Applied Evidence

CASE A 37-year-old white woman presents for an employment physical. Your nurse reports that she also has a complaint of headaches, that she scored an 8 on the Alcohol Use Disorders identification Test-consumption (AUDiT-c), and that the result on her patient health Questionnaire (phQ-2) suggests a depressive disorder. You ask the patient whether she has served in the military and discover that, in the last 4 years, she served 2 year-long tours in Afghanistan with her Army reserve unit, returning home 6 months ago.  Since her return, she has lost her job due to chronic tardiness (sleeping through her alarm, she says) and admits she has “started drinking again.” Her visit with you this day is only to undergo the physical exam required by her new employer. What are your next steps with this patient? What resources can you use to help her?

As long as human beings have engaged in combat, there have often been extraordinarily damaging psychiatric1  injuries among those who survive. Combat survivability today is 84% to 90%, the highest in the history of armed conflict,^2,3 thanks to improvements in personal protective gear, vehicle armor, rapid casualty evacuation, and surgical resuscitation and stabilization that is “far forward” on the battlefield. These survivors are subsequently at high risk for a host of other medical conditions, which commonly include traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), depression, suicide, and substance abuse.^4-8 

Family physicians—both civilian and uniformed—may be the first to encounter these individuals. Of the more than 2.4 million US service members who have been deployed to Afghanistan or Iraq in support of Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF), nearly 60% are no longer on active duty.

Among this group, only half receive care from the US Department of Veterans Affairs (VA).⁹ Despite a concerted effort on the part of the Department of Defense (DoD) and the VA to develop and distribute effective, evidenced-based treatment protocols for veterans with combat-related conditions, major gaps remain in the care provided to combat veterans.¹⁰

This article seeks to help fill that gap by providing the information you need to recognize and treat common combat-related illness, as well as resources to help improve the quality of life for veterans and their families (TABLE 1).

Initial roadblocks to care

One of the biggest challenges in treating veterans with behavioral health issues is the fact that only 23% to 40% of those with mental illness seek care.¹¹ Among the reasons veterans have offered for avoiding behavioral health care are a fear of the stigma associated with mental illness, concern that treatment will negatively affect their career, lack of comfort with mental health professionals, and the perception that mental health treatment is a “last resort.”¹² Unfortunately, efforts by the DoD leadership to overcome these inherent biases have been largely unsuccessful¹³ and much work is still required to see that service members get the care they need.

Due to low rates of self-reporting, effective screening is essential. With this in mind, the DoD has implemented the deployment health assessment program (DHAP), which requires service members to be screened for common conditions within 60 days of deployment, within 30 days of returning, and again at 90 to 180 days after their return.

While the long-term effects of this program are yet to be determined, results to date are promising. Since the DHAP was implemented, there has been a significant decrease in occupationally impairing mental health problems and suicidal ideation requiring medical evacuation from a combat theater.¹⁴

FPs should begin with a simple question. Many of the 20+ million veterans living in the United States will not be wearing a uniform when they enter your office. Simply asking all of your patients, “Have you or a loved one ever served in the military?” may help you discover service-related questions or concerns.^15,16 Underscoring the importance of such screening is the recent decision by the American Academy of Family Physicians to partner with First Lady Michelle Obama and Dr. Jill Biden in a new campaign called “Joining Forces,” which aims to support veterans and their families.¹⁶

Mild traumatic brain injury: Common—though overlooked

A TBI is any temporary or permanent neurologic dysfunction after a blow to the head.^10,17 TBI is classified based on severity and mechanism (direct blow to the head or exposure to blast waves). Mild TBI (mTBI) is commonly referred to as a concussion and usually is not associated with loss of consciousness or altered mental status. Brain imaging results are also normal with mTBI. Severe TBI, on the other hand, is associated with prolonged loss of consciousness, altered mental status, and abnormal brain imaging results (TABLE 2).¹⁷

A unique obstacle to accurate evaluation in the field. It is important to emphasize that mTBI is a clinical diagnosis, and its detection requires honest patient communication. This can be problematic with motivated soldiers who are anxious to continue the mission and fear that any admission of symptoms might delay a return to their unit. As with a concussed athlete eager to return to the field of play, the clinical diagnosis of mTBI requires a high index of clinical suspicion and constant vigilance by the health care provider. Despite being the most common combat- related injury, mTBI is often overlooked due to the absence of obvious physical injuries.⁴ Recent data suggest that 28% to 60% of ser- vice members evacuated from combat have a TBI. Most of these injuries (77%) are mTBI.^18-20 Improved personal protective equipment (including Kevlar helmets and body armor) and the high number of blast-related injuries are likely responsible for the high incidence of mTBI among OEF/OIF veterans.^8,21,22 The prevalence of mTBI among service members not evacuated is estimated to be 20% to 30%.²⁰ Veterans with non–cancer-related pain who are treated with opioid analgesics have an increased risk of adverse clinical outcomes compared with those not treated with opioids.

Symptoms can persist. Most patients with mTBI completely recover within 30 days of the injury. Unfortunately, 10% to 15% of mTBI patients develop chronic problems lasting months to years.⁴ Residual symptoms most commonly include headache, irritability, depression, sleep disturbance, impaired reasoning, memory problems, and difficulty concentrating. These symptoms are not unique to mTBI and overlap with comorbid combat diagnoses like PTSD, depression, and sleep deprivation.¹⁰ The following tools can help physicians determine whether mTBI is present.

Checking for possible mtBi. In the field, patients with possible mTBI can be screened rapidly using the Military Acute Concussion Evaluation (MACE, found at www.dvbic.org), a modification of the validated and widely used Sideline Assessment of Concussion (SAC) tool. More challenging is evaluating potential mTBI patients who present weeks or months after a traumatic event, for which there are no simple confirmatory tests. In this event, conduct a thorough neurological evaluation that includes vestibular, vision, postural, and neurocognitive assessments. For patients with persistent symptoms or possible anatomic brain abnormalities, magnetic resonance imaging (MRI) is the imaging modality of choice. Patients with complications or a questionable diagnosis are best managed in consultation with a neurologist.

Initial treatment of mtBi is symptom-based. When practical, try nonpharmacologic interventions first (TABLE 3).¹⁰ In particular, have the patient avoid further high-risk exposures that could lead to second impact syndrome (an issue increasingly recognized in contact sports). Also critical are physical and cognitive rest and the restoration of sleep until the patient is completely asymptomatic.

If the patient exhibits irritability and depression, selective serotonin reuptake inhibitors (SSRIs) are first-line treatment. Avoid narcotics and sedative-hypnotic sleep medications if treating comorbidities such as pain and sleep deprivation. The VA/DoD guideline on managing concussion and mTBI provides additional detailed, evidence-based treatment recommendations.¹⁷

Reliving the horror again and again: PTSD

PTSD is a persistent and, at times, debilitating clinical syndrome that develops after exposure to a psychologically traumatic event. It’s the second most common illness among OEF/OIF combat veterans, with an estimated prevalence of 3% to 20%, a finding consistent with prior wars.^6,23-25 In the case of combat veterans, the inciting event usually involves an actual or perceived risk of death or serious injury. The individual’s response to the event involves intense fear, helplessness, or horror. The traumatic event is persistently re-experienced through intrusive and disturbing recollections or dreams that cause intense psychological distress. This, in turn, leads to a state of persistent sympathetic arousal. As symptoms are often triggered by specific cues, individuals with PTSD actively seek to avoid thoughts, situations, or stimuli associated with the event.^23,26

Symptoms commonly associated with PTSD include difficulty falling or staying asleep, recurrent nightmares, hypervigilance, and an exaggerated startle response. Individuals with PTSD also have a poorer sense of well-being, a higher rate of work absenteeism, and significantly more somatic complaints than age-matched peers.²⁷ For symptoms to be attributable to PTSD, their onset must follow a recent inciting event and must also cause clinically significant distress or impairment in social, occupational, or other areas of daily living. Common comorbid illnesses include mTBI, depression, and substance abuse. As with mTBI, the presence of multiple comorbidities in patients with PTSD can complicate evaluation, diagnosis, and treatment.

Diagnosis. PTSD is subdivided into acute (symptoms lasting more than one month but less than 3 months after the traumatic event) and chronic (symptoms lasting longer than 3 months after the traumatic event).²⁸ The distinction of acute or chronic does not affect treatment, but it is useful information for the patient to have regarding prognosis and eventual outcome. Like mTBI, PTSD is a clinical diagnosis made only after a thorough, structured diagnostic interview. The use of a validated, self-administered checklist, such as the Post-Traumatic Checklist-Military (PCL-M), allows for an efficient review of a patient’s symptoms and a reliable way to track treatment progress (http://www.ptsd.va.gov/professional/ pages/assessments/ptsd-checklist.asp).

Treatment Options. Effective evidence-based treatments for PTSD are cognitive behavioral therapy, eye movement desensitization and reprocessing (EMDR), and pharmacotherapy. SSRIs and serotonin- norepinephrine reuptake inhibitors (SNRIs) have the strongest evidence for pharmacologic benefit in the treatment of PTSD.^28,29 Other helpful medications are prazosin for nightmares and trazodone for sleep. Family physicians can use these medications as part of a patient-centered collaboration with the rest of the integrated care team, to offer the best chance for treatment success.^10,28,30

Depression: Vets are reluctant to self-report

Combat experience is a significant risk factor for major depression. Estimates of the lifetime prevalence of depression in the general US population vary from 9% to 25% in women and 5% to 12% in men. By contrast, the prevalence of depression in OIF/OEF veterans ranges from 2% to 37%.^24,31,32

Screening can yield false negatives. Many combat veterans are reluctant to self-report behavioral conditions, including depression. Screening, therefore, is important to identify potential depression and allow for intervention. Validated screening tools for depression include the PHQ-2 and PHQ-9, which are easy to use in the office setting. (See http://www.cqaimh.org/pdf/ tool_phq2.pdf [PHQ-2] and http://www. integration.samhsa.gov/images/res/ PHQ%20-%20Questions.pdf [PHQ-9]). Importantly, some veterans will have a negative depression screen on return from deployment, and then test positive 6 to 12 months later.²⁴ The complicated relationship between substance abuse and behavioral health reinforces the need for screening, early diagnosis, and a multidisciplinary approach to treatment.Explanations for the early false-negative results include the excitement of being home and patients intentionally answering questions inaccurately to avoid excessive screening at their home base.¹¹

Treatment is most effective with a combination approach. As with most cases of depression, combining psychotherapy and psychopharmacology appears to be most effective for treating depression related to combat experience.^33,34 While SSRIs and SNRIs are typical first-line pharmacologic agents, combat veterans often have comorbid mTBI, PTSD, or substance abuse issues that may influence the initial choice of therapy³⁵ (TABLE 3).¹⁰

Suicide is on the rise in the military

Historically, the incidence of suicide has been 25% lower in military personnel than in civilian peers.³⁶ However, between 2005 and 2009, the incidence of suicide in the Marine Corps and Army almost doubled.³⁷ While the exact reasons remain unknown, it is likely due to prolonged and repeated deployments to a combat environment.¹² While the incidence of suicide has been particularly high in the Army (22 per 100,000 active-duty and reserve personnel per year), all services have been affected. In fact, since 2009, the number of suicides among active duty service members exceeds those killed in action.³⁷

Consider all veterans to be at risk for suicide, and screen accordingly. An effective screening tool is the Columbia-Suicide Severity Rating Scale (C-SSRS), which is able to predict those most at risk for an impending suicide attempt.³⁴ Service members identified as high risk for suicide require unhindered access to care. The VA has worked to improve access to care and provide evidence-based point-of-care treatment strategies.³⁸ Available resources can be found in TABLE 1.

Unfortunately, even with effective screening and treatment, not all suicides can be prevented. Studies have demonstrated that approximately 65% of service members who commit suicide had no known history of communicating their suicidal intent. Since 2009, the number of suicides among active duty service members exceeds those killed in action.Sadly, 25% of service members who committed suicide had seen a mental health provider within the previous 30 days.³⁹

Alcohol abuse is common; opioids present a unique risk

Excessive use of alcohol and recreational and prescription drugs is common among OEF/ OIF veterans, especially those with comorbid mental health disorders. Retrospective cross-sectional studies show that 11% to 20% of OEF/OIF veterans met DSM-IV-TR diagnostic criteria for substance use disorders.^40-42 At highest risk are single enlisted men under the age of 24 in the Army or Marine Corps who serve in a combat-specific capacity. Interestingly, the prevalence of substance use disorders among OEF/OIF veterans closely mirrors that reported in epidemiologic studies of Vietnam veterans (11%-14%).⁴¹ This similarity, combined with the 39% lifetime prevalence of substance use disorders among Vietnam veterans, may foreshadow a similar lifetime prevalence of substance use disorders among OEF/OIF veterans.⁴¹

Most-abused substances. Alcohol is the most commonly abused substance among OEF/OIF veterans (10%-20%).^40,41,43-45 Other abused substances include opioids (prescribed or illicitly obtained), synthetic marijuana (“Spice” and “K2”), and “bath salts” (synthetic stimulants) (W.M. Sauve, MD, personal communication, August 27, 2012).

OEF/OIF veterans seem to be at particular risk for developing problems related to opioid use. A 2012 retrospective cohort study showed that veterans with non–cancer- related pain diagnoses treated with opioid analgesics had an increased risk for adverse clinical outcomes compared with those not treated with opioid analgesics (9.5% vs 4.1%; relative risk [RR]=2.33; 95% confidence interval [CI], 2.20-2.46). These outcomes included traumatic accidents, overdoses, self-inflicted injuries, and injuries related to violence. This study also demonstrated that, compared with veterans without mental illness, veterans with mental illness (particularly PTSD) and non–cancer-related pain were significantly more likely to receive opioids to treat their pain and had a higher risk of adverse clinical outcomes, including overdose.^46,47

Recreational use of synthetic marijuana and “bath salts” has increased in recent years. These substances are commonly labeled “not for human consumption,” which allows them to remain outside US Food and Drug Administration (FDA) regulation and be sold legally in the United States. Efforts to prohibit the sale or possession of these drugs, including the Federal Synthetic Bath Salt Ban in 2012, have fallen short, often due to creative product ”re-engineering.”³³ Synthetic marijuana and stimulants are inexpensive, readily available, and perceived by users to be safe. Health care providers are often unaware that their patients are using these products. Adverse health outcomes associated with the use of these synthetic drugs include memory loss, depression, and psychosis.

