When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

Illicit drug use in the United States continues to rise. In 2014, 27 million people reported using an illicit drug in the previous 30 days. This corresponds to nearly 1 in every 10 Americans.

Use of marijuana has the highest prevalence, followed distantly by pain relievers, tranquilizers, stimulants, and cocaine. Resources for drug users who want to quit are difficult to access – and even if those resources are available, they may be constrained.

For patients struggling with alcohol dependence who want to quit, Alcoholics Anonymous (AA) is the most well-known and ubiquitous 12-step mutual help organization (MHO). Other MHOs, such as Narcotics Anonymous (NA), exist for illicit substances such as opiates (e.g., heroin), stimulants, or cannabis. Shared experiences are hypothesized to maximize therapeutic benefit.

But what, then, should we do if somebody struggling with illicit substance dependence wants to remain abstinent from drugs and there are only AA groups around?

Harvard investigators suggest that support from AA for patients with illicit substance addiction is not associated with early discontinuation or compromised recovery. To evaluate this, researchers examined treatment outcomes among young adults participating in residential treatment in Minnesota (Alcohol Alcohol. 2014 Nov;49[6]:645-3).

Four groups of patients with drug use disorder were evaluated: alcohol, cannabis, opiates, or stimulants. The goal was to compare the relative success of individuals with fellowship “mismatch” (e.g., attending AA but was a primary user of cannabis), compared with those who had a fellowship match. Success during aftercare was defined as percentage of days abstinent and attendance at the MHO.

Investigators observed that in the first 3 months after discharge from the residential treatment program, a significant proportion (79%) of the meetings attended by the cannabis, opiates, or stimulant users were AA meetings. This mismatch was unrelated to 12-step attendance at 6 and 12 months, or to percentage of days abstinent.

Available literature suggests that 12-step MHO participation is a predictor of better treatment outcomes. The findings from this study suggest that AA attendance among patients recovering from cannabis, opiates, or stimulant use disorder is beneficial. Patients with illicit drug use disorder should be encouraged to attend AA if other MHOs are not accessible.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no financial disclosures relevant to this article.

Illicit drug use in the United States continues to rise. In 2014, 27 million people reported using an illicit drug in the previous 30 days. This corresponds to nearly 1 in every 10 Americans.

Use of marijuana has the highest prevalence, followed distantly by pain relievers, tranquilizers, stimulants, and cocaine. Resources for drug users who want to quit are difficult to access – and even if those resources are available, they may be constrained.

For patients struggling with alcohol dependence who want to quit, Alcoholics Anonymous (AA) is the most well-known and ubiquitous 12-step mutual help organization (MHO). Other MHOs, such as Narcotics Anonymous (NA), exist for illicit substances such as opiates (e.g., heroin), stimulants, or cannabis. Shared experiences are hypothesized to maximize therapeutic benefit.

But what, then, should we do if somebody struggling with illicit substance dependence wants to remain abstinent from drugs and there are only AA groups around?

Harvard investigators suggest that support from AA for patients with illicit substance addiction is not associated with early discontinuation or compromised recovery. To evaluate this, researchers examined treatment outcomes among young adults participating in residential treatment in Minnesota (Alcohol Alcohol. 2014 Nov;49[6]:645-3).

Four groups of patients with drug use disorder were evaluated: alcohol, cannabis, opiates, or stimulants. The goal was to compare the relative success of individuals with fellowship “mismatch” (e.g., attending AA but was a primary user of cannabis), compared with those who had a fellowship match. Success during aftercare was defined as percentage of days abstinent and attendance at the MHO.

Investigators observed that in the first 3 months after discharge from the residential treatment program, a significant proportion (79%) of the meetings attended by the cannabis, opiates, or stimulant users were AA meetings. This mismatch was unrelated to 12-step attendance at 6 and 12 months, or to percentage of days abstinent.

Available literature suggests that 12-step MHO participation is a predictor of better treatment outcomes. The findings from this study suggest that AA attendance among patients recovering from cannabis, opiates, or stimulant use disorder is beneficial. Patients with illicit drug use disorder should be encouraged to attend AA if other MHOs are not accessible.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no financial disclosures relevant to this article.

Illicit drug use in the United States continues to rise. In 2014, 27 million people reported using an illicit drug in the previous 30 days. This corresponds to nearly 1 in every 10 Americans.

Use of marijuana has the highest prevalence, followed distantly by pain relievers, tranquilizers, stimulants, and cocaine. Resources for drug users who want to quit are difficult to access – and even if those resources are available, they may be constrained.

For patients struggling with alcohol dependence who want to quit, Alcoholics Anonymous (AA) is the most well-known and ubiquitous 12-step mutual help organization (MHO). Other MHOs, such as Narcotics Anonymous (NA), exist for illicit substances such as opiates (e.g., heroin), stimulants, or cannabis. Shared experiences are hypothesized to maximize therapeutic benefit.

But what, then, should we do if somebody struggling with illicit substance dependence wants to remain abstinent from drugs and there are only AA groups around?

Harvard investigators suggest that support from AA for patients with illicit substance addiction is not associated with early discontinuation or compromised recovery. To evaluate this, researchers examined treatment outcomes among young adults participating in residential treatment in Minnesota (Alcohol Alcohol. 2014 Nov;49[6]:645-3).

Four groups of patients with drug use disorder were evaluated: alcohol, cannabis, opiates, or stimulants. The goal was to compare the relative success of individuals with fellowship “mismatch” (e.g., attending AA but was a primary user of cannabis), compared with those who had a fellowship match. Success during aftercare was defined as percentage of days abstinent and attendance at the MHO.

Investigators observed that in the first 3 months after discharge from the residential treatment program, a significant proportion (79%) of the meetings attended by the cannabis, opiates, or stimulant users were AA meetings. This mismatch was unrelated to 12-step attendance at 6 and 12 months, or to percentage of days abstinent.

Available literature suggests that 12-step MHO participation is a predictor of better treatment outcomes. The findings from this study suggest that AA attendance among patients recovering from cannabis, opiates, or stimulant use disorder is beneficial. Patients with illicit drug use disorder should be encouraged to attend AA if other MHOs are not accessible.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no financial disclosures relevant to this article.

Myth: Psoriasis Is Infectious The precise cause of psoriasis is unknown, but researchers believe the immune system and genetics play major roles in its development, according to the National Psoriasis Foundation. The skin cells in patients with psoriasis grow at an abnormally fast rate, which causes the buildup of psoriasis lesions. Usually, something triggers psoriasis to flare.

A common misconception among patients is that psoriasis is caused by an infection. Psoriasis is not contagious and psoriasis lesions are not infectious.

However, psoriasis patients are more prone to infections than those without psoriasis. Risk factors for serious infections in psoriasis patients include immune dysregulation, systemic immunosuppressive medications, and comorbid health conditions such as diabetes mellitus or obesity. A 2016 study revealed an increased incidence of serious infections (eg, cellulitis, herpes simplex virus infection, any fungal infection, infectious arthritis, methicillin-resistant Staphylococcus aureus) in hospitalized patients with psoriasis. Higher rates were seen among nonwhite and non-privately insured patients.

In a 2011 study, the likelihood of infectious diseases in patients with psoriasis was twice as high as the reference population. The risk was highest in patients with more severe psoriasis but was not associated with recent systemic antipsoriatic drug dispensing. Respiratory tract, abdominal, and skin infections occurred most frequently in patients with psoriasis.

Poor access to adequate dermatologic care may contribute to higher rates of infections. Dermatologists must closely monitor patients with psoriasis for infection. More research is needed to develop interventions for prevention.

Expert Commentary Psoriasis patients have long faced discrimination because of an  irrational fear that their disease was somehow contagious. In fact this is completely false. This highlights the need for education of the public, so that they understand the true causes and nature of the disease.
—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Psoriasis Is Infectious The precise cause of psoriasis is unknown, but researchers believe the immune system and genetics play major roles in its development, according to the National Psoriasis Foundation. The skin cells in patients with psoriasis grow at an abnormally fast rate, which causes the buildup of psoriasis lesions. Usually, something triggers psoriasis to flare.

A common misconception among patients is that psoriasis is caused by an infection. Psoriasis is not contagious and psoriasis lesions are not infectious.

However, psoriasis patients are more prone to infections than those without psoriasis. Risk factors for serious infections in psoriasis patients include immune dysregulation, systemic immunosuppressive medications, and comorbid health conditions such as diabetes mellitus or obesity. A 2016 study revealed an increased incidence of serious infections (eg, cellulitis, herpes simplex virus infection, any fungal infection, infectious arthritis, methicillin-resistant Staphylococcus aureus) in hospitalized patients with psoriasis. Higher rates were seen among nonwhite and non-privately insured patients.

In a 2011 study, the likelihood of infectious diseases in patients with psoriasis was twice as high as the reference population. The risk was highest in patients with more severe psoriasis but was not associated with recent systemic antipsoriatic drug dispensing. Respiratory tract, abdominal, and skin infections occurred most frequently in patients with psoriasis.

