cognitive and emotive

  4. VHA Handbook 1004.08, Disclosure of Adverse Events to Patient

  5. Institutional and Clinical Disclosure of AEs

  6. Psychological and physical needs of patients after an AE

  7. Disclosure linking risk management to patient safety in a health care system

  8. Legal implications for disclosure

  9. State apology laws

10. Implementing disclosure programs in health care facilities

11. Facility support for providers after a patient AE

The principles of empathic communication and the core elements of AE disclosure to patients are reinforced during small-group simulations with actors portraying patients or family members. Each small-group simulation typically involves 3 to 4 workshop participants and 1 to 2 actors. Participants are given the task of conducting a clinical or institutional disclosure.

A facilitator manages each simulation, based on a scripted scenario or teaching film viewed by workshop participants. In the simulations attendees assume the roles of hospital staff that might be realistically involved in disclosure conversations, including executive leaders, physicians, nurses, risk managers, pharmacists, chaplains, and social workers.

Simulations average 5 to 7 minutes and are followed by a debriefing, including simulation participants, workshop facilitators, and the professional actor, who remain in character. By the end of each 2-day workshop, all attendees have participated in multiple small-group simulations of both clinical and institutional disclosures. Pre- and postworkshop knowledge questions and program evaluation data are collected with immediate-response polling technology used throughout the workshop.

Between 20 and 40 HCPs attended each workshop, which was designed for clinical and administrative leaders as well as others supporting the disclosure process, such as nurse managers, patient safety managers, social workers, chaplains, and pharmacists. The facility director, chief of staff, risk manager, and lawyers from the Regional Counsel office all play an important role in institutional disclosures and all were strongly encouraged to attend. The DTP facilitators observed the importance of senior executive leadership—participation, which enhanced dialogue in the large group sessions and small-group simulation-based learning.

DTP Workshop Results

Fourteen workshops were conducted for 346 employees from 26 VAMCs in 2012. Audience response technology was used to elicit participant feedback regarding workshop quality and effectiveness. Additional questions were asked as a pre/post-test of subject matter knowledge. Following the workshop, the participants showed a 30% overall improvement over preworkshop tests (Table), and 95% of participants favorably rated the workshop for quality and effectiveness.

There was a positive association between workshops with facility directors and actively engaged chiefs of staff in attendance and higher improvement scores in the test of knowledge. Among the top 7 performers on this test, 6 were individual facilities hosting the workshops and 1 VISN hosting for several facility representatives. Eleven of the 14 workshops with these characteristics (3 of which included VISN directors) evidenced more than 20% improvement on the test knowledge. These findings confirmed the original program design intended for individual facilities with leadership in attendance.

Iterative improvements were made to the program throughout 2012 based on feedback from workshop attendees, the National Office of Risk Management, the National Center for Ethics in Health Care and participating VA facilities and VISNs.

Despite these encouraging results, the DTP has some significant limitations: It is expensive, labor intensive, and dependent on faculty with expertise in clinical medicine, bioethics, and the law. Considering tight federal budgets, justifying the expenses to host a training program is difficult for a VAMC compared with that of other spending priorities. The actual and opportunity costs of travel to host sites for several facilitators and a group of professional actors to conduct a 2-day workshop for busy HCPs is not trivial.

Another limitation is the use of immediate response technology for data collection. Although this method maximizes response rates and seems to keep attendees engaged in presentations and discussions, technical failures could result in dropped responses, and ultimately the choice to respond is dependent on participant willingness to use the device.

Conclusion

Encouraging results suggest a bright future for the DTP, which has relevance for any health care organization, including the VA, academic affiliates, or those in the private sector. Wherever health care is delivered, providers will have the difficult task of disclosing AEs to meet their duty of care when patients experience harm. Learning empathic communication skills and successful strategies for disclosure will enhance this interaction and contribute to the maintenance of trust that is critical to the provider–patient relationship.

The DTP workshop has a flexible design and can be packaged to accommodate host medical centers for workshops of 1 to 2 days’ duration. The didactic presentations are constant, whereas the number of simulations will vary, depending on the length of the workshop (2-3 simulations for 1 day and 5-7 for two days). Participants from every workshop consistently cite that the simulations with professional actors are a powerful learning experience of significant personal value.

The DTP was developed as a unique, simulation-based program for clinicians, administrators, and allied health care personnel to enhance the effective disclosure of AEs to patients. Feedback from participants in 14 workshops in 2012 cited the value of the program with a high favorability rating. In a test of knowledge, participants also demonstrated an increase in learning. This feedback from the health care professionals who have attended the workshops has validated the pedagogic design of the program, which leverages adult learning principles of learning through experience. This approach was described by Aristotle in his best-known work on ethics, Nicomachean Ethics, “For the things we have to learn before we can do them, we learn by doing them.”¹⁵ 

Acknowledgements
For their significant contributions to the development and implementation of the VHA Disclosure Training Program, the authors thank Aaliyah Eaves-Leanos, Mary Duke, Lindsay Hall, and Uzair Munis. We thank the Institute for Healthcare Communication for their assistance in the program development. We express our utmost appreciation to Lee Taft for his many invaluable contributions to this program, including the critical role he continues to assume as a faculty member in the workshops. And, we are grateful for the continued contributions from our talented professional actors of Heyman Talent in Louisville, KY.

We express our sincere gratitude for their continuous feedback and important technical advice informing iterative improvements in the DTP workshops throughout 2012 from Virginia Ashby Sharpe (VA National Center for Ethics in Health Care); Yuri Walker (director of the Risk Management Program); and Barbara Rose (data analyst in the Risk Management Program), all at the VA central office in Washington, DC. And finally, we thank Heather Woodward-Hagg, Director of the VA Center for Applied Systems Engineering in Indianapolis, IN for her continued support in making DTP workshops available to VA Medical Centers throughout the country upon request.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

In 1987, the chief of staff of the Lexington VAMC and the staff attorney for the VA Regional Counsel Office in Lexington, Kentucky, discovered that a recent patient death was due to a mistake made in the medical care provided at their facility. They decided to disclose what happened to the family who had no knowledge of this mistake in care because “it was the right thing to do.”

The Lexington Model for disclosure, as it became known worldwide, continued to flourish under the leadership of Kraman and Hamm.^1,2 The VA National Center for Ethics in Health Care adopted these principles of disclosure in drafting a national VHA policy directive in 2008, which was updated in 2012.³ However, despite the ethical and professional imperatives, disclosing adverse events (AEs) to patients and family members has continued to be one of the most difficult challenges in the practice of medicine.

VHA policy has made a distinction between clinical disclosure, conducted by a clinician with a patient as a routine professional practice, and institutional disclosure, conducted by institutional leadership for an AE rising above a threshold of serious patient harm. According to VHA Director of Risk Management Yuri Walker in a 2013 personal communication, the frequency of institutional disclosure reports from VAMCs since 2011 have reflected significant variation in disclosure practice among facilities of similar size and complexity.

In this report, the authors share their experience developing and delivering a simulation-based disclosure training program in the VHA intended to close the gap between policy expectations and practical challenges for providers and institutions when facing the task of disclosing an AE to patients and families.

Medical Error Disclosure

It is not difficult to understand why health care providers (HCPs) are uncomfortable about disclosing AEs to patients. The study by Delbanco and Bell describes physicians experiencing guilt, shame, and fear of retribution after a patient experiences an AE. The resulting silence and avoidance of the patient only compounds patient harm.⁴ Many HCPs believe disclosure will lead to tort claims, provide evidence against their defense, encourage reporting to the National Practitioners’ Databank, and damage their reputations with a potentially negative impact on their careers.^5-7

In a 2009 survey of 1,891 practicing physicians in the U.S., one-third did not agree with disclosing serious medical errors to patients.⁸ Another survey of physicians reported wide variations in responses about whether they would offer an apology after making a medical mistake.⁹ Therefore, a gap between patient expectations and HCP communication when a medical mistake occurs should be expected.¹⁰

Few HCPs receive training in empathic communication skills for effective disclosure of AEs to patients and families.¹¹ In a survey of 3,171 physicians in the U.S. and Canada, Waterman and colleagues found that only 10% of physicians believed they had adequate support from their health care organizations (HCOs) after an AE occurred, even though 86% expressed significant interest in receiving training on the disclosure of AEs.¹² Despite this gap, some medical educators, such as Katie Watson at Northwestern University, are successfully demonstrating the power of teaching medical students improvisational acting skills to enhance professionalism and communication in future physician–patient interaction.¹³

Disclosure Training Program

In 2010, the Lexington VAMC was awarded a 3-year VA Systems Improvement Capability Grant, which funded the development of a Disclosure Training Program (DTP). A team of investigators designed a 2-day workshop based on principles of experiential learning. Each workshop incorporated interactive teaching techniques using filmed clinical vignettes to provide a context for facilitated small-group disclosure simulations with professional actors.¹⁴ A total of 14 workshops were conducted for 346 participants from December 2011 to September 2012.

The DTP workshop integrates focused didactic sessions with interactive audience-workshop facilitator discussion, debriefing of teaching films, and disclosure simulations, with the majority of time spent the conducting and debriefing of simulations. Core content addressed during workshop activities included the following:

  1. Historical origins of disclosure policy at the VHA

  2. Ethical obligation, professional duty, and legal mandates for disclosure

  3. Empathic communication–cognitive and emotive

  4. VHA Handbook 1004.08, Disclosure of Adverse Events to Patient

  5. Institutional and Clinical Disclosure of AEs

  6. Psychological and physical needs of patients after an AE

  7. Disclosure linking risk management to patient safety in a health care system

  8. Legal implications for disclosure

  9. State apology laws

10. Implementing disclosure programs in health care facilities

11. Facility support for providers after a patient AE

The principles of empathic communication and the core elements of AE disclosure to patients are reinforced during small-group simulations with actors portraying patients or family members. Each small-group simulation typically involves 3 to 4 workshop participants and 1 to 2 actors. Participants are given the task of conducting a clinical or institutional disclosure.

A facilitator manages each simulation, based on a scripted scenario or teaching film viewed by workshop participants. In the simulations attendees assume the roles of hospital staff that might be realistically involved in disclosure conversations, including executive leaders, physicians, nurses, risk managers, pharmacists, chaplains, and social workers.

Simulations average 5 to 7 minutes and are followed by a debriefing, including simulation participants, workshop facilitators, and the professional actor, who remain in character. By the end of each 2-day workshop, all attendees have participated in multiple small-group simulations of both clinical and institutional disclosures. Pre- and postworkshop knowledge questions and program evaluation data are collected with immediate-response polling technology used throughout the workshop.

Between 20 and 40 HCPs attended each workshop, which was designed for clinical and administrative leaders as well as others supporting the disclosure process, such as nurse managers, patient safety managers, social workers, chaplains, and pharmacists. The facility director, chief of staff, risk manager, and lawyers from the Regional Counsel office all play an important role in institutional disclosures and all were strongly encouraged to attend. The DTP facilitators observed the importance of senior executive leadership—participation, which enhanced dialogue in the large group sessions and small-group simulation-based learning.

DTP Workshop Results

Fourteen workshops were conducted for 346 employees from 26 VAMCs in 2012. Audience response technology was used to elicit participant feedback regarding workshop quality and effectiveness. Additional questions were asked as a pre/post-test of subject matter knowledge. Following the workshop, the participants showed a 30% overall improvement over preworkshop tests (Table), and 95% of participants favorably rated the workshop for quality and effectiveness.

There was a positive association between workshops with facility directors and actively engaged chiefs of staff in attendance and higher improvement scores in the test of knowledge. Among the top 7 performers on this test, 6 were individual facilities hosting the workshops and 1 VISN hosting for several facility representatives. Eleven of the 14 workshops with these characteristics (3 of which included VISN directors) evidenced more than 20% improvement on the test knowledge. These findings confirmed the original program design intended for individual facilities with leadership in attendance.

Iterative improvements were made to the program throughout 2012 based on feedback from workshop attendees, the National Office of Risk Management, the National Center for Ethics in Health Care and participating VA facilities and VISNs.

Despite these encouraging results, the DTP has some significant limitations: It is expensive, labor intensive, and dependent on faculty with expertise in clinical medicine, bioethics, and the law. Considering tight federal budgets, justifying the expenses to host a training program is difficult for a VAMC compared with that of other spending priorities. The actual and opportunity costs of travel to host sites for several facilitators and a group of professional actors to conduct a 2-day workshop for busy HCPs is not trivial.

Another limitation is the use of immediate response technology for data collection. Although this method maximizes response rates and seems to keep attendees engaged in presentations and discussions, technical failures could result in dropped responses, and ultimately the choice to respond is dependent on participant willingness to use the device.

Conclusion

Encouraging results suggest a bright future for the DTP, which has relevance for any health care organization, including the VA, academic affiliates, or those in the private sector. Wherever health care is delivered, providers will have the difficult task of disclosing AEs to meet their duty of care when patients experience harm. Learning empathic communication skills and successful strategies for disclosure will enhance this interaction and contribute to the maintenance of trust that is critical to the provider–patient relationship.

The DTP workshop has a flexible design and can be packaged to accommodate host medical centers for workshops of 1 to 2 days’ duration. The didactic presentations are constant, whereas the number of simulations will vary, depending on the length of the workshop (2-3 simulations for 1 day and 5-7 for two days). Participants from every workshop consistently cite that the simulations with professional actors are a powerful learning experience of significant personal value.

The DTP was developed as a unique, simulation-based program for clinicians, administrators, and allied health care personnel to enhance the effective disclosure of AEs to patients. Feedback from participants in 14 workshops in 2012 cited the value of the program with a high favorability rating. In a test of knowledge, participants also demonstrated an increase in learning. This feedback from the health care professionals who have attended the workshops has validated the pedagogic design of the program, which leverages adult learning principles of learning through experience. This approach was described by Aristotle in his best-known work on ethics, Nicomachean Ethics, “For the things we have to learn before we can do them, we learn by doing them.”¹⁵ 

Acknowledgements
For their significant contributions to the development and implementation of the VHA Disclosure Training Program, the authors thank Aaliyah Eaves-Leanos, Mary Duke, Lindsay Hall, and Uzair Munis. We thank the Institute for Healthcare Communication for their assistance in the program development. We express our utmost appreciation to Lee Taft for his many invaluable contributions to this program, including the critical role he continues to assume as a faculty member in the workshops. And, we are grateful for the continued contributions from our talented professional actors of Heyman Talent in Louisville, KY.

We express our sincere gratitude for their continuous feedback and important technical advice informing iterative improvements in the DTP workshops throughout 2012 from Virginia Ashby Sharpe (VA National Center for Ethics in Health Care); Yuri Walker (director of the Risk Management Program); and Barbara Rose (data analyst in the Risk Management Program), all at the VA central office in Washington, DC. And finally, we thank Heather Woodward-Hagg, Director of the VA Center for Applied Systems Engineering in Indianapolis, IN for her continued support in making DTP workshops available to VA Medical Centers throughout the country upon request.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

In 1987, the chief of staff of the Lexington VAMC and the staff attorney for the VA Regional Counsel Office in Lexington, Kentucky, discovered that a recent patient death was due to a mistake made in the medical care provided at their facility. They decided to disclose what happened to the family who had no knowledge of this mistake in care because “it was the right thing to do.”

The Lexington Model for disclosure, as it became known worldwide, continued to flourish under the leadership of Kraman and Hamm.^1,2 The VA National Center for Ethics in Health Care adopted these principles of disclosure in drafting a national VHA policy directive in 2008, which was updated in 2012.³ However, despite the ethical and professional imperatives, disclosing adverse events (AEs) to patients and family members has continued to be one of the most difficult challenges in the practice of medicine.

VHA policy has made a distinction between clinical disclosure, conducted by a clinician with a patient as a routine professional practice, and institutional disclosure, conducted by institutional leadership for an AE rising above a threshold of serious patient harm. According to VHA Director of Risk Management Yuri Walker in a 2013 personal communication, the frequency of institutional disclosure reports from VAMCs since 2011 have reflected significant variation in disclosure practice among facilities of similar size and complexity.

In this report, the authors share their experience developing and delivering a simulation-based disclosure training program in the VHA intended to close the gap between policy expectations and practical challenges for providers and institutions when facing the task of disclosing an AE to patients and families.