These alcohol and drug screens can help
One efficient screening tool to identify veterans at risk for alcohol abuse is the AUDIT-C, developed by the World Health Organization. This brief 3-question test identifies past-year hazardous drinking and alcohol abuse or dependence with >79% sensitivity and >56% specificity in male veterans, and >66% sensitivity and >87% specificity in female veterans. These numbers are similar to those provided by the full 10-question AUDIT.^48,49 The Drug Abuse Screen Test-10 (DAST-10) provides a similar screening instrument for other substances. Condensed from the original DAST-28 instrument, the DAST-10 identifies high-risk substance abuse with 74% to 94% sensitivity and 68% to 88% specificity.³

Screen for comorbidities. When you see veterans with a diagnosis of substance abuse, also evaluate for comorbid disease. Most veterans with substance use disorders (82%-93%) have at least one other mental health diagnosis (a 45% greater risk than that of civilians with substance abuse disorders),⁵⁰ most commonly PTSD, depression, anxiety, and adjustment disorders.^41,44,45 A number of hypotheses exist to explain the association between substance use disorders and other mental health diagnoses (“dual diagnoses”). The prevailing theory, in both veteran and civilian populations, is that substance abuse is an attempt to self-treat mental illness. Other evidence suggests that substance abuse promotes the development of mental illness, either by leading to a higher risk for traumatic experiences (increasing the chance of developing PTSD) or through a direct biochemical mechanism. Finally, con- current substance use disorder and mental illness may be due to an undefined genetic or biological vulnerability.^38,44 This complicated relationship between substance abuse and behavioral health reinforces the need for screening, early diagnosis, and a comprehensive, multidisciplinary approach to treatment.

Treatment options. Office-based treatment options for narcotic and alcohol abuse and dependency are available to family physicians. Methadone has been used since the 1950s to treat opioid addiction and remains one of the mainstays of outpatient treatment.^47,51 Originally, methadone was restricted to detoxification and maintenance treatment in narcotic addiction treatment programs approved by the FDA. In 1976, this restriction was lifted, and all physicians registered with the Drug Enforcement Agency (DEA) were permitted to prescribe methadone for analgesia.

In 2002, the FDA approved buprenorphine monotherapy and the combination product buprenorphine/naloxone for the treatment of opioid addiction. The prescribing of buprenorphine products requires physicians to undergo extra training, declare to the DEA their intent to prescribe buprenorphine, and obtain a special DEA identification number.^52,53 Physicians interested in finding out more about buprenorphine treatment and prescribing requirements can go to the Substance Abuse and Mental Health Services Administration (SAMHSA) Web page at http://samhsa.gov.

Naltrexone is an opioid receptor agonist that is used primarily to treat alcohol dependency, and is thought to work by reducing the craving for alcohol. Multiple studies have proven the efficacy of naltrexone in an outpatient setting when used alone or in combination with psychotherapy.^54,55 If you are uncomfortable or unfamiliar with the use or prescribing of these medications, referral to a substance abuse clinic specializing in dual-diagnosis treatment (TABLE 1) may offer optimal outcomes for patients with substance abuse disorders and other mental illness.

Cognitive behavioral therapy—including coping skills training, relapse prevention, contingency management, and behavioral couples’ therapy—and 12-step treatment programs are evidence-based options for the treatment of substance abuse disorders. Behavioral counseling interventions in the primary care setting (typically lasting 5-15 minutes) result in decreases in alcohol consumption, heavy drinking episodes, drinking above recommended amounts, and the number of days spent in the hospital, but have not been demonstrated to affect mortality, alcohol-related liver problems, outpatient visits, legal problems, or quality of life.⁵⁶ Resources can be found at www.niaaa.nih.gov. For patients with dual diagnoses, it is not yet known whether sequential therapy (in which substance abuse is treated first, followed by treatment of the comorbid mental illness) or concurrent therapy results in better outcomes.⁵⁷

CASE Your patient’s history of recent combat service, acknowledgement of employment and behavioral difficulties, and initial screening results lead you to diagnose alcoholism and depression. Additionally, she denies any suicidal ideation, but admits to experimenting with synthetic marijuana. After some discussion, she agrees to see your clinic’s social worker, and you start her on an SSri with scheduled follow-up.

CORRESPONDENCE
Shawn Kane, MD, USASoc, Attn: Surgeon (AomD), 2929 Desert Storm Drive, Ft. Bragg, NC 28310, or PO Box 3639 Pinehurst, NC 28374; [email protected]

CASE A 37-year-old white woman presents for an employment physical. Your nurse reports that she also has a complaint of headaches, that she scored an 8 on the Alcohol Use Disorders identification Test-consumption (AUDiT-c), and that the result on her patient health Questionnaire (phQ-2) suggests a depressive disorder. You ask the patient whether she has served in the military and discover that, in the last 4 years, she served 2 year-long tours in Afghanistan with her Army reserve unit, returning home 6 months ago.  Since her return, she has lost her job due to chronic tardiness (sleeping through her alarm, she says) and admits she has “started drinking again.” Her visit with you this day is only to undergo the physical exam required by her new employer. What are your next steps with this patient? What resources can you use to help her?

As long as human beings have engaged in combat, there have often been extraordinarily damaging psychiatric1  injuries among those who survive. Combat survivability today is 84% to 90%, the highest in the history of armed conflict,^2,3 thanks to improvements in personal protective gear, vehicle armor, rapid casualty evacuation, and surgical resuscitation and stabilization that is “far forward” on the battlefield. These survivors are subsequently at high risk for a host of other medical conditions, which commonly include traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), depression, suicide, and substance abuse.^4-8 

Family physicians—both civilian and uniformed—may be the first to encounter these individuals. Of the more than 2.4 million US service members who have been deployed to Afghanistan or Iraq in support of Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF), nearly 60% are no longer on active duty.

Among this group, only half receive care from the US Department of Veterans Affairs (VA).⁹ Despite a concerted effort on the part of the Department of Defense (DoD) and the VA to develop and distribute effective, evidenced-based treatment protocols for veterans with combat-related conditions, major gaps remain in the care provided to combat veterans.¹⁰

This article seeks to help fill that gap by providing the information you need to recognize and treat common combat-related illness, as well as resources to help improve the quality of life for veterans and their families (TABLE 1).

Initial roadblocks to care

One of the biggest challenges in treating veterans with behavioral health issues is the fact that only 23% to 40% of those with mental illness seek care.¹¹ Among the reasons veterans have offered for avoiding behavioral health care are a fear of the stigma associated with mental illness, concern that treatment will negatively affect their career, lack of comfort with mental health professionals, and the perception that mental health treatment is a “last resort.”¹² Unfortunately, efforts by the DoD leadership to overcome these inherent biases have been largely unsuccessful¹³ and much work is still required to see that service members get the care they need.

Due to low rates of self-reporting, effective screening is essential. With this in mind, the DoD has implemented the deployment health assessment program (DHAP), which requires service members to be screened for common conditions within 60 days of deployment, within 30 days of returning, and again at 90 to 180 days after their return.

While the long-term effects of this program are yet to be determined, results to date are promising. Since the DHAP was implemented, there has been a significant decrease in occupationally impairing mental health problems and suicidal ideation requiring medical evacuation from a combat theater.¹⁴

FPs should begin with a simple question. Many of the 20+ million veterans living in the United States will not be wearing a uniform when they enter your office. Simply asking all of your patients, “Have you or a loved one ever served in the military?” may help you discover service-related questions or concerns.^15,16 Underscoring the importance of such screening is the recent decision by the American Academy of Family Physicians to partner with First Lady Michelle Obama and Dr. Jill Biden in a new campaign called “Joining Forces,” which aims to support veterans and their families.¹⁶

Mild traumatic brain injury: Common—though overlooked

A TBI is any temporary or permanent neurologic dysfunction after a blow to the head.^10,17 TBI is classified based on severity and mechanism (direct blow to the head or exposure to blast waves). Mild TBI (mTBI) is commonly referred to as a concussion and usually is not associated with loss of consciousness or altered mental status. Brain imaging results are also normal with mTBI. Severe TBI, on the other hand, is associated with prolonged loss of consciousness, altered mental status, and abnormal brain imaging results (TABLE 2).¹⁷

A unique obstacle to accurate evaluation in the field. It is important to emphasize that mTBI is a clinical diagnosis, and its detection requires honest patient communication. This can be problematic with motivated soldiers who are anxious to continue the mission and fear that any admission of symptoms might delay a return to their unit. As with a concussed athlete eager to return to the field of play, the clinical diagnosis of mTBI requires a high index of clinical suspicion and constant vigilance by the health care provider. Despite being the most common combat- related injury, mTBI is often overlooked due to the absence of obvious physical injuries.⁴ Recent data suggest that 28% to 60% of ser- vice members evacuated from combat have a TBI. Most of these injuries (77%) are mTBI.^18-20 Improved personal protective equipment (including Kevlar helmets and body armor) and the high number of blast-related injuries are likely responsible for the high incidence of mTBI among OEF/OIF veterans.^8,21,22 The prevalence of mTBI among service members not evacuated is estimated to be 20% to 30%.²⁰ Veterans with non–cancer-related pain who are treated with opioid analgesics have an increased risk of adverse clinical outcomes compared with those not treated with opioids.

Symptoms can persist. Most patients with mTBI completely recover within 30 days of the injury. Unfortunately, 10% to 15% of mTBI patients develop chronic problems lasting months to years.⁴ Residual symptoms most commonly include headache, irritability, depression, sleep disturbance, impaired reasoning, memory problems, and difficulty concentrating. These symptoms are not unique to mTBI and overlap with comorbid combat diagnoses like PTSD, depression, and sleep deprivation.¹⁰ The following tools can help physicians determine whether mTBI is present.

Checking for possible mtBi. In the field, patients with possible mTBI can be screened rapidly using the Military Acute Concussion Evaluation (MACE, found at www.dvbic.org), a modification of the validated and widely used Sideline Assessment of Concussion (SAC) tool. More challenging is evaluating potential mTBI patients who present weeks or months after a traumatic event, for which there are no simple confirmatory tests. In this event, conduct a thorough neurological evaluation that includes vestibular, vision, postural, and neurocognitive assessments. For patients with persistent symptoms or possible anatomic brain abnormalities, magnetic resonance imaging (MRI) is the imaging modality of choice. Patients with complications or a questionable diagnosis are best managed in consultation with a neurologist.

Initial treatment of mtBi is symptom-based. When practical, try nonpharmacologic interventions first (TABLE 3).¹⁰ In particular, have the patient avoid further high-risk exposures that could lead to second impact syndrome (an issue increasingly recognized in contact sports). Also critical are physical and cognitive rest and the restoration of sleep until the patient is completely asymptomatic.

If the patient exhibits irritability and depression, selective serotonin reuptake inhibitors (SSRIs) are first-line treatment. Avoid narcotics and sedative-hypnotic sleep medications if treating comorbidities such as pain and sleep deprivation. The VA/DoD guideline on managing concussion and mTBI provides additional detailed, evidence-based treatment recommendations.¹⁷

Reliving the horror again and again: PTSD

PTSD is a persistent and, at times, debilitating clinical syndrome that develops after exposure to a psychologically traumatic event. It’s the second most common illness among OEF/OIF combat veterans, with an estimated prevalence of 3% to 20%, a finding consistent with prior wars.^6,23-25 In the case of combat veterans, the inciting event usually involves an actual or perceived risk of death or serious injury. The individual’s response to the event involves intense fear, helplessness, or horror. The traumatic event is persistently re-experienced through intrusive and disturbing recollections or dreams that cause intense psychological distress. This, in turn, leads to a state of persistent sympathetic arousal. As symptoms are often triggered by specific cues, individuals with PTSD actively seek to avoid thoughts, situations, or stimuli associated with the event.^23,26

Symptoms commonly associated with PTSD include difficulty falling or staying asleep, recurrent nightmares, hypervigilance, and an exaggerated startle response. Individuals with PTSD also have a poorer sense of well-being, a higher rate of work absenteeism, and significantly more somatic complaints than age-matched peers.²⁷ For symptoms to be attributable to PTSD, their onset must follow a recent inciting event and must also cause clinically significant distress or impairment in social, occupational, or other areas of daily living. Common comorbid illnesses include mTBI, depression, and substance abuse. As with mTBI, the presence of multiple comorbidities in patients with PTSD can complicate evaluation, diagnosis, and treatment.

Diagnosis. PTSD is subdivided into acute (symptoms lasting more than one month but less than 3 months after the traumatic event) and chronic (symptoms lasting longer than 3 months after the traumatic event).²⁸ The distinction of acute or chronic does not affect treatment, but it is useful information for the patient to have regarding prognosis and eventual outcome. Like mTBI, PTSD is a clinical diagnosis made only after a thorough, structured diagnostic interview. The use of a validated, self-administered checklist, such as the Post-Traumatic Checklist-Military (PCL-M), allows for an efficient review of a patient’s symptoms and a reliable way to track treatment progress (http://www.ptsd.va.gov/professional/ pages/assessments/ptsd-checklist.asp).

Treatment Options. Effective evidence-based treatments for PTSD are cognitive behavioral therapy, eye movement desensitization and reprocessing (EMDR), and pharmacotherapy. SSRIs and serotonin- norepinephrine reuptake inhibitors (SNRIs) have the strongest evidence for pharmacologic benefit in the treatment of PTSD.^28,29 Other helpful medications are prazosin for nightmares and trazodone for sleep. Family physicians can use these medications as part of a patient-centered collaboration with the rest of the integrated care team, to offer the best chance for treatment success.^10,28,30

Depression: Vets are reluctant to self-report

Combat experience is a significant risk factor for major depression. Estimates of the lifetime prevalence of depression in the general US population vary from 9% to 25% in women and 5% to 12% in men. By contrast, the prevalence of depression in OIF/OEF veterans ranges from 2% to 37%.^24,31,32

Screening can yield false negatives. Many combat veterans are reluctant to self-report behavioral conditions, including depression. Screening, therefore, is important to identify potential depression and allow for intervention. Validated screening tools for depression include the PHQ-2 and PHQ-9, which are easy to use in the office setting. (See http://www.cqaimh.org/pdf/ tool_phq2.pdf [PHQ-2] and http://www. integration.samhsa.gov/images/res/ PHQ%20-%20Questions.pdf [PHQ-9]). Importantly, some veterans will have a negative depression screen on return from deployment, and then test positive 6 to 12 months later.²⁴ The complicated relationship between substance abuse and behavioral health reinforces the need for screening, early diagnosis, and a multidisciplinary approach to treatment.Explanations for the early false-negative results include the excitement of being home and patients intentionally answering questions inaccurately to avoid excessive screening at their home base.¹¹

Treatment is most effective with a combination approach. As with most cases of depression, combining psychotherapy and psychopharmacology appears to be most effective for treating depression related to combat experience.^33,34 While SSRIs and SNRIs are typical first-line pharmacologic agents, combat veterans often have comorbid mTBI, PTSD, or substance abuse issues that may influence the initial choice of therapy³⁵ (TABLE 3).¹⁰

Suicide is on the rise in the military

Historically, the incidence of suicide has been 25% lower in military personnel than in civilian peers.³⁶ However, between 2005 and 2009, the incidence of suicide in the Marine Corps and Army almost doubled.³⁷ While the exact reasons remain unknown, it is likely due to prolonged and repeated deployments to a combat environment.¹² While the incidence of suicide has been particularly high in the Army (22 per 100,000 active-duty and reserve personnel per year), all services have been affected. In fact, since 2009, the number of suicides among active duty service members exceeds those killed in action.³⁷

Consider all veterans to be at risk for suicide, and screen accordingly. An effective screening tool is the Columbia-Suicide Severity Rating Scale (C-SSRS), which is able to predict those most at risk for an impending suicide attempt.³⁴ Service members identified as high risk for suicide require unhindered access to care. The VA has worked to improve access to care and provide evidence-based point-of-care treatment strategies.³⁸ Available resources can be found in TABLE 1.