Poor access to adequate dermatologic care may contribute to higher rates of infections. Dermatologists must closely monitor patients with psoriasis for infection. More research is needed to develop interventions for prevention.

Expert Commentary Psoriasis patients have long faced discrimination because of an  irrational fear that their disease was somehow contagious. In fact this is completely false. This highlights the need for education of the public, so that they understand the true causes and nature of the disease.
—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Psoriasis Is Infectious The precise cause of psoriasis is unknown, but researchers believe the immune system and genetics play major roles in its development, according to the National Psoriasis Foundation. The skin cells in patients with psoriasis grow at an abnormally fast rate, which causes the buildup of psoriasis lesions. Usually, something triggers psoriasis to flare.

A common misconception among patients is that psoriasis is caused by an infection. Psoriasis is not contagious and psoriasis lesions are not infectious.

However, psoriasis patients are more prone to infections than those without psoriasis. Risk factors for serious infections in psoriasis patients include immune dysregulation, systemic immunosuppressive medications, and comorbid health conditions such as diabetes mellitus or obesity. A 2016 study revealed an increased incidence of serious infections (eg, cellulitis, herpes simplex virus infection, any fungal infection, infectious arthritis, methicillin-resistant Staphylococcus aureus) in hospitalized patients with psoriasis. Higher rates were seen among nonwhite and non-privately insured patients.

In a 2011 study, the likelihood of infectious diseases in patients with psoriasis was twice as high as the reference population. The risk was highest in patients with more severe psoriasis but was not associated with recent systemic antipsoriatic drug dispensing. Respiratory tract, abdominal, and skin infections occurred most frequently in patients with psoriasis.

Poor access to adequate dermatologic care may contribute to higher rates of infections. Dermatologists must closely monitor patients with psoriasis for infection. More research is needed to develop interventions for prevention.

Expert Commentary Psoriasis patients have long faced discrimination because of an  irrational fear that their disease was somehow contagious. In fact this is completely false. This highlights the need for education of the public, so that they understand the true causes and nature of the disease.
—Jeffrey M. Weinberg, MD (New York, New York)

Direct-to-consumer marketing (DTCM) is the promotion of health-related products or services directly to patients. Although this topic is not new to orthopedics, several emerging trends hold troubling implications for patients as well as orthopedic surgeons, particularly surgeons in training.

Orthopedics DTCM most commonly involves television and print advertisements. Supporters contend DTCM is an empowering educational tool that increases awareness of medical ailments and encourages patients to seek treatment. Opponents point to inaccuracies and misleading claims. Bhattacharyya and colleagues¹ found that about half the claims in orthopedic print advertisements were not supported by clinical evidence. Woloshin and colleagues² found that information in DTCM was vague and often was designed to act on the emotions. Patients misled by these claims and innately seeking improvement could present with unreasonable expectations and difficult discussions that can be detrimental to the patient–physician relationship.³Given changing patient demographics and the information revolution, the effects of DTCM likely will continue to grow. Total joint arthroplasty (TJA), which represents Medicare’s largest expenditure,⁴ is a classic example. Today’s TJA patients are younger, more active, and better educated, and they live longer, have higher expectations, and are more reliant on the media.⁵ Television is no longer our main medium—the internet is the source of healthcare education for 70% of adults in the United States.⁶Healthcare reform has also brought significant changes in the delivery of DTCM. In an era of competition for market share brought by increased demand and decreased reimbursement, DTCM has evolved into sales pitches by hospitals and physicians. Robotic joint replacement, minimally invasive surgery (MIS), use of the anterior hip approach, use of sex-specific or high-flexion knee implants, and other practices have become popular marketing tools for surgery centers competing for new patients. As a result, patients often present not only with a complaint but with a request for a particular procedure.^4,5 Labovitch and colleagues⁷ found that 70% of MIS information on the internet was produced by hospitals and private medical groups, and only 6% was produced by industry. Although the vast majority of the sources reported on the advantages of MIS, only 15% explained patient eligibility, and a mere 9% supplied references for examination of peer-reviewed data. Another unfortunate consequence of DCTM is “physician shopping.” Bozic and colleagues⁴ found that patients exposed to DCTM were more likely to demand a specific surgery, approach, or implant and were less open to alternatives; in addition, they saw more than one surgeon before deciding on joint arthroplasty.

The effects of DTCM on resident and fellowship training require serious consideration. An emphasis on technology has come at the expense of learning the science and art of orthopedics.⁸ Physicians in training are pressured both to produce more and to use whichever specific technique or product a patient requests.⁴ Similarly, orthopedic surgeons are seeing job advertisements that read, “Training in robotic surgery or anterior approach is preferred.” Employer pressure can have profound implications for residents and fellows, who may feel compelled to learn these techniques. To a large degree, residents and fellows learn by accompanying their mentors and closely observing their decision-making processes and interactions with patients. Decisions regarding fellowships should not be influenced by surgical techniques or implant choices but by the quality and breadth of clinical experience.

DTCM likely will continue to shape all aspects of care. Claims made by physicians and hospitals are especially troubling because patients trust these sources. We face the challenge of reaffirming our commitment to patients and orthopedic surgeons. As the leader in musculoskeletal education, the American Academy of Orthopaedic Surgeons (AAOS) not only must provide educational material that is compatible with current technological media but must address current controversies and misleading claims. Toward that end, AAOS can expand its patient website, OrthoInfo, to include information on new technologies and surgical techniques pertaining to each musculoskeletal condition. Educating the public about risk factors for poor surgical outcomes is equally important in order to moderate unrealistic expectations and stimulate discussions on risks involved in unnecessary or potentially harmful technologies. The American Association of Hip and Knee Surgeons (AAHKS) has already embarked on this approach. Orthopedic surgeons should continue to abide by the standards of professionalism—maintaining the tenet of “First do no harm,” resisting the temptations of consumerism, and giving patients accurate information. Taking these measures may help reduce physician shopping and strengthen the patient–physician relationship. We physicians are the guardians of patients’ well-being. We also owe it to orthopedic surgeons in training to provide well-balanced, unbiased education. The focus of training should not be on techniques for gaining market edge but on learning evidence-based medicine and surgical principles. In our burdened healthcare system, curbing DTCM has the potential to decrease unnecessary use of resources and improve the quality of education and patient care.

Am J Orthop. 2016;45(6):E335-E336. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Direct-to-consumer marketing (DTCM) is the promotion of health-related products or services directly to patients. Although this topic is not new to orthopedics, several emerging trends hold troubling implications for patients as well as orthopedic surgeons, particularly surgeons in training.

Orthopedics DTCM most commonly involves television and print advertisements. Supporters contend DTCM is an empowering educational tool that increases awareness of medical ailments and encourages patients to seek treatment. Opponents point to inaccuracies and misleading claims. Bhattacharyya and colleagues¹ found that about half the claims in orthopedic print advertisements were not supported by clinical evidence. Woloshin and colleagues² found that information in DTCM was vague and often was designed to act on the emotions. Patients misled by these claims and innately seeking improvement could present with unreasonable expectations and difficult discussions that can be detrimental to the patient–physician relationship.³Given changing patient demographics and the information revolution, the effects of DTCM likely will continue to grow. Total joint arthroplasty (TJA), which represents Medicare’s largest expenditure,⁴ is a classic example. Today’s TJA patients are younger, more active, and better educated, and they live longer, have higher expectations, and are more reliant on the media.⁵ Television is no longer our main medium—the internet is the source of healthcare education for 70% of adults in the United States.⁶Healthcare reform has also brought significant changes in the delivery of DTCM. In an era of competition for market share brought by increased demand and decreased reimbursement, DTCM has evolved into sales pitches by hospitals and physicians. Robotic joint replacement, minimally invasive surgery (MIS), use of the anterior hip approach, use of sex-specific or high-flexion knee implants, and other practices have become popular marketing tools for surgery centers competing for new patients. As a result, patients often present not only with a complaint but with a request for a particular procedure.^4,5 Labovitch and colleagues⁷ found that 70% of MIS information on the internet was produced by hospitals and private medical groups, and only 6% was produced by industry. Although the vast majority of the sources reported on the advantages of MIS, only 15% explained patient eligibility, and a mere 9% supplied references for examination of peer-reviewed data. Another unfortunate consequence of DCTM is “physician shopping.” Bozic and colleagues⁴ found that patients exposed to DCTM were more likely to demand a specific surgery, approach, or implant and were less open to alternatives; in addition, they saw more than one surgeon before deciding on joint arthroplasty.

The effects of DTCM on resident and fellowship training require serious consideration. An emphasis on technology has come at the expense of learning the science and art of orthopedics.⁸ Physicians in training are pressured both to produce more and to use whichever specific technique or product a patient requests.⁴ Similarly, orthopedic surgeons are seeing job advertisements that read, “Training in robotic surgery or anterior approach is preferred.” Employer pressure can have profound implications for residents and fellows, who may feel compelled to learn these techniques. To a large degree, residents and fellows learn by accompanying their mentors and closely observing their decision-making processes and interactions with patients. Decisions regarding fellowships should not be influenced by surgical techniques or implant choices but by the quality and breadth of clinical experience.