Medical Error Disclosure

It is not difficult to understand why health care providers (HCPs) are uncomfortable about disclosing AEs to patients. The study by Delbanco and Bell describes physicians experiencing guilt, shame, and fear of retribution after a patient experiences an AE. The resulting silence and avoidance of the patient only compounds patient harm.⁴ Many HCPs believe disclosure will lead to tort claims, provide evidence against their defense, encourage reporting to the National Practitioners’ Databank, and damage their reputations with a potentially negative impact on their careers.^5-7

In a 2009 survey of 1,891 practicing physicians in the U.S., one-third did not agree with disclosing serious medical errors to patients.⁸ Another survey of physicians reported wide variations in responses about whether they would offer an apology after making a medical mistake.⁹ Therefore, a gap between patient expectations and HCP communication when a medical mistake occurs should be expected.¹⁰

Few HCPs receive training in empathic communication skills for effective disclosure of AEs to patients and families.¹¹ In a survey of 3,171 physicians in the U.S. and Canada, Waterman and colleagues found that only 10% of physicians believed they had adequate support from their health care organizations (HCOs) after an AE occurred, even though 86% expressed significant interest in receiving training on the disclosure of AEs.¹² Despite this gap, some medical educators, such as Katie Watson at Northwestern University, are successfully demonstrating the power of teaching medical students improvisational acting skills to enhance professionalism and communication in future physician–patient interaction.¹³

Disclosure Training Program

In 2010, the Lexington VAMC was awarded a 3-year VA Systems Improvement Capability Grant, which funded the development of a Disclosure Training Program (DTP). A team of investigators designed a 2-day workshop based on principles of experiential learning. Each workshop incorporated interactive teaching techniques using filmed clinical vignettes to provide a context for facilitated small-group disclosure simulations with professional actors.¹⁴ A total of 14 workshops were conducted for 346 participants from December 2011 to September 2012.

The DTP workshop integrates focused didactic sessions with interactive audience-workshop facilitator discussion, debriefing of teaching films, and disclosure simulations, with the majority of time spent the conducting and debriefing of simulations. Core content addressed during workshop activities included the following:

  1. Historical origins of disclosure policy at the VHA

  2. Ethical obligation, professional duty, and legal mandates for disclosure

  3. Empathic communication–cognitive and emotive

  4. VHA Handbook 1004.08, Disclosure of Adverse Events to Patient

  5. Institutional and Clinical Disclosure of AEs

  6. Psychological and physical needs of patients after an AE

  7. Disclosure linking risk management to patient safety in a health care system

  8. Legal implications for disclosure

  9. State apology laws

10. Implementing disclosure programs in health care facilities

11. Facility support for providers after a patient AE

The principles of empathic communication and the core elements of AE disclosure to patients are reinforced during small-group simulations with actors portraying patients or family members. Each small-group simulation typically involves 3 to 4 workshop participants and 1 to 2 actors. Participants are given the task of conducting a clinical or institutional disclosure.

A facilitator manages each simulation, based on a scripted scenario or teaching film viewed by workshop participants. In the simulations attendees assume the roles of hospital staff that might be realistically involved in disclosure conversations, including executive leaders, physicians, nurses, risk managers, pharmacists, chaplains, and social workers.

Simulations average 5 to 7 minutes and are followed by a debriefing, including simulation participants, workshop facilitators, and the professional actor, who remain in character. By the end of each 2-day workshop, all attendees have participated in multiple small-group simulations of both clinical and institutional disclosures. Pre- and postworkshop knowledge questions and program evaluation data are collected with immediate-response polling technology used throughout the workshop.

Between 20 and 40 HCPs attended each workshop, which was designed for clinical and administrative leaders as well as others supporting the disclosure process, such as nurse managers, patient safety managers, social workers, chaplains, and pharmacists. The facility director, chief of staff, risk manager, and lawyers from the Regional Counsel office all play an important role in institutional disclosures and all were strongly encouraged to attend. The DTP facilitators observed the importance of senior executive leadership—participation, which enhanced dialogue in the large group sessions and small-group simulation-based learning.

DTP Workshop Results

Fourteen workshops were conducted for 346 employees from 26 VAMCs in 2012. Audience response technology was used to elicit participant feedback regarding workshop quality and effectiveness. Additional questions were asked as a pre/post-test of subject matter knowledge. Following the workshop, the participants showed a 30% overall improvement over preworkshop tests (Table), and 95% of participants favorably rated the workshop for quality and effectiveness.

There was a positive association between workshops with facility directors and actively engaged chiefs of staff in attendance and higher improvement scores in the test of knowledge. Among the top 7 performers on this test, 6 were individual facilities hosting the workshops and 1 VISN hosting for several facility representatives. Eleven of the 14 workshops with these characteristics (3 of which included VISN directors) evidenced more than 20% improvement on the test knowledge. These findings confirmed the original program design intended for individual facilities with leadership in attendance.

Iterative improvements were made to the program throughout 2012 based on feedback from workshop attendees, the National Office of Risk Management, the National Center for Ethics in Health Care and participating VA facilities and VISNs.

Despite these encouraging results, the DTP has some significant limitations: It is expensive, labor intensive, and dependent on faculty with expertise in clinical medicine, bioethics, and the law. Considering tight federal budgets, justifying the expenses to host a training program is difficult for a VAMC compared with that of other spending priorities. The actual and opportunity costs of travel to host sites for several facilitators and a group of professional actors to conduct a 2-day workshop for busy HCPs is not trivial.

Another limitation is the use of immediate response technology for data collection. Although this method maximizes response rates and seems to keep attendees engaged in presentations and discussions, technical failures could result in dropped responses, and ultimately the choice to respond is dependent on participant willingness to use the device.

Conclusion

Encouraging results suggest a bright future for the DTP, which has relevance for any health care organization, including the VA, academic affiliates, or those in the private sector. Wherever health care is delivered, providers will have the difficult task of disclosing AEs to meet their duty of care when patients experience harm. Learning empathic communication skills and successful strategies for disclosure will enhance this interaction and contribute to the maintenance of trust that is critical to the provider–patient relationship.

The DTP workshop has a flexible design and can be packaged to accommodate host medical centers for workshops of 1 to 2 days’ duration. The didactic presentations are constant, whereas the number of simulations will vary, depending on the length of the workshop (2-3 simulations for 1 day and 5-7 for two days). Participants from every workshop consistently cite that the simulations with professional actors are a powerful learning experience of significant personal value.

The DTP was developed as a unique, simulation-based program for clinicians, administrators, and allied health care personnel to enhance the effective disclosure of AEs to patients. Feedback from participants in 14 workshops in 2012 cited the value of the program with a high favorability rating. In a test of knowledge, participants also demonstrated an increase in learning. This feedback from the health care professionals who have attended the workshops has validated the pedagogic design of the program, which leverages adult learning principles of learning through experience. This approach was described by Aristotle in his best-known work on ethics, Nicomachean Ethics, “For the things we have to learn before we can do them, we learn by doing them.”¹⁵ 

Acknowledgements
For their significant contributions to the development and implementation of the VHA Disclosure Training Program, the authors thank Aaliyah Eaves-Leanos, Mary Duke, Lindsay Hall, and Uzair Munis. We thank the Institute for Healthcare Communication for their assistance in the program development. We express our utmost appreciation to Lee Taft for his many invaluable contributions to this program, including the critical role he continues to assume as a faculty member in the workshops. And, we are grateful for the continued contributions from our talented professional actors of Heyman Talent in Louisville, KY.

We express our sincere gratitude for their continuous feedback and important technical advice informing iterative improvements in the DTP workshops throughout 2012 from Virginia Ashby Sharpe (VA National Center for Ethics in Health Care); Yuri Walker (director of the Risk Management Program); and Barbara Rose (data analyst in the Risk Management Program), all at the VA central office in Washington, DC. And finally, we thank Heather Woodward-Hagg, Director of the VA Center for Applied Systems Engineering in Indianapolis, IN for her continued support in making DTP workshops available to VA Medical Centers throughout the country upon request.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Monoclonal antibodies

Credit: Linda Bartlett

Preclinical research suggests the B-cell activating receptor (BAFF-R) may be a promising therapeutic target for treatment-resistant leukemia.

A monoclonal antibody (mAb) that targets BAFF-R overcame resistance to nilotinib and enhanced the efficacy of both nilotinib and vincristine in vitro.

The mAb, called B-1239, also demonstrated antileukemic effects in mouse models, when given alone. But it did not appear to improve upon the effects of nilotinib when given in combination.

Nora Heisterkamp, PhD, of Children’s Hospital Los Angeles in California, and her colleagues reported these findings in Molecular Cancer Therapeutics.

In a previous study, the researchers had shown that BAFF-R is expressed on pre-B ALL cells but not on their normal counterparts.

“We’ve now demonstrated that BAFF-R is a strong potential therapeutic target for treating chemotherapy-resistant leukemia cells, without damaging healthy cells,” Dr Heisterkamp said.

She and her colleagues began this research by generating pre-B ALL cells from the bone marrow of wild-type mice and BAFF-R-null mice with a retroviral vector carrying the BCR/ABL oncogene. They found that wild-type pre-B-ALL cells expressed high levels of BAFF-R.

The team then treated both wild-type and BAFF-R-deficient leukemic cells with nilotinib. The wild-type cells developed resistance to nilotinib in 9 to 10 days, but the BAFF-R-deficient cells were eradicated by treatment.

The researchers next tested the effects of B-1239, a human codon-optimized anti-BAFF-R mAb. B-1239 bound to BAFF-R on both Ph-positive and Ph-negative ALL cells in vitro, and the mAb inhibited BAFF-R in a dose-dependent manner.

In pre-B-ALL cells, B-1239 alone had little effect on cell viability or proliferation. However, when combined with vincristine or nilotinib, B-1239 reduced cell count and viability more than either agent alone.

The researchers also found that B-1239 stimulated natural killer cell-mediated cytotoxicity in patient-derived ALL cells. And the mAb stimulated phagocytosis by macrophages.

Finally, Dr Heisterkamp and her colleagues tested B-1239 in mice transplanted with TXL2 cells. Mice received human IgG, B-1239 alone, nilotinib alone, or nilotinib and B-1239.

At 12 days after the last treatment, leukemia cell numbers in the circulation of control mice and B-1239-treated mice were comparable.

However, B-1239-treated mice showed significant inhibition of ALL cell growth in the bone marrow and spleen, when compared to control mice. mAb-treated mice also had significantly lower spleen weights than controls.

Nilotinib alone also significantly reduced the ALL cell burden in the peripheral blood, spleen, and bone marrow, when compared to controls. But there was no significant difference in these measures between mice that received nilotinib alone or nilotinib plus B-1239.

Nevertheless, Dr Heisterkamp and her colleagues said they will continue to evaluate the use of B-1239 for the treatment of ALL.

Monoclonal antibodies

Credit: Linda Bartlett

Preclinical research suggests the B-cell activating receptor (BAFF-R) may be a promising therapeutic target for treatment-resistant leukemia.

A monoclonal antibody (mAb) that targets BAFF-R overcame resistance to nilotinib and enhanced the efficacy of both nilotinib and vincristine in vitro.

The mAb, called B-1239, also demonstrated antileukemic effects in mouse models, when given alone. But it did not appear to improve upon the effects of nilotinib when given in combination.

Nora Heisterkamp, PhD, of Children’s Hospital Los Angeles in California, and her colleagues reported these findings in Molecular Cancer Therapeutics.

In a previous study, the researchers had shown that BAFF-R is expressed on pre-B ALL cells but not on their normal counterparts.

“We’ve now demonstrated that BAFF-R is a strong potential therapeutic target for treating chemotherapy-resistant leukemia cells, without damaging healthy cells,” Dr Heisterkamp said.

She and her colleagues began this research by generating pre-B ALL cells from the bone marrow of wild-type mice and BAFF-R-null mice with a retroviral vector carrying the BCR/ABL oncogene. They found that wild-type pre-B-ALL cells expressed high levels of BAFF-R.

The team then treated both wild-type and BAFF-R-deficient leukemic cells with nilotinib. The wild-type cells developed resistance to nilotinib in 9 to 10 days, but the BAFF-R-deficient cells were eradicated by treatment.

The researchers next tested the effects of B-1239, a human codon-optimized anti-BAFF-R mAb. B-1239 bound to BAFF-R on both Ph-positive and Ph-negative ALL cells in vitro, and the mAb inhibited BAFF-R in a dose-dependent manner.

In pre-B-ALL cells, B-1239 alone had little effect on cell viability or proliferation. However, when combined with vincristine or nilotinib, B-1239 reduced cell count and viability more than either agent alone.

The researchers also found that B-1239 stimulated natural killer cell-mediated cytotoxicity in patient-derived ALL cells. And the mAb stimulated phagocytosis by macrophages.

Finally, Dr Heisterkamp and her colleagues tested B-1239 in mice transplanted with TXL2 cells. Mice received human IgG, B-1239 alone, nilotinib alone, or nilotinib and B-1239.

At 12 days after the last treatment, leukemia cell numbers in the circulation of control mice and B-1239-treated mice were comparable.

However, B-1239-treated mice showed significant inhibition of ALL cell growth in the bone marrow and spleen, when compared to control mice. mAb-treated mice also had significantly lower spleen weights than controls.

Nilotinib alone also significantly reduced the ALL cell burden in the peripheral blood, spleen, and bone marrow, when compared to controls. But there was no significant difference in these measures between mice that received nilotinib alone or nilotinib plus B-1239.

Nevertheless, Dr Heisterkamp and her colleagues said they will continue to evaluate the use of B-1239 for the treatment of ALL.

Monoclonal antibodies

Credit: Linda Bartlett

Preclinical research suggests the B-cell activating receptor (BAFF-R) may be a promising therapeutic target for treatment-resistant leukemia.

A monoclonal antibody (mAb) that targets BAFF-R overcame resistance to nilotinib and enhanced the efficacy of both nilotinib and vincristine in vitro.

The mAb, called B-1239, also demonstrated antileukemic effects in mouse models, when given alone. But it did not appear to improve upon the effects of nilotinib when given in combination.

Nora Heisterkamp, PhD, of Children’s Hospital Los Angeles in California, and her colleagues reported these findings in Molecular Cancer Therapeutics.

In a previous study, the researchers had shown that BAFF-R is expressed on pre-B ALL cells but not on their normal counterparts.

“We’ve now demonstrated that BAFF-R is a strong potential therapeutic target for treating chemotherapy-resistant leukemia cells, without damaging healthy cells,” Dr Heisterkamp said.

She and her colleagues began this research by generating pre-B ALL cells from the bone marrow of wild-type mice and BAFF-R-null mice with a retroviral vector carrying the BCR/ABL oncogene. They found that wild-type pre-B-ALL cells expressed high levels of BAFF-R.

The team then treated both wild-type and BAFF-R-deficient leukemic cells with nilotinib. The wild-type cells developed resistance to nilotinib in 9 to 10 days, but the BAFF-R-deficient cells were eradicated by treatment.

The researchers next tested the effects of B-1239, a human codon-optimized anti-BAFF-R mAb. B-1239 bound to BAFF-R on both Ph-positive and Ph-negative ALL cells in vitro, and the mAb inhibited BAFF-R in a dose-dependent manner.

In pre-B-ALL cells, B-1239 alone had little effect on cell viability or proliferation. However, when combined with vincristine or nilotinib, B-1239 reduced cell count and viability more than either agent alone.

The researchers also found that B-1239 stimulated natural killer cell-mediated cytotoxicity in patient-derived ALL cells. And the mAb stimulated phagocytosis by macrophages.

Finally, Dr Heisterkamp and her colleagues tested B-1239 in mice transplanted with TXL2 cells. Mice received human IgG, B-1239 alone, nilotinib alone, or nilotinib and B-1239.

At 12 days after the last treatment, leukemia cell numbers in the circulation of control mice and B-1239-treated mice were comparable.

However, B-1239-treated mice showed significant inhibition of ALL cell growth in the bone marrow and spleen, when compared to control mice. mAb-treated mice also had significantly lower spleen weights than controls.

Nilotinib alone also significantly reduced the ALL cell burden in the peripheral blood, spleen, and bone marrow, when compared to controls. But there was no significant difference in these measures between mice that received nilotinib alone or nilotinib plus B-1239.

Nevertheless, Dr Heisterkamp and her colleagues said they will continue to evaluate the use of B-1239 for the treatment of ALL.

More older adults suffer from depression in a VHA setting (11%) than those in non-VHA settings (1%-5%).¹ Depression and anxiety are evaluated less often in older adults and undertreated compared with younger adults.^2-4 Unfortunately, older adults with depression and anxiety are vulnerable to suicide and disability; and they more frequently use medical services, such as the emergency department compared with older adults without these conditions.^5-7

However, pharmacologic and behavioral treatments for late-life mood and anxiety disorders are available and are effective.⁸ These findings raise important questions about improving access to mental health care for older veterans with mood disorders. The VA Palo Alto Health Care System (VAPAHCS) Geriatric Research Education and Clinical Center (GRECC) fulfills one GRECC mission of carrying out transformative clinical demonstration projects by developing programs to address geriatric mood disorders.