Unfortunately, even with effective screening and treatment, not all suicides can be prevented. Studies have demonstrated that approximately 65% of service members who commit suicide had no known history of communicating their suicidal intent. Since 2009, the number of suicides among active duty service members exceeds those killed in action.Sadly, 25% of service members who committed suicide had seen a mental health provider within the previous 30 days.³⁹

Alcohol abuse is common; opioids present a unique risk

Excessive use of alcohol and recreational and prescription drugs is common among OEF/ OIF veterans, especially those with comorbid mental health disorders. Retrospective cross-sectional studies show that 11% to 20% of OEF/OIF veterans met DSM-IV-TR diagnostic criteria for substance use disorders.^40-42 At highest risk are single enlisted men under the age of 24 in the Army or Marine Corps who serve in a combat-specific capacity. Interestingly, the prevalence of substance use disorders among OEF/OIF veterans closely mirrors that reported in epidemiologic studies of Vietnam veterans (11%-14%).⁴¹ This similarity, combined with the 39% lifetime prevalence of substance use disorders among Vietnam veterans, may foreshadow a similar lifetime prevalence of substance use disorders among OEF/OIF veterans.⁴¹

Most-abused substances. Alcohol is the most commonly abused substance among OEF/OIF veterans (10%-20%).^40,41,43-45 Other abused substances include opioids (prescribed or illicitly obtained), synthetic marijuana (“Spice” and “K2”), and “bath salts” (synthetic stimulants) (W.M. Sauve, MD, personal communication, August 27, 2012).

OEF/OIF veterans seem to be at particular risk for developing problems related to opioid use. A 2012 retrospective cohort study showed that veterans with non–cancer- related pain diagnoses treated with opioid analgesics had an increased risk for adverse clinical outcomes compared with those not treated with opioid analgesics (9.5% vs 4.1%; relative risk [RR]=2.33; 95% confidence interval [CI], 2.20-2.46). These outcomes included traumatic accidents, overdoses, self-inflicted injuries, and injuries related to violence. This study also demonstrated that, compared with veterans without mental illness, veterans with mental illness (particularly PTSD) and non–cancer-related pain were significantly more likely to receive opioids to treat their pain and had a higher risk of adverse clinical outcomes, including overdose.^46,47

Recreational use of synthetic marijuana and “bath salts” has increased in recent years. These substances are commonly labeled “not for human consumption,” which allows them to remain outside US Food and Drug Administration (FDA) regulation and be sold legally in the United States. Efforts to prohibit the sale or possession of these drugs, including the Federal Synthetic Bath Salt Ban in 2012, have fallen short, often due to creative product ”re-engineering.”³³ Synthetic marijuana and stimulants are inexpensive, readily available, and perceived by users to be safe. Health care providers are often unaware that their patients are using these products. Adverse health outcomes associated with the use of these synthetic drugs include memory loss, depression, and psychosis.

These alcohol and drug screens can help
One efficient screening tool to identify veterans at risk for alcohol abuse is the AUDIT-C, developed by the World Health Organization. This brief 3-question test identifies past-year hazardous drinking and alcohol abuse or dependence with >79% sensitivity and >56% specificity in male veterans, and >66% sensitivity and >87% specificity in female veterans. These numbers are similar to those provided by the full 10-question AUDIT.^48,49 The Drug Abuse Screen Test-10 (DAST-10) provides a similar screening instrument for other substances. Condensed from the original DAST-28 instrument, the DAST-10 identifies high-risk substance abuse with 74% to 94% sensitivity and 68% to 88% specificity.³

Screen for comorbidities. When you see veterans with a diagnosis of substance abuse, also evaluate for comorbid disease. Most veterans with substance use disorders (82%-93%) have at least one other mental health diagnosis (a 45% greater risk than that of civilians with substance abuse disorders),⁵⁰ most commonly PTSD, depression, anxiety, and adjustment disorders.^41,44,45 A number of hypotheses exist to explain the association between substance use disorders and other mental health diagnoses (“dual diagnoses”). The prevailing theory, in both veteran and civilian populations, is that substance abuse is an attempt to self-treat mental illness. Other evidence suggests that substance abuse promotes the development of mental illness, either by leading to a higher risk for traumatic experiences (increasing the chance of developing PTSD) or through a direct biochemical mechanism. Finally, con- current substance use disorder and mental illness may be due to an undefined genetic or biological vulnerability.^38,44 This complicated relationship between substance abuse and behavioral health reinforces the need for screening, early diagnosis, and a comprehensive, multidisciplinary approach to treatment.

Treatment options. Office-based treatment options for narcotic and alcohol abuse and dependency are available to family physicians. Methadone has been used since the 1950s to treat opioid addiction and remains one of the mainstays of outpatient treatment.^47,51 Originally, methadone was restricted to detoxification and maintenance treatment in narcotic addiction treatment programs approved by the FDA. In 1976, this restriction was lifted, and all physicians registered with the Drug Enforcement Agency (DEA) were permitted to prescribe methadone for analgesia.

In 2002, the FDA approved buprenorphine monotherapy and the combination product buprenorphine/naloxone for the treatment of opioid addiction. The prescribing of buprenorphine products requires physicians to undergo extra training, declare to the DEA their intent to prescribe buprenorphine, and obtain a special DEA identification number.^52,53 Physicians interested in finding out more about buprenorphine treatment and prescribing requirements can go to the Substance Abuse and Mental Health Services Administration (SAMHSA) Web page at http://samhsa.gov.

Naltrexone is an opioid receptor agonist that is used primarily to treat alcohol dependency, and is thought to work by reducing the craving for alcohol. Multiple studies have proven the efficacy of naltrexone in an outpatient setting when used alone or in combination with psychotherapy.^54,55 If you are uncomfortable or unfamiliar with the use or prescribing of these medications, referral to a substance abuse clinic specializing in dual-diagnosis treatment (TABLE 1) may offer optimal outcomes for patients with substance abuse disorders and other mental illness.

Cognitive behavioral therapy—including coping skills training, relapse prevention, contingency management, and behavioral couples’ therapy—and 12-step treatment programs are evidence-based options for the treatment of substance abuse disorders. Behavioral counseling interventions in the primary care setting (typically lasting 5-15 minutes) result in decreases in alcohol consumption, heavy drinking episodes, drinking above recommended amounts, and the number of days spent in the hospital, but have not been demonstrated to affect mortality, alcohol-related liver problems, outpatient visits, legal problems, or quality of life.⁵⁶ Resources can be found at www.niaaa.nih.gov. For patients with dual diagnoses, it is not yet known whether sequential therapy (in which substance abuse is treated first, followed by treatment of the comorbid mental illness) or concurrent therapy results in better outcomes.⁵⁷

CASE Your patient’s history of recent combat service, acknowledgement of employment and behavioral difficulties, and initial screening results lead you to diagnose alcoholism and depression. Additionally, she denies any suicidal ideation, but admits to experimenting with synthetic marijuana. After some discussion, she agrees to see your clinic’s social worker, and you start her on an SSri with scheduled follow-up.

CORRESPONDENCE
Shawn Kane, MD, USASoc, Attn: Surgeon (AomD), 2929 Desert Storm Drive, Ft. Bragg, NC 28310, or PO Box 3639 Pinehurst, NC 28374; [email protected]

CASE A 37-year-old white woman presents for an employment physical. Your nurse reports that she also has a complaint of headaches, that she scored an 8 on the Alcohol Use Disorders identification Test-consumption (AUDiT-c), and that the result on her patient health Questionnaire (phQ-2) suggests a depressive disorder. You ask the patient whether she has served in the military and discover that, in the last 4 years, she served 2 year-long tours in Afghanistan with her Army reserve unit, returning home 6 months ago.  Since her return, she has lost her job due to chronic tardiness (sleeping through her alarm, she says) and admits she has “started drinking again.” Her visit with you this day is only to undergo the physical exam required by her new employer. What are your next steps with this patient? What resources can you use to help her?

As long as human beings have engaged in combat, there have often been extraordinarily damaging psychiatric1  injuries among those who survive. Combat survivability today is 84% to 90%, the highest in the history of armed conflict,^2,3 thanks to improvements in personal protective gear, vehicle armor, rapid casualty evacuation, and surgical resuscitation and stabilization that is “far forward” on the battlefield. These survivors are subsequently at high risk for a host of other medical conditions, which commonly include traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), depression, suicide, and substance abuse.^4-8 

Family physicians—both civilian and uniformed—may be the first to encounter these individuals. Of the more than 2.4 million US service members who have been deployed to Afghanistan or Iraq in support of Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF), nearly 60% are no longer on active duty.

Among this group, only half receive care from the US Department of Veterans Affairs (VA).⁹ Despite a concerted effort on the part of the Department of Defense (DoD) and the VA to develop and distribute effective, evidenced-based treatment protocols for veterans with combat-related conditions, major gaps remain in the care provided to combat veterans.¹⁰

This article seeks to help fill that gap by providing the information you need to recognize and treat common combat-related illness, as well as resources to help improve the quality of life for veterans and their families (TABLE 1).

Initial roadblocks to care

One of the biggest challenges in treating veterans with behavioral health issues is the fact that only 23% to 40% of those with mental illness seek care.¹¹ Among the reasons veterans have offered for avoiding behavioral health care are a fear of the stigma associated with mental illness, concern that treatment will negatively affect their career, lack of comfort with mental health professionals, and the perception that mental health treatment is a “last resort.”¹² Unfortunately, efforts by the DoD leadership to overcome these inherent biases have been largely unsuccessful¹³ and much work is still required to see that service members get the care they need.

Due to low rates of self-reporting, effective screening is essential. With this in mind, the DoD has implemented the deployment health assessment program (DHAP), which requires service members to be screened for common conditions within 60 days of deployment, within 30 days of returning, and again at 90 to 180 days after their return.

While the long-term effects of this program are yet to be determined, results to date are promising. Since the DHAP was implemented, there has been a significant decrease in occupationally impairing mental health problems and suicidal ideation requiring medical evacuation from a combat theater.¹⁴

FPs should begin with a simple question. Many of the 20+ million veterans living in the United States will not be wearing a uniform when they enter your office. Simply asking all of your patients, “Have you or a loved one ever served in the military?” may help you discover service-related questions or concerns.^15,16 Underscoring the importance of such screening is the recent decision by the American Academy of Family Physicians to partner with First Lady Michelle Obama and Dr. Jill Biden in a new campaign called “Joining Forces,” which aims to support veterans and their families.¹⁶

Mild traumatic brain injury: Common—though overlooked

A TBI is any temporary or permanent neurologic dysfunction after a blow to the head.^10,17 TBI is classified based on severity and mechanism (direct blow to the head or exposure to blast waves). Mild TBI (mTBI) is commonly referred to as a concussion and usually is not associated with loss of consciousness or altered mental status. Brain imaging results are also normal with mTBI. Severe TBI, on the other hand, is associated with prolonged loss of consciousness, altered mental status, and abnormal brain imaging results (TABLE 2).¹⁷

A unique obstacle to accurate evaluation in the field. It is important to emphasize that mTBI is a clinical diagnosis, and its detection requires honest patient communication. This can be problematic with motivated soldiers who are anxious to continue the mission and fear that any admission of symptoms might delay a return to their unit. As with a concussed athlete eager to return to the field of play, the clinical diagnosis of mTBI requires a high index of clinical suspicion and constant vigilance by the health care provider. Despite being the most common combat- related injury, mTBI is often overlooked due to the absence of obvious physical injuries.⁴ Recent data suggest that 28% to 60% of ser- vice members evacuated from combat have a TBI. Most of these injuries (77%) are mTBI.^18-20 Improved personal protective equipment (including Kevlar helmets and body armor) and the high number of blast-related injuries are likely responsible for the high incidence of mTBI among OEF/OIF veterans.^8,21,22 The prevalence of mTBI among service members not evacuated is estimated to be 20% to 30%.²⁰ Veterans with non–cancer-related pain who are treated with opioid analgesics have an increased risk of adverse clinical outcomes compared with those not treated with opioids.

Symptoms can persist. Most patients with mTBI completely recover within 30 days of the injury. Unfortunately, 10% to 15% of mTBI patients develop chronic problems lasting months to years.⁴ Residual symptoms most commonly include headache, irritability, depression, sleep disturbance, impaired reasoning, memory problems, and difficulty concentrating. These symptoms are not unique to mTBI and overlap with comorbid combat diagnoses like PTSD, depression, and sleep deprivation.¹⁰ The following tools can help physicians determine whether mTBI is present.

Checking for possible mtBi. In the field, patients with possible mTBI can be screened rapidly using the Military Acute Concussion Evaluation (MACE, found at www.dvbic.org), a modification of the validated and widely used Sideline Assessment of Concussion (SAC) tool. More challenging is evaluating potential mTBI patients who present weeks or months after a traumatic event, for which there are no simple confirmatory tests. In this event, conduct a thorough neurological evaluation that includes vestibular, vision, postural, and neurocognitive assessments. For patients with persistent symptoms or possible anatomic brain abnormalities, magnetic resonance imaging (MRI) is the imaging modality of choice. Patients with complications or a questionable diagnosis are best managed in consultation with a neurologist.