DTCM likely will continue to shape all aspects of care. Claims made by physicians and hospitals are especially troubling because patients trust these sources. We face the challenge of reaffirming our commitment to patients and orthopedic surgeons. As the leader in musculoskeletal education, the American Academy of Orthopaedic Surgeons (AAOS) not only must provide educational material that is compatible with current technological media but must address current controversies and misleading claims. Toward that end, AAOS can expand its patient website, OrthoInfo, to include information on new technologies and surgical techniques pertaining to each musculoskeletal condition. Educating the public about risk factors for poor surgical outcomes is equally important in order to moderate unrealistic expectations and stimulate discussions on risks involved in unnecessary or potentially harmful technologies. The American Association of Hip and Knee Surgeons (AAHKS) has already embarked on this approach. Orthopedic surgeons should continue to abide by the standards of professionalism—maintaining the tenet of “First do no harm,” resisting the temptations of consumerism, and giving patients accurate information. Taking these measures may help reduce physician shopping and strengthen the patient–physician relationship. We physicians are the guardians of patients’ well-being. We also owe it to orthopedic surgeons in training to provide well-balanced, unbiased education. The focus of training should not be on techniques for gaining market edge but on learning evidence-based medicine and surgical principles. In our burdened healthcare system, curbing DTCM has the potential to decrease unnecessary use of resources and improve the quality of education and patient care.

Am J Orthop. 2016;45(6):E335-E336. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Direct-to-consumer marketing (DTCM) is the promotion of health-related products or services directly to patients. Although this topic is not new to orthopedics, several emerging trends hold troubling implications for patients as well as orthopedic surgeons, particularly surgeons in training.

Orthopedics DTCM most commonly involves television and print advertisements. Supporters contend DTCM is an empowering educational tool that increases awareness of medical ailments and encourages patients to seek treatment. Opponents point to inaccuracies and misleading claims. Bhattacharyya and colleagues¹ found that about half the claims in orthopedic print advertisements were not supported by clinical evidence. Woloshin and colleagues² found that information in DTCM was vague and often was designed to act on the emotions. Patients misled by these claims and innately seeking improvement could present with unreasonable expectations and difficult discussions that can be detrimental to the patient–physician relationship.³Given changing patient demographics and the information revolution, the effects of DTCM likely will continue to grow. Total joint arthroplasty (TJA), which represents Medicare’s largest expenditure,⁴ is a classic example. Today’s TJA patients are younger, more active, and better educated, and they live longer, have higher expectations, and are more reliant on the media.⁵ Television is no longer our main medium—the internet is the source of healthcare education for 70% of adults in the United States.⁶Healthcare reform has also brought significant changes in the delivery of DTCM. In an era of competition for market share brought by increased demand and decreased reimbursement, DTCM has evolved into sales pitches by hospitals and physicians. Robotic joint replacement, minimally invasive surgery (MIS), use of the anterior hip approach, use of sex-specific or high-flexion knee implants, and other practices have become popular marketing tools for surgery centers competing for new patients. As a result, patients often present not only with a complaint but with a request for a particular procedure.^4,5 Labovitch and colleagues⁷ found that 70% of MIS information on the internet was produced by hospitals and private medical groups, and only 6% was produced by industry. Although the vast majority of the sources reported on the advantages of MIS, only 15% explained patient eligibility, and a mere 9% supplied references for examination of peer-reviewed data. Another unfortunate consequence of DCTM is “physician shopping.” Bozic and colleagues⁴ found that patients exposed to DCTM were more likely to demand a specific surgery, approach, or implant and were less open to alternatives; in addition, they saw more than one surgeon before deciding on joint arthroplasty.

The effects of DTCM on resident and fellowship training require serious consideration. An emphasis on technology has come at the expense of learning the science and art of orthopedics.⁸ Physicians in training are pressured both to produce more and to use whichever specific technique or product a patient requests.⁴ Similarly, orthopedic surgeons are seeing job advertisements that read, “Training in robotic surgery or anterior approach is preferred.” Employer pressure can have profound implications for residents and fellows, who may feel compelled to learn these techniques. To a large degree, residents and fellows learn by accompanying their mentors and closely observing their decision-making processes and interactions with patients. Decisions regarding fellowships should not be influenced by surgical techniques or implant choices but by the quality and breadth of clinical experience.

DTCM likely will continue to shape all aspects of care. Claims made by physicians and hospitals are especially troubling because patients trust these sources. We face the challenge of reaffirming our commitment to patients and orthopedic surgeons. As the leader in musculoskeletal education, the American Academy of Orthopaedic Surgeons (AAOS) not only must provide educational material that is compatible with current technological media but must address current controversies and misleading claims. Toward that end, AAOS can expand its patient website, OrthoInfo, to include information on new technologies and surgical techniques pertaining to each musculoskeletal condition. Educating the public about risk factors for poor surgical outcomes is equally important in order to moderate unrealistic expectations and stimulate discussions on risks involved in unnecessary or potentially harmful technologies. The American Association of Hip and Knee Surgeons (AAHKS) has already embarked on this approach. Orthopedic surgeons should continue to abide by the standards of professionalism—maintaining the tenet of “First do no harm,” resisting the temptations of consumerism, and giving patients accurate information. Taking these measures may help reduce physician shopping and strengthen the patient–physician relationship. We physicians are the guardians of patients’ well-being. We also owe it to orthopedic surgeons in training to provide well-balanced, unbiased education. The focus of training should not be on techniques for gaining market edge but on learning evidence-based medicine and surgical principles. In our burdened healthcare system, curbing DTCM has the potential to decrease unnecessary use of resources and improve the quality of education and patient care.

Am J Orthop. 2016;45(6):E335-E336. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Treatment of patients admitted to the hospital with an upper respiratory infection is often complicated by the lack of diagnostics. Even in cases where a patient has a confirmed case of influenza, there is still the possibility that they may have, or become infected by, a secondary bacterial infection. This leads clinicians to treat patients empirically with antibiotics, which can result in unnecessary antibiotic use among patients without a bacterial infection.

Though antibiotics can be a lifesaving drug, their use is not without risks. Estimates suggest that 20% of patients taking common antibiotics experience some side effect. While most side effects are not life-threatening gastrointestinal effects, other nonnegligible side effects include anaphylactic shock, drug‐induced liver injury, increases in the risk of retinal detachment, serious arrhythmias, and superinfection with resistant bacteria. Antibiotics can also lead to secondary infections, such as Clostridium difficile.

Yet, despite these risks, there has been limited research on the percentage of patients with influenza who actually have a bacterial coinfection. A recent systematic review and meta-analysis conducted by my colleagues at Johns Hopkins University and the Center for Disease Dynamics, Economics & Policy examined the frequency of bacterial coinfection among hospitalized patients with influenza and identified the most common infecting bacterial species.

The findings, published in the journal Influenza and Other Respiratory Viruses, found that in the majority of studies, between 11% and 35% of patients with confirmed influenza had a bacterial coinfection. The most common coinfecting bacteria were found to be Streptococcus pneumoniae and Staphylococcus aureus. Combined, S. pneumoniae and S. aureus accounted for more than 60% of the identified coinfecting bacteria; however, many other bacterial species were found to cause infections as well.

The results suggest that while bacterial infection is common in influenza patients, only about a quarter of patients are likely to be infected. However, the studies were widely heterogeneous, both in patient makeup and results. Analyses of age, setting, enrollment year, study type, study size, and bacterial collection methods did not reveal a source for the heterogeneity in results. Thus, additional factors, such as patient comorbidities or prior antibiotic use, which could not be systematically assessed, may affect the likelihood of coinfection.

Given that the symptoms of influenza and bacterial infection often overlap, correctly diagnosing bacterial coinfection without a laboratory culture can present a challenge. This diagnostic uncertainty leads to significant overuse of antibiotics in patients with influenza alone. Most influenza cases will never result in serious bacterial infections (particularly in nonhospitalized patients), and thus a lot of antibiotic use is unnecessary. As mentioned earlier, unnecessary antibiotic use poses a nonnegligible risk to patients, but it also contributes significantly to rising rates of antibiotic resistance, a major public health issue.

The results from this study highlight that the majority of patients hospitalized with influenza are unlikely to be coinfected with a bacterial pathogen. Thus, it is important for clinicians to appropriately treat patients with antiviral drugs, and ensure that bacterial testing is done when presumptively starting patients on antibiotics. Based on the microbiology results, antibiotics can be stopped if no pathogen is identified or altered to be more appropriate depending on the pathogen found.