The VHA has successfully implemented the nationwide integration of mental health management into primary care settings.⁹ To design and implement these programs locally, in 2007, all VHAs were invited to submit proposals related to mental health primary care integration. Local sites were given flexibility in their use of different evidence-based models for delivery of this integrated care.

Collaborative Models

Three models of mental health integration into primary care were adopted within VHA. All have resulted in improved patient outcomes.⁹ The co-located model places a behavioral health specialist within the same setting as primary care providers (PCPs), who shares in the evaluation, treatment planning, and monitoring of mental health outcomes. In the care management model, care managers facilitate evaluation and maintain communication with PCPs, but are not co-located with the PCPs. The third model is a blended model in which both a behavioral health specialist and a care manager may be involved in the management of mental health care. The care management model resulted in better participation in the evaluation and engagement in pharmacotherapy by older veterans in 2 VHA medical centers.¹⁰

Persistent Barriers for Older Veterans

The mental health-primary care integration initiative laid important foundations for improving access to mental health care. To provide a truly veteran-centered care option, however, programs require monitoring and analysis of the factors that impact care delivery and access. A recent evaluation of a local integration program, using a co-located model (ie, Primary Care Behavioral Health [PCBH]), demonstrated that there were several factors affecting older veterans’ access to mental health treatment.¹¹ Older veterans with depression were less receptive to a mental health referral; 62% of older veterans refused mental health referrals compared with 32% of younger veterans who refused. Older veterans were less likely to complete at least 1 mental health clinic appointment, which was due in part to clinic location. All veterans were more likely to follow up with a mental health referral if first seen by the PCBH staff vs a referral by PCPs.

Geriatric-Specific Modifications to PCBH

The VAPAHCS GRECC, collaborating with the outpatient psychiatry service and the PCBH, sought to improve current mental health services for older veterans. Several barriers were identified: (1) limitations in types of interventions available to older veterans in the current PCBH and mental health programs; (2) the PCBH staff required geriatrics training, as recommended by the American Psychological Association¹²; and (3) resistance to receiving care in mental health clinics located several miles from the primary care setting. Therefore, a new pilot program was planned to address these barriers.

The Office of Geriatrics and Extended Care provided the funding for the initial program costs, and in September 2010, the Geriatric Primary Care Behavioral Health program (Geri-PCBH) was launched. The GRECC staff worked closely with the PCBH staff to offer a new service tailored to older veterans’ specific needs, which addressed the previously described program limitations.

Geri-PCBH Program

The Geri-PCBH program is a blended collaborative care model that provides outpatient-based mental health evaluation and treatment of mood disorders for older (aged ≥ 65 years) veterans. It is co-located with PCBH and PCPs within the primary care setting. The program extends PCBH services by providing psychotherapy that is contextually modified for older veterans. Older veterans may present with different therapy concerns than do younger veterans, such as caregiving, death of loved ones, and numerous and chronic medical illnesses. Illnesses may result in polypharmacy, giving rise to the need for understanding potential medication interactions in providing pharmacotherapy.

Within the program, geriatrics-trained psychologists and social workers offer psychotherapy. In addition, a geriatrician with expertise in polypharmacy offers pharmacotherapy. Psychotherapy, pharmacotherapy, or both are offered and initiated following evaluation and discussion with the veteran. Veterans are either referred by the PCBH staff because they screened positive for depression (Patient Health Questionnaire-2 [PHQ-2] ≥ 2) during a regularly scheduled primary care clinic appointment or they are directly referred by primary care physicians for suspected mood problems. Veterans are then contacted immediately by a staff member for a baseline assessment appointment with a geriatrician and one of the therapists. The type of treatment and goals of therapy are determined during the initial meeting. The program is a training site for psychology and social work interns, to increase their geriatric mental health training.

Evaluation and Results

To determine improvements compared to PCBH program outcomes, the patients who attended the initial Geri-PCBH evaluation/intake appointment were tracked. A total of 79 older veterans were referred (average age, 82.7 years; range, aged 66-96 years); 14 veterans were ineligible due to significant cognitive impairment or lack of depressive symptoms. Compared with the 38% rate of attendance at intake for mental health referrals in the PCBH program, the Geri-PCBH program demonstrated a 90% attendance rate at the initial evaluation appointment. Fifty-five older veterans enrolled and received therapy: 39 received only psychotherapy, 14 received psychotherapy and antidepressant therapy, and 2 received only antidepressant therapy. Over the first 2 years of the program, 2 senior therapists and 5 trainees were able to see 53 patients for an average of 7 sessions per patient, which translated to about 14% of each therapist’s time.

To determine the impact on patients, measures of depression (Hamilton Depression Rating Scale [HDRS]; Geriatric Depression Scale Short Form [GDS-SF]; and Patient Health Questionnaire 9 Item [PHQ-9]), anxiety (Mini Psychiatric Evaluation Scale-Generalized Anxiety subscale [MINI-GAD]), overall distress (clinical global inventory), and functional status (12-item World Health Organization Disability Assessment Scale [WHODAS]) were administered at baseline, posttreatment, and 3 months posttreatment. The veterans demonstrated a significant decrease (> 50% decline on mood symptoms) on the HDRS, GDS, PHQ-9, and MINI-GAD subscale, which were all sustained 3 months posttreatment (Figure).

Although the overall disability score did not improve, the percentage of older veterans reporting “bad” or “moderate” health decreased (pre = 42%; post = 31.1%; 3-month follow-up = 20.9%); while those reporting “good” or “very good” health increased (pre = 58%; post = 65.7%; 3-month follow-up = 79.2%) by the 3-month follow-up. Veterans also reported very high satisfaction rates with the program overall (Mean = 30, standard deviation = 2.03; anchors for measure: 0 = not satisfied; 32 = highly satisfied).

Patient Testimonials

“Not in my wildest dreams did I think I’d ever share, on this level, my personal, past and present life…You have been so helpful and allowed me to move forward with pride and self respect.”

“It makes you feel a lot better. I enjoy life more now than I used to. That first time that [my therapist and I] talked, she convinced me just a change in attitude was a big thing. And since I changed my attitude and started listening to people, it’s made a heck of a difference.”

Discussion and Conclusion

The results of the Geri-PCBH evaluation demonstrated improvements in acceptance by older veterans with depression of mental health referrals and in increased access to treatment. The program addressed several identified barriers, such as having a more accessible location, offering treatment by experienced geriatrics-trained providers, and providing a range of mental health services tailored to older veterans’ needs. These factors may have increased older veterans’ willingness to attend mental health referrals to the Geri-PCBH program. Having initial assessments done soon after initial referral (usually < 2 weeks) and calling patients personally to explain the program and make appointments likely improved referral acceptance.

There are some limits to implementing this program in other settings related to variability in staffing, infrastructure, and resources available. The project is currently sustained with the present staff, with the goal of expanding services by telehealth technology to disseminate the program to older veterans in rural settings.

The VHA has made impressive strides toward improving the lives of older veterans with depression and anxiety. The program described here provides an example of how quality improvement efforts, which take into account the specific needs of the older veteran, can lead to a dramatic impact on the services offered and more importantly on veterans’ mental health and functional abilities. 

Acknowledgements
This material is the result of work supported with funding by the Office of Geriatrics and Extended Care T21T Fund-10/11 060B2 and resources and use of facilities at the VA Palo Alto Health Care System in Palo Alto, California.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

More older adults suffer from depression in a VHA setting (11%) than those in non-VHA settings (1%-5%).¹ Depression and anxiety are evaluated less often in older adults and undertreated compared with younger adults.^2-4 Unfortunately, older adults with depression and anxiety are vulnerable to suicide and disability; and they more frequently use medical services, such as the emergency department compared with older adults without these conditions.^5-7

However, pharmacologic and behavioral treatments for late-life mood and anxiety disorders are available and are effective.⁸ These findings raise important questions about improving access to mental health care for older veterans with mood disorders. The VA Palo Alto Health Care System (VAPAHCS) Geriatric Research Education and Clinical Center (GRECC) fulfills one GRECC mission of carrying out transformative clinical demonstration projects by developing programs to address geriatric mood disorders.

The VHA has successfully implemented the nationwide integration of mental health management into primary care settings.⁹ To design and implement these programs locally, in 2007, all VHAs were invited to submit proposals related to mental health primary care integration. Local sites were given flexibility in their use of different evidence-based models for delivery of this integrated care.

Collaborative Models

Three models of mental health integration into primary care were adopted within VHA. All have resulted in improved patient outcomes.⁹ The co-located model places a behavioral health specialist within the same setting as primary care providers (PCPs), who shares in the evaluation, treatment planning, and monitoring of mental health outcomes. In the care management model, care managers facilitate evaluation and maintain communication with PCPs, but are not co-located with the PCPs. The third model is a blended model in which both a behavioral health specialist and a care manager may be involved in the management of mental health care. The care management model resulted in better participation in the evaluation and engagement in pharmacotherapy by older veterans in 2 VHA medical centers.¹⁰

Persistent Barriers for Older Veterans

The mental health-primary care integration initiative laid important foundations for improving access to mental health care. To provide a truly veteran-centered care option, however, programs require monitoring and analysis of the factors that impact care delivery and access. A recent evaluation of a local integration program, using a co-located model (ie, Primary Care Behavioral Health [PCBH]), demonstrated that there were several factors affecting older veterans’ access to mental health treatment.¹¹ Older veterans with depression were less receptive to a mental health referral; 62% of older veterans refused mental health referrals compared with 32% of younger veterans who refused. Older veterans were less likely to complete at least 1 mental health clinic appointment, which was due in part to clinic location. All veterans were more likely to follow up with a mental health referral if first seen by the PCBH staff vs a referral by PCPs.

Geriatric-Specific Modifications to PCBH

The VAPAHCS GRECC, collaborating with the outpatient psychiatry service and the PCBH, sought to improve current mental health services for older veterans. Several barriers were identified: (1) limitations in types of interventions available to older veterans in the current PCBH and mental health programs; (2) the PCBH staff required geriatrics training, as recommended by the American Psychological Association¹²; and (3) resistance to receiving care in mental health clinics located several miles from the primary care setting. Therefore, a new pilot program was planned to address these barriers.

The Office of Geriatrics and Extended Care provided the funding for the initial program costs, and in September 2010, the Geriatric Primary Care Behavioral Health program (Geri-PCBH) was launched. The GRECC staff worked closely with the PCBH staff to offer a new service tailored to older veterans’ specific needs, which addressed the previously described program limitations.

Geri-PCBH Program

The Geri-PCBH program is a blended collaborative care model that provides outpatient-based mental health evaluation and treatment of mood disorders for older (aged ≥ 65 years) veterans. It is co-located with PCBH and PCPs within the primary care setting. The program extends PCBH services by providing psychotherapy that is contextually modified for older veterans. Older veterans may present with different therapy concerns than do younger veterans, such as caregiving, death of loved ones, and numerous and chronic medical illnesses. Illnesses may result in polypharmacy, giving rise to the need for understanding potential medication interactions in providing pharmacotherapy.

Within the program, geriatrics-trained psychologists and social workers offer psychotherapy. In addition, a geriatrician with expertise in polypharmacy offers pharmacotherapy. Psychotherapy, pharmacotherapy, or both are offered and initiated following evaluation and discussion with the veteran. Veterans are either referred by the PCBH staff because they screened positive for depression (Patient Health Questionnaire-2 [PHQ-2] ≥ 2) during a regularly scheduled primary care clinic appointment or they are directly referred by primary care physicians for suspected mood problems. Veterans are then contacted immediately by a staff member for a baseline assessment appointment with a geriatrician and one of the therapists. The type of treatment and goals of therapy are determined during the initial meeting. The program is a training site for psychology and social work interns, to increase their geriatric mental health training.

Evaluation and Results

To determine improvements compared to PCBH program outcomes, the patients who attended the initial Geri-PCBH evaluation/intake appointment were tracked. A total of 79 older veterans were referred (average age, 82.7 years; range, aged 66-96 years); 14 veterans were ineligible due to significant cognitive impairment or lack of depressive symptoms. Compared with the 38% rate of attendance at intake for mental health referrals in the PCBH program, the Geri-PCBH program demonstrated a 90% attendance rate at the initial evaluation appointment. Fifty-five older veterans enrolled and received therapy: 39 received only psychotherapy, 14 received psychotherapy and antidepressant therapy, and 2 received only antidepressant therapy. Over the first 2 years of the program, 2 senior therapists and 5 trainees were able to see 53 patients for an average of 7 sessions per patient, which translated to about 14% of each therapist’s time.

To determine the impact on patients, measures of depression (Hamilton Depression Rating Scale [HDRS]; Geriatric Depression Scale Short Form [GDS-SF]; and Patient Health Questionnaire 9 Item [PHQ-9]), anxiety (Mini Psychiatric Evaluation Scale-Generalized Anxiety subscale [MINI-GAD]), overall distress (clinical global inventory), and functional status (12-item World Health Organization Disability Assessment Scale [WHODAS]) were administered at baseline, posttreatment, and 3 months posttreatment. The veterans demonstrated a significant decrease (> 50% decline on mood symptoms) on the HDRS, GDS, PHQ-9, and MINI-GAD subscale, which were all sustained 3 months posttreatment (Figure).

Although the overall disability score did not improve, the percentage of older veterans reporting “bad” or “moderate” health decreased (pre = 42%; post = 31.1%; 3-month follow-up = 20.9%); while those reporting “good” or “very good” health increased (pre = 58%; post = 65.7%; 3-month follow-up = 79.2%) by the 3-month follow-up. Veterans also reported very high satisfaction rates with the program overall (Mean = 30, standard deviation = 2.03; anchors for measure: 0 = not satisfied; 32 = highly satisfied).

Patient Testimonials

“Not in my wildest dreams did I think I’d ever share, on this level, my personal, past and present life…You have been so helpful and allowed me to move forward with pride and self respect.”

“It makes you feel a lot better. I enjoy life more now than I used to. That first time that [my therapist and I] talked, she convinced me just a change in attitude was a big thing. And since I changed my attitude and started listening to people, it’s made a heck of a difference.”

Discussion and Conclusion

The results of the Geri-PCBH evaluation demonstrated improvements in acceptance by older veterans with depression of mental health referrals and in increased access to treatment. The program addressed several identified barriers, such as having a more accessible location, offering treatment by experienced geriatrics-trained providers, and providing a range of mental health services tailored to older veterans’ needs. These factors may have increased older veterans’ willingness to attend mental health referrals to the Geri-PCBH program. Having initial assessments done soon after initial referral (usually < 2 weeks) and calling patients personally to explain the program and make appointments likely improved referral acceptance.

There are some limits to implementing this program in other settings related to variability in staffing, infrastructure, and resources available. The project is currently sustained with the present staff, with the goal of expanding services by telehealth technology to disseminate the program to older veterans in rural settings.

The VHA has made impressive strides toward improving the lives of older veterans with depression and anxiety. The program described here provides an example of how quality improvement efforts, which take into account the specific needs of the older veteran, can lead to a dramatic impact on the services offered and more importantly on veterans’ mental health and functional abilities. 

Acknowledgements
This material is the result of work supported with funding by the Office of Geriatrics and Extended Care T21T Fund-10/11 060B2 and resources and use of facilities at the VA Palo Alto Health Care System in Palo Alto, California.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

More older adults suffer from depression in a VHA setting (11%) than those in non-VHA settings (1%-5%).¹ Depression and anxiety are evaluated less often in older adults and undertreated compared with younger adults.^2-4 Unfortunately, older adults with depression and anxiety are vulnerable to suicide and disability; and they more frequently use medical services, such as the emergency department compared with older adults without these conditions.^5-7

However, pharmacologic and behavioral treatments for late-life mood and anxiety disorders are available and are effective.⁸ These findings raise important questions about improving access to mental health care for older veterans with mood disorders. The VA Palo Alto Health Care System (VAPAHCS) Geriatric Research Education and Clinical Center (GRECC) fulfills one GRECC mission of carrying out transformative clinical demonstration projects by developing programs to address geriatric mood disorders.

The VHA has successfully implemented the nationwide integration of mental health management into primary care settings.⁹ To design and implement these programs locally, in 2007, all VHAs were invited to submit proposals related to mental health primary care integration. Local sites were given flexibility in their use of different evidence-based models for delivery of this integrated care.