Initial treatment of mtBi is symptom-based. When practical, try nonpharmacologic interventions first (TABLE 3).¹⁰ In particular, have the patient avoid further high-risk exposures that could lead to second impact syndrome (an issue increasingly recognized in contact sports). Also critical are physical and cognitive rest and the restoration of sleep until the patient is completely asymptomatic.

If the patient exhibits irritability and depression, selective serotonin reuptake inhibitors (SSRIs) are first-line treatment. Avoid narcotics and sedative-hypnotic sleep medications if treating comorbidities such as pain and sleep deprivation. The VA/DoD guideline on managing concussion and mTBI provides additional detailed, evidence-based treatment recommendations.¹⁷

Reliving the horror again and again: PTSD

PTSD is a persistent and, at times, debilitating clinical syndrome that develops after exposure to a psychologically traumatic event. It’s the second most common illness among OEF/OIF combat veterans, with an estimated prevalence of 3% to 20%, a finding consistent with prior wars.^6,23-25 In the case of combat veterans, the inciting event usually involves an actual or perceived risk of death or serious injury. The individual’s response to the event involves intense fear, helplessness, or horror. The traumatic event is persistently re-experienced through intrusive and disturbing recollections or dreams that cause intense psychological distress. This, in turn, leads to a state of persistent sympathetic arousal. As symptoms are often triggered by specific cues, individuals with PTSD actively seek to avoid thoughts, situations, or stimuli associated with the event.^23,26

Symptoms commonly associated with PTSD include difficulty falling or staying asleep, recurrent nightmares, hypervigilance, and an exaggerated startle response. Individuals with PTSD also have a poorer sense of well-being, a higher rate of work absenteeism, and significantly more somatic complaints than age-matched peers.²⁷ For symptoms to be attributable to PTSD, their onset must follow a recent inciting event and must also cause clinically significant distress or impairment in social, occupational, or other areas of daily living. Common comorbid illnesses include mTBI, depression, and substance abuse. As with mTBI, the presence of multiple comorbidities in patients with PTSD can complicate evaluation, diagnosis, and treatment.

Diagnosis. PTSD is subdivided into acute (symptoms lasting more than one month but less than 3 months after the traumatic event) and chronic (symptoms lasting longer than 3 months after the traumatic event).²⁸ The distinction of acute or chronic does not affect treatment, but it is useful information for the patient to have regarding prognosis and eventual outcome. Like mTBI, PTSD is a clinical diagnosis made only after a thorough, structured diagnostic interview. The use of a validated, self-administered checklist, such as the Post-Traumatic Checklist-Military (PCL-M), allows for an efficient review of a patient’s symptoms and a reliable way to track treatment progress (http://www.ptsd.va.gov/professional/ pages/assessments/ptsd-checklist.asp).

Treatment Options. Effective evidence-based treatments for PTSD are cognitive behavioral therapy, eye movement desensitization and reprocessing (EMDR), and pharmacotherapy. SSRIs and serotonin- norepinephrine reuptake inhibitors (SNRIs) have the strongest evidence for pharmacologic benefit in the treatment of PTSD.^28,29 Other helpful medications are prazosin for nightmares and trazodone for sleep. Family physicians can use these medications as part of a patient-centered collaboration with the rest of the integrated care team, to offer the best chance for treatment success.^10,28,30

Depression: Vets are reluctant to self-report

Combat experience is a significant risk factor for major depression. Estimates of the lifetime prevalence of depression in the general US population vary from 9% to 25% in women and 5% to 12% in men. By contrast, the prevalence of depression in OIF/OEF veterans ranges from 2% to 37%.^24,31,32

Screening can yield false negatives. Many combat veterans are reluctant to self-report behavioral conditions, including depression. Screening, therefore, is important to identify potential depression and allow for intervention. Validated screening tools for depression include the PHQ-2 and PHQ-9, which are easy to use in the office setting. (See http://www.cqaimh.org/pdf/ tool_phq2.pdf [PHQ-2] and http://www. integration.samhsa.gov/images/res/ PHQ%20-%20Questions.pdf [PHQ-9]). Importantly, some veterans will have a negative depression screen on return from deployment, and then test positive 6 to 12 months later.²⁴ The complicated relationship between substance abuse and behavioral health reinforces the need for screening, early diagnosis, and a multidisciplinary approach to treatment.Explanations for the early false-negative results include the excitement of being home and patients intentionally answering questions inaccurately to avoid excessive screening at their home base.¹¹

Treatment is most effective with a combination approach. As with most cases of depression, combining psychotherapy and psychopharmacology appears to be most effective for treating depression related to combat experience.^33,34 While SSRIs and SNRIs are typical first-line pharmacologic agents, combat veterans often have comorbid mTBI, PTSD, or substance abuse issues that may influence the initial choice of therapy³⁵ (TABLE 3).¹⁰

Suicide is on the rise in the military

Historically, the incidence of suicide has been 25% lower in military personnel than in civilian peers.³⁶ However, between 2005 and 2009, the incidence of suicide in the Marine Corps and Army almost doubled.³⁷ While the exact reasons remain unknown, it is likely due to prolonged and repeated deployments to a combat environment.¹² While the incidence of suicide has been particularly high in the Army (22 per 100,000 active-duty and reserve personnel per year), all services have been affected. In fact, since 2009, the number of suicides among active duty service members exceeds those killed in action.³⁷

Consider all veterans to be at risk for suicide, and screen accordingly. An effective screening tool is the Columbia-Suicide Severity Rating Scale (C-SSRS), which is able to predict those most at risk for an impending suicide attempt.³⁴ Service members identified as high risk for suicide require unhindered access to care. The VA has worked to improve access to care and provide evidence-based point-of-care treatment strategies.³⁸ Available resources can be found in TABLE 1.

Unfortunately, even with effective screening and treatment, not all suicides can be prevented. Studies have demonstrated that approximately 65% of service members who commit suicide had no known history of communicating their suicidal intent. Since 2009, the number of suicides among active duty service members exceeds those killed in action.Sadly, 25% of service members who committed suicide had seen a mental health provider within the previous 30 days.³⁹

Alcohol abuse is common; opioids present a unique risk

Excessive use of alcohol and recreational and prescription drugs is common among OEF/ OIF veterans, especially those with comorbid mental health disorders. Retrospective cross-sectional studies show that 11% to 20% of OEF/OIF veterans met DSM-IV-TR diagnostic criteria for substance use disorders.^40-42 At highest risk are single enlisted men under the age of 24 in the Army or Marine Corps who serve in a combat-specific capacity. Interestingly, the prevalence of substance use disorders among OEF/OIF veterans closely mirrors that reported in epidemiologic studies of Vietnam veterans (11%-14%).⁴¹ This similarity, combined with the 39% lifetime prevalence of substance use disorders among Vietnam veterans, may foreshadow a similar lifetime prevalence of substance use disorders among OEF/OIF veterans.⁴¹

Most-abused substances. Alcohol is the most commonly abused substance among OEF/OIF veterans (10%-20%).^40,41,43-45 Other abused substances include opioids (prescribed or illicitly obtained), synthetic marijuana (“Spice” and “K2”), and “bath salts” (synthetic stimulants) (W.M. Sauve, MD, personal communication, August 27, 2012).

OEF/OIF veterans seem to be at particular risk for developing problems related to opioid use. A 2012 retrospective cohort study showed that veterans with non–cancer- related pain diagnoses treated with opioid analgesics had an increased risk for adverse clinical outcomes compared with those not treated with opioid analgesics (9.5% vs 4.1%; relative risk [RR]=2.33; 95% confidence interval [CI], 2.20-2.46). These outcomes included traumatic accidents, overdoses, self-inflicted injuries, and injuries related to violence. This study also demonstrated that, compared with veterans without mental illness, veterans with mental illness (particularly PTSD) and non–cancer-related pain were significantly more likely to receive opioids to treat their pain and had a higher risk of adverse clinical outcomes, including overdose.^46,47

Recreational use of synthetic marijuana and “bath salts” has increased in recent years. These substances are commonly labeled “not for human consumption,” which allows them to remain outside US Food and Drug Administration (FDA) regulation and be sold legally in the United States. Efforts to prohibit the sale or possession of these drugs, including the Federal Synthetic Bath Salt Ban in 2012, have fallen short, often due to creative product ”re-engineering.”³³ Synthetic marijuana and stimulants are inexpensive, readily available, and perceived by users to be safe. Health care providers are often unaware that their patients are using these products. Adverse health outcomes associated with the use of these synthetic drugs include memory loss, depression, and psychosis.

These alcohol and drug screens can help
One efficient screening tool to identify veterans at risk for alcohol abuse is the AUDIT-C, developed by the World Health Organization. This brief 3-question test identifies past-year hazardous drinking and alcohol abuse or dependence with >79% sensitivity and >56% specificity in male veterans, and >66% sensitivity and >87% specificity in female veterans. These numbers are similar to those provided by the full 10-question AUDIT.^48,49 The Drug Abuse Screen Test-10 (DAST-10) provides a similar screening instrument for other substances. Condensed from the original DAST-28 instrument, the DAST-10 identifies high-risk substance abuse with 74% to 94% sensitivity and 68% to 88% specificity.³

Screen for comorbidities. When you see veterans with a diagnosis of substance abuse, also evaluate for comorbid disease. Most veterans with substance use disorders (82%-93%) have at least one other mental health diagnosis (a 45% greater risk than that of civilians with substance abuse disorders),⁵⁰ most commonly PTSD, depression, anxiety, and adjustment disorders.^41,44,45 A number of hypotheses exist to explain the association between substance use disorders and other mental health diagnoses (“dual diagnoses”). The prevailing theory, in both veteran and civilian populations, is that substance abuse is an attempt to self-treat mental illness. Other evidence suggests that substance abuse promotes the development of mental illness, either by leading to a higher risk for traumatic experiences (increasing the chance of developing PTSD) or through a direct biochemical mechanism. Finally, con- current substance use disorder and mental illness may be due to an undefined genetic or biological vulnerability.^38,44 This complicated relationship between substance abuse and behavioral health reinforces the need for screening, early diagnosis, and a comprehensive, multidisciplinary approach to treatment.

Treatment options. Office-based treatment options for narcotic and alcohol abuse and dependency are available to family physicians. Methadone has been used since the 1950s to treat opioid addiction and remains one of the mainstays of outpatient treatment.^47,51 Originally, methadone was restricted to detoxification and maintenance treatment in narcotic addiction treatment programs approved by the FDA. In 1976, this restriction was lifted, and all physicians registered with the Drug Enforcement Agency (DEA) were permitted to prescribe methadone for analgesia.

In 2002, the FDA approved buprenorphine monotherapy and the combination product buprenorphine/naloxone for the treatment of opioid addiction. The prescribing of buprenorphine products requires physicians to undergo extra training, declare to the DEA their intent to prescribe buprenorphine, and obtain a special DEA identification number.^52,53 Physicians interested in finding out more about buprenorphine treatment and prescribing requirements can go to the Substance Abuse and Mental Health Services Administration (SAMHSA) Web page at http://samhsa.gov.

Naltrexone is an opioid receptor agonist that is used primarily to treat alcohol dependency, and is thought to work by reducing the craving for alcohol. Multiple studies have proven the efficacy of naltrexone in an outpatient setting when used alone or in combination with psychotherapy.^54,55 If you are uncomfortable or unfamiliar with the use or prescribing of these medications, referral to a substance abuse clinic specializing in dual-diagnosis treatment (TABLE 1) may offer optimal outcomes for patients with substance abuse disorders and other mental illness.

Cognitive behavioral therapy—including coping skills training, relapse prevention, contingency management, and behavioral couples’ therapy—and 12-step treatment programs are evidence-based options for the treatment of substance abuse disorders. Behavioral counseling interventions in the primary care setting (typically lasting 5-15 minutes) result in decreases in alcohol consumption, heavy drinking episodes, drinking above recommended amounts, and the number of days spent in the hospital, but have not been demonstrated to affect mortality, alcohol-related liver problems, outpatient visits, legal problems, or quality of life.⁵⁶ Resources can be found at www.niaaa.nih.gov. For patients with dual diagnoses, it is not yet known whether sequential therapy (in which substance abuse is treated first, followed by treatment of the comorbid mental illness) or concurrent therapy results in better outcomes.⁵⁷

CASE Your patient’s history of recent combat service, acknowledgement of employment and behavioral difficulties, and initial screening results lead you to diagnose alcoholism and depression. Additionally, she denies any suicidal ideation, but admits to experimenting with synthetic marijuana. After some discussion, she agrees to see your clinic’s social worker, and you start her on an SSri with scheduled follow-up.

CORRESPONDENCE
Shawn Kane, MD, USASoc, Attn: Surgeon (AomD), 2929 Desert Storm Drive, Ft. Bragg, NC 28310, or PO Box 3639 Pinehurst, NC 28374; [email protected]

It’s a scenario all office-based physicians are familiar with: Your day has been going well, and all your appointments have been (relatively) on time. But when you scan your afternoon schedule your mood shifts from buoyant to crestfallen. The reason: Three patients whom you find particularly frustrating are slotted for the last appointments of the day.

CASE 1 Mr. E, age 44, a high-powered attorney, has chronic headache that he has complained off and on about for several years. He has no other past medical history. Physical examination strongly suggests that Mr. E suffers from tension-type headaches, but he continues to demand magnetic resonance imaging (MRI) of the brain. “I think there’s something wrong in there,” he has stated repeatedly. “If my last doctor, who is one of the best in the country, ordered an MRI for me, why can’t you?”

CASE 2 Mr. A is a 37-year-old man who lost his home in a hurricane 3 years ago. Although he sustained only minor physical injuries, Mr. A appears to have lost his sense of well-being. He has developed chronic—and debilitating— musculoskeletal pain in his neck and low back in the aftermath of the storm and has been unable to work since then.

At his last 2 visits, Mr. A requested increasing doses of oxycodone, insisting that nothing else alleviates the pain. When you suggested a nonopioid analgesic, he broke down in tears. “Nobody takes my injuries seriously! My insurance doesn’t want to compensate me for my losses. Now you don’t even believe I’m in pain.”

CASE 3 Ms. S is a 65-year-old socially isolated widow who lost her husband several years ago. She has a history of multiple somatic complaints, including fatigue, abdominal pain, back pain, joint pain, and dizziness. As a result, she has undergone numerous diagnostic procedures, including esophagastroduodenoscopy, colonoscopy, and various blood tests, all of which have been negative. Ms. S consistently requires longer than the usual 20-minute visit. When you try to end an appointment, she typically brings up new issues. “Two days ago, i had this pain by my belly button and left shoulder blade. i think that there must be something wrong with me. Can you examine me?” she asked toward the end of her last visit 6 weeks ago.