Although the findings of this study suggest we need a more thorough analysis of the issue, the results should still aid clinicians by improving their understanding of the likelihood of bacterial coinfection in hospitalized patients with influenza, and thus help them balance the need to minimize patient risks as well as the individual and societal risks of nonessential antibiotic use.

Eili Klein, PhD, is assistant professor in the department of emergency medicine at Johns Hopkins Medicine, Baltimore.

Treatment of patients admitted to the hospital with an upper respiratory infection is often complicated by the lack of diagnostics. Even in cases where a patient has a confirmed case of influenza, there is still the possibility that they may have, or become infected by, a secondary bacterial infection. This leads clinicians to treat patients empirically with antibiotics, which can result in unnecessary antibiotic use among patients without a bacterial infection.

Though antibiotics can be a lifesaving drug, their use is not without risks. Estimates suggest that 20% of patients taking common antibiotics experience some side effect. While most side effects are not life-threatening gastrointestinal effects, other nonnegligible side effects include anaphylactic shock, drug‐induced liver injury, increases in the risk of retinal detachment, serious arrhythmias, and superinfection with resistant bacteria. Antibiotics can also lead to secondary infections, such as Clostridium difficile.

Yet, despite these risks, there has been limited research on the percentage of patients with influenza who actually have a bacterial coinfection. A recent systematic review and meta-analysis conducted by my colleagues at Johns Hopkins University and the Center for Disease Dynamics, Economics & Policy examined the frequency of bacterial coinfection among hospitalized patients with influenza and identified the most common infecting bacterial species.

The findings, published in the journal Influenza and Other Respiratory Viruses, found that in the majority of studies, between 11% and 35% of patients with confirmed influenza had a bacterial coinfection. The most common coinfecting bacteria were found to be Streptococcus pneumoniae and Staphylococcus aureus. Combined, S. pneumoniae and S. aureus accounted for more than 60% of the identified coinfecting bacteria; however, many other bacterial species were found to cause infections as well.

The results suggest that while bacterial infection is common in influenza patients, only about a quarter of patients are likely to be infected. However, the studies were widely heterogeneous, both in patient makeup and results. Analyses of age, setting, enrollment year, study type, study size, and bacterial collection methods did not reveal a source for the heterogeneity in results. Thus, additional factors, such as patient comorbidities or prior antibiotic use, which could not be systematically assessed, may affect the likelihood of coinfection.

Given that the symptoms of influenza and bacterial infection often overlap, correctly diagnosing bacterial coinfection without a laboratory culture can present a challenge. This diagnostic uncertainty leads to significant overuse of antibiotics in patients with influenza alone. Most influenza cases will never result in serious bacterial infections (particularly in nonhospitalized patients), and thus a lot of antibiotic use is unnecessary. As mentioned earlier, unnecessary antibiotic use poses a nonnegligible risk to patients, but it also contributes significantly to rising rates of antibiotic resistance, a major public health issue.

The results from this study highlight that the majority of patients hospitalized with influenza are unlikely to be coinfected with a bacterial pathogen. Thus, it is important for clinicians to appropriately treat patients with antiviral drugs, and ensure that bacterial testing is done when presumptively starting patients on antibiotics. Based on the microbiology results, antibiotics can be stopped if no pathogen is identified or altered to be more appropriate depending on the pathogen found.

Although the findings of this study suggest we need a more thorough analysis of the issue, the results should still aid clinicians by improving their understanding of the likelihood of bacterial coinfection in hospitalized patients with influenza, and thus help them balance the need to minimize patient risks as well as the individual and societal risks of nonessential antibiotic use.

Eili Klein, PhD, is assistant professor in the department of emergency medicine at Johns Hopkins Medicine, Baltimore.

Treatment of patients admitted to the hospital with an upper respiratory infection is often complicated by the lack of diagnostics. Even in cases where a patient has a confirmed case of influenza, there is still the possibility that they may have, or become infected by, a secondary bacterial infection. This leads clinicians to treat patients empirically with antibiotics, which can result in unnecessary antibiotic use among patients without a bacterial infection.

Though antibiotics can be a lifesaving drug, their use is not without risks. Estimates suggest that 20% of patients taking common antibiotics experience some side effect. While most side effects are not life-threatening gastrointestinal effects, other nonnegligible side effects include anaphylactic shock, drug‐induced liver injury, increases in the risk of retinal detachment, serious arrhythmias, and superinfection with resistant bacteria. Antibiotics can also lead to secondary infections, such as Clostridium difficile.

Yet, despite these risks, there has been limited research on the percentage of patients with influenza who actually have a bacterial coinfection. A recent systematic review and meta-analysis conducted by my colleagues at Johns Hopkins University and the Center for Disease Dynamics, Economics & Policy examined the frequency of bacterial coinfection among hospitalized patients with influenza and identified the most common infecting bacterial species.

The findings, published in the journal Influenza and Other Respiratory Viruses, found that in the majority of studies, between 11% and 35% of patients with confirmed influenza had a bacterial coinfection. The most common coinfecting bacteria were found to be Streptococcus pneumoniae and Staphylococcus aureus. Combined, S. pneumoniae and S. aureus accounted for more than 60% of the identified coinfecting bacteria; however, many other bacterial species were found to cause infections as well.

The results suggest that while bacterial infection is common in influenza patients, only about a quarter of patients are likely to be infected. However, the studies were widely heterogeneous, both in patient makeup and results. Analyses of age, setting, enrollment year, study type, study size, and bacterial collection methods did not reveal a source for the heterogeneity in results. Thus, additional factors, such as patient comorbidities or prior antibiotic use, which could not be systematically assessed, may affect the likelihood of coinfection.

Given that the symptoms of influenza and bacterial infection often overlap, correctly diagnosing bacterial coinfection without a laboratory culture can present a challenge. This diagnostic uncertainty leads to significant overuse of antibiotics in patients with influenza alone. Most influenza cases will never result in serious bacterial infections (particularly in nonhospitalized patients), and thus a lot of antibiotic use is unnecessary. As mentioned earlier, unnecessary antibiotic use poses a nonnegligible risk to patients, but it also contributes significantly to rising rates of antibiotic resistance, a major public health issue.

The results from this study highlight that the majority of patients hospitalized with influenza are unlikely to be coinfected with a bacterial pathogen. Thus, it is important for clinicians to appropriately treat patients with antiviral drugs, and ensure that bacterial testing is done when presumptively starting patients on antibiotics. Based on the microbiology results, antibiotics can be stopped if no pathogen is identified or altered to be more appropriate depending on the pathogen found.

Although the findings of this study suggest we need a more thorough analysis of the issue, the results should still aid clinicians by improving their understanding of the likelihood of bacterial coinfection in hospitalized patients with influenza, and thus help them balance the need to minimize patient risks as well as the individual and societal risks of nonessential antibiotic use.

Eili Klein, PhD, is assistant professor in the department of emergency medicine at Johns Hopkins Medicine, Baltimore.

Many patients with diabetic foot infections receive methicillin-resistant Staphylococcus aureus antibiotics unnecessarily, according to Kelly Reveles, PharmD, and her associates.

Among the 318 patients with diabetic foot infections (DFIs) in the study, S. aureus was the most common pathogen, accounting for 146 cases. MRSA accounted for 47 of S. aureus cases, and 15% of overall cases. Although MRSA accounted for a relatively small number of cases, MRSA antibiotics were administered to 86% of all patients, resulting in 71% of all patients receiving the treatment unnecessarily.

Independent risk factors for MRSA DFI were male sex and bone involvement. Other risk factors included previous MRSA infection, more severe infection, and a higher white cell count. The most common comorbidities of DFI were hypertension, dyslipidemia, and obesity.

“The improper use of antibiotics unnecessarily exposes the patient to potential complications of the therapy. Furthermore, the overuse of antibiotics drives antimicrobial resistance and is likely to increase the health care burden,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0161658).

[email protected]

Many patients with diabetic foot infections receive methicillin-resistant Staphylococcus aureus antibiotics unnecessarily, according to Kelly Reveles, PharmD, and her associates.

Among the 318 patients with diabetic foot infections (DFIs) in the study, S. aureus was the most common pathogen, accounting for 146 cases. MRSA accounted for 47 of S. aureus cases, and 15% of overall cases. Although MRSA accounted for a relatively small number of cases, MRSA antibiotics were administered to 86% of all patients, resulting in 71% of all patients receiving the treatment unnecessarily.

Independent risk factors for MRSA DFI were male sex and bone involvement. Other risk factors included previous MRSA infection, more severe infection, and a higher white cell count. The most common comorbidities of DFI were hypertension, dyslipidemia, and obesity.

“The improper use of antibiotics unnecessarily exposes the patient to potential complications of the therapy. Furthermore, the overuse of antibiotics drives antimicrobial resistance and is likely to increase the health care burden,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0161658).

[email protected]

Many patients with diabetic foot infections receive methicillin-resistant Staphylococcus aureus antibiotics unnecessarily, according to Kelly Reveles, PharmD, and her associates.