Collaborative Models

Three models of mental health integration into primary care were adopted within VHA. All have resulted in improved patient outcomes.⁹ The co-located model places a behavioral health specialist within the same setting as primary care providers (PCPs), who shares in the evaluation, treatment planning, and monitoring of mental health outcomes. In the care management model, care managers facilitate evaluation and maintain communication with PCPs, but are not co-located with the PCPs. The third model is a blended model in which both a behavioral health specialist and a care manager may be involved in the management of mental health care. The care management model resulted in better participation in the evaluation and engagement in pharmacotherapy by older veterans in 2 VHA medical centers.¹⁰

Persistent Barriers for Older Veterans

The mental health-primary care integration initiative laid important foundations for improving access to mental health care. To provide a truly veteran-centered care option, however, programs require monitoring and analysis of the factors that impact care delivery and access. A recent evaluation of a local integration program, using a co-located model (ie, Primary Care Behavioral Health [PCBH]), demonstrated that there were several factors affecting older veterans’ access to mental health treatment.¹¹ Older veterans with depression were less receptive to a mental health referral; 62% of older veterans refused mental health referrals compared with 32% of younger veterans who refused. Older veterans were less likely to complete at least 1 mental health clinic appointment, which was due in part to clinic location. All veterans were more likely to follow up with a mental health referral if first seen by the PCBH staff vs a referral by PCPs.

Geriatric-Specific Modifications to PCBH

The VAPAHCS GRECC, collaborating with the outpatient psychiatry service and the PCBH, sought to improve current mental health services for older veterans. Several barriers were identified: (1) limitations in types of interventions available to older veterans in the current PCBH and mental health programs; (2) the PCBH staff required geriatrics training, as recommended by the American Psychological Association¹²; and (3) resistance to receiving care in mental health clinics located several miles from the primary care setting. Therefore, a new pilot program was planned to address these barriers.

The Office of Geriatrics and Extended Care provided the funding for the initial program costs, and in September 2010, the Geriatric Primary Care Behavioral Health program (Geri-PCBH) was launched. The GRECC staff worked closely with the PCBH staff to offer a new service tailored to older veterans’ specific needs, which addressed the previously described program limitations.

Geri-PCBH Program

The Geri-PCBH program is a blended collaborative care model that provides outpatient-based mental health evaluation and treatment of mood disorders for older (aged ≥ 65 years) veterans. It is co-located with PCBH and PCPs within the primary care setting. The program extends PCBH services by providing psychotherapy that is contextually modified for older veterans. Older veterans may present with different therapy concerns than do younger veterans, such as caregiving, death of loved ones, and numerous and chronic medical illnesses. Illnesses may result in polypharmacy, giving rise to the need for understanding potential medication interactions in providing pharmacotherapy.

Within the program, geriatrics-trained psychologists and social workers offer psychotherapy. In addition, a geriatrician with expertise in polypharmacy offers pharmacotherapy. Psychotherapy, pharmacotherapy, or both are offered and initiated following evaluation and discussion with the veteran. Veterans are either referred by the PCBH staff because they screened positive for depression (Patient Health Questionnaire-2 [PHQ-2] ≥ 2) during a regularly scheduled primary care clinic appointment or they are directly referred by primary care physicians for suspected mood problems. Veterans are then contacted immediately by a staff member for a baseline assessment appointment with a geriatrician and one of the therapists. The type of treatment and goals of therapy are determined during the initial meeting. The program is a training site for psychology and social work interns, to increase their geriatric mental health training.

Evaluation and Results

To determine improvements compared to PCBH program outcomes, the patients who attended the initial Geri-PCBH evaluation/intake appointment were tracked. A total of 79 older veterans were referred (average age, 82.7 years; range, aged 66-96 years); 14 veterans were ineligible due to significant cognitive impairment or lack of depressive symptoms. Compared with the 38% rate of attendance at intake for mental health referrals in the PCBH program, the Geri-PCBH program demonstrated a 90% attendance rate at the initial evaluation appointment. Fifty-five older veterans enrolled and received therapy: 39 received only psychotherapy, 14 received psychotherapy and antidepressant therapy, and 2 received only antidepressant therapy. Over the first 2 years of the program, 2 senior therapists and 5 trainees were able to see 53 patients for an average of 7 sessions per patient, which translated to about 14% of each therapist’s time.

To determine the impact on patients, measures of depression (Hamilton Depression Rating Scale [HDRS]; Geriatric Depression Scale Short Form [GDS-SF]; and Patient Health Questionnaire 9 Item [PHQ-9]), anxiety (Mini Psychiatric Evaluation Scale-Generalized Anxiety subscale [MINI-GAD]), overall distress (clinical global inventory), and functional status (12-item World Health Organization Disability Assessment Scale [WHODAS]) were administered at baseline, posttreatment, and 3 months posttreatment. The veterans demonstrated a significant decrease (> 50% decline on mood symptoms) on the HDRS, GDS, PHQ-9, and MINI-GAD subscale, which were all sustained 3 months posttreatment (Figure).

Although the overall disability score did not improve, the percentage of older veterans reporting “bad” or “moderate” health decreased (pre = 42%; post = 31.1%; 3-month follow-up = 20.9%); while those reporting “good” or “very good” health increased (pre = 58%; post = 65.7%; 3-month follow-up = 79.2%) by the 3-month follow-up. Veterans also reported very high satisfaction rates with the program overall (Mean = 30, standard deviation = 2.03; anchors for measure: 0 = not satisfied; 32 = highly satisfied).

Patient Testimonials

“Not in my wildest dreams did I think I’d ever share, on this level, my personal, past and present life…You have been so helpful and allowed me to move forward with pride and self respect.”

“It makes you feel a lot better. I enjoy life more now than I used to. That first time that [my therapist and I] talked, she convinced me just a change in attitude was a big thing. And since I changed my attitude and started listening to people, it’s made a heck of a difference.”

Discussion and Conclusion

The results of the Geri-PCBH evaluation demonstrated improvements in acceptance by older veterans with depression of mental health referrals and in increased access to treatment. The program addressed several identified barriers, such as having a more accessible location, offering treatment by experienced geriatrics-trained providers, and providing a range of mental health services tailored to older veterans’ needs. These factors may have increased older veterans’ willingness to attend mental health referrals to the Geri-PCBH program. Having initial assessments done soon after initial referral (usually < 2 weeks) and calling patients personally to explain the program and make appointments likely improved referral acceptance.

There are some limits to implementing this program in other settings related to variability in staffing, infrastructure, and resources available. The project is currently sustained with the present staff, with the goal of expanding services by telehealth technology to disseminate the program to older veterans in rural settings.

The VHA has made impressive strides toward improving the lives of older veterans with depression and anxiety. The program described here provides an example of how quality improvement efforts, which take into account the specific needs of the older veteran, can lead to a dramatic impact on the services offered and more importantly on veterans’ mental health and functional abilities. 

Acknowledgements
This material is the result of work supported with funding by the Office of Geriatrics and Extended Care T21T Fund-10/11 060B2 and resources and use of facilities at the VA Palo Alto Health Care System in Palo Alto, California.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Glasses of wine

Contrary to previous findings, a new study suggests the antioxidant resveratrol is not associated with improvements in health, including reducing the risk of cancer.

Researchers found that Italians who consumed a diet rich in resveratrol—a compound in red wine, dark chocolate, and berries—lived no longer than and were just as likely to develop cardiovascular disease or cancer as Italians who consumed smaller amounts of the antioxidant.

However, the investigators said unknown compounds in these foods and drinks may still confer health benefits.

“The story of resveratrol turns out to be another case where you get a lot of hype about health benefits that doesn’t stand the test of time,” said study author Richard D. Semba, MD, MPH, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“The thinking was that certain foods are good for you because they contain resveratrol. We didn’t find that at all.”

Dr Semba and his colleagues recounted their findings in JAMA Internal Medicine.

Their study included 783 subjects, all of whom were older than 65 years of age. Participants were part of the Aging in the Chianti Region study, conducted from 1998 to 2009 in 2 Italian villages where supplement use is uncommon and the consumption of red wine is the norm. The subjects were not on any prescribed diet.

The researchers wanted to determine if diet-related resveratrol levels were associated with inflammation, cancer, cardiovascular disease, and death. So they collected urine samples from study participants and used advanced mass spectrometry to analyze the samples for metabolites of resveratrol.

After accounting for such factors as age and gender, the investigators found that subjects with the highest concentration of resveratrol metabolites were no less likely to have died of any cause than subjects with the lowest levels of resveratrol in their urine.

Likewise, the concentration of resveratrol was not associated with inflammatory markers (serum CRP, IL-6, IL-1β,TNF), cardiovascular disease, or cancer rates.

During 9 years of follow-up, 268 participants (34.3%) died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of subjects who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P=0.67).

Of the 734 participants who were free of cancer at enrollment, 34 (4.6%) developed cancer during follow-up. The proportions of subjects with incident cancer from the lowest to the highest quartiles of resveratrol were 4.4%, 4.9%, 5.0%, and 4.3%, respectively (P=0.98).

Of the 639 subjects who were free of cardiovascular disease at enrollment, 174 (27.2%) developed cardiovascular disease during follow-up. The proportions of participants with incident cardiovascular disease from the lowest to the highest quartiles of resveratrol were 22.3%, 29.6%, 28.4%, and 28.0%, respectively (P=0.44).

Despite these negative results, Dr Semba noted that studies have shown the consumption of red wine, dark chocolate, and berries does reduce inflammation in some people and still appears to protect the heart.

“It’s just that the benefits, if they are there, must come from other polyphenols or substances found in those foodstuffs,” he said. “These are complex foods, and all we really know from our study is that the benefits are probably not due to resveratrol.”

Glasses of wine

Contrary to previous findings, a new study suggests the antioxidant resveratrol is not associated with improvements in health, including reducing the risk of cancer.

Researchers found that Italians who consumed a diet rich in resveratrol—a compound in red wine, dark chocolate, and berries—lived no longer than and were just as likely to develop cardiovascular disease or cancer as Italians who consumed smaller amounts of the antioxidant.

However, the investigators said unknown compounds in these foods and drinks may still confer health benefits.

“The story of resveratrol turns out to be another case where you get a lot of hype about health benefits that doesn’t stand the test of time,” said study author Richard D. Semba, MD, MPH, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“The thinking was that certain foods are good for you because they contain resveratrol. We didn’t find that at all.”

Dr Semba and his colleagues recounted their findings in JAMA Internal Medicine.

Their study included 783 subjects, all of whom were older than 65 years of age. Participants were part of the Aging in the Chianti Region study, conducted from 1998 to 2009 in 2 Italian villages where supplement use is uncommon and the consumption of red wine is the norm. The subjects were not on any prescribed diet.

The researchers wanted to determine if diet-related resveratrol levels were associated with inflammation, cancer, cardiovascular disease, and death. So they collected urine samples from study participants and used advanced mass spectrometry to analyze the samples for metabolites of resveratrol.

After accounting for such factors as age and gender, the investigators found that subjects with the highest concentration of resveratrol metabolites were no less likely to have died of any cause than subjects with the lowest levels of resveratrol in their urine.

Likewise, the concentration of resveratrol was not associated with inflammatory markers (serum CRP, IL-6, IL-1β,TNF), cardiovascular disease, or cancer rates.

During 9 years of follow-up, 268 participants (34.3%) died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of subjects who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P=0.67).

Of the 734 participants who were free of cancer at enrollment, 34 (4.6%) developed cancer during follow-up. The proportions of subjects with incident cancer from the lowest to the highest quartiles of resveratrol were 4.4%, 4.9%, 5.0%, and 4.3%, respectively (P=0.98).

Of the 639 subjects who were free of cardiovascular disease at enrollment, 174 (27.2%) developed cardiovascular disease during follow-up. The proportions of participants with incident cardiovascular disease from the lowest to the highest quartiles of resveratrol were 22.3%, 29.6%, 28.4%, and 28.0%, respectively (P=0.44).

Despite these negative results, Dr Semba noted that studies have shown the consumption of red wine, dark chocolate, and berries does reduce inflammation in some people and still appears to protect the heart.

“It’s just that the benefits, if they are there, must come from other polyphenols or substances found in those foodstuffs,” he said. “These are complex foods, and all we really know from our study is that the benefits are probably not due to resveratrol.”

Glasses of wine

Contrary to previous findings, a new study suggests the antioxidant resveratrol is not associated with improvements in health, including reducing the risk of cancer.

Researchers found that Italians who consumed a diet rich in resveratrol—a compound in red wine, dark chocolate, and berries—lived no longer than and were just as likely to develop cardiovascular disease or cancer as Italians who consumed smaller amounts of the antioxidant.

However, the investigators said unknown compounds in these foods and drinks may still confer health benefits.

“The story of resveratrol turns out to be another case where you get a lot of hype about health benefits that doesn’t stand the test of time,” said study author Richard D. Semba, MD, MPH, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“The thinking was that certain foods are good for you because they contain resveratrol. We didn’t find that at all.”

Dr Semba and his colleagues recounted their findings in JAMA Internal Medicine.

Their study included 783 subjects, all of whom were older than 65 years of age. Participants were part of the Aging in the Chianti Region study, conducted from 1998 to 2009 in 2 Italian villages where supplement use is uncommon and the consumption of red wine is the norm. The subjects were not on any prescribed diet.

The researchers wanted to determine if diet-related resveratrol levels were associated with inflammation, cancer, cardiovascular disease, and death. So they collected urine samples from study participants and used advanced mass spectrometry to analyze the samples for metabolites of resveratrol.

After accounting for such factors as age and gender, the investigators found that subjects with the highest concentration of resveratrol metabolites were no less likely to have died of any cause than subjects with the lowest levels of resveratrol in their urine.

Likewise, the concentration of resveratrol was not associated with inflammatory markers (serum CRP, IL-6, IL-1β,TNF), cardiovascular disease, or cancer rates.

During 9 years of follow-up, 268 participants (34.3%) died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of subjects who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P=0.67).

Of the 734 participants who were free of cancer at enrollment, 34 (4.6%) developed cancer during follow-up. The proportions of subjects with incident cancer from the lowest to the highest quartiles of resveratrol were 4.4%, 4.9%, 5.0%, and 4.3%, respectively (P=0.98).

Of the 639 subjects who were free of cardiovascular disease at enrollment, 174 (27.2%) developed cardiovascular disease during follow-up. The proportions of participants with incident cardiovascular disease from the lowest to the highest quartiles of resveratrol were 22.3%, 29.6%, 28.4%, and 28.0%, respectively (P=0.44).

Despite these negative results, Dr Semba noted that studies have shown the consumption of red wine, dark chocolate, and berries does reduce inflammation in some people and still appears to protect the heart.

“It’s just that the benefits, if they are there, must come from other polyphenols or substances found in those foodstuffs,” he said. “These are complex foods, and all we really know from our study is that the benefits are probably not due to resveratrol.”

Doctor and patient

Credit: NIH

As a result of Medicare Fraud Strike Force operations in 6 US cities, 90 healthcare professionals have been charged with fraud.

These individuals—doctors, nurses, healthcare company owners, and others—are accused of participating in Medicare fraud schemes involving approximately $260 million in false billings.

They have been charged with various crimes, including conspiracy to commit healthcare fraud, violations of the anti-kickback statutes, and money laundering.

According to court documents, the defendants allegedly participated in schemes to submit claims to Medicare for treatments that were medically unnecessary and often never provided.

In many cases, court documents allege that patient recruiters, Medicare beneficiaries, and other co-conspirators were paid cash kickbacks in return for supplying beneficiary information to providers so the providers could then submit fraudulent bills to Medicare for services that were medically unnecessary or never performed.

“[T]he crimes charged represent the face of healthcare fraud today—doctors billing for services that were never rendered, supply companies providing motorized wheelchairs that were never needed, recruiters paying kickbacks to get Medicare billing numbers of patients,” said Acting Assistant Attorney General David O’Neil.

Case details

In Miami, Florida, 50 defendants were charged for their alleged participation in various fraud schemes involving approximately $65.5 million in false billings for home healthcare and mental health services, as well as pharmacy fraud.

Two of these defendants were charged in connection with a $23 million pharmacy kickback and laundering scheme. Court documents allege that the defendants solicited kickbacks from a pharmacy owner for Medicare beneficiary information, which was used to bill for drugs that were never dispensed.

The kickbacks were concealed as bi-weekly payments under a sham services contract and were laundered through shell entities owned by the defendants.

Eleven individuals were charged by the Medicare Strike Force in Houston, Texas. Five Houston-area physicians were charged with conspiring to bill Medicare for medically unnecessary home health services. According to court documents, the defendant doctors were paid by 2 co-conspirators to sign off on home healthcare services that were not necessary and often never provided.

Eight defendants were charged in Los Angeles, California, for their roles in schemes to defraud Medicare of approximately $32 million.

One doctor was charged for causing almost $24 million in losses to Medicare through his own fraudulent billing and referrals for durable medical equipment, including more than 1000 expensive power wheelchairs, and home health services that were not medically necessary and frequently not provided.

In Detroit, Michigan, 7 defendants were charged for their roles in fraud schemes involving approximately $30 million in false claims for medically unnecessary services, including home health services, psychotherapy, and infusion therapy.

Four of these individuals were charged in a $28 million fraud scheme, where a physician billed for expensive tests, physical therapy, and injections that were not necessary and not provided.