The burden of difficult patient encounters

Cases such as these are frustrating, not so much for their clinical complexity, but rather because of the elusiveness of satisfying doctor-patient interactions. Besides a litany of physical complaints, such patients typically present with anxiety, depression, and other psychiatric symptoms; express dissatisfaction with the care they are receiving; and repeatedly request tests and interventions that are not medically indicated.¹

From a primary care perspective, such cases can be frustrating and time- consuming, significantly contribute to exhaustion and burnout, and result in unnecessary health care expenditures.¹ (See “Unexplained complaints in primary care: Evidence of action bias” also in this issue to learn more.) Studies suggest that family physicians see such patients on a daily basis, and rate about one patient in 6 as a “difficult” case.^2,3

Physician attitudes, training play a role
Research has established other critical spheres of influence that conspire to create difficult or frustrating patient encounters, including “system” factors (ie, reduced duration of visits and interrupted visits)⁴ and physician factors. In fact, physicians’ negative attitude toward psychosocial aspects of patient care may be a more potent factor in shaping difficult encounters than any patient characteristic.^3,5

Consider the following statements:

• “Talking about psychosocial issues causes more trouble than it is worth.”
• “I do not focus on psychosocial problems until I have ruled out organic disease.”
• “I am too pressed for time to routinely investigate psychosocial issues.”

Such sentiments, which have been associated with difficult encounters, are part of the 32-item Physician Belief Scale, developed 30 years ago and still used to assess beliefs about psychosocial aspects of patient care held by primary care physicians.⁶

Lack of training is a potential problem, as well. In one survey, more than half of directors of family medicine programs agreed that training in mental health is inadequate.⁷Thus, family physicians often respond to patients like Mr. E, Mr. A, and Ms. S by becoming irritated or avoiding further interaction. A more appropriate response is for the physician to self-acknowledge his or her emotions, then to engage in an empathic interaction in keeping with patient expectations.⁴

As mental health treatment becomes more integrated within family medicine,⁸ pointers for handling difficult patient encounters can be gleaned from the traditional psychiatric approach to difficult or frustrating cases. Indeed, we believe that what is now known as a “patient-centered approach” is rooted in traditions and techniques that psychiatrists and psychologists have used for decades.⁹

Core principles for handling frustrating cases

A useful approach to the difficult patient encounter, detailed in the TABLE that we created, is based on 3 key principles:

• The doctor-patient relationship should be the target for change.
• The patient’s emotional experience should be an explicit focus of the clinical interaction.
• The patient’s perspective should guide the clinical encounter.

In our experience, when the interaction between patient and doctor shifts from searching for specific pathologies to building a collaborative relationship, previously recalcitrant symptoms often improve.

Use these communication techniques
There are 2 main ways to elicit a conversation about personal issues, including emotions, with patients. One is to directly ask patients to describe the distress they are experiencing and elicit the emotions connected to this distress. The other is to invite a discussion about emotional issues indirectly, by asking patients how the symptoms affect their lives and what they think is causing the problem or by selectively sharing an emotional experience of your own.

Once a patient has shared emotions, you will need to show support and empathy in order to build an alliance. There is more than one way to do this, and methods can be used alone or in combination, depending on the particular situation. (You’ll find examples in the TABLE.)

Name the affect. The simple act of naming the patient’s affect or emotional expression (eg, “You sound sad”) is surprisingly helpful, as it lets patients know they have been “heard.”

Validate. You can also validate patients like Mr. E, Mr. A, and Ms. S by stating that their emotional reactions are legitimate, praising them for how well they have coped with difficult symptoms, and acknowledging the seriousness and complexity of their situations.

Align. Once a patient expresses his or her interests and goals, aligning yourself with them (eg, “I want to do everything in my power to help you reduce your pain...”) will elicit hope and improve patient satisfaction.

And 2 mnemonic devices—detailed in the box ^10,11—can help you improve the way you communicate with patients.

Communication can also be nonverbal, such as thoughtful nodding or a timely therapeutic silence. The former is characterized by slow, steady, and purposeful movement accompanied by eye contact; in the latter case, you simply resist the urge to immediately respond after a patient has revealed something emotionally laden, and wait a few seconds to take in what has been said.

How to provide therapeutic structure

Family physicians can further manage patient behaviors that they find bothersome by implementing changes in the way they organize and conduct patient visits. Studies of patients with complex somatic symptoms offer additional hints for the management of frustrating cases. The following strategies can lead to positive outcomes, including a decrease in disability and health care costs.¹²

Schedule regular brief visits. Mr. E, Mr. A, and Ms. S should have frequent and regular, but brief, appointments (eg, 15 minutes every 2 weeks for 2 months). Proactively schedule return visits, rather than waiting for the patient to call for an appointment PRN.¹¹ Sharing this kind of plan gives such patients a concrete time line and clear evidence of support. Avoid the temptation to schedule difficult cases for the last time slot of the day, as going over the allotted time can insidiously give some patients the expectation of progressively longer visits.

Set the agenda. To prevent “doorknob questions” like Ms. S’s new symptoms, reported just as you’re about to leave the exam room, the agenda must be set at the outset of the visit. This can be done by asking, “What did you want to discuss today?”, “Is there anything else you want to address today?”, or “What else did you need taken care of?”¹³ Explicitly inquiring about patient expectations at the start of the visit lets patients like Ms. S know that they are being taken seriously. If the agenda still balloons, you can simply state, “You deserve more than 15 minutes for all these issues. Let’s pick the top 2 for today and tackle others at our next visit in 2 weeks.” To further save time, you can ask the patient to bring a symptom diary or written agenda to the appointment. We’ve found that many anxious patients benefit from this exercise.

Avoid the urge to act. When a patient suffers from unexplained symptoms, effective interventions require physicians to avoid certain “reflex” behaviors—repeatedly performing diagnostic tests, prescribing medications for symptoms of unknown etiology, insinuating that the problem is “in your head,” formulating ambiguous diagnoses, and repeating physical exams.¹² Such physician behaviors tend to reinforce the pathology in patients with unexplained symptoms. The time saved avoiding these pitfalls is better invested in exploring personal issues and stressors.

The point is that such patients should be reassured via discussion, rather than with dubious diagnostic labels and potentially dangerous drugs. This approach has been shown to improve patients’ physical functioning while reducing medical expenditures.¹²

Into action with our 3 cases

CASE 1 Given these principles, how would you handle Mr. E, the patient who is demanding an MRI for a simple tension headache? Although placating him by ordering the test, providing a referral to a specialist, or defending your recommendation through medical reasoning may seem to be more intuitive (or a “quick fix”), these strategies often lead to excessive medical spending, transfer of the burden to a specialist colleague, and ongoing frustration and dissatisfaction on the part of the patient. In this case, validation may be a more useful approach.

“I can totally understand why you’re frustrated that we disagree,” you might say to Mr. E. “But you’re right! you definitely deserve the best care. That’s why I’m recommending against the MRI, as I feel that would be a suboptimal approach.”

Often patients like Mr. E will require repeated validation of their suffering and frustration. The key is to be persistent in validating their feelings without compromising your own principles in providing optimal medical care.

CASE 2 Let’s turn now to Mr. A, who is requesting escalating doses of opioids. Some physicians might write the prescription for the dose he’s insisting on, while others draw a hard boundary by refusing to prescribe above a certain dose or beyond a specific time frame. Both strategies may compromise optimal care or endanger the doctor-patient alliance. Another quick solution would be to provide a referral to a psychiatrist, without further discussion.

Although the techniques we’ve outlined require practice, they need not be time-consuming. In cases like that of Mr. A, however, the patient’s demands are often a sign of more complicated emotions and dynamics below the surface. So you might respond by stating, “I’m sorry to hear that things haven’t been going well. How are you feeling about these things? How does the oxycodone help you? In what way doesn’t it help?”

It is important here to understand how the medication serves the patient—in addition to the ways it hurts him—in order for him to feel understood. Inviting Mr. A to have an open-ended discussion may allow him to reveal what is the real source of his distress—losing his job and his home.

CASE 3 Now let’s turn to Ms. S, who is convinced that she has a physical malady despite negative exams and tests. In truth, she may be depressed or anxious over her husband’s death. One way to address this is to confront the patient directly by suggesting that she has depression triggered by her husband’s death. But this strategy—if used too early—may feel like an accusation, make her angry, and jeopardize your relationship with her.

An alternative approach would be to say, “I think your problems are long-standing and could require a while to treat. Let’s see each other every 2 weeks for the next 2 months so we get adequate time to work on them.” This would be an example of structuring more frequent visits, while also validating the distressing nature of her symptoms.

These strategies are evidence-based
These techniques, while easily adaptable to primary care, are grounded in psychotherapy theory and are evidence-based. A seminal randomized controlled trial conducted more than 30 years ago showed that a patient-centered interview incorporating a number of these techniques bolstered physicians’ knowledge, interviewing skills, attitudes, and ability to manage patients with unexplained complaints.¹⁴

A multicenter study analyzed audio recordings of strategies used by primary care physicians to deny patient requests for a particular medication. It revealed that explanations based on patient perspectives were significantly more likely to result in excellent patient satisfaction than biomedical explanations or other explanatory approaches.¹⁵ Research has also shown that agenda-setting improves both patient and provider satisfaction.¹⁶

Some cases will still be frustrating, and some “difficult” patients will still need a psychiatric referral at some point—ideally, to a psychiatric or psychological consultant who collaborates closely with the primary care clinic.^17,18

Family physicians sometimes worry that the communication techniques we’ve outlined cannot be incorporated into an already harried primary care visit. Many may think it’s better not ask at all than risk opening a Pandora’s box. We urge you to reconsider. Although the techniques we’ve outlined certainly require practice, they need not be time-consuming.¹⁹ By embracing this management approach, you can improve patient satisfaction while enhancing your own repertoire of doctoring skills.

CORRESPONDENCE

Alan R. Teo, MD, MS, 3710 SW US Veterans Hospital Road, Portland, OR 97239; [email protected]

ACKNOWLEDGEMENT

The authors thank Drs. Michael Fetters and Rod Hayward for their help in the development of the manuscript.

It’s a scenario all office-based physicians are familiar with: Your day has been going well, and all your appointments have been (relatively) on time. But when you scan your afternoon schedule your mood shifts from buoyant to crestfallen. The reason: Three patients whom you find particularly frustrating are slotted for the last appointments of the day.

CASE 1 Mr. E, age 44, a high-powered attorney, has chronic headache that he has complained off and on about for several years. He has no other past medical history. Physical examination strongly suggests that Mr. E suffers from tension-type headaches, but he continues to demand magnetic resonance imaging (MRI) of the brain. “I think there’s something wrong in there,” he has stated repeatedly. “If my last doctor, who is one of the best in the country, ordered an MRI for me, why can’t you?”

CASE 2 Mr. A is a 37-year-old man who lost his home in a hurricane 3 years ago. Although he sustained only minor physical injuries, Mr. A appears to have lost his sense of well-being. He has developed chronic—and debilitating— musculoskeletal pain in his neck and low back in the aftermath of the storm and has been unable to work since then.

At his last 2 visits, Mr. A requested increasing doses of oxycodone, insisting that nothing else alleviates the pain. When you suggested a nonopioid analgesic, he broke down in tears. “Nobody takes my injuries seriously! My insurance doesn’t want to compensate me for my losses. Now you don’t even believe I’m in pain.”

CASE 3 Ms. S is a 65-year-old socially isolated widow who lost her husband several years ago. She has a history of multiple somatic complaints, including fatigue, abdominal pain, back pain, joint pain, and dizziness. As a result, she has undergone numerous diagnostic procedures, including esophagastroduodenoscopy, colonoscopy, and various blood tests, all of which have been negative. Ms. S consistently requires longer than the usual 20-minute visit. When you try to end an appointment, she typically brings up new issues. “Two days ago, i had this pain by my belly button and left shoulder blade. i think that there must be something wrong with me. Can you examine me?” she asked toward the end of her last visit 6 weeks ago.

The burden of difficult patient encounters

Cases such as these are frustrating, not so much for their clinical complexity, but rather because of the elusiveness of satisfying doctor-patient interactions. Besides a litany of physical complaints, such patients typically present with anxiety, depression, and other psychiatric symptoms; express dissatisfaction with the care they are receiving; and repeatedly request tests and interventions that are not medically indicated.¹

From a primary care perspective, such cases can be frustrating and time- consuming, significantly contribute to exhaustion and burnout, and result in unnecessary health care expenditures.¹ (See “Unexplained complaints in primary care: Evidence of action bias” also in this issue to learn more.) Studies suggest that family physicians see such patients on a daily basis, and rate about one patient in 6 as a “difficult” case.^2,3

Physician attitudes, training play a role
Research has established other critical spheres of influence that conspire to create difficult or frustrating patient encounters, including “system” factors (ie, reduced duration of visits and interrupted visits)⁴ and physician factors. In fact, physicians’ negative attitude toward psychosocial aspects of patient care may be a more potent factor in shaping difficult encounters than any patient characteristic.^3,5

Consider the following statements:

• “Talking about psychosocial issues causes more trouble than it is worth.”
• “I do not focus on psychosocial problems until I have ruled out organic disease.”
• “I am too pressed for time to routinely investigate psychosocial issues.”

Such sentiments, which have been associated with difficult encounters, are part of the 32-item Physician Belief Scale, developed 30 years ago and still used to assess beliefs about psychosocial aspects of patient care held by primary care physicians.⁶

Lack of training is a potential problem, as well. In one survey, more than half of directors of family medicine programs agreed that training in mental health is inadequate.⁷Thus, family physicians often respond to patients like Mr. E, Mr. A, and Ms. S by becoming irritated or avoiding further interaction. A more appropriate response is for the physician to self-acknowledge his or her emotions, then to engage in an empathic interaction in keeping with patient expectations.⁴

As mental health treatment becomes more integrated within family medicine,⁸ pointers for handling difficult patient encounters can be gleaned from the traditional psychiatric approach to difficult or frustrating cases. Indeed, we believe that what is now known as a “patient-centered approach” is rooted in traditions and techniques that psychiatrists and psychologists have used for decades.⁹

Core principles for handling frustrating cases

A useful approach to the difficult patient encounter, detailed in the TABLE that we created, is based on 3 key principles:

• The doctor-patient relationship should be the target for change.
• The patient’s emotional experience should be an explicit focus of the clinical interaction.
• The patient’s perspective should guide the clinical encounter.

In our experience, when the interaction between patient and doctor shifts from searching for specific pathologies to building a collaborative relationship, previously recalcitrant symptoms often improve.