Among the 318 patients with diabetic foot infections (DFIs) in the study, S. aureus was the most common pathogen, accounting for 146 cases. MRSA accounted for 47 of S. aureus cases, and 15% of overall cases. Although MRSA accounted for a relatively small number of cases, MRSA antibiotics were administered to 86% of all patients, resulting in 71% of all patients receiving the treatment unnecessarily.

Independent risk factors for MRSA DFI were male sex and bone involvement. Other risk factors included previous MRSA infection, more severe infection, and a higher white cell count. The most common comorbidities of DFI were hypertension, dyslipidemia, and obesity.

“The improper use of antibiotics unnecessarily exposes the patient to potential complications of the therapy. Furthermore, the overuse of antibiotics drives antimicrobial resistance and is likely to increase the health care burden,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0161658).

[email protected]

There is ample evidence in the medical literature, as well as clinical experience, that patients seeking help for chemical dependency benefit from pharmacotherapy. It is common, however, for physicians, patients, and family to balk at the idea. Even within the psychiatry community, where there should be better understanding of substance use disorders, many practitioners hesitate to employ medications, especially for alcohol use disorder (AUD).

Efficacy for such FDA-approved medications has been demonstrated in well-designed, randomized controlled trials, but many trainees, and even experienced professionals, have never seen these medications used effectively and appropriately. Medication-assisted treatment (MAT) is not an alternative to biopsychosocial approaches but is an augmentation that can (1) help stabilize the patient until he (she) can be educated in relapse prevention skills and (2) allow the brain to rewire and heal until he regains impulse control.

Diverse presentations

Do you remember that patient who often arrived for appointments intoxicated, promising that he plans to cut down? How about the man you saw in the emergency department with an elevated blood alcohol level, who was constantly endorsing suicidal thoughts that subsided when he reached clinical sobriety? What about the college student who often was treated for alcohol poisoning after binge drinking on weekends, but who never considered this behavior problematic? And, how about the elderly woman who was evaluated for anxiety, but had been drinking 4 beers nightly for the past 30 years?

Despite the diverse presentations, these patients all have a chronic disease and we fail them when we do not apply evidence-based medicine to their treatment.

As psychiatrists, we encounter many patients with AUD as a primary or comorbid diagnosis. This is a global problem associated with significant human and financial cost. With 80% of American adolescents having reported using alcohol in the past year, the problem will continue to grow.¹ Furthermore, a greater prevalence of AUD is noted in clinical populations undergoing psychiatric treatment.² Ongoing alcohol abuse complicates the course of medical and psychiatric conditions and incites significant societal exclusion.

Pharmacotherapy is underutilized

Despite an increase in the use of psychotropic medications for treating psychiatric illness, pharmacotherapy for AUD is under­utilized: only 3% of patients have received an FDA-approved treatment.^2,3 Nearly one-third of adults are affected by AUD during their lifetime, yet only 20% seek help.³ Management today remains limited to episodic, brief inpatient detoxification and psychosocial therapy.

Recovery rates are highest when addiction treatment that monitors abstinence is continuous; yet, for most part, alcohol addiction is treated in discrete episodes upon relapse. Although MAT is recommended by experts for “moderate” and “severe” substance use disorders, practitioners, in general, have demonstrated considerable resistance to using this modality as part of routine practice.^4,5 This is regrettable: Regardless of terminology used to describe their condition, these people suffer a potentially fatal disease characterized by high post-treatment recidivism.

Neuroscience supports the brain disease model of addiction, with neuro­plasticity changes being made during phases of drug use. Medications are shown to assist in preventing relapse while the brain is healing and normal emotional and decision-making capacities are being restored.⁶

Why hesitate to use pharmacotherapeutics?

There are diverse pharmacotherapeutic options that can be pursued for treating AUD with minimal disruption to home and work life. Alarmingly, many trainees have never prescribed or even considered such medications. Despite modest effect sizes in randomized controlled trials, efficacy has been demonstrated in reducing relapse rates and overall severity of drinking days.^4,5 So, from where does the ambivalence of patients and providers about using these treatments to achieve lasting recovery stem?

Starting MAT certainly requires both parties to be in agreement. A patient might decline medication because of a fear of dependence or because he overestimates his ability to achieve remission on his own. There also may be financial barriers in a current alcohol treatment system that is traditionally non-medically oriented. Prescribers also fail to offer medications because of:

• lack of familiarity with available agents
• absence of guidelines for use
• disbelief that the condition is treatable.

Given that treatment often is based on a 12-step approach, such as Alcoholics Anonymous (AA), providers might hesitate to prescribe medication for an illness that is thought to be managed through psychosocial interventions, such as group and motivational therapy.

Therapeutic options

Choice of medication depends on the prescriber’s comfort level, reputation of the medication, potential side-effect profile, medical contraindications, and affordability; the most important consideration, however, should be the overall goals and expectations of the patient.

There are 4 FDA-approved medications for AUD (Table); many others are off-label. It is advisable to start with an FDA-approved medication such as disulfiram for the motivated patient who has a collaborator and desires complete abstinence; naltrexone for a patient who wants to cut down on intake (a long-acting formulation can be used for poorly adherent patients); and acamprosate for a patient with at least some established sobriety who needs help with post-withdrawal sleep disturbances.

Psychosocial interventions

Medications are just 1 tool in recovery; patients should be engaged in a program of counseling. Encourage attendance at AA meetings. An up-and-coming concept is the use of smartphone applications to prevent relapse (or even induce remission); apps that provide an accurate blood alcohol tracking systems and integrated psychosocial therapies are in the pipeline. The novel Reddit online forum r/StopDrinking is a 24-hour peer-support community that relies on
fellowship, accountability, monitoring, and anonymity; the forum can compete with
motivational interviewing for efficacy in increasing abstinence and preventing relapse.

There is ample evidence in the medical literature, as well as clinical experience, that patients seeking help for chemical dependency benefit from pharmacotherapy. It is common, however, for physicians, patients, and family to balk at the idea. Even within the psychiatry community, where there should be better understanding of substance use disorders, many practitioners hesitate to employ medications, especially for alcohol use disorder (AUD).

Efficacy for such FDA-approved medications has been demonstrated in well-designed, randomized controlled trials, but many trainees, and even experienced professionals, have never seen these medications used effectively and appropriately. Medication-assisted treatment (MAT) is not an alternative to biopsychosocial approaches but is an augmentation that can (1) help stabilize the patient until he (she) can be educated in relapse prevention skills and (2) allow the brain to rewire and heal until he regains impulse control.

Diverse presentations

Do you remember that patient who often arrived for appointments intoxicated, promising that he plans to cut down? How about the man you saw in the emergency department with an elevated blood alcohol level, who was constantly endorsing suicidal thoughts that subsided when he reached clinical sobriety? What about the college student who often was treated for alcohol poisoning after binge drinking on weekends, but who never considered this behavior problematic? And, how about the elderly woman who was evaluated for anxiety, but had been drinking 4 beers nightly for the past 30 years?

Despite the diverse presentations, these patients all have a chronic disease and we fail them when we do not apply evidence-based medicine to their treatment.

As psychiatrists, we encounter many patients with AUD as a primary or comorbid diagnosis. This is a global problem associated with significant human and financial cost. With 80% of American adolescents having reported using alcohol in the past year, the problem will continue to grow.¹ Furthermore, a greater prevalence of AUD is noted in clinical populations undergoing psychiatric treatment.² Ongoing alcohol abuse complicates the course of medical and psychiatric conditions and incites significant societal exclusion.

Pharmacotherapy is underutilized

Despite an increase in the use of psychotropic medications for treating psychiatric illness, pharmacotherapy for AUD is under­utilized: only 3% of patients have received an FDA-approved treatment.^2,3 Nearly one-third of adults are affected by AUD during their lifetime, yet only 20% seek help.³ Management today remains limited to episodic, brief inpatient detoxification and psychosocial therapy.

Recovery rates are highest when addiction treatment that monitors abstinence is continuous; yet, for most part, alcohol addiction is treated in discrete episodes upon relapse. Although MAT is recommended by experts for “moderate” and “severe” substance use disorders, practitioners, in general, have demonstrated considerable resistance to using this modality as part of routine practice.^4,5 This is regrettable: Regardless of terminology used to describe their condition, these people suffer a potentially fatal disease characterized by high post-treatment recidivism.

Neuroscience supports the brain disease model of addiction, with neuro­plasticity changes being made during phases of drug use. Medications are shown to assist in preventing relapse while the brain is healing and normal emotional and decision-making capacities are being restored.⁶

Why hesitate to use pharmacotherapeutics?

There are diverse pharmacotherapeutic options that can be pursued for treating AUD with minimal disruption to home and work life. Alarmingly, many trainees have never prescribed or even considered such medications. Despite modest effect sizes in randomized controlled trials, efficacy has been demonstrated in reducing relapse rates and overall severity of drinking days.^4,5 So, from where does the ambivalence of patients and providers about using these treatments to achieve lasting recovery stem?