Court documents allege that when the physician’s billings raised red flags, he was put on payment review by Medicare. He was allegedly able to continue his scheme and evade detection by continuing to bill using the billing information of other Medicare providers, sometimes without their knowledge.

In Tampa, Florida, 7 individuals were charged in a variety of schemes, ranging from fraudulent physical therapy billings to a scheme involving millions of dollars in physician services and tests that never occurred.

Five of these individuals were charged for their alleged roles in a $12 million healthcare fraud and money laundering scheme that involved billing Medicare using names of beneficiaries from Miami-Dade County for services purportedly provided in Tampa-area clinics, 280 miles away. The defendants then allegedly laundered the proceeds through a number of transactions involving several shell entities.

In Brooklyn, New York, the Strike Force announced an indictment against Syed Imran Ahmed, MD, in connection with his alleged $85 million scheme involving billings for surgeries that never occurred. Dr Ahmed had been arrested last month and charged by complaint. He is now charged with healthcare fraud and making false statements.

The Brooklyn Strike Force also charged 6 other individuals, including a physician and 2 billers who allegedly concocted a $14.4 million scheme in which they recruited elderly Medicare beneficiaries and billed Medicare for medically unnecessary vitamin infusions, diagnostic tests, and physical and occupational therapy supposedly provided to these patients.

The cases are being prosecuted and investigated by Medicare Fraud Strike Force teams comprised of attorneys from the Fraud Section of the Justice Department’s Criminal Division and from the US Attorney’s Offices for the Southern District of Florida, the Eastern District of Michigan, the Eastern District of New York, the Southern District of Texas, the Central District of California, the Middle District of Louisiana, the Northern District of Illinois and the Middle District of Florida; and agents from the Federal Bureau of Investigation, Department of Health and Human Services (HHS)-Office of Inspector General (OIG), and state Medicaid Fraud Control Units.

About the Medicare Fraud Strike Force

This is the seventh national Medicare fraud takedown in Medicare Fraud Strike Force history. The Strike Force’s operations are part of the Health Care Fraud Prevention & Enforcement Action Team (HEAT), a joint initiative announced in May 2009 between the Department of Justice and the HHS to focus their efforts to prevent and deter fraud and enforce current anti-fraud laws around the country.

Since their inception in March 2007, Strike Force operations in 9 locations have charged almost 1900 defendants who collectively have falsely billed the Medicare program for almost $6 billion.

In addition, the Centers for Medicare & Medicaid Services, working in conjunction with HHS-OIG, has suspended enrollments of high-risk providers in 5 Strike Force locations and has removed more than 17,000 providers from the Medicare program since 2011.

The joint Department of Justice and HHS Medicare Fraud Strike Force is a multi-agency team of federal, state, and local investigators designed to combat Medicare fraud through the use of Medicare data analysis techniques and an increased focus on community policing.

To learn more, visit www.stopmedicarefraud.gov.

Doctor and patient

Credit: NIH

As a result of Medicare Fraud Strike Force operations in 6 US cities, 90 healthcare professionals have been charged with fraud.

These individuals—doctors, nurses, healthcare company owners, and others—are accused of participating in Medicare fraud schemes involving approximately $260 million in false billings.

They have been charged with various crimes, including conspiracy to commit healthcare fraud, violations of the anti-kickback statutes, and money laundering.

According to court documents, the defendants allegedly participated in schemes to submit claims to Medicare for treatments that were medically unnecessary and often never provided.

In many cases, court documents allege that patient recruiters, Medicare beneficiaries, and other co-conspirators were paid cash kickbacks in return for supplying beneficiary information to providers so the providers could then submit fraudulent bills to Medicare for services that were medically unnecessary or never performed.

“[T]he crimes charged represent the face of healthcare fraud today—doctors billing for services that were never rendered, supply companies providing motorized wheelchairs that were never needed, recruiters paying kickbacks to get Medicare billing numbers of patients,” said Acting Assistant Attorney General David O’Neil.

Case details

In Miami, Florida, 50 defendants were charged for their alleged participation in various fraud schemes involving approximately $65.5 million in false billings for home healthcare and mental health services, as well as pharmacy fraud.

Two of these defendants were charged in connection with a $23 million pharmacy kickback and laundering scheme. Court documents allege that the defendants solicited kickbacks from a pharmacy owner for Medicare beneficiary information, which was used to bill for drugs that were never dispensed.

The kickbacks were concealed as bi-weekly payments under a sham services contract and were laundered through shell entities owned by the defendants.

Eleven individuals were charged by the Medicare Strike Force in Houston, Texas. Five Houston-area physicians were charged with conspiring to bill Medicare for medically unnecessary home health services. According to court documents, the defendant doctors were paid by 2 co-conspirators to sign off on home healthcare services that were not necessary and often never provided.

Eight defendants were charged in Los Angeles, California, for their roles in schemes to defraud Medicare of approximately $32 million.

One doctor was charged for causing almost $24 million in losses to Medicare through his own fraudulent billing and referrals for durable medical equipment, including more than 1000 expensive power wheelchairs, and home health services that were not medically necessary and frequently not provided.

In Detroit, Michigan, 7 defendants were charged for their roles in fraud schemes involving approximately $30 million in false claims for medically unnecessary services, including home health services, psychotherapy, and infusion therapy.

Four of these individuals were charged in a $28 million fraud scheme, where a physician billed for expensive tests, physical therapy, and injections that were not necessary and not provided.

Court documents allege that when the physician’s billings raised red flags, he was put on payment review by Medicare. He was allegedly able to continue his scheme and evade detection by continuing to bill using the billing information of other Medicare providers, sometimes without their knowledge.

In Tampa, Florida, 7 individuals were charged in a variety of schemes, ranging from fraudulent physical therapy billings to a scheme involving millions of dollars in physician services and tests that never occurred.

Five of these individuals were charged for their alleged roles in a $12 million healthcare fraud and money laundering scheme that involved billing Medicare using names of beneficiaries from Miami-Dade County for services purportedly provided in Tampa-area clinics, 280 miles away. The defendants then allegedly laundered the proceeds through a number of transactions involving several shell entities.

In Brooklyn, New York, the Strike Force announced an indictment against Syed Imran Ahmed, MD, in connection with his alleged $85 million scheme involving billings for surgeries that never occurred. Dr Ahmed had been arrested last month and charged by complaint. He is now charged with healthcare fraud and making false statements.

The Brooklyn Strike Force also charged 6 other individuals, including a physician and 2 billers who allegedly concocted a $14.4 million scheme in which they recruited elderly Medicare beneficiaries and billed Medicare for medically unnecessary vitamin infusions, diagnostic tests, and physical and occupational therapy supposedly provided to these patients.

The cases are being prosecuted and investigated by Medicare Fraud Strike Force teams comprised of attorneys from the Fraud Section of the Justice Department’s Criminal Division and from the US Attorney’s Offices for the Southern District of Florida, the Eastern District of Michigan, the Eastern District of New York, the Southern District of Texas, the Central District of California, the Middle District of Louisiana, the Northern District of Illinois and the Middle District of Florida; and agents from the Federal Bureau of Investigation, Department of Health and Human Services (HHS)-Office of Inspector General (OIG), and state Medicaid Fraud Control Units.

About the Medicare Fraud Strike Force

This is the seventh national Medicare fraud takedown in Medicare Fraud Strike Force history. The Strike Force’s operations are part of the Health Care Fraud Prevention & Enforcement Action Team (HEAT), a joint initiative announced in May 2009 between the Department of Justice and the HHS to focus their efforts to prevent and deter fraud and enforce current anti-fraud laws around the country.

Since their inception in March 2007, Strike Force operations in 9 locations have charged almost 1900 defendants who collectively have falsely billed the Medicare program for almost $6 billion.

In addition, the Centers for Medicare & Medicaid Services, working in conjunction with HHS-OIG, has suspended enrollments of high-risk providers in 5 Strike Force locations and has removed more than 17,000 providers from the Medicare program since 2011.

The joint Department of Justice and HHS Medicare Fraud Strike Force is a multi-agency team of federal, state, and local investigators designed to combat Medicare fraud through the use of Medicare data analysis techniques and an increased focus on community policing.

To learn more, visit www.stopmedicarefraud.gov.

Doctor and patient

Credit: NIH

As a result of Medicare Fraud Strike Force operations in 6 US cities, 90 healthcare professionals have been charged with fraud.

These individuals—doctors, nurses, healthcare company owners, and others—are accused of participating in Medicare fraud schemes involving approximately $260 million in false billings.

They have been charged with various crimes, including conspiracy to commit healthcare fraud, violations of the anti-kickback statutes, and money laundering.

According to court documents, the defendants allegedly participated in schemes to submit claims to Medicare for treatments that were medically unnecessary and often never provided.

In many cases, court documents allege that patient recruiters, Medicare beneficiaries, and other co-conspirators were paid cash kickbacks in return for supplying beneficiary information to providers so the providers could then submit fraudulent bills to Medicare for services that were medically unnecessary or never performed.

“[T]he crimes charged represent the face of healthcare fraud today—doctors billing for services that were never rendered, supply companies providing motorized wheelchairs that were never needed, recruiters paying kickbacks to get Medicare billing numbers of patients,” said Acting Assistant Attorney General David O’Neil.

Case details

In Miami, Florida, 50 defendants were charged for their alleged participation in various fraud schemes involving approximately $65.5 million in false billings for home healthcare and mental health services, as well as pharmacy fraud.

Two of these defendants were charged in connection with a $23 million pharmacy kickback and laundering scheme. Court documents allege that the defendants solicited kickbacks from a pharmacy owner for Medicare beneficiary information, which was used to bill for drugs that were never dispensed.

The kickbacks were concealed as bi-weekly payments under a sham services contract and were laundered through shell entities owned by the defendants.

Eleven individuals were charged by the Medicare Strike Force in Houston, Texas. Five Houston-area physicians were charged with conspiring to bill Medicare for medically unnecessary home health services. According to court documents, the defendant doctors were paid by 2 co-conspirators to sign off on home healthcare services that were not necessary and often never provided.

Eight defendants were charged in Los Angeles, California, for their roles in schemes to defraud Medicare of approximately $32 million.

One doctor was charged for causing almost $24 million in losses to Medicare through his own fraudulent billing and referrals for durable medical equipment, including more than 1000 expensive power wheelchairs, and home health services that were not medically necessary and frequently not provided.

In Detroit, Michigan, 7 defendants were charged for their roles in fraud schemes involving approximately $30 million in false claims for medically unnecessary services, including home health services, psychotherapy, and infusion therapy.

Four of these individuals were charged in a $28 million fraud scheme, where a physician billed for expensive tests, physical therapy, and injections that were not necessary and not provided.

Court documents allege that when the physician’s billings raised red flags, he was put on payment review by Medicare. He was allegedly able to continue his scheme and evade detection by continuing to bill using the billing information of other Medicare providers, sometimes without their knowledge.

In Tampa, Florida, 7 individuals were charged in a variety of schemes, ranging from fraudulent physical therapy billings to a scheme involving millions of dollars in physician services and tests that never occurred.

Five of these individuals were charged for their alleged roles in a $12 million healthcare fraud and money laundering scheme that involved billing Medicare using names of beneficiaries from Miami-Dade County for services purportedly provided in Tampa-area clinics, 280 miles away. The defendants then allegedly laundered the proceeds through a number of transactions involving several shell entities.

In Brooklyn, New York, the Strike Force announced an indictment against Syed Imran Ahmed, MD, in connection with his alleged $85 million scheme involving billings for surgeries that never occurred. Dr Ahmed had been arrested last month and charged by complaint. He is now charged with healthcare fraud and making false statements.

The Brooklyn Strike Force also charged 6 other individuals, including a physician and 2 billers who allegedly concocted a $14.4 million scheme in which they recruited elderly Medicare beneficiaries and billed Medicare for medically unnecessary vitamin infusions, diagnostic tests, and physical and occupational therapy supposedly provided to these patients.

The cases are being prosecuted and investigated by Medicare Fraud Strike Force teams comprised of attorneys from the Fraud Section of the Justice Department’s Criminal Division and from the US Attorney’s Offices for the Southern District of Florida, the Eastern District of Michigan, the Eastern District of New York, the Southern District of Texas, the Central District of California, the Middle District of Louisiana, the Northern District of Illinois and the Middle District of Florida; and agents from the Federal Bureau of Investigation, Department of Health and Human Services (HHS)-Office of Inspector General (OIG), and state Medicaid Fraud Control Units.

About the Medicare Fraud Strike Force

This is the seventh national Medicare fraud takedown in Medicare Fraud Strike Force history. The Strike Force’s operations are part of the Health Care Fraud Prevention & Enforcement Action Team (HEAT), a joint initiative announced in May 2009 between the Department of Justice and the HHS to focus their efforts to prevent and deter fraud and enforce current anti-fraud laws around the country.

Since their inception in March 2007, Strike Force operations in 9 locations have charged almost 1900 defendants who collectively have falsely billed the Medicare program for almost $6 billion.

In addition, the Centers for Medicare & Medicaid Services, working in conjunction with HHS-OIG, has suspended enrollments of high-risk providers in 5 Strike Force locations and has removed more than 17,000 providers from the Medicare program since 2011.

The joint Department of Justice and HHS Medicare Fraud Strike Force is a multi-agency team of federal, state, and local investigators designed to combat Medicare fraud through the use of Medicare data analysis techniques and an increased focus on community policing.

To learn more, visit www.stopmedicarefraud.gov.

Malaria-carrying mosquito

Credit: James Gathany

Data that tracks cell phone activity can help us more accurately target antimalaria interventions, according to a paper published in Malaria Journal.

Researchers used anonymized cell phone records to measure population movements within Namibia, Africa, over a year.

By combining this data with information about malaria cases, topography, and climate, the group was able to identify geographical “hotspots” of the disease and design targeted plans for its elimination.

“If we are to eliminate this disease, we need to deploy the right measures in the right place, but figures on human movement patterns in endemic regions are hard to come by and often restricted to local travel surveys and census-based migration data,” said study author Andrew Tatem, PhD, of the University of Southampton in the UK.

“Our study demonstrates that the rapid global proliferation of mobile phones now provides us with an opportunity to study the movement of people, using sample sizes running in to millions. This data, combined with disease-case-based mapping, can help us plan where and how to intervene.”

Dr Tatem and his colleagues looked at anonymized Call Data Records from 2010 to 2011, provided by Mobile Telecommunications Limited. The data represented 9 billion communications from 1.19 million unique subscribers, around 52% of the population of Namibia.

The researchers analyzed aggregated movements of phone users between urban areas and urban and rural areas, in conjunction with data based on rapid diagnostic testing of malaria and information on the climate, environment, and topography of the country.

In this way, the team identified communities that were strongly connected by relatively higher levels of population movement. They quantified the net export and import of travelers and mapped malaria infection risks by region.

The researchers said these malaria risk maps can aid the design of targeted interventions to reduce the number of malaria cases exported to other regions and help manage the risk of infection in places that import the disease.

In fact, the maps have already helped the Namibia National Vector-borne Diseases Control Programme improve their targeting of malaria interventions to communities most at risk.

Specifically, the maps prompted the organization to target insecticide-treated bed net distribution in the Omusati, Kavango, and Zambezi regions in 2013.

“The importation of malaria from outside a country will always be a crucial focus of disease control programs, but movement of the disease within countries is also of huge significance,” Dr Tatem said. “Understanding the human element of this movement should be a critical component when designing elimination strategies—to help target resources most efficiently.”

“The use of mobile phone data is one example of how new technologies are overcoming past problems of quantifying and gaining a better understanding of human movement patterns in relation to disease control.”

Malaria-carrying mosquito

Credit: James Gathany

Data that tracks cell phone activity can help us more accurately target antimalaria interventions, according to a paper published in Malaria Journal.

Researchers used anonymized cell phone records to measure population movements within Namibia, Africa, over a year.

By combining this data with information about malaria cases, topography, and climate, the group was able to identify geographical “hotspots” of the disease and design targeted plans for its elimination.

“If we are to eliminate this disease, we need to deploy the right measures in the right place, but figures on human movement patterns in endemic regions are hard to come by and often restricted to local travel surveys and census-based migration data,” said study author Andrew Tatem, PhD, of the University of Southampton in the UK.

“Our study demonstrates that the rapid global proliferation of mobile phones now provides us with an opportunity to study the movement of people, using sample sizes running in to millions. This data, combined with disease-case-based mapping, can help us plan where and how to intervene.”

Dr Tatem and his colleagues looked at anonymized Call Data Records from 2010 to 2011, provided by Mobile Telecommunications Limited. The data represented 9 billion communications from 1.19 million unique subscribers, around 52% of the population of Namibia.