Use these communication techniques
There are 2 main ways to elicit a conversation about personal issues, including emotions, with patients. One is to directly ask patients to describe the distress they are experiencing and elicit the emotions connected to this distress. The other is to invite a discussion about emotional issues indirectly, by asking patients how the symptoms affect their lives and what they think is causing the problem or by selectively sharing an emotional experience of your own.

Once a patient has shared emotions, you will need to show support and empathy in order to build an alliance. There is more than one way to do this, and methods can be used alone or in combination, depending on the particular situation. (You’ll find examples in the TABLE.)

Name the affect. The simple act of naming the patient’s affect or emotional expression (eg, “You sound sad”) is surprisingly helpful, as it lets patients know they have been “heard.”

Validate. You can also validate patients like Mr. E, Mr. A, and Ms. S by stating that their emotional reactions are legitimate, praising them for how well they have coped with difficult symptoms, and acknowledging the seriousness and complexity of their situations.

Align. Once a patient expresses his or her interests and goals, aligning yourself with them (eg, “I want to do everything in my power to help you reduce your pain...”) will elicit hope and improve patient satisfaction.

And 2 mnemonic devices—detailed in the box ^10,11—can help you improve the way you communicate with patients.

Communication can also be nonverbal, such as thoughtful nodding or a timely therapeutic silence. The former is characterized by slow, steady, and purposeful movement accompanied by eye contact; in the latter case, you simply resist the urge to immediately respond after a patient has revealed something emotionally laden, and wait a few seconds to take in what has been said.

How to provide therapeutic structure

Family physicians can further manage patient behaviors that they find bothersome by implementing changes in the way they organize and conduct patient visits. Studies of patients with complex somatic symptoms offer additional hints for the management of frustrating cases. The following strategies can lead to positive outcomes, including a decrease in disability and health care costs.¹²

Schedule regular brief visits. Mr. E, Mr. A, and Ms. S should have frequent and regular, but brief, appointments (eg, 15 minutes every 2 weeks for 2 months). Proactively schedule return visits, rather than waiting for the patient to call for an appointment PRN.¹¹ Sharing this kind of plan gives such patients a concrete time line and clear evidence of support. Avoid the temptation to schedule difficult cases for the last time slot of the day, as going over the allotted time can insidiously give some patients the expectation of progressively longer visits.

Set the agenda. To prevent “doorknob questions” like Ms. S’s new symptoms, reported just as you’re about to leave the exam room, the agenda must be set at the outset of the visit. This can be done by asking, “What did you want to discuss today?”, “Is there anything else you want to address today?”, or “What else did you need taken care of?”¹³ Explicitly inquiring about patient expectations at the start of the visit lets patients like Ms. S know that they are being taken seriously. If the agenda still balloons, you can simply state, “You deserve more than 15 minutes for all these issues. Let’s pick the top 2 for today and tackle others at our next visit in 2 weeks.” To further save time, you can ask the patient to bring a symptom diary or written agenda to the appointment. We’ve found that many anxious patients benefit from this exercise.

Avoid the urge to act. When a patient suffers from unexplained symptoms, effective interventions require physicians to avoid certain “reflex” behaviors—repeatedly performing diagnostic tests, prescribing medications for symptoms of unknown etiology, insinuating that the problem is “in your head,” formulating ambiguous diagnoses, and repeating physical exams.¹² Such physician behaviors tend to reinforce the pathology in patients with unexplained symptoms. The time saved avoiding these pitfalls is better invested in exploring personal issues and stressors.

The point is that such patients should be reassured via discussion, rather than with dubious diagnostic labels and potentially dangerous drugs. This approach has been shown to improve patients’ physical functioning while reducing medical expenditures.¹²

Into action with our 3 cases

CASE 1 Given these principles, how would you handle Mr. E, the patient who is demanding an MRI for a simple tension headache? Although placating him by ordering the test, providing a referral to a specialist, or defending your recommendation through medical reasoning may seem to be more intuitive (or a “quick fix”), these strategies often lead to excessive medical spending, transfer of the burden to a specialist colleague, and ongoing frustration and dissatisfaction on the part of the patient. In this case, validation may be a more useful approach.

“I can totally understand why you’re frustrated that we disagree,” you might say to Mr. E. “But you’re right! you definitely deserve the best care. That’s why I’m recommending against the MRI, as I feel that would be a suboptimal approach.”

Often patients like Mr. E will require repeated validation of their suffering and frustration. The key is to be persistent in validating their feelings without compromising your own principles in providing optimal medical care.

CASE 2 Let’s turn now to Mr. A, who is requesting escalating doses of opioids. Some physicians might write the prescription for the dose he’s insisting on, while others draw a hard boundary by refusing to prescribe above a certain dose or beyond a specific time frame. Both strategies may compromise optimal care or endanger the doctor-patient alliance. Another quick solution would be to provide a referral to a psychiatrist, without further discussion.

Although the techniques we’ve outlined require practice, they need not be time-consuming. In cases like that of Mr. A, however, the patient’s demands are often a sign of more complicated emotions and dynamics below the surface. So you might respond by stating, “I’m sorry to hear that things haven’t been going well. How are you feeling about these things? How does the oxycodone help you? In what way doesn’t it help?”

It is important here to understand how the medication serves the patient—in addition to the ways it hurts him—in order for him to feel understood. Inviting Mr. A to have an open-ended discussion may allow him to reveal what is the real source of his distress—losing his job and his home.

CASE 3 Now let’s turn to Ms. S, who is convinced that she has a physical malady despite negative exams and tests. In truth, she may be depressed or anxious over her husband’s death. One way to address this is to confront the patient directly by suggesting that she has depression triggered by her husband’s death. But this strategy—if used too early—may feel like an accusation, make her angry, and jeopardize your relationship with her.

An alternative approach would be to say, “I think your problems are long-standing and could require a while to treat. Let’s see each other every 2 weeks for the next 2 months so we get adequate time to work on them.” This would be an example of structuring more frequent visits, while also validating the distressing nature of her symptoms.

These strategies are evidence-based
These techniques, while easily adaptable to primary care, are grounded in psychotherapy theory and are evidence-based. A seminal randomized controlled trial conducted more than 30 years ago showed that a patient-centered interview incorporating a number of these techniques bolstered physicians’ knowledge, interviewing skills, attitudes, and ability to manage patients with unexplained complaints.¹⁴

A multicenter study analyzed audio recordings of strategies used by primary care physicians to deny patient requests for a particular medication. It revealed that explanations based on patient perspectives were significantly more likely to result in excellent patient satisfaction than biomedical explanations or other explanatory approaches.¹⁵ Research has also shown that agenda-setting improves both patient and provider satisfaction.¹⁶

Some cases will still be frustrating, and some “difficult” patients will still need a psychiatric referral at some point—ideally, to a psychiatric or psychological consultant who collaborates closely with the primary care clinic.^17,18

Family physicians sometimes worry that the communication techniques we’ve outlined cannot be incorporated into an already harried primary care visit. Many may think it’s better not ask at all than risk opening a Pandora’s box. We urge you to reconsider. Although the techniques we’ve outlined certainly require practice, they need not be time-consuming.¹⁹ By embracing this management approach, you can improve patient satisfaction while enhancing your own repertoire of doctoring skills.

CORRESPONDENCE

Alan R. Teo, MD, MS, 3710 SW US Veterans Hospital Road, Portland, OR 97239; [email protected]

ACKNOWLEDGEMENT

The authors thank Drs. Michael Fetters and Rod Hayward for their help in the development of the manuscript.

It’s a scenario all office-based physicians are familiar with: Your day has been going well, and all your appointments have been (relatively) on time. But when you scan your afternoon schedule your mood shifts from buoyant to crestfallen. The reason: Three patients whom you find particularly frustrating are slotted for the last appointments of the day.

CASE 1 Mr. E, age 44, a high-powered attorney, has chronic headache that he has complained off and on about for several years. He has no other past medical history. Physical examination strongly suggests that Mr. E suffers from tension-type headaches, but he continues to demand magnetic resonance imaging (MRI) of the brain. “I think there’s something wrong in there,” he has stated repeatedly. “If my last doctor, who is one of the best in the country, ordered an MRI for me, why can’t you?”

CASE 2 Mr. A is a 37-year-old man who lost his home in a hurricane 3 years ago. Although he sustained only minor physical injuries, Mr. A appears to have lost his sense of well-being. He has developed chronic—and debilitating— musculoskeletal pain in his neck and low back in the aftermath of the storm and has been unable to work since then.

At his last 2 visits, Mr. A requested increasing doses of oxycodone, insisting that nothing else alleviates the pain. When you suggested a nonopioid analgesic, he broke down in tears. “Nobody takes my injuries seriously! My insurance doesn’t want to compensate me for my losses. Now you don’t even believe I’m in pain.”

CASE 3 Ms. S is a 65-year-old socially isolated widow who lost her husband several years ago. She has a history of multiple somatic complaints, including fatigue, abdominal pain, back pain, joint pain, and dizziness. As a result, she has undergone numerous diagnostic procedures, including esophagastroduodenoscopy, colonoscopy, and various blood tests, all of which have been negative. Ms. S consistently requires longer than the usual 20-minute visit. When you try to end an appointment, she typically brings up new issues. “Two days ago, i had this pain by my belly button and left shoulder blade. i think that there must be something wrong with me. Can you examine me?” she asked toward the end of her last visit 6 weeks ago.

The burden of difficult patient encounters

Cases such as these are frustrating, not so much for their clinical complexity, but rather because of the elusiveness of satisfying doctor-patient interactions. Besides a litany of physical complaints, such patients typically present with anxiety, depression, and other psychiatric symptoms; express dissatisfaction with the care they are receiving; and repeatedly request tests and interventions that are not medically indicated.¹

From a primary care perspective, such cases can be frustrating and time- consuming, significantly contribute to exhaustion and burnout, and result in unnecessary health care expenditures.¹ (See “Unexplained complaints in primary care: Evidence of action bias” also in this issue to learn more.) Studies suggest that family physicians see such patients on a daily basis, and rate about one patient in 6 as a “difficult” case.^2,3

Physician attitudes, training play a role
Research has established other critical spheres of influence that conspire to create difficult or frustrating patient encounters, including “system” factors (ie, reduced duration of visits and interrupted visits)⁴ and physician factors. In fact, physicians’ negative attitude toward psychosocial aspects of patient care may be a more potent factor in shaping difficult encounters than any patient characteristic.^3,5

Consider the following statements:

• “Talking about psychosocial issues causes more trouble than it is worth.”
• “I do not focus on psychosocial problems until I have ruled out organic disease.”
• “I am too pressed for time to routinely investigate psychosocial issues.”

Such sentiments, which have been associated with difficult encounters, are part of the 32-item Physician Belief Scale, developed 30 years ago and still used to assess beliefs about psychosocial aspects of patient care held by primary care physicians.⁶

Lack of training is a potential problem, as well. In one survey, more than half of directors of family medicine programs agreed that training in mental health is inadequate.⁷Thus, family physicians often respond to patients like Mr. E, Mr. A, and Ms. S by becoming irritated or avoiding further interaction. A more appropriate response is for the physician to self-acknowledge his or her emotions, then to engage in an empathic interaction in keeping with patient expectations.⁴

As mental health treatment becomes more integrated within family medicine,⁸ pointers for handling difficult patient encounters can be gleaned from the traditional psychiatric approach to difficult or frustrating cases. Indeed, we believe that what is now known as a “patient-centered approach” is rooted in traditions and techniques that psychiatrists and psychologists have used for decades.⁹

Core principles for handling frustrating cases

A useful approach to the difficult patient encounter, detailed in the TABLE that we created, is based on 3 key principles:

• The doctor-patient relationship should be the target for change.
• The patient’s emotional experience should be an explicit focus of the clinical interaction.
• The patient’s perspective should guide the clinical encounter.

In our experience, when the interaction between patient and doctor shifts from searching for specific pathologies to building a collaborative relationship, previously recalcitrant symptoms often improve.

Use these communication techniques
There are 2 main ways to elicit a conversation about personal issues, including emotions, with patients. One is to directly ask patients to describe the distress they are experiencing and elicit the emotions connected to this distress. The other is to invite a discussion about emotional issues indirectly, by asking patients how the symptoms affect their lives and what they think is causing the problem or by selectively sharing an emotional experience of your own.

Once a patient has shared emotions, you will need to show support and empathy in order to build an alliance. There is more than one way to do this, and methods can be used alone or in combination, depending on the particular situation. (You’ll find examples in the TABLE.)

Name the affect. The simple act of naming the patient’s affect or emotional expression (eg, “You sound sad”) is surprisingly helpful, as it lets patients know they have been “heard.”

Validate. You can also validate patients like Mr. E, Mr. A, and Ms. S by stating that their emotional reactions are legitimate, praising them for how well they have coped with difficult symptoms, and acknowledging the seriousness and complexity of their situations.

Align. Once a patient expresses his or her interests and goals, aligning yourself with them (eg, “I want to do everything in my power to help you reduce your pain...”) will elicit hope and improve patient satisfaction.

And 2 mnemonic devices—detailed in the box ^10,11—can help you improve the way you communicate with patients.

Communication can also be nonverbal, such as thoughtful nodding or a timely therapeutic silence. The former is characterized by slow, steady, and purposeful movement accompanied by eye contact; in the latter case, you simply resist the urge to immediately respond after a patient has revealed something emotionally laden, and wait a few seconds to take in what has been said.

How to provide therapeutic structure

Family physicians can further manage patient behaviors that they find bothersome by implementing changes in the way they organize and conduct patient visits. Studies of patients with complex somatic symptoms offer additional hints for the management of frustrating cases. The following strategies can lead to positive outcomes, including a decrease in disability and health care costs.¹²

Schedule regular brief visits. Mr. E, Mr. A, and Ms. S should have frequent and regular, but brief, appointments (eg, 15 minutes every 2 weeks for 2 months). Proactively schedule return visits, rather than waiting for the patient to call for an appointment PRN.¹¹ Sharing this kind of plan gives such patients a concrete time line and clear evidence of support. Avoid the temptation to schedule difficult cases for the last time slot of the day, as going over the allotted time can insidiously give some patients the expectation of progressively longer visits.

Set the agenda. To prevent “doorknob questions” like Ms. S’s new symptoms, reported just as you’re about to leave the exam room, the agenda must be set at the outset of the visit. This can be done by asking, “What did you want to discuss today?”, “Is there anything else you want to address today?”, or “What else did you need taken care of?”¹³ Explicitly inquiring about patient expectations at the start of the visit lets patients like Ms. S know that they are being taken seriously. If the agenda still balloons, you can simply state, “You deserve more than 15 minutes for all these issues. Let’s pick the top 2 for today and tackle others at our next visit in 2 weeks.” To further save time, you can ask the patient to bring a symptom diary or written agenda to the appointment. We’ve found that many anxious patients benefit from this exercise.