Starting MAT certainly requires both parties to be in agreement. A patient might decline medication because of a fear of dependence or because he overestimates his ability to achieve remission on his own. There also may be financial barriers in a current alcohol treatment system that is traditionally non-medically oriented. Prescribers also fail to offer medications because of:

• lack of familiarity with available agents
• absence of guidelines for use
• disbelief that the condition is treatable.

Given that treatment often is based on a 12-step approach, such as Alcoholics Anonymous (AA), providers might hesitate to prescribe medication for an illness that is thought to be managed through psychosocial interventions, such as group and motivational therapy.

Therapeutic options

Choice of medication depends on the prescriber’s comfort level, reputation of the medication, potential side-effect profile, medical contraindications, and affordability; the most important consideration, however, should be the overall goals and expectations of the patient.

There are 4 FDA-approved medications for AUD (Table); many others are off-label. It is advisable to start with an FDA-approved medication such as disulfiram for the motivated patient who has a collaborator and desires complete abstinence; naltrexone for a patient who wants to cut down on intake (a long-acting formulation can be used for poorly adherent patients); and acamprosate for a patient with at least some established sobriety who needs help with post-withdrawal sleep disturbances.

Psychosocial interventions

Medications are just 1 tool in recovery; patients should be engaged in a program of counseling. Encourage attendance at AA meetings. An up-and-coming concept is the use of smartphone applications to prevent relapse (or even induce remission); apps that provide an accurate blood alcohol tracking systems and integrated psychosocial therapies are in the pipeline. The novel Reddit online forum r/StopDrinking is a 24-hour peer-support community that relies on
fellowship, accountability, monitoring, and anonymity; the forum can compete with
motivational interviewing for efficacy in increasing abstinence and preventing relapse.

There is ample evidence in the medical literature, as well as clinical experience, that patients seeking help for chemical dependency benefit from pharmacotherapy. It is common, however, for physicians, patients, and family to balk at the idea. Even within the psychiatry community, where there should be better understanding of substance use disorders, many practitioners hesitate to employ medications, especially for alcohol use disorder (AUD).

Efficacy for such FDA-approved medications has been demonstrated in well-designed, randomized controlled trials, but many trainees, and even experienced professionals, have never seen these medications used effectively and appropriately. Medication-assisted treatment (MAT) is not an alternative to biopsychosocial approaches but is an augmentation that can (1) help stabilize the patient until he (she) can be educated in relapse prevention skills and (2) allow the brain to rewire and heal until he regains impulse control.

Diverse presentations

Do you remember that patient who often arrived for appointments intoxicated, promising that he plans to cut down? How about the man you saw in the emergency department with an elevated blood alcohol level, who was constantly endorsing suicidal thoughts that subsided when he reached clinical sobriety? What about the college student who often was treated for alcohol poisoning after binge drinking on weekends, but who never considered this behavior problematic? And, how about the elderly woman who was evaluated for anxiety, but had been drinking 4 beers nightly for the past 30 years?

Despite the diverse presentations, these patients all have a chronic disease and we fail them when we do not apply evidence-based medicine to their treatment.

As psychiatrists, we encounter many patients with AUD as a primary or comorbid diagnosis. This is a global problem associated with significant human and financial cost. With 80% of American adolescents having reported using alcohol in the past year, the problem will continue to grow.¹ Furthermore, a greater prevalence of AUD is noted in clinical populations undergoing psychiatric treatment.² Ongoing alcohol abuse complicates the course of medical and psychiatric conditions and incites significant societal exclusion.

Pharmacotherapy is underutilized

Despite an increase in the use of psychotropic medications for treating psychiatric illness, pharmacotherapy for AUD is under­utilized: only 3% of patients have received an FDA-approved treatment.^2,3 Nearly one-third of adults are affected by AUD during their lifetime, yet only 20% seek help.³ Management today remains limited to episodic, brief inpatient detoxification and psychosocial therapy.

Recovery rates are highest when addiction treatment that monitors abstinence is continuous; yet, for most part, alcohol addiction is treated in discrete episodes upon relapse. Although MAT is recommended by experts for “moderate” and “severe” substance use disorders, practitioners, in general, have demonstrated considerable resistance to using this modality as part of routine practice.^4,5 This is regrettable: Regardless of terminology used to describe their condition, these people suffer a potentially fatal disease characterized by high post-treatment recidivism.

Neuroscience supports the brain disease model of addiction, with neuro­plasticity changes being made during phases of drug use. Medications are shown to assist in preventing relapse while the brain is healing and normal emotional and decision-making capacities are being restored.⁶

Why hesitate to use pharmacotherapeutics?

There are diverse pharmacotherapeutic options that can be pursued for treating AUD with minimal disruption to home and work life. Alarmingly, many trainees have never prescribed or even considered such medications. Despite modest effect sizes in randomized controlled trials, efficacy has been demonstrated in reducing relapse rates and overall severity of drinking days.^4,5 So, from where does the ambivalence of patients and providers about using these treatments to achieve lasting recovery stem?

Starting MAT certainly requires both parties to be in agreement. A patient might decline medication because of a fear of dependence or because he overestimates his ability to achieve remission on his own. There also may be financial barriers in a current alcohol treatment system that is traditionally non-medically oriented. Prescribers also fail to offer medications because of:

• lack of familiarity with available agents
• absence of guidelines for use
• disbelief that the condition is treatable.

Given that treatment often is based on a 12-step approach, such as Alcoholics Anonymous (AA), providers might hesitate to prescribe medication for an illness that is thought to be managed through psychosocial interventions, such as group and motivational therapy.

Therapeutic options

Choice of medication depends on the prescriber’s comfort level, reputation of the medication, potential side-effect profile, medical contraindications, and affordability; the most important consideration, however, should be the overall goals and expectations of the patient.

There are 4 FDA-approved medications for AUD (Table); many others are off-label. It is advisable to start with an FDA-approved medication such as disulfiram for the motivated patient who has a collaborator and desires complete abstinence; naltrexone for a patient who wants to cut down on intake (a long-acting formulation can be used for poorly adherent patients); and acamprosate for a patient with at least some established sobriety who needs help with post-withdrawal sleep disturbances.

Psychosocial interventions

Medications are just 1 tool in recovery; patients should be engaged in a program of counseling. Encourage attendance at AA meetings. An up-and-coming concept is the use of smartphone applications to prevent relapse (or even induce remission); apps that provide an accurate blood alcohol tracking systems and integrated psychosocial therapies are in the pipeline. The novel Reddit online forum r/StopDrinking is a 24-hour peer-support community that relies on
fellowship, accountability, monitoring, and anonymity; the forum can compete with
motivational interviewing for efficacy in increasing abstinence and preventing relapse.

Despite staff and budget reductions, local health departments (LHDs) are finding ways to expand services in some areas, according to a survey by the National Association of County and City Health Officials (NACCHO). One-third of LHDs reported reducing services of at least 1 program area, such as immunization, diabetes screening, and high blood pressure screening. However, one-fourth said they were expanding population-based preventive programs for obesity, drug, alcohol, and tobacco.

The association has periodically surveyed LHDs since 2008 to assess the impact of the economic recession. In 2014, NACCHO renamed the survey “The Forces of Change” and expanded it to take in a wider range of factors. The 16-question online survey, distributed during January-February 2015, went to 948 LHDs in the U.S. (excluding Rhode Island and Hawaii, which have no LHDs), representing one-third of all LHDs. Of the 690 top executives who responded, 353 represented small, 271 medium, and 66 large LHDs.

Related: Meta-Analysis Examines Quality of VA Health Care

At the peak of budget cuts, in 2009, 45% reported budget decreases. Since then, about 1 in 4 LHDs is still reporting budget cuts compared with the previous year; 27% expect budget decreases to continue into the next year.

Since 2008, NACCHO says, 51,700 jobs have been lost. More than half the 3,400 lost in 2014 were due to attrition; the rest to layoffs. The number of lost jobs was “most marked” among large LHDs: Sixty-one percent of those reported at least 1 job lost, followed by 41% of medium and 26% of small LHDs.

Related: Pharmacists in the Emergency Department: Feasibility and Cost

For many LHDs, “the cumulative effects of budget cuts and job losses” have not been reversed as the economy recovered. Some are trying creative workarounds, such as collaborations with primary care providers (PCPs). For example, 61% report actively encouraging PCPs to use evidence-based public health services, such as interventions to reduce asthma triggers.

However, < 10% of LHDs were actively engaged in new systems of care with PCPs, such as State Innovation Models (multipayer health care payment and service delivery models), patient-centered medical homes, or accountable care organizations (networks of health care providers voluntarily responsible for providing coordinated care). And < 70% are engaged in or exploring partnerships with nonprofit hospitals, which NACCHO says “might benefit multiple stakeholders and the community at large.”