The researchers analyzed aggregated movements of phone users between urban areas and urban and rural areas, in conjunction with data based on rapid diagnostic testing of malaria and information on the climate, environment, and topography of the country.

In this way, the team identified communities that were strongly connected by relatively higher levels of population movement. They quantified the net export and import of travelers and mapped malaria infection risks by region.

The researchers said these malaria risk maps can aid the design of targeted interventions to reduce the number of malaria cases exported to other regions and help manage the risk of infection in places that import the disease.

In fact, the maps have already helped the Namibia National Vector-borne Diseases Control Programme improve their targeting of malaria interventions to communities most at risk.

Specifically, the maps prompted the organization to target insecticide-treated bed net distribution in the Omusati, Kavango, and Zambezi regions in 2013.

“The importation of malaria from outside a country will always be a crucial focus of disease control programs, but movement of the disease within countries is also of huge significance,” Dr Tatem said. “Understanding the human element of this movement should be a critical component when designing elimination strategies—to help target resources most efficiently.”

“The use of mobile phone data is one example of how new technologies are overcoming past problems of quantifying and gaining a better understanding of human movement patterns in relation to disease control.”

Malaria-carrying mosquito

Credit: James Gathany

Data that tracks cell phone activity can help us more accurately target antimalaria interventions, according to a paper published in Malaria Journal.

Researchers used anonymized cell phone records to measure population movements within Namibia, Africa, over a year.

By combining this data with information about malaria cases, topography, and climate, the group was able to identify geographical “hotspots” of the disease and design targeted plans for its elimination.

“If we are to eliminate this disease, we need to deploy the right measures in the right place, but figures on human movement patterns in endemic regions are hard to come by and often restricted to local travel surveys and census-based migration data,” said study author Andrew Tatem, PhD, of the University of Southampton in the UK.

“Our study demonstrates that the rapid global proliferation of mobile phones now provides us with an opportunity to study the movement of people, using sample sizes running in to millions. This data, combined with disease-case-based mapping, can help us plan where and how to intervene.”

Dr Tatem and his colleagues looked at anonymized Call Data Records from 2010 to 2011, provided by Mobile Telecommunications Limited. The data represented 9 billion communications from 1.19 million unique subscribers, around 52% of the population of Namibia.

The researchers analyzed aggregated movements of phone users between urban areas and urban and rural areas, in conjunction with data based on rapid diagnostic testing of malaria and information on the climate, environment, and topography of the country.

In this way, the team identified communities that were strongly connected by relatively higher levels of population movement. They quantified the net export and import of travelers and mapped malaria infection risks by region.

The researchers said these malaria risk maps can aid the design of targeted interventions to reduce the number of malaria cases exported to other regions and help manage the risk of infection in places that import the disease.

In fact, the maps have already helped the Namibia National Vector-borne Diseases Control Programme improve their targeting of malaria interventions to communities most at risk.

Specifically, the maps prompted the organization to target insecticide-treated bed net distribution in the Omusati, Kavango, and Zambezi regions in 2013.

“The importation of malaria from outside a country will always be a crucial focus of disease control programs, but movement of the disease within countries is also of huge significance,” Dr Tatem said. “Understanding the human element of this movement should be a critical component when designing elimination strategies—to help target resources most efficiently.”

“The use of mobile phone data is one example of how new technologies are overcoming past problems of quantifying and gaining a better understanding of human movement patterns in relation to disease control.”

"Why do I need to do research if I'm going into private practice anyway?"

I have heard this question multiple times throughout my career as a resident, fellow, and attending thoracic surgeon. The truth is, there are multiple reasons, any of which is sufficient to justify your participation in clinical research during training. First, and perhaps most importantly, it teaches you to critically appraise the literature.

This is a skill that will serve you well throughout your career, guiding your clinical decision making, regardless if you choose private practice or academic surgery.

Another reason is that performing clinical research allows you to become a content expert on a specific topic early in your career. This knowledge base is something that will serve as a foundation for ongoing learning and may help in designing future studies.

Once your project is complete, it will be your ticket to attend and present at regional, national, or international meetings. There is no better forum to gain public recognition for your investigative efforts and network with potential future partners than societal meetings.

Formal and informal interviews routinely occur at these gatherings and you do not want to be left out because you chose not to participate in research as a trainee. Finally, it is your responsibility to the patients that you have sworn to treat.

There are many ways to care for patients, and pushing back the frontiers of medical knowledge is as important as the day-to-day tasks that you perform on the ward or in the operating room.

So, now that you have decided that you want to participate in a research project as a trainee, how do you make it happen? Before you begin a project, you will have to choose a mentor; a topic; a clear, novel question; and the appropriate study design.

Chances are that at some point, a mentor helped guide you toward a career in cardiovascular surgery. A research mentor is just as important as a clinical mentor for a young surgeon. The most important trait that you should seek out in a research mentor is the ability to delineate important questions. All too often, residents and fellows are approached by attending surgeons with good intentions, but bad research ideas. Trainees then feel obligated to take them up on the project (in order to not appear like a slacker) and for various reasons, it does not result in an abstract, presentation, or publication. In fact, all it results in is frustration, a distaste for investigation, and wasted time.

The bottom line is that only you can protect your time, and as a surgical trainee, you must guard it ferociously. Look for a mentor that is an expert in your field of interest and who has a track record of publications.

He or she must be a logical thinker who can help you delineate a clear, novel question, choose the appropriate study design, guide your writing of the manuscript, and direct your submission to the appropriate meetings and journals.

Finally, your mentor must be dedicated to your success. We are all busy, but if your mentor cannot find the time to routinely meet with you at every step of your project, you need to find a new mentor.

Choosing a clear, novel clinical question starts with choosing an appropriate topic (Table 1). With the right topic and question, the hypothesis is obvious, it is easy to define your endpoints, and your study design will fall into place. But with the wrong question, your study will lack focus, it will be difficult to explain the relevance of your study, and you will not want to present your data on the podium. An example of a good question is: "Do patients with a given disease treated with operation X live longer than those treated with operation Y?"

Stay away from the lure of "Let's review our experience of operation X…" or "Why don't I see how many of operation Y we've done over the past 10 years…" These topics are vague and do not ask a specific question. There must be a clear hypothesis for any study that is expected to produce meaningful results.

Once you have chosen an appropriate question, you must decide on a study design. Although case reports are marginally publishable, they will not answer your clinical questions. For many reasons, randomized, controlled trials, the gold standard of research, are difficult to design, carry out, and complete in your short time as a trainee.

The good news is that well-designed and sufficiently powered observational studies often give similar results as randomized, controlled studies. Examples of common observational study designs include cohort studies, case control studies, and cross-sectional studies (Table 2).

Each study design is different and your mentor should be able to help you decide which is the best to answer the question you want to ask.
In the design of a study, one of the most important principles is defining a priori end points.

Every study will have one primary end point that reflects the hypothesis. Secondary endpoints are interesting and potentially helpful, but are not the main message. It will be important to meet with a statistician before you start data collection. Understanding the statistics to be used will allow you to collect your data in the correct way (categorical vs. continuous, etc.). Reviewing charts is very time consuming and you have to do everything in your power to ensure you do it only once.

The next step is to create a research proposal. To do this, you will need to go to the literature and see what published data relate to your study. Perhaps, there are previous studies examining your question with conflicting results?
Or if your question has not been previously investigated, what supporting literature suggests that yours is the next logical study? Your proposal should include a background section (1-2 paragraphs), hypothesis (1 sentence), the specific aims of the study (1-3 sentences), methods (2-4 paragraphs), anticipated results (1 paragraph), proposed timeline, and anticipated meeting to which it will be submitted. Your mentor will revise and critique the proposal and eventually give you a signature of approval. This proposal serves many purposes. It will allow you to fully understand the study before you begin, some form of it is usually required for the Institutional Review Board application, it will serve as the outline for your eventual manuscript, and it sets a timeline for completion of the project. Without an agreed-upon deadline, too many good studies are left in various states of completion when the trainee moves on, and are never finished. The deadline should be based on the meeting that you and your mentor agree is appropriate for reporting your results.

Most would agree that data collection is the most painful part of doing clinical research. However, there are a few tricks to ease your pain. First, there are many databases available that you may be able to harvest data from to minimize your chart work (Table 3). Before you hit the charts, it is essential to think through every step of the project. Anticipate problems (where in the chart will you locate each data point), do not collect unnecessary data points (postoperative data #3 serum [Na+] when looking at survival of thoracoscopic vs. open lobectomy), meet with your statistician beforehand to collect data for the correct analysis, collect the raw data (creatinine and weight, not presence of renal failure and obesity).

Finally, be sure that your data are backed up in multiple places. Some prefer to collect data on paper then enter it later into a spreadsheet. This ensures a hard copy of the data exists regardless if the electronic version is lost.

After the data are collected and the statistics are done, you will be faced with interpreting your results and composing an abstract and manuscript. If your study is focused and hypothesis driven, this step should be fairly straightforward. Schedule time with your mentor and discuss the results to ensure your interpretation of the data is correct.

Next using your proposal as an outline, put together a rough draft of a manuscript. Remember that manuscripts are the currency of academia. If you do not present and publish your work, you have not fully capitalized on the hard work you have put in to your study.

Your mentor will need to revise your manuscript repeatedly; use it as a learning experience for critiquing the literature and writing future manuscripts. He or she likely knows what editors and readers will be looking for in your finished product. Remember, you will need multiple revisions of the abstract and manuscript, so plan adequate time prior to your deadline for writing.

Most institutions have medical illustrators available for hire; consider including a drawing or photograph if it legitimately adds content to your manuscript.
The final step in the process is presenting your work in front of experts who likely know more about cardiothoracic surgery than you. Just remember, no one knows more about your data than you.

Prepare relentlessly for your talk, take a deep breath before you walk on stage, speak with confidence, and if you don't know the answer to a given question from the audience, admit it. Soon enough you will be the expert in the audience asking the tough questions. Then spend as much time as possible after the session speaking with audience members about you and your study.

You will meet lifelong colleagues, and maybe even your future partner. For many, research is a rewarding lifelong endeavor. For others, it is a means of learning to critically appraise the literature and landing a job. Either way, you cannot afford not to do research as a trainee.

Acknowledgment: I would like to thank my friend and colleague, Dr. Stephen H. McKellar (University of Utah), for his advice on performing research as a cardiothoracic trainee.

Dr. Seder is in the department of cardiovascular and thoracic surgery at Rush University Medical Center, Chicago. 

"Why do I need to do research if I'm going into private practice anyway?"

I have heard this question multiple times throughout my career as a resident, fellow, and attending thoracic surgeon. The truth is, there are multiple reasons, any of which is sufficient to justify your participation in clinical research during training. First, and perhaps most importantly, it teaches you to critically appraise the literature.

This is a skill that will serve you well throughout your career, guiding your clinical decision making, regardless if you choose private practice or academic surgery.

Another reason is that performing clinical research allows you to become a content expert on a specific topic early in your career. This knowledge base is something that will serve as a foundation for ongoing learning and may help in designing future studies.

Once your project is complete, it will be your ticket to attend and present at regional, national, or international meetings. There is no better forum to gain public recognition for your investigative efforts and network with potential future partners than societal meetings.

Formal and informal interviews routinely occur at these gatherings and you do not want to be left out because you chose not to participate in research as a trainee. Finally, it is your responsibility to the patients that you have sworn to treat.

There are many ways to care for patients, and pushing back the frontiers of medical knowledge is as important as the day-to-day tasks that you perform on the ward or in the operating room.

So, now that you have decided that you want to participate in a research project as a trainee, how do you make it happen? Before you begin a project, you will have to choose a mentor; a topic; a clear, novel question; and the appropriate study design.

Chances are that at some point, a mentor helped guide you toward a career in cardiovascular surgery. A research mentor is just as important as a clinical mentor for a young surgeon. The most important trait that you should seek out in a research mentor is the ability to delineate important questions. All too often, residents and fellows are approached by attending surgeons with good intentions, but bad research ideas. Trainees then feel obligated to take them up on the project (in order to not appear like a slacker) and for various reasons, it does not result in an abstract, presentation, or publication. In fact, all it results in is frustration, a distaste for investigation, and wasted time.

The bottom line is that only you can protect your time, and as a surgical trainee, you must guard it ferociously. Look for a mentor that is an expert in your field of interest and who has a track record of publications.

He or she must be a logical thinker who can help you delineate a clear, novel question, choose the appropriate study design, guide your writing of the manuscript, and direct your submission to the appropriate meetings and journals.

Finally, your mentor must be dedicated to your success. We are all busy, but if your mentor cannot find the time to routinely meet with you at every step of your project, you need to find a new mentor.

Choosing a clear, novel clinical question starts with choosing an appropriate topic (Table 1). With the right topic and question, the hypothesis is obvious, it is easy to define your endpoints, and your study design will fall into place. But with the wrong question, your study will lack focus, it will be difficult to explain the relevance of your study, and you will not want to present your data on the podium. An example of a good question is: "Do patients with a given disease treated with operation X live longer than those treated with operation Y?"

Stay away from the lure of "Let's review our experience of operation X…" or "Why don't I see how many of operation Y we've done over the past 10 years…" These topics are vague and do not ask a specific question. There must be a clear hypothesis for any study that is expected to produce meaningful results.

Once you have chosen an appropriate question, you must decide on a study design. Although case reports are marginally publishable, they will not answer your clinical questions. For many reasons, randomized, controlled trials, the gold standard of research, are difficult to design, carry out, and complete in your short time as a trainee.

The good news is that well-designed and sufficiently powered observational studies often give similar results as randomized, controlled studies. Examples of common observational study designs include cohort studies, case control studies, and cross-sectional studies (Table 2).

Each study design is different and your mentor should be able to help you decide which is the best to answer the question you want to ask.
In the design of a study, one of the most important principles is defining a priori end points.

Every study will have one primary end point that reflects the hypothesis. Secondary endpoints are interesting and potentially helpful, but are not the main message. It will be important to meet with a statistician before you start data collection. Understanding the statistics to be used will allow you to collect your data in the correct way (categorical vs. continuous, etc.). Reviewing charts is very time consuming and you have to do everything in your power to ensure you do it only once.

The next step is to create a research proposal. To do this, you will need to go to the literature and see what published data relate to your study. Perhaps, there are previous studies examining your question with conflicting results?
Or if your question has not been previously investigated, what supporting literature suggests that yours is the next logical study? Your proposal should include a background section (1-2 paragraphs), hypothesis (1 sentence), the specific aims of the study (1-3 sentences), methods (2-4 paragraphs), anticipated results (1 paragraph), proposed timeline, and anticipated meeting to which it will be submitted. Your mentor will revise and critique the proposal and eventually give you a signature of approval. This proposal serves many purposes. It will allow you to fully understand the study before you begin, some form of it is usually required for the Institutional Review Board application, it will serve as the outline for your eventual manuscript, and it sets a timeline for completion of the project. Without an agreed-upon deadline, too many good studies are left in various states of completion when the trainee moves on, and are never finished. The deadline should be based on the meeting that you and your mentor agree is appropriate for reporting your results.

Most would agree that data collection is the most painful part of doing clinical research. However, there are a few tricks to ease your pain. First, there are many databases available that you may be able to harvest data from to minimize your chart work (Table 3). Before you hit the charts, it is essential to think through every step of the project. Anticipate problems (where in the chart will you locate each data point), do not collect unnecessary data points (postoperative data #3 serum [Na+] when looking at survival of thoracoscopic vs. open lobectomy), meet with your statistician beforehand to collect data for the correct analysis, collect the raw data (creatinine and weight, not presence of renal failure and obesity).

Finally, be sure that your data are backed up in multiple places. Some prefer to collect data on paper then enter it later into a spreadsheet. This ensures a hard copy of the data exists regardless if the electronic version is lost.

After the data are collected and the statistics are done, you will be faced with interpreting your results and composing an abstract and manuscript. If your study is focused and hypothesis driven, this step should be fairly straightforward. Schedule time with your mentor and discuss the results to ensure your interpretation of the data is correct.

Next using your proposal as an outline, put together a rough draft of a manuscript. Remember that manuscripts are the currency of academia. If you do not present and publish your work, you have not fully capitalized on the hard work you have put in to your study.

Your mentor will need to revise your manuscript repeatedly; use it as a learning experience for critiquing the literature and writing future manuscripts. He or she likely knows what editors and readers will be looking for in your finished product. Remember, you will need multiple revisions of the abstract and manuscript, so plan adequate time prior to your deadline for writing.

Most institutions have medical illustrators available for hire; consider including a drawing or photograph if it legitimately adds content to your manuscript.
The final step in the process is presenting your work in front of experts who likely know more about cardiothoracic surgery than you. Just remember, no one knows more about your data than you.