Avoid the urge to act. When a patient suffers from unexplained symptoms, effective interventions require physicians to avoid certain “reflex” behaviors—repeatedly performing diagnostic tests, prescribing medications for symptoms of unknown etiology, insinuating that the problem is “in your head,” formulating ambiguous diagnoses, and repeating physical exams.¹² Such physician behaviors tend to reinforce the pathology in patients with unexplained symptoms. The time saved avoiding these pitfalls is better invested in exploring personal issues and stressors.

The point is that such patients should be reassured via discussion, rather than with dubious diagnostic labels and potentially dangerous drugs. This approach has been shown to improve patients’ physical functioning while reducing medical expenditures.¹²

Into action with our 3 cases

CASE 1 Given these principles, how would you handle Mr. E, the patient who is demanding an MRI for a simple tension headache? Although placating him by ordering the test, providing a referral to a specialist, or defending your recommendation through medical reasoning may seem to be more intuitive (or a “quick fix”), these strategies often lead to excessive medical spending, transfer of the burden to a specialist colleague, and ongoing frustration and dissatisfaction on the part of the patient. In this case, validation may be a more useful approach.

“I can totally understand why you’re frustrated that we disagree,” you might say to Mr. E. “But you’re right! you definitely deserve the best care. That’s why I’m recommending against the MRI, as I feel that would be a suboptimal approach.”

Often patients like Mr. E will require repeated validation of their suffering and frustration. The key is to be persistent in validating their feelings without compromising your own principles in providing optimal medical care.

CASE 2 Let’s turn now to Mr. A, who is requesting escalating doses of opioids. Some physicians might write the prescription for the dose he’s insisting on, while others draw a hard boundary by refusing to prescribe above a certain dose or beyond a specific time frame. Both strategies may compromise optimal care or endanger the doctor-patient alliance. Another quick solution would be to provide a referral to a psychiatrist, without further discussion.

Although the techniques we’ve outlined require practice, they need not be time-consuming. In cases like that of Mr. A, however, the patient’s demands are often a sign of more complicated emotions and dynamics below the surface. So you might respond by stating, “I’m sorry to hear that things haven’t been going well. How are you feeling about these things? How does the oxycodone help you? In what way doesn’t it help?”

It is important here to understand how the medication serves the patient—in addition to the ways it hurts him—in order for him to feel understood. Inviting Mr. A to have an open-ended discussion may allow him to reveal what is the real source of his distress—losing his job and his home.

CASE 3 Now let’s turn to Ms. S, who is convinced that she has a physical malady despite negative exams and tests. In truth, she may be depressed or anxious over her husband’s death. One way to address this is to confront the patient directly by suggesting that she has depression triggered by her husband’s death. But this strategy—if used too early—may feel like an accusation, make her angry, and jeopardize your relationship with her.

An alternative approach would be to say, “I think your problems are long-standing and could require a while to treat. Let’s see each other every 2 weeks for the next 2 months so we get adequate time to work on them.” This would be an example of structuring more frequent visits, while also validating the distressing nature of her symptoms.

These strategies are evidence-based
These techniques, while easily adaptable to primary care, are grounded in psychotherapy theory and are evidence-based. A seminal randomized controlled trial conducted more than 30 years ago showed that a patient-centered interview incorporating a number of these techniques bolstered physicians’ knowledge, interviewing skills, attitudes, and ability to manage patients with unexplained complaints.¹⁴

A multicenter study analyzed audio recordings of strategies used by primary care physicians to deny patient requests for a particular medication. It revealed that explanations based on patient perspectives were significantly more likely to result in excellent patient satisfaction than biomedical explanations or other explanatory approaches.¹⁵ Research has also shown that agenda-setting improves both patient and provider satisfaction.¹⁶

Some cases will still be frustrating, and some “difficult” patients will still need a psychiatric referral at some point—ideally, to a psychiatric or psychological consultant who collaborates closely with the primary care clinic.^17,18

Family physicians sometimes worry that the communication techniques we’ve outlined cannot be incorporated into an already harried primary care visit. Many may think it’s better not ask at all than risk opening a Pandora’s box. We urge you to reconsider. Although the techniques we’ve outlined certainly require practice, they need not be time-consuming.¹⁹ By embracing this management approach, you can improve patient satisfaction while enhancing your own repertoire of doctoring skills.

CORRESPONDENCE

Alan R. Teo, MD, MS, 3710 SW US Veterans Hospital Road, Portland, OR 97239; [email protected]

ACKNOWLEDGEMENT

The authors thank Drs. Michael Fetters and Rod Hayward for their help in the development of the manuscript.

Some finger injuries require little more than icing; others are more serious, often emergent, conditions with outcomes that are dependent on an accurate diagnosis and rapid initiation of treatment.

The 5 cases that follow describe injuries with varying degrees of severity. Read each case and select the multiple-choice answer you think is most appropriate. Then read on to find out if you were right—and to learn more about the clinical presentation, diagnosis, and treatment for each type of injury.

CASE 1 A 45-year-old auto body worker walks into your office at 5:30 pm, just as your staff is closing up for the day. A few hours ago, he reports, he was spray-painting a car with a paint gun when he felt a sudden pain in his right index finger. His immediate thought was that he had torn something, but the pain quickly subsided. So he continued to work—until about 45 minutes ago, when the pain became so intense that he knew he needed medical care right away.

Examination reveals redness and increased skin temperature on the radial palmar side of the proximal interphalangeal (PIP) joint of the index finger. Two-point discrimination is decreased to 10 mm, vs 5 mm on the same finger of the opposite hand. The patient can flex his PIP and distal interphalangeal (DIP) joints but complains of pain and stiffness. You obtain x-rays of the injured
finger (FIGURE 1).

WHAT'S YOUR NEXT STEP?

Answer: Send the auto-body worker to the nearest ED and call ahead (A).The risk for amputation of a finger with a high-pressure injection injury is high, unless aggressive surgical debridement is done within 6 hours.

This patient sustained a high-pressure injection injury to the PIP joint of his right index finger. The patient’s description of how the injury occurred suggested this, and the radiograph confirmed it by showing some paint under the skin (See arrow, FIGURE 1). Such injuries occur when a high pressure (typically from a hose) forces air or a substance—eg, diesel fuel, paint, or solvent—through the skin into the finger.

Although high-pressure injection injury often has a benign presentation, it is actually a medical emergency. If aggressive surgical debridement does not occur within a 6-hour window, the patient runs a high risk for amputation of the digit.¹ A hand surgeon should be contacted as soon as possible.

The severity of the injury varies, depending on the amount of pressure (amputation rates are as high as 43% when the pressure per square inch >1000), the type of material injected (diesel fuel is the most toxic), and the location.^1,2

Instruct the patient to remove any jewelry, such as a wedding band or watch, on the affected hand or wrist, and to keep the hand elevated. Broad-spectrum antibiotics should be started right away, and a tetanus booster given, if needed. Do not apply heat or use local anesthesia, as both can increase the swelling.²

CASE 2 A 17-year-old cheerleader comes to see you on Monday afternoon, after injuring her left pinky during a Friday night game. The patient, who is right-handed, points to the left PIP joint when you ask where it hurts, and tells you that the finger is stiff. She has been icing it since the injury occurred, to make sure she is ready to cheer by next weekend.

The injury occurred when she was spotting another cheerleader during a routine, the patient reports, adding that the pinky was “dislocated.” The coach “popped” it back in place and buddy-taped the injured finger to her ring finger.

The patient is able to flex and extend the DIP joint on the pinky when the PIP joint is stabilized. She can also flex the PIP joint unassisted, but has difficulty extending it. The digit demonstrates slight flexion of the PIP joint. You note tenderness over both collateral ligaments and the dorsum of the PIP joint, but not over the volar aspect of the injured finger, and order x-rays (FIGURE 2).

WHAT'S YOUR NEXT STEP?

Answer: Refer the cheerleader to a hand surgeon (B).

This patient has a rupture of the central extensor tendon of the pinky finger at the PIP joint. The mechanism of injury and her inability to completely extend the injured finger at the PIP joint alert you to this type of injury. An x-ray may sometimes be normal but in this case, it shows the flexion of the PIP joint. Surgical repair of the rupture should be scheduled without delay.³

Most injuries at this joint occur from forced extension, not flexion, and result in a volar plate rupture.⁴ If swelling and pain make evaluation of an acute dislocation injury difficult, splinting in the “safe hand” position for 72 hours while icing the injured finger will make it possible to do a more detailed follow-up exam.³

Extended periods of splinting can make the PIP joint very stiff, however—and harder to treat than the original injury.⁵  If the rupture of the central extensor tendon is undetected or simply not treated, a Boutonniere deformity, in which the PIP joint is flexed and the DIP joint is hyperextended, is the likely result.³

CASE 3 A 24-year-old man “jammed” his right ring finger while trying to catch a ball that was passed to him during a pick-up basketball game. He has rested and iced the finger for a couple of days, but it’s still painful and hard to move. He has no significant medical history and has been taking only acetaminophen for the pain.

Examination reveals that the injured finger has good capillary refill, 2-point discrimination is intact at 5 mm, and the other fingers on his right hand have no deformities and a normal range of motion. On the injured finger, however, the DIP joint is swollen and tender; it cannot be fully extended (FiGURE 3).

WHAT'S YOUR DIAGNOSIS?

Answer: The basketball player has mallet finger (C).

Mallet finger typically occurs on the dominant hand. The key physical finding is that the joint is “stuck” in flexion, which is evident during an exam and on x-ray. Although the DIP joint may be passively fully extended, the patient with mallet finger is unable to actively extend it.

Mallet injuries, which are common in sports and associated with minor trauma, are typically caused by sudden forced flexion of the DIP joint during active extension of the finger. This can either stretch or tear the extensor tendon or lead to avulsion of the tendon insertion from the dorsum of the distal phalanx, with or without a fragment of bone. The injury is called a “soft” mallet finger when there is no bone involvement and a “bony” mallet finger when an avulsion is present, like the one that is evident on the FIGURE 3 x-ray (see arrow).

In some cases, the deformity associated with mallet finger may be delayed by a few hours, or a few days.On clinical examination, the finger may or may not have an obvious deformity; similarly, you won’t always see bruising, swelling, or tenderness over the DIP joint.⁶ The work-up should include posterior/anterior, oblique, and lateral x-rays, followed by an examination of the soft tissue and a range-of-motion evaluation of the metacarpophalangeal and PIP joints. In acute injuries, tenderness is elicited with palpation over the dorsal aspect of the DIP joint. Although most patients develop an extensor lag at the DIP joint immediately after injury, the deformity may be delayed by a few hours or even days.^6,7

Nonsurgical management is the standard of care for most mallet injuries, including mallet fractures involving less than one-third of the articular surface with no associated DIP joint subluxation.⁷

If there is no displacement, round-the-clock splinting to keep the joint in extension for a minimum of 6 weeks is indicated, followed by 2 to 3 weeks of nighttime splinting. It is important that the splinting allow for complete extension of the DIP joint but flexion of the PIP joint. Keeping the PIP in extension for prolonged periods can lead to permanent stiffness of the joint, while failure to provide any immobilization may lead to permanent deformity.

Surgery is indicated for a fracture fragment involving >30% of the joint surface (as demonstrated in the radiograph), volar subluxation, or a swan neck deformity—and when conservative therapy fails.⁷

CASE 4 An 18-year-old high school football player presents with pain and swelling at the tip of his right ring finger from an injury that occurred a week ago. When the player he was trying to tackle broke away, the patient says, he immediately felt pain and a “pop” in the finger.

The DIP joint of his right ring finger is swollen (FIGURE 4), but appears normal otherwise. When you isolate the joint, however, the patient is unable to flex it. You can palpate a stump on the volar surface of the finger.

What’s your next step?

Answer: Order an ultrasound of the football player’s finger and palm (C).

This patient has Jersey finger, caused by a traumatic avulsion of the flexor digitorum profundus (FDP) from the distal phalanx and diagnosed based on the mechanism of injury and the patient’s inability to flex the DIP joint. The injury often does not show on x-rays, and the diagnosis may be missed for several weeks.

Jersey finger, caused by a traumatic avulsion of the flexor digitorum profundus from the distal phalanx, requires surgical reattachment within 10 days.

Jersey finger usually happens in sports like football or rugby, where players tackle each other, and involves forced, passive extension of the DIP joint at a time of active flexion. Management of Jersey finger starts with splinting, with both the DIP and PIP in slight flexion. Surgical reattachment of the flexor tendon is needed, with best results when it is done within 7 to 10 days of injury.⁴

You may be able to palpate the tendon stump in the palm or along the digit; bony avulsions can be trapped at the flexor sheath. Soft tissue swelling can be misleading, however, and the point of maximal tenderness is not an accurate means of identifying the avulsed tendon stump.⁸

Ultrasound is effective in differentiating between a partial and full thickness rupture and in localizing the distal tendon stump.⁸ MRI is usually reserved for precise evaluation of the tendon edges, to aid in operative planning. If the tendon is retracted to the palm, scarring may be irreversible because of the lack of blood supply.

Athletes typically return to play 12 weeks after injury, starting with protected activity and progressing to full gripping/grasping. Physical therapy and/or occupational therapy will be needed after the surgical wound has healed.

CASE 5 A 40-year-old construction worker who smashed his left index finger with a hammer one day ago presents with severe pain in his fingertip, which he is unable to move. On examination, you find that the distal finger is swollen and there is extensive ecchymosis and swelling underneath the nail. The finger has normal sensation, but you are unable to see capillary refill due to a large hematoma.

X-rays (FIGURE 5) reveal a distal tuft fracture. The patient’s main concern is the pain, and he asks what you can do to relieve it.

What’s your next step?

Answer: Perform fenestration of the construction worker’s nail (B).

This patient has a closed fracture of the distal phalanx, called a tuft fracture, and a sub-ungual hematoma, evident from the x-ray and the physical presentation.

In some cases, the deformity associated with mallet finger may be delayed by a few hours, or a few days. Subungual hematoma requires fenestration with a needle to create small holes in the nail. If the nail bed is lacerated, the nail is removed and the injured nail bed repaired with sutures.