Related: Implementing the EQUiPPED Medication Management Program at 5 VA Emergency Departments

Despite staff and budget reductions, local health departments (LHDs) are finding ways to expand services in some areas, according to a survey by the National Association of County and City Health Officials (NACCHO). One-third of LHDs reported reducing services of at least 1 program area, such as immunization, diabetes screening, and high blood pressure screening. However, one-fourth said they were expanding population-based preventive programs for obesity, drug, alcohol, and tobacco.

The association has periodically surveyed LHDs since 2008 to assess the impact of the economic recession. In 2014, NACCHO renamed the survey “The Forces of Change” and expanded it to take in a wider range of factors. The 16-question online survey, distributed during January-February 2015, went to 948 LHDs in the U.S. (excluding Rhode Island and Hawaii, which have no LHDs), representing one-third of all LHDs. Of the 690 top executives who responded, 353 represented small, 271 medium, and 66 large LHDs.

Related: Meta-Analysis Examines Quality of VA Health Care

At the peak of budget cuts, in 2009, 45% reported budget decreases. Since then, about 1 in 4 LHDs is still reporting budget cuts compared with the previous year; 27% expect budget decreases to continue into the next year.

Since 2008, NACCHO says, 51,700 jobs have been lost. More than half the 3,400 lost in 2014 were due to attrition; the rest to layoffs. The number of lost jobs was “most marked” among large LHDs: Sixty-one percent of those reported at least 1 job lost, followed by 41% of medium and 26% of small LHDs.

Related: Pharmacists in the Emergency Department: Feasibility and Cost

For many LHDs, “the cumulative effects of budget cuts and job losses” have not been reversed as the economy recovered. Some are trying creative workarounds, such as collaborations with primary care providers (PCPs). For example, 61% report actively encouraging PCPs to use evidence-based public health services, such as interventions to reduce asthma triggers.

However, < 10% of LHDs were actively engaged in new systems of care with PCPs, such as State Innovation Models (multipayer health care payment and service delivery models), patient-centered medical homes, or accountable care organizations (networks of health care providers voluntarily responsible for providing coordinated care). And < 70% are engaged in or exploring partnerships with nonprofit hospitals, which NACCHO says “might benefit multiple stakeholders and the community at large.”

Related: Implementing the EQUiPPED Medication Management Program at 5 VA Emergency Departments

Despite staff and budget reductions, local health departments (LHDs) are finding ways to expand services in some areas, according to a survey by the National Association of County and City Health Officials (NACCHO). One-third of LHDs reported reducing services of at least 1 program area, such as immunization, diabetes screening, and high blood pressure screening. However, one-fourth said they were expanding population-based preventive programs for obesity, drug, alcohol, and tobacco.

The association has periodically surveyed LHDs since 2008 to assess the impact of the economic recession. In 2014, NACCHO renamed the survey “The Forces of Change” and expanded it to take in a wider range of factors. The 16-question online survey, distributed during January-February 2015, went to 948 LHDs in the U.S. (excluding Rhode Island and Hawaii, which have no LHDs), representing one-third of all LHDs. Of the 690 top executives who responded, 353 represented small, 271 medium, and 66 large LHDs.

Related: Meta-Analysis Examines Quality of VA Health Care

At the peak of budget cuts, in 2009, 45% reported budget decreases. Since then, about 1 in 4 LHDs is still reporting budget cuts compared with the previous year; 27% expect budget decreases to continue into the next year.

Since 2008, NACCHO says, 51,700 jobs have been lost. More than half the 3,400 lost in 2014 were due to attrition; the rest to layoffs. The number of lost jobs was “most marked” among large LHDs: Sixty-one percent of those reported at least 1 job lost, followed by 41% of medium and 26% of small LHDs.

Related: Pharmacists in the Emergency Department: Feasibility and Cost

For many LHDs, “the cumulative effects of budget cuts and job losses” have not been reversed as the economy recovered. Some are trying creative workarounds, such as collaborations with primary care providers (PCPs). For example, 61% report actively encouraging PCPs to use evidence-based public health services, such as interventions to reduce asthma triggers.

However, < 10% of LHDs were actively engaged in new systems of care with PCPs, such as State Innovation Models (multipayer health care payment and service delivery models), patient-centered medical homes, or accountable care organizations (networks of health care providers voluntarily responsible for providing coordinated care). And < 70% are engaged in or exploring partnerships with nonprofit hospitals, which NACCHO says “might benefit multiple stakeholders and the community at large.”

Related: Implementing the EQUiPPED Medication Management Program at 5 VA Emergency Departments

To demonstrate the impact of a structured peer mentorship program in a large size service-oriented hospitalist group with 71 full-time hospitalist and 21 full-time APPs serving a daily census of 400 patients, we piloted a structured peer mentorship project from June 2015 until December 2015 with 10 new hospitalist hires. Each new hire was paired with a senior hospitalist colleague for a total of four weeks over a period of two months and the outcomes were measured through a 10-question anonymous survey at the end of 90 days. The survey response rate was 80%. The questions pertained to the effectiveness of mentorship program, practice group culture orientation, adherence to high-yield patient satisfaction behaviors related to Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, work efficiency, job satisfaction, navigating through various hospital floors, efficient clinical staff communication, hand of care sign-out process, understanding of various hospitalist shifts and open-ended feedback.

Our results revealed that 100% of the new hires recommended to continue the on-boarding mentorship program on a permanent basis and 95% of the responses on the Likert scale were either very positive or positive. The total cost of the mentorship program was estimated to be 2-3 moon-lighting shifts ($2400-$3600) for the group. This cost was mainly associated with extra staffing needed during the first half of the shadowing week since the mentor was carrying half of the daily census. The marginal benefits of the program were far more and long lasting than the short-term cost. The program assisted in early acclimatization to the practice group culture, provider engagement and satisfaction and early productivity. It also has the potential to increase retention in a high-turnover hospitalist work field. We conclude that effective peer mentorship can play an important role in the organizational success of a large hospitalist program. Successful mentoring programs require proper understanding, planning, resource allocation, implementation and evaluation. From increased morale to increased productivity, the benefits are numerous. Mentoring is a tangible way to show employees that they are valued and that the organization’s future includes them.

— Muhammad Nabeel, MD, FACP, Clinical Assistant Professor, College of Human Medicine, Michigan State University, GRMEP; Hospitalist, Spectrum Health Medical Group, Grand Rapids, MI

— Rashelle Ludolph, MHA, MBA (Second Author), Director Operations, Acute Care Medicine, Spectrum Health Medical Group, Grand Rapids, MI

To demonstrate the impact of a structured peer mentorship program in a large size service-oriented hospitalist group with 71 full-time hospitalist and 21 full-time APPs serving a daily census of 400 patients, we piloted a structured peer mentorship project from June 2015 until December 2015 with 10 new hospitalist hires. Each new hire was paired with a senior hospitalist colleague for a total of four weeks over a period of two months and the outcomes were measured through a 10-question anonymous survey at the end of 90 days. The survey response rate was 80%. The questions pertained to the effectiveness of mentorship program, practice group culture orientation, adherence to high-yield patient satisfaction behaviors related to Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, work efficiency, job satisfaction, navigating through various hospital floors, efficient clinical staff communication, hand of care sign-out process, understanding of various hospitalist shifts and open-ended feedback.

Our results revealed that 100% of the new hires recommended to continue the on-boarding mentorship program on a permanent basis and 95% of the responses on the Likert scale were either very positive or positive. The total cost of the mentorship program was estimated to be 2-3 moon-lighting shifts ($2400-$3600) for the group. This cost was mainly associated with extra staffing needed during the first half of the shadowing week since the mentor was carrying half of the daily census. The marginal benefits of the program were far more and long lasting than the short-term cost. The program assisted in early acclimatization to the practice group culture, provider engagement and satisfaction and early productivity. It also has the potential to increase retention in a high-turnover hospitalist work field. We conclude that effective peer mentorship can play an important role in the organizational success of a large hospitalist program. Successful mentoring programs require proper understanding, planning, resource allocation, implementation and evaluation. From increased morale to increased productivity, the benefits are numerous. Mentoring is a tangible way to show employees that they are valued and that the organization’s future includes them.

— Muhammad Nabeel, MD, FACP, Clinical Assistant Professor, College of Human Medicine, Michigan State University, GRMEP; Hospitalist, Spectrum Health Medical Group, Grand Rapids, MI

— Rashelle Ludolph, MHA, MBA (Second Author), Director Operations, Acute Care Medicine, Spectrum Health Medical Group, Grand Rapids, MI

To demonstrate the impact of a structured peer mentorship program in a large size service-oriented hospitalist group with 71 full-time hospitalist and 21 full-time APPs serving a daily census of 400 patients, we piloted a structured peer mentorship project from June 2015 until December 2015 with 10 new hospitalist hires. Each new hire was paired with a senior hospitalist colleague for a total of four weeks over a period of two months and the outcomes were measured through a 10-question anonymous survey at the end of 90 days. The survey response rate was 80%. The questions pertained to the effectiveness of mentorship program, practice group culture orientation, adherence to high-yield patient satisfaction behaviors related to Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, work efficiency, job satisfaction, navigating through various hospital floors, efficient clinical staff communication, hand of care sign-out process, understanding of various hospitalist shifts and open-ended feedback.