Prepare relentlessly for your talk, take a deep breath before you walk on stage, speak with confidence, and if you don't know the answer to a given question from the audience, admit it. Soon enough you will be the expert in the audience asking the tough questions. Then spend as much time as possible after the session speaking with audience members about you and your study.

You will meet lifelong colleagues, and maybe even your future partner. For many, research is a rewarding lifelong endeavor. For others, it is a means of learning to critically appraise the literature and landing a job. Either way, you cannot afford not to do research as a trainee.

Acknowledgment: I would like to thank my friend and colleague, Dr. Stephen H. McKellar (University of Utah), for his advice on performing research as a cardiothoracic trainee.

Dr. Seder is in the department of cardiovascular and thoracic surgery at Rush University Medical Center, Chicago. 

"Why do I need to do research if I'm going into private practice anyway?"

I have heard this question multiple times throughout my career as a resident, fellow, and attending thoracic surgeon. The truth is, there are multiple reasons, any of which is sufficient to justify your participation in clinical research during training. First, and perhaps most importantly, it teaches you to critically appraise the literature.

This is a skill that will serve you well throughout your career, guiding your clinical decision making, regardless if you choose private practice or academic surgery.

Another reason is that performing clinical research allows you to become a content expert on a specific topic early in your career. This knowledge base is something that will serve as a foundation for ongoing learning and may help in designing future studies.

Once your project is complete, it will be your ticket to attend and present at regional, national, or international meetings. There is no better forum to gain public recognition for your investigative efforts and network with potential future partners than societal meetings.

Formal and informal interviews routinely occur at these gatherings and you do not want to be left out because you chose not to participate in research as a trainee. Finally, it is your responsibility to the patients that you have sworn to treat.

There are many ways to care for patients, and pushing back the frontiers of medical knowledge is as important as the day-to-day tasks that you perform on the ward or in the operating room.

So, now that you have decided that you want to participate in a research project as a trainee, how do you make it happen? Before you begin a project, you will have to choose a mentor; a topic; a clear, novel question; and the appropriate study design.

Chances are that at some point, a mentor helped guide you toward a career in cardiovascular surgery. A research mentor is just as important as a clinical mentor for a young surgeon. The most important trait that you should seek out in a research mentor is the ability to delineate important questions. All too often, residents and fellows are approached by attending surgeons with good intentions, but bad research ideas. Trainees then feel obligated to take them up on the project (in order to not appear like a slacker) and for various reasons, it does not result in an abstract, presentation, or publication. In fact, all it results in is frustration, a distaste for investigation, and wasted time.

The bottom line is that only you can protect your time, and as a surgical trainee, you must guard it ferociously. Look for a mentor that is an expert in your field of interest and who has a track record of publications.

He or she must be a logical thinker who can help you delineate a clear, novel question, choose the appropriate study design, guide your writing of the manuscript, and direct your submission to the appropriate meetings and journals.

Finally, your mentor must be dedicated to your success. We are all busy, but if your mentor cannot find the time to routinely meet with you at every step of your project, you need to find a new mentor.

Choosing a clear, novel clinical question starts with choosing an appropriate topic (Table 1). With the right topic and question, the hypothesis is obvious, it is easy to define your endpoints, and your study design will fall into place. But with the wrong question, your study will lack focus, it will be difficult to explain the relevance of your study, and you will not want to present your data on the podium. An example of a good question is: "Do patients with a given disease treated with operation X live longer than those treated with operation Y?"

Stay away from the lure of "Let's review our experience of operation X…" or "Why don't I see how many of operation Y we've done over the past 10 years…" These topics are vague and do not ask a specific question. There must be a clear hypothesis for any study that is expected to produce meaningful results.

Once you have chosen an appropriate question, you must decide on a study design. Although case reports are marginally publishable, they will not answer your clinical questions. For many reasons, randomized, controlled trials, the gold standard of research, are difficult to design, carry out, and complete in your short time as a trainee.

The good news is that well-designed and sufficiently powered observational studies often give similar results as randomized, controlled studies. Examples of common observational study designs include cohort studies, case control studies, and cross-sectional studies (Table 2).

Each study design is different and your mentor should be able to help you decide which is the best to answer the question you want to ask.
In the design of a study, one of the most important principles is defining a priori end points.

Every study will have one primary end point that reflects the hypothesis. Secondary endpoints are interesting and potentially helpful, but are not the main message. It will be important to meet with a statistician before you start data collection. Understanding the statistics to be used will allow you to collect your data in the correct way (categorical vs. continuous, etc.). Reviewing charts is very time consuming and you have to do everything in your power to ensure you do it only once.

The next step is to create a research proposal. To do this, you will need to go to the literature and see what published data relate to your study. Perhaps, there are previous studies examining your question with conflicting results?
Or if your question has not been previously investigated, what supporting literature suggests that yours is the next logical study? Your proposal should include a background section (1-2 paragraphs), hypothesis (1 sentence), the specific aims of the study (1-3 sentences), methods (2-4 paragraphs), anticipated results (1 paragraph), proposed timeline, and anticipated meeting to which it will be submitted. Your mentor will revise and critique the proposal and eventually give you a signature of approval. This proposal serves many purposes. It will allow you to fully understand the study before you begin, some form of it is usually required for the Institutional Review Board application, it will serve as the outline for your eventual manuscript, and it sets a timeline for completion of the project. Without an agreed-upon deadline, too many good studies are left in various states of completion when the trainee moves on, and are never finished. The deadline should be based on the meeting that you and your mentor agree is appropriate for reporting your results.

Most would agree that data collection is the most painful part of doing clinical research. However, there are a few tricks to ease your pain. First, there are many databases available that you may be able to harvest data from to minimize your chart work (Table 3). Before you hit the charts, it is essential to think through every step of the project. Anticipate problems (where in the chart will you locate each data point), do not collect unnecessary data points (postoperative data #3 serum [Na+] when looking at survival of thoracoscopic vs. open lobectomy), meet with your statistician beforehand to collect data for the correct analysis, collect the raw data (creatinine and weight, not presence of renal failure and obesity).

Finally, be sure that your data are backed up in multiple places. Some prefer to collect data on paper then enter it later into a spreadsheet. This ensures a hard copy of the data exists regardless if the electronic version is lost.

After the data are collected and the statistics are done, you will be faced with interpreting your results and composing an abstract and manuscript. If your study is focused and hypothesis driven, this step should be fairly straightforward. Schedule time with your mentor and discuss the results to ensure your interpretation of the data is correct.

Next using your proposal as an outline, put together a rough draft of a manuscript. Remember that manuscripts are the currency of academia. If you do not present and publish your work, you have not fully capitalized on the hard work you have put in to your study.

Your mentor will need to revise your manuscript repeatedly; use it as a learning experience for critiquing the literature and writing future manuscripts. He or she likely knows what editors and readers will be looking for in your finished product. Remember, you will need multiple revisions of the abstract and manuscript, so plan adequate time prior to your deadline for writing.

Most institutions have medical illustrators available for hire; consider including a drawing or photograph if it legitimately adds content to your manuscript.
The final step in the process is presenting your work in front of experts who likely know more about cardiothoracic surgery than you. Just remember, no one knows more about your data than you.

Prepare relentlessly for your talk, take a deep breath before you walk on stage, speak with confidence, and if you don't know the answer to a given question from the audience, admit it. Soon enough you will be the expert in the audience asking the tough questions. Then spend as much time as possible after the session speaking with audience members about you and your study.

You will meet lifelong colleagues, and maybe even your future partner. For many, research is a rewarding lifelong endeavor. For others, it is a means of learning to critically appraise the literature and landing a job. Either way, you cannot afford not to do research as a trainee.

Acknowledgment: I would like to thank my friend and colleague, Dr. Stephen H. McKellar (University of Utah), for his advice on performing research as a cardiothoracic trainee.

Dr. Seder is in the department of cardiovascular and thoracic surgery at Rush University Medical Center, Chicago. 

The answer is yes!

I was not involved in the design of CREST, but I do have a responsibility to interpret the results and incorporate them into my clinical approach. When MI occurred after carotid endarterectomy (CEA) or carotid artery stenting (CAS) in CREST, the 1-year mortality was 14.2% versus 2.2% among those who did not have an MI (Blackshear et al. Circulation 2011;123:2571). This is consistent with the vascular literature, which is chock-full of strongly compelling data showing that we should take cardiac risk into account when planning our therapy.

It is not a mystery as to who is at risk for an MI. The significant independent risk factors for MI in CREST were known coronary artery disease or previous coronary revascularization. Since this is well known to us prior to treatment, shouldn’t this information be part of our therapeutic plan?

Suppose I said that perioperative MI is not important after abdominal aortic aneurysm repair, fem-pop bypass, or distal bypass?

A large part of the growth of endovascular approaches in recent years has been motivated by our best efforts to avoid MI. Think of the early days of endovascular aneurysm repair, prior to establishment of this as standard of care for most patients, and how many patients were treated with stent-grafts in an attempt to avoid cardiac risk. How could we now claim that it is unimportant?

There were two independent risk factors for mortality during CREST that increased the hazard ratio more than two times: stroke and MI (FDA panel presentation, Jan. 26, 2011).

The reason to revascularize the carotid is to prevent stroke, and this is a worthwhile endeavor. However, if the patient is harmed in some other way, especially in a manner associated with dramatically increased mortality, shouldn’t we understand that?

At some point, with further technological development, mesh-covered carotid stents, customized protection devices, and more informed patient selection, the stroke risk of CAS is likely to decrease. At that point, our relative concern about the risk of MI and the importance of MI as an endpoint is likely to increase, not decrease.

There is no doubt that we all fear stroke. Unfortunately, when something bad happens to a patient, they don’t get to select which complication they are going to have. We owe it to our patients to do what we can to diminish all the risks they face. I cannot envision an honest and useful future carotid trial design in which MI is not considered an endpoint.

Dr. Peter A. Schneider is chief of the division of vascular surgery, Hawaii Permanente Medical Group and Kaiser Foundation Hospital, Honolulu.

The answer is no!

Being given a choice between MI and stroke is like asking someone if they would rather be rich and healthy or poor and sick. The best option is to have neither an MI nor a stroke following carotid intervention. However, when given this unpleasant choice, the participants in CREST clearly stated that MI was preferable to either major or minor stroke. How often have we heard our patients state, "Doc, I’m not afraid to die, but I don’t want to live disabled from a stroke"?

A quality-of-life assessment was carried out in CREST patients using an SF-36.

This questionnaire looked at both the physical and the emotional effect of the complications of stroke and MI compared with those who were complication free.

One year after a complication, the patients stated that the worst thing that happened was a major stroke. The next worse thing was a minor stroke.

Myocardial infarction, 1 year later, from the patient’s perspective, was a nonevent. The argument that has been used regarding the importance of MI is that it has an adverse effect on life expectancy.

This is true, and it has been confirmed in several trials including CREST. The surprise finding is that stroke, including so-called minor strokes, also reduced life expectancy.

In CREST, 4 years following an adjudicated MI, the mortality rate was 19.1% versus 6.7% for those not suffering an MI.

However, the 4-year mortality rate among patients having suffered a stroke was 20%.

Therefore, compromised survival occurred equally among those patients following either stroke or MI.

However, not only did patients suffering a stroke have an equally high mortality, the group was further compromised by neurologic disability among the survivors, whereas the survivors following MI returned to their precomplication status.

Therefore, from the patients’ subjective status as well as objective clinical considerations, stroke is clearly more deleterious than MI.

Dr. Wesley S. Moore is a vascular and endovascular surgeon, and professor and chief, emeritus, of the division of vascular surgery, University of California, Los Angeles, Medical Center.

The answer is yes!

I was not involved in the design of CREST, but I do have a responsibility to interpret the results and incorporate them into my clinical approach. When MI occurred after carotid endarterectomy (CEA) or carotid artery stenting (CAS) in CREST, the 1-year mortality was 14.2% versus 2.2% among those who did not have an MI (Blackshear et al. Circulation 2011;123:2571). This is consistent with the vascular literature, which is chock-full of strongly compelling data showing that we should take cardiac risk into account when planning our therapy.

It is not a mystery as to who is at risk for an MI. The significant independent risk factors for MI in CREST were known coronary artery disease or previous coronary revascularization. Since this is well known to us prior to treatment, shouldn’t this information be part of our therapeutic plan?

Suppose I said that perioperative MI is not important after abdominal aortic aneurysm repair, fem-pop bypass, or distal bypass?

A large part of the growth of endovascular approaches in recent years has been motivated by our best efforts to avoid MI. Think of the early days of endovascular aneurysm repair, prior to establishment of this as standard of care for most patients, and how many patients were treated with stent-grafts in an attempt to avoid cardiac risk. How could we now claim that it is unimportant?

There were two independent risk factors for mortality during CREST that increased the hazard ratio more than two times: stroke and MI (FDA panel presentation, Jan. 26, 2011).

The reason to revascularize the carotid is to prevent stroke, and this is a worthwhile endeavor. However, if the patient is harmed in some other way, especially in a manner associated with dramatically increased mortality, shouldn’t we understand that?

At some point, with further technological development, mesh-covered carotid stents, customized protection devices, and more informed patient selection, the stroke risk of CAS is likely to decrease. At that point, our relative concern about the risk of MI and the importance of MI as an endpoint is likely to increase, not decrease.

There is no doubt that we all fear stroke. Unfortunately, when something bad happens to a patient, they don’t get to select which complication they are going to have. We owe it to our patients to do what we can to diminish all the risks they face. I cannot envision an honest and useful future carotid trial design in which MI is not considered an endpoint.

Dr. Peter A. Schneider is chief of the division of vascular surgery, Hawaii Permanente Medical Group and Kaiser Foundation Hospital, Honolulu.

The answer is no!

Being given a choice between MI and stroke is like asking someone if they would rather be rich and healthy or poor and sick. The best option is to have neither an MI nor a stroke following carotid intervention. However, when given this unpleasant choice, the participants in CREST clearly stated that MI was preferable to either major or minor stroke. How often have we heard our patients state, "Doc, I’m not afraid to die, but I don’t want to live disabled from a stroke"?

A quality-of-life assessment was carried out in CREST patients using an SF-36.

This questionnaire looked at both the physical and the emotional effect of the complications of stroke and MI compared with those who were complication free.

One year after a complication, the patients stated that the worst thing that happened was a major stroke. The next worse thing was a minor stroke.

Myocardial infarction, 1 year later, from the patient’s perspective, was a nonevent. The argument that has been used regarding the importance of MI is that it has an adverse effect on life expectancy.

This is true, and it has been confirmed in several trials including CREST. The surprise finding is that stroke, including so-called minor strokes, also reduced life expectancy.

In CREST, 4 years following an adjudicated MI, the mortality rate was 19.1% versus 6.7% for those not suffering an MI.

However, the 4-year mortality rate among patients having suffered a stroke was 20%.

Therefore, compromised survival occurred equally among those patients following either stroke or MI.

However, not only did patients suffering a stroke have an equally high mortality, the group was further compromised by neurologic disability among the survivors, whereas the survivors following MI returned to their precomplication status.

Therefore, from the patients’ subjective status as well as objective clinical considerations, stroke is clearly more deleterious than MI.

Dr. Wesley S. Moore is a vascular and endovascular surgeon, and professor and chief, emeritus, of the division of vascular surgery, University of California, Los Angeles, Medical Center.

The answer is yes!

I was not involved in the design of CREST, but I do have a responsibility to interpret the results and incorporate them into my clinical approach. When MI occurred after carotid endarterectomy (CEA) or carotid artery stenting (CAS) in CREST, the 1-year mortality was 14.2% versus 2.2% among those who did not have an MI (Blackshear et al. Circulation 2011;123:2571). This is consistent with the vascular literature, which is chock-full of strongly compelling data showing that we should take cardiac risk into account when planning our therapy.

It is not a mystery as to who is at risk for an MI. The significant independent risk factors for MI in CREST were known coronary artery disease or previous coronary revascularization. Since this is well known to us prior to treatment, shouldn’t this information be part of our therapeutic plan?

Suppose I said that perioperative MI is not important after abdominal aortic aneurysm repair, fem-pop bypass, or distal bypass?

A large part of the growth of endovascular approaches in recent years has been motivated by our best efforts to avoid MI. Think of the early days of endovascular aneurysm repair, prior to establishment of this as standard of care for most patients, and how many patients were treated with stent-grafts in an attempt to avoid cardiac risk. How could we now claim that it is unimportant?

There were two independent risk factors for mortality during CREST that increased the hazard ratio more than two times: stroke and MI (FDA panel presentation, Jan. 26, 2011).

The reason to revascularize the carotid is to prevent stroke, and this is a worthwhile endeavor. However, if the patient is harmed in some other way, especially in a manner associated with dramatically increased mortality, shouldn’t we understand that?