Our results revealed that 100% of the new hires recommended to continue the on-boarding mentorship program on a permanent basis and 95% of the responses on the Likert scale were either very positive or positive. The total cost of the mentorship program was estimated to be 2-3 moon-lighting shifts ($2400-$3600) for the group. This cost was mainly associated with extra staffing needed during the first half of the shadowing week since the mentor was carrying half of the daily census. The marginal benefits of the program were far more and long lasting than the short-term cost. The program assisted in early acclimatization to the practice group culture, provider engagement and satisfaction and early productivity. It also has the potential to increase retention in a high-turnover hospitalist work field. We conclude that effective peer mentorship can play an important role in the organizational success of a large hospitalist program. Successful mentoring programs require proper understanding, planning, resource allocation, implementation and evaluation. From increased morale to increased productivity, the benefits are numerous. Mentoring is a tangible way to show employees that they are valued and that the organization’s future includes them.

— Muhammad Nabeel, MD, FACP, Clinical Assistant Professor, College of Human Medicine, Michigan State University, GRMEP; Hospitalist, Spectrum Health Medical Group, Grand Rapids, MI

— Rashelle Ludolph, MHA, MBA (Second Author), Director Operations, Acute Care Medicine, Spectrum Health Medical Group, Grand Rapids, MI

HSCT preparation

Photo by Chad McNeeley

BARCELONA—Results from 2 studies suggest an immunogene therapy can provide a clinical benefit in adults with high-risk hematologic malignancies undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT).

When compared to historical controls, patients who received the immunogene therapy, Zalmoxis, had lower rates of non-relapse mortality (NRM) and chronic graft-vs-host disease (GVHD), as well as improved overall survival (OS).

The only adverse event related to Zalmoxis was GVHD, which was resolved.

These data were presented at the EBMT International Transplant Course. The studies were funded by MolMed S.p.A., the company developing Zalmoxis.

About the therapy

Zalmoxis is a treatment consisting of allogeneic, genetically modified T cells. The cells are intended to be given to haplo-HSCT recipients to help fight off infection, enhance the success of the transplant, and support long-lasting anticancer effects.

Because the genetically modified T cells can also cause GVHD, they are equipped with a suicide gene, which makes them susceptible to treatment with ganciclovir or valganciclovir. So if a patient develops GVHD, he or she can receive ganciclovir/valganciclovir, which should kill the modified T cells and prevent further development of GVHD.

Trial data

The data presented at the EBMT International Transplant Course were from the phase 1/2 TK007 trial and the ongoing phase 3 TK008 trial.

The TK007 trial included haplo-HSCT recipients with various high-risk hematologic malignancies, while the TK008 trial is enrolling patients with high-risk acute leukemia who are undergoing haplo-HSCT.

Researchers have compared 37 Zalmoxis-treated patients from these trials to 140 contemporaneous control patients from the database of the EBMT registry.

Results of this pair-matched analysis showed an OS improvement in Zalmoxis-treated patients, which was driven by a reduction in NRM. The OS was 49% in the Zalmoxis group and 37% in controls (P=0.01), and the NRM was 22% and 43%, respectively (P=0.014).

Among controls dying from non-relapse causes, the majority (78%) died from either infection (56%) or GVHD (22%), while the only adverse event related to Zalmoxis treatment was GVHD. And this GVHD was fully resolved by activating the suicide-gene system with ganciclovir treatment, without any GVHD-related death.

Furthermore, the incidence of chronic GVHD was lower in Zalmoxis-treated patients than in controls—6% and 25%, respectively (P=0.04).

Therefore, the researchers concluded that the protective effects of Zalmoxis in controlling infection and GVHD mainly drove the decreased NRM in the Zalmoxis group.

These data supported the European Commission’s recent decision to grant conditional marketing authorization for Zalmoxis.

HSCT preparation

Photo by Chad McNeeley

BARCELONA—Results from 2 studies suggest an immunogene therapy can provide a clinical benefit in adults with high-risk hematologic malignancies undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT).

When compared to historical controls, patients who received the immunogene therapy, Zalmoxis, had lower rates of non-relapse mortality (NRM) and chronic graft-vs-host disease (GVHD), as well as improved overall survival (OS).

The only adverse event related to Zalmoxis was GVHD, which was resolved.

These data were presented at the EBMT International Transplant Course. The studies were funded by MolMed S.p.A., the company developing Zalmoxis.

About the therapy

Zalmoxis is a treatment consisting of allogeneic, genetically modified T cells. The cells are intended to be given to haplo-HSCT recipients to help fight off infection, enhance the success of the transplant, and support long-lasting anticancer effects.

Because the genetically modified T cells can also cause GVHD, they are equipped with a suicide gene, which makes them susceptible to treatment with ganciclovir or valganciclovir. So if a patient develops GVHD, he or she can receive ganciclovir/valganciclovir, which should kill the modified T cells and prevent further development of GVHD.

Trial data

The data presented at the EBMT International Transplant Course were from the phase 1/2 TK007 trial and the ongoing phase 3 TK008 trial.

The TK007 trial included haplo-HSCT recipients with various high-risk hematologic malignancies, while the TK008 trial is enrolling patients with high-risk acute leukemia who are undergoing haplo-HSCT.

Researchers have compared 37 Zalmoxis-treated patients from these trials to 140 contemporaneous control patients from the database of the EBMT registry.

Results of this pair-matched analysis showed an OS improvement in Zalmoxis-treated patients, which was driven by a reduction in NRM. The OS was 49% in the Zalmoxis group and 37% in controls (P=0.01), and the NRM was 22% and 43%, respectively (P=0.014).

Among controls dying from non-relapse causes, the majority (78%) died from either infection (56%) or GVHD (22%), while the only adverse event related to Zalmoxis treatment was GVHD. And this GVHD was fully resolved by activating the suicide-gene system with ganciclovir treatment, without any GVHD-related death.

Furthermore, the incidence of chronic GVHD was lower in Zalmoxis-treated patients than in controls—6% and 25%, respectively (P=0.04).

Therefore, the researchers concluded that the protective effects of Zalmoxis in controlling infection and GVHD mainly drove the decreased NRM in the Zalmoxis group.

These data supported the European Commission’s recent decision to grant conditional marketing authorization for Zalmoxis.

HSCT preparation

Photo by Chad McNeeley

BARCELONA—Results from 2 studies suggest an immunogene therapy can provide a clinical benefit in adults with high-risk hematologic malignancies undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT).

When compared to historical controls, patients who received the immunogene therapy, Zalmoxis, had lower rates of non-relapse mortality (NRM) and chronic graft-vs-host disease (GVHD), as well as improved overall survival (OS).

The only adverse event related to Zalmoxis was GVHD, which was resolved.

These data were presented at the EBMT International Transplant Course. The studies were funded by MolMed S.p.A., the company developing Zalmoxis.

About the therapy

Zalmoxis is a treatment consisting of allogeneic, genetically modified T cells. The cells are intended to be given to haplo-HSCT recipients to help fight off infection, enhance the success of the transplant, and support long-lasting anticancer effects.

Because the genetically modified T cells can also cause GVHD, they are equipped with a suicide gene, which makes them susceptible to treatment with ganciclovir or valganciclovir. So if a patient develops GVHD, he or she can receive ganciclovir/valganciclovir, which should kill the modified T cells and prevent further development of GVHD.

Trial data

The data presented at the EBMT International Transplant Course were from the phase 1/2 TK007 trial and the ongoing phase 3 TK008 trial.

The TK007 trial included haplo-HSCT recipients with various high-risk hematologic malignancies, while the TK008 trial is enrolling patients with high-risk acute leukemia who are undergoing haplo-HSCT.

Researchers have compared 37 Zalmoxis-treated patients from these trials to 140 contemporaneous control patients from the database of the EBMT registry.

Results of this pair-matched analysis showed an OS improvement in Zalmoxis-treated patients, which was driven by a reduction in NRM. The OS was 49% in the Zalmoxis group and 37% in controls (P=0.01), and the NRM was 22% and 43%, respectively (P=0.014).

Among controls dying from non-relapse causes, the majority (78%) died from either infection (56%) or GVHD (22%), while the only adverse event related to Zalmoxis treatment was GVHD. And this GVHD was fully resolved by activating the suicide-gene system with ganciclovir treatment, without any GVHD-related death.

Furthermore, the incidence of chronic GVHD was lower in Zalmoxis-treated patients than in controls—6% and 25%, respectively (P=0.04).

Therefore, the researchers concluded that the protective effects of Zalmoxis in controlling infection and GVHD mainly drove the decreased NRM in the Zalmoxis group.

These data supported the European Commission’s recent decision to grant conditional marketing authorization for Zalmoxis.