At some point, with further technological development, mesh-covered carotid stents, customized protection devices, and more informed patient selection, the stroke risk of CAS is likely to decrease. At that point, our relative concern about the risk of MI and the importance of MI as an endpoint is likely to increase, not decrease.

There is no doubt that we all fear stroke. Unfortunately, when something bad happens to a patient, they don’t get to select which complication they are going to have. We owe it to our patients to do what we can to diminish all the risks they face. I cannot envision an honest and useful future carotid trial design in which MI is not considered an endpoint.

Dr. Peter A. Schneider is chief of the division of vascular surgery, Hawaii Permanente Medical Group and Kaiser Foundation Hospital, Honolulu.

The answer is no!

Being given a choice between MI and stroke is like asking someone if they would rather be rich and healthy or poor and sick. The best option is to have neither an MI nor a stroke following carotid intervention. However, when given this unpleasant choice, the participants in CREST clearly stated that MI was preferable to either major or minor stroke. How often have we heard our patients state, "Doc, I’m not afraid to die, but I don’t want to live disabled from a stroke"?

A quality-of-life assessment was carried out in CREST patients using an SF-36.

This questionnaire looked at both the physical and the emotional effect of the complications of stroke and MI compared with those who were complication free.

One year after a complication, the patients stated that the worst thing that happened was a major stroke. The next worse thing was a minor stroke.

Myocardial infarction, 1 year later, from the patient’s perspective, was a nonevent. The argument that has been used regarding the importance of MI is that it has an adverse effect on life expectancy.

This is true, and it has been confirmed in several trials including CREST. The surprise finding is that stroke, including so-called minor strokes, also reduced life expectancy.

In CREST, 4 years following an adjudicated MI, the mortality rate was 19.1% versus 6.7% for those not suffering an MI.

However, the 4-year mortality rate among patients having suffered a stroke was 20%.

Therefore, compromised survival occurred equally among those patients following either stroke or MI.

However, not only did patients suffering a stroke have an equally high mortality, the group was further compromised by neurologic disability among the survivors, whereas the survivors following MI returned to their precomplication status.

Therefore, from the patients’ subjective status as well as objective clinical considerations, stroke is clearly more deleterious than MI.

Dr. Wesley S. Moore is a vascular and endovascular surgeon, and professor and chief, emeritus, of the division of vascular surgery, University of California, Los Angeles, Medical Center.

CHICAGO – Early recognition of mesenteric ischemia in young adults and children is essential to prevent bowel loss and other serious consequences associated with this rare condition, Dr. Michael Dalsing said at a vascular surgery symposium.

Mesenteric ischemia is generally seen in the elderly as the result of atherosclerotic and embolic occlusive diseases. Because young adults and children typically don’t have any of the telltale associated comorbidities such as cardiac arrhythmia or coronary artery disease to point physicians in this direction, the diagnosis of mesenteric ischemia is often delayed or misinterpreted as appendicitis, cholecystitis, or intra-abdominal abscess, he said.

Patrice Wendling/Frontline Medical News

Among 26 young adults under age 40 years who presented with acute mesenteric ischemia, only 6 were properly diagnosed preoperatively (Wien. Med. Wochenschr. 2012;162:349-53). The postoperative complication and mortality rates reached 61.5% and 27%, which is typical in this population, despite their otherwise good health, said Dr. Dalsing, director of vascular surgery at Indiana University, Indianapolis.

The hallmarks of acute mesenteric ischemia are standard in both young and old patients and include abdominal pain out of proportion to the physical exam, nausea, vomiting, and/or diarrhea. Acidosis, acute renal failure, and septic shock/sepsis can develop in roughly half of patients with more extensive liver or bowel ischemia or necrosis. The signs and symptoms of chronic ischemia are weight loss, food fear, and postprandial abdominal pain.

"For chronic mesenteric ischemia, what’s the important message? Consider the diagnosis," Dr. Dalsing said. "Do the imaging, find out what you have, and then you can worry about ancillary testing because, in general, these aren’t going to be your typical etiologies. In fact, they’re not standard fare at all."

The broad and atypical list of etiologies to consider in those under age 40 years include congenital aortic anomalies, hypercoagulable states, inflammatory conditions, collagen vascular disorders, and environmental agents such as cocaine use, smoking, or trauma. While MI is often suspected in those using cocaine, the vasoconstrictive effects of the drug can also cause vasospasm of the smaller branches of the mesenteric vessels, leading to nonocclusive mesenteric ischemia, he explained.

Once a diagnosis of chronic mesenteric ischemia is made in a young patient, management consists of fluid resuscitation, broad spectrum antibiotics, bowel rest, and imaging, often with a CT angiogram. The need for additional work-up, including hypercoagulable and inflammatory marker panels, varies based on initial clinical symptoms.

If vascular compromise is identified, the overall management goals should be to remove frankly necrotic bowel, reperfuse ischemic bowel, limit the resection length when possible to prevent short-gut syndrome, and treat the underlying etiology, Dr. Dalsing advised. Anticoagulation is also integral to prevent thrombus propagation.

Just six cases of mesenteric ischemia have been diagnosed at Indiana University in young adults over the last 16 years, with Takayasu’s arteritis the most common etiology, he noted. This includes a 20-year-old woman with a 5-year history of Takayasu’s, who presented with worsening abdominal pain despite remission of her Takayasu’s, as indicated by a normal sedimentation rate.

Repeat CT imaging revealed more than 70% celiac artery stenosis and more than 50% stenosis of the superior mesenteric artery (SMA). A median arcuate ligament division and celiac and SMA bypass graft, both with reverse saphenous vein originating from bilateral iliac arteries, was performed. "She’s had dramatic improvement" in her symptoms and remains on clopidogrel (Plavix) and low-dose steroids, Dr. Dalsing said.

Courtesy Wikimedia Commons/James Heilman, MD/Creative Commons Attribution

A second patient with Takayasu’s presented with a 4-month history of abdominal pain, a 50-pound weight loss, stenosis of all major mesenteric arteries, and bowel pneumatosis. Despite this, her sedimentation rate was only slightly elevated at 33 mm/hour, and all other coagulation and inflammatory tests were normal. She remains symptom free at 2 years on daily aspirin after undergoing an emergent right common iliac-to-SMA bypass graft with reversed saphenous vein and bowel resection.

In cases in which bypass grafting is necessary, the internal iliac artery is the preferred conduit in children since the saphenous vein is very thin walled and thus, more prone to aneurysmal degeneration, Dr. Dalsing observed. In grown patients, the saphenous vein may be the best conduit in terms of ease of harvest and adequate length for even bifurcated grafts or C-loop alignment.

During postoperative follow-up, special effort should be taken because of the young age of these patients to reduce the detrimental effects of radiation from recurrent CT angiograms, he said. Patients with symptomatic improvement are followed at 1 month postoperatively with a physical exam that includes their weight and a mesenteric duplex to evaluate graft or stent patency. This is repeated every 6 months for 1-2 years, and decreased to yearly visits, if no disease progression is detected. More aggressive imaging with CT angiography is reserved for patients with recurrent symptoms or if duplex ultrasound is insufficient or shows progressive disease, he said at the meeting, sponsored by Northwestern University.

Dr. Dalsing reported having no financial disclosures.

[email protected]

CHICAGO – Early recognition of mesenteric ischemia in young adults and children is essential to prevent bowel loss and other serious consequences associated with this rare condition, Dr. Michael Dalsing said at a vascular surgery symposium.

Mesenteric ischemia is generally seen in the elderly as the result of atherosclerotic and embolic occlusive diseases. Because young adults and children typically don’t have any of the telltale associated comorbidities such as cardiac arrhythmia or coronary artery disease to point physicians in this direction, the diagnosis of mesenteric ischemia is often delayed or misinterpreted as appendicitis, cholecystitis, or intra-abdominal abscess, he said.

Patrice Wendling/Frontline Medical News

Among 26 young adults under age 40 years who presented with acute mesenteric ischemia, only 6 were properly diagnosed preoperatively (Wien. Med. Wochenschr. 2012;162:349-53). The postoperative complication and mortality rates reached 61.5% and 27%, which is typical in this population, despite their otherwise good health, said Dr. Dalsing, director of vascular surgery at Indiana University, Indianapolis.

The hallmarks of acute mesenteric ischemia are standard in both young and old patients and include abdominal pain out of proportion to the physical exam, nausea, vomiting, and/or diarrhea. Acidosis, acute renal failure, and septic shock/sepsis can develop in roughly half of patients with more extensive liver or bowel ischemia or necrosis. The signs and symptoms of chronic ischemia are weight loss, food fear, and postprandial abdominal pain.

"For chronic mesenteric ischemia, what’s the important message? Consider the diagnosis," Dr. Dalsing said. "Do the imaging, find out what you have, and then you can worry about ancillary testing because, in general, these aren’t going to be your typical etiologies. In fact, they’re not standard fare at all."

The broad and atypical list of etiologies to consider in those under age 40 years include congenital aortic anomalies, hypercoagulable states, inflammatory conditions, collagen vascular disorders, and environmental agents such as cocaine use, smoking, or trauma. While MI is often suspected in those using cocaine, the vasoconstrictive effects of the drug can also cause vasospasm of the smaller branches of the mesenteric vessels, leading to nonocclusive mesenteric ischemia, he explained.

Once a diagnosis of chronic mesenteric ischemia is made in a young patient, management consists of fluid resuscitation, broad spectrum antibiotics, bowel rest, and imaging, often with a CT angiogram. The need for additional work-up, including hypercoagulable and inflammatory marker panels, varies based on initial clinical symptoms.

If vascular compromise is identified, the overall management goals should be to remove frankly necrotic bowel, reperfuse ischemic bowel, limit the resection length when possible to prevent short-gut syndrome, and treat the underlying etiology, Dr. Dalsing advised. Anticoagulation is also integral to prevent thrombus propagation.

Just six cases of mesenteric ischemia have been diagnosed at Indiana University in young adults over the last 16 years, with Takayasu’s arteritis the most common etiology, he noted. This includes a 20-year-old woman with a 5-year history of Takayasu’s, who presented with worsening abdominal pain despite remission of her Takayasu’s, as indicated by a normal sedimentation rate.

Repeat CT imaging revealed more than 70% celiac artery stenosis and more than 50% stenosis of the superior mesenteric artery (SMA). A median arcuate ligament division and celiac and SMA bypass graft, both with reverse saphenous vein originating from bilateral iliac arteries, was performed. "She’s had dramatic improvement" in her symptoms and remains on clopidogrel (Plavix) and low-dose steroids, Dr. Dalsing said.

Courtesy Wikimedia Commons/James Heilman, MD/Creative Commons Attribution

A second patient with Takayasu’s presented with a 4-month history of abdominal pain, a 50-pound weight loss, stenosis of all major mesenteric arteries, and bowel pneumatosis. Despite this, her sedimentation rate was only slightly elevated at 33 mm/hour, and all other coagulation and inflammatory tests were normal. She remains symptom free at 2 years on daily aspirin after undergoing an emergent right common iliac-to-SMA bypass graft with reversed saphenous vein and bowel resection.

In cases in which bypass grafting is necessary, the internal iliac artery is the preferred conduit in children since the saphenous vein is very thin walled and thus, more prone to aneurysmal degeneration, Dr. Dalsing observed. In grown patients, the saphenous vein may be the best conduit in terms of ease of harvest and adequate length for even bifurcated grafts or C-loop alignment.

During postoperative follow-up, special effort should be taken because of the young age of these patients to reduce the detrimental effects of radiation from recurrent CT angiograms, he said. Patients with symptomatic improvement are followed at 1 month postoperatively with a physical exam that includes their weight and a mesenteric duplex to evaluate graft or stent patency. This is repeated every 6 months for 1-2 years, and decreased to yearly visits, if no disease progression is detected. More aggressive imaging with CT angiography is reserved for patients with recurrent symptoms or if duplex ultrasound is insufficient or shows progressive disease, he said at the meeting, sponsored by Northwestern University.

Dr. Dalsing reported having no financial disclosures.

[email protected]

CHICAGO – Early recognition of mesenteric ischemia in young adults and children is essential to prevent bowel loss and other serious consequences associated with this rare condition, Dr. Michael Dalsing said at a vascular surgery symposium.

Mesenteric ischemia is generally seen in the elderly as the result of atherosclerotic and embolic occlusive diseases. Because young adults and children typically don’t have any of the telltale associated comorbidities such as cardiac arrhythmia or coronary artery disease to point physicians in this direction, the diagnosis of mesenteric ischemia is often delayed or misinterpreted as appendicitis, cholecystitis, or intra-abdominal abscess, he said.

Patrice Wendling/Frontline Medical News

Among 26 young adults under age 40 years who presented with acute mesenteric ischemia, only 6 were properly diagnosed preoperatively (Wien. Med. Wochenschr. 2012;162:349-53). The postoperative complication and mortality rates reached 61.5% and 27%, which is typical in this population, despite their otherwise good health, said Dr. Dalsing, director of vascular surgery at Indiana University, Indianapolis.

The hallmarks of acute mesenteric ischemia are standard in both young and old patients and include abdominal pain out of proportion to the physical exam, nausea, vomiting, and/or diarrhea. Acidosis, acute renal failure, and septic shock/sepsis can develop in roughly half of patients with more extensive liver or bowel ischemia or necrosis. The signs and symptoms of chronic ischemia are weight loss, food fear, and postprandial abdominal pain.

"For chronic mesenteric ischemia, what’s the important message? Consider the diagnosis," Dr. Dalsing said. "Do the imaging, find out what you have, and then you can worry about ancillary testing because, in general, these aren’t going to be your typical etiologies. In fact, they’re not standard fare at all."

The broad and atypical list of etiologies to consider in those under age 40 years include congenital aortic anomalies, hypercoagulable states, inflammatory conditions, collagen vascular disorders, and environmental agents such as cocaine use, smoking, or trauma. While MI is often suspected in those using cocaine, the vasoconstrictive effects of the drug can also cause vasospasm of the smaller branches of the mesenteric vessels, leading to nonocclusive mesenteric ischemia, he explained.

Once a diagnosis of chronic mesenteric ischemia is made in a young patient, management consists of fluid resuscitation, broad spectrum antibiotics, bowel rest, and imaging, often with a CT angiogram. The need for additional work-up, including hypercoagulable and inflammatory marker panels, varies based on initial clinical symptoms.

If vascular compromise is identified, the overall management goals should be to remove frankly necrotic bowel, reperfuse ischemic bowel, limit the resection length when possible to prevent short-gut syndrome, and treat the underlying etiology, Dr. Dalsing advised. Anticoagulation is also integral to prevent thrombus propagation.

Just six cases of mesenteric ischemia have been diagnosed at Indiana University in young adults over the last 16 years, with Takayasu’s arteritis the most common etiology, he noted. This includes a 20-year-old woman with a 5-year history of Takayasu’s, who presented with worsening abdominal pain despite remission of her Takayasu’s, as indicated by a normal sedimentation rate.

Repeat CT imaging revealed more than 70% celiac artery stenosis and more than 50% stenosis of the superior mesenteric artery (SMA). A median arcuate ligament division and celiac and SMA bypass graft, both with reverse saphenous vein originating from bilateral iliac arteries, was performed. "She’s had dramatic improvement" in her symptoms and remains on clopidogrel (Plavix) and low-dose steroids, Dr. Dalsing said.

Courtesy Wikimedia Commons/James Heilman, MD/Creative Commons Attribution

A second patient with Takayasu’s presented with a 4-month history of abdominal pain, a 50-pound weight loss, stenosis of all major mesenteric arteries, and bowel pneumatosis. Despite this, her sedimentation rate was only slightly elevated at 33 mm/hour, and all other coagulation and inflammatory tests were normal. She remains symptom free at 2 years on daily aspirin after undergoing an emergent right common iliac-to-SMA bypass graft with reversed saphenous vein and bowel resection.

In cases in which bypass grafting is necessary, the internal iliac artery is the preferred conduit in children since the saphenous vein is very thin walled and thus, more prone to aneurysmal degeneration, Dr. Dalsing observed. In grown patients, the saphenous vein may be the best conduit in terms of ease of harvest and adequate length for even bifurcated grafts or C-loop alignment.

During postoperative follow-up, special effort should be taken because of the young age of these patients to reduce the detrimental effects of radiation from recurrent CT angiograms, he said. Patients with symptomatic improvement are followed at 1 month postoperatively with a physical exam that includes their weight and a mesenteric duplex to evaluate graft or stent patency. This is repeated every 6 months for 1-2 years, and decreased to yearly visits, if no disease progression is detected. More aggressive imaging with CT angiography is reserved for patients with recurrent symptoms or if duplex ultrasound is insufficient or shows progressive disease, he said at the meeting, sponsored by Northwestern University.

Dr. Dalsing reported having no financial disclosures.

[email protected]