Tuft fractures sometimes require reduction. More often, they are stable and minimally displaced and can be managed conservatively, with splinting with a padded aluminum splint or a fingertip guard (Stax splint) for 3 to 4 weeks. Antibiotics are not indicated unless there is suspicion of an overlying or secondary infection. Referral to a hand surgeon is required for severe crush injuries, avulsion of the nail matrix, and open fractures of the distal phalanx.^5,6

Some finger injuries require little more than icing; others are more serious, often emergent, conditions with outcomes that are dependent on an accurate diagnosis and rapid initiation of treatment.

The 5 cases that follow describe injuries with varying degrees of severity. Read each case and select the multiple-choice answer you think is most appropriate. Then read on to find out if you were right—and to learn more about the clinical presentation, diagnosis, and treatment for each type of injury.

CASE 1 A 45-year-old auto body worker walks into your office at 5:30 pm, just as your staff is closing up for the day. A few hours ago, he reports, he was spray-painting a car with a paint gun when he felt a sudden pain in his right index finger. His immediate thought was that he had torn something, but the pain quickly subsided. So he continued to work—until about 45 minutes ago, when the pain became so intense that he knew he needed medical care right away.

Examination reveals redness and increased skin temperature on the radial palmar side of the proximal interphalangeal (PIP) joint of the index finger. Two-point discrimination is decreased to 10 mm, vs 5 mm on the same finger of the opposite hand. The patient can flex his PIP and distal interphalangeal (DIP) joints but complains of pain and stiffness. You obtain x-rays of the injured
finger (FIGURE 1).

WHAT'S YOUR NEXT STEP?

Answer: Send the auto-body worker to the nearest ED and call ahead (A).The risk for amputation of a finger with a high-pressure injection injury is high, unless aggressive surgical debridement is done within 6 hours.

This patient sustained a high-pressure injection injury to the PIP joint of his right index finger. The patient’s description of how the injury occurred suggested this, and the radiograph confirmed it by showing some paint under the skin (See arrow, FIGURE 1). Such injuries occur when a high pressure (typically from a hose) forces air or a substance—eg, diesel fuel, paint, or solvent—through the skin into the finger.

Although high-pressure injection injury often has a benign presentation, it is actually a medical emergency. If aggressive surgical debridement does not occur within a 6-hour window, the patient runs a high risk for amputation of the digit.¹ A hand surgeon should be contacted as soon as possible.

The severity of the injury varies, depending on the amount of pressure (amputation rates are as high as 43% when the pressure per square inch >1000), the type of material injected (diesel fuel is the most toxic), and the location.^1,2

Instruct the patient to remove any jewelry, such as a wedding band or watch, on the affected hand or wrist, and to keep the hand elevated. Broad-spectrum antibiotics should be started right away, and a tetanus booster given, if needed. Do not apply heat or use local anesthesia, as both can increase the swelling.²

CASE 2 A 17-year-old cheerleader comes to see you on Monday afternoon, after injuring her left pinky during a Friday night game. The patient, who is right-handed, points to the left PIP joint when you ask where it hurts, and tells you that the finger is stiff. She has been icing it since the injury occurred, to make sure she is ready to cheer by next weekend.

The injury occurred when she was spotting another cheerleader during a routine, the patient reports, adding that the pinky was “dislocated.” The coach “popped” it back in place and buddy-taped the injured finger to her ring finger.

The patient is able to flex and extend the DIP joint on the pinky when the PIP joint is stabilized. She can also flex the PIP joint unassisted, but has difficulty extending it. The digit demonstrates slight flexion of the PIP joint. You note tenderness over both collateral ligaments and the dorsum of the PIP joint, but not over the volar aspect of the injured finger, and order x-rays (FIGURE 2).

WHAT'S YOUR NEXT STEP?

Answer: Refer the cheerleader to a hand surgeon (B).

This patient has a rupture of the central extensor tendon of the pinky finger at the PIP joint. The mechanism of injury and her inability to completely extend the injured finger at the PIP joint alert you to this type of injury. An x-ray may sometimes be normal but in this case, it shows the flexion of the PIP joint. Surgical repair of the rupture should be scheduled without delay.³

Most injuries at this joint occur from forced extension, not flexion, and result in a volar plate rupture.⁴ If swelling and pain make evaluation of an acute dislocation injury difficult, splinting in the “safe hand” position for 72 hours while icing the injured finger will make it possible to do a more detailed follow-up exam.³

Extended periods of splinting can make the PIP joint very stiff, however—and harder to treat than the original injury.⁵  If the rupture of the central extensor tendon is undetected or simply not treated, a Boutonniere deformity, in which the PIP joint is flexed and the DIP joint is hyperextended, is the likely result.³

CASE 3 A 24-year-old man “jammed” his right ring finger while trying to catch a ball that was passed to him during a pick-up basketball game. He has rested and iced the finger for a couple of days, but it’s still painful and hard to move. He has no significant medical history and has been taking only acetaminophen for the pain.

Examination reveals that the injured finger has good capillary refill, 2-point discrimination is intact at 5 mm, and the other fingers on his right hand have no deformities and a normal range of motion. On the injured finger, however, the DIP joint is swollen and tender; it cannot be fully extended (FiGURE 3).

WHAT'S YOUR DIAGNOSIS?

Answer: The basketball player has mallet finger (C).

Mallet finger typically occurs on the dominant hand. The key physical finding is that the joint is “stuck” in flexion, which is evident during an exam and on x-ray. Although the DIP joint may be passively fully extended, the patient with mallet finger is unable to actively extend it.

Mallet injuries, which are common in sports and associated with minor trauma, are typically caused by sudden forced flexion of the DIP joint during active extension of the finger. This can either stretch or tear the extensor tendon or lead to avulsion of the tendon insertion from the dorsum of the distal phalanx, with or without a fragment of bone. The injury is called a “soft” mallet finger when there is no bone involvement and a “bony” mallet finger when an avulsion is present, like the one that is evident on the FIGURE 3 x-ray (see arrow).

In some cases, the deformity associated with mallet finger may be delayed by a few hours, or a few days.On clinical examination, the finger may or may not have an obvious deformity; similarly, you won’t always see bruising, swelling, or tenderness over the DIP joint.⁶ The work-up should include posterior/anterior, oblique, and lateral x-rays, followed by an examination of the soft tissue and a range-of-motion evaluation of the metacarpophalangeal and PIP joints. In acute injuries, tenderness is elicited with palpation over the dorsal aspect of the DIP joint. Although most patients develop an extensor lag at the DIP joint immediately after injury, the deformity may be delayed by a few hours or even days.^6,7

Nonsurgical management is the standard of care for most mallet injuries, including mallet fractures involving less than one-third of the articular surface with no associated DIP joint subluxation.⁷

If there is no displacement, round-the-clock splinting to keep the joint in extension for a minimum of 6 weeks is indicated, followed by 2 to 3 weeks of nighttime splinting. It is important that the splinting allow for complete extension of the DIP joint but flexion of the PIP joint. Keeping the PIP in extension for prolonged periods can lead to permanent stiffness of the joint, while failure to provide any immobilization may lead to permanent deformity.

Surgery is indicated for a fracture fragment involving >30% of the joint surface (as demonstrated in the radiograph), volar subluxation, or a swan neck deformity—and when conservative therapy fails.⁷

CASE 4 An 18-year-old high school football player presents with pain and swelling at the tip of his right ring finger from an injury that occurred a week ago. When the player he was trying to tackle broke away, the patient says, he immediately felt pain and a “pop” in the finger.

The DIP joint of his right ring finger is swollen (FIGURE 4), but appears normal otherwise. When you isolate the joint, however, the patient is unable to flex it. You can palpate a stump on the volar surface of the finger.

What’s your next step?

Answer: Order an ultrasound of the football player’s finger and palm (C).

This patient has Jersey finger, caused by a traumatic avulsion of the flexor digitorum profundus (FDP) from the distal phalanx and diagnosed based on the mechanism of injury and the patient’s inability to flex the DIP joint. The injury often does not show on x-rays, and the diagnosis may be missed for several weeks.

Jersey finger, caused by a traumatic avulsion of the flexor digitorum profundus from the distal phalanx, requires surgical reattachment within 10 days.

Jersey finger usually happens in sports like football or rugby, where players tackle each other, and involves forced, passive extension of the DIP joint at a time of active flexion. Management of Jersey finger starts with splinting, with both the DIP and PIP in slight flexion. Surgical reattachment of the flexor tendon is needed, with best results when it is done within 7 to 10 days of injury.⁴

You may be able to palpate the tendon stump in the palm or along the digit; bony avulsions can be trapped at the flexor sheath. Soft tissue swelling can be misleading, however, and the point of maximal tenderness is not an accurate means of identifying the avulsed tendon stump.⁸

Ultrasound is effective in differentiating between a partial and full thickness rupture and in localizing the distal tendon stump.⁸ MRI is usually reserved for precise evaluation of the tendon edges, to aid in operative planning. If the tendon is retracted to the palm, scarring may be irreversible because of the lack of blood supply.

Athletes typically return to play 12 weeks after injury, starting with protected activity and progressing to full gripping/grasping. Physical therapy and/or occupational therapy will be needed after the surgical wound has healed.

CASE 5 A 40-year-old construction worker who smashed his left index finger with a hammer one day ago presents with severe pain in his fingertip, which he is unable to move. On examination, you find that the distal finger is swollen and there is extensive ecchymosis and swelling underneath the nail. The finger has normal sensation, but you are unable to see capillary refill due to a large hematoma.

X-rays (FIGURE 5) reveal a distal tuft fracture. The patient’s main concern is the pain, and he asks what you can do to relieve it.

What’s your next step?

Answer: Perform fenestration of the construction worker’s nail (B).

This patient has a closed fracture of the distal phalanx, called a tuft fracture, and a sub-ungual hematoma, evident from the x-ray and the physical presentation.

In some cases, the deformity associated with mallet finger may be delayed by a few hours, or a few days. Subungual hematoma requires fenestration with a needle to create small holes in the nail. If the nail bed is lacerated, the nail is removed and the injured nail bed repaired with sutures.

Tuft fractures sometimes require reduction. More often, they are stable and minimally displaced and can be managed conservatively, with splinting with a padded aluminum splint or a fingertip guard (Stax splint) for 3 to 4 weeks. Antibiotics are not indicated unless there is suspicion of an overlying or secondary infection. Referral to a hand surgeon is required for severe crush injuries, avulsion of the nail matrix, and open fractures of the distal phalanx.^5,6

Some finger injuries require little more than icing; others are more serious, often emergent, conditions with outcomes that are dependent on an accurate diagnosis and rapid initiation of treatment.

The 5 cases that follow describe injuries with varying degrees of severity. Read each case and select the multiple-choice answer you think is most appropriate. Then read on to find out if you were right—and to learn more about the clinical presentation, diagnosis, and treatment for each type of injury.

CASE 1 A 45-year-old auto body worker walks into your office at 5:30 pm, just as your staff is closing up for the day. A few hours ago, he reports, he was spray-painting a car with a paint gun when he felt a sudden pain in his right index finger. His immediate thought was that he had torn something, but the pain quickly subsided. So he continued to work—until about 45 minutes ago, when the pain became so intense that he knew he needed medical care right away.

Examination reveals redness and increased skin temperature on the radial palmar side of the proximal interphalangeal (PIP) joint of the index finger. Two-point discrimination is decreased to 10 mm, vs 5 mm on the same finger of the opposite hand. The patient can flex his PIP and distal interphalangeal (DIP) joints but complains of pain and stiffness. You obtain x-rays of the injured
finger (FIGURE 1).

WHAT'S YOUR NEXT STEP?

Answer: Send the auto-body worker to the nearest ED and call ahead (A).The risk for amputation of a finger with a high-pressure injection injury is high, unless aggressive surgical debridement is done within 6 hours.

This patient sustained a high-pressure injection injury to the PIP joint of his right index finger. The patient’s description of how the injury occurred suggested this, and the radiograph confirmed it by showing some paint under the skin (See arrow, FIGURE 1). Such injuries occur when a high pressure (typically from a hose) forces air or a substance—eg, diesel fuel, paint, or solvent—through the skin into the finger.

Although high-pressure injection injury often has a benign presentation, it is actually a medical emergency. If aggressive surgical debridement does not occur within a 6-hour window, the patient runs a high risk for amputation of the digit.¹ A hand surgeon should be contacted as soon as possible.

The severity of the injury varies, depending on the amount of pressure (amputation rates are as high as 43% when the pressure per square inch >1000), the type of material injected (diesel fuel is the most toxic), and the location.^1,2

Instruct the patient to remove any jewelry, such as a wedding band or watch, on the affected hand or wrist, and to keep the hand elevated. Broad-spectrum antibiotics should be started right away, and a tetanus booster given, if needed. Do not apply heat or use local anesthesia, as both can increase the swelling.²

CASE 2 A 17-year-old cheerleader comes to see you on Monday afternoon, after injuring her left pinky during a Friday night game. The patient, who is right-handed, points to the left PIP joint when you ask where it hurts, and tells you that the finger is stiff. She has been icing it since the injury occurred, to make sure she is ready to cheer by next weekend.

The injury occurred when she was spotting another cheerleader during a routine, the patient reports, adding that the pinky was “dislocated.” The coach “popped” it back in place and buddy-taped the injured finger to her ring finger.

The patient is able to flex and extend the DIP joint on the pinky when the PIP joint is stabilized. She can also flex the PIP joint unassisted, but has difficulty extending it. The digit demonstrates slight flexion of the PIP joint. You note tenderness over both collateral ligaments and the dorsum of the PIP joint, but not over the volar aspect of the injured finger, and order x-rays (FIGURE 2).

WHAT'S YOUR NEXT STEP?

Answer: Refer the cheerleader to a hand surgeon (B).

This patient has a rupture of the central extensor tendon of the pinky finger at the PIP joint. The mechanism of injury and her inability to completely extend the injured finger at the PIP joint alert you to this type of injury. An x-ray may sometimes be normal but in this case, it shows the flexion of the PIP joint. Surgical repair of the rupture should be scheduled without delay.³

Most injuries at this joint occur from forced extension, not flexion, and result in a volar plate rupture.⁴ If swelling and pain make evaluation of an acute dislocation injury difficult, splinting in the “safe hand” position for 72 hours while icing the injured finger will make it possible to do a more detailed follow-up exam.³

Extended periods of splinting can make the PIP joint very stiff, however—and harder to treat than the original injury.⁵  If the rupture of the central extensor tendon is undetected or simply not treated, a Boutonniere deformity, in which the PIP joint is flexed and the DIP joint is hyperextended, is the likely result.³

CASE 3 A 24-year-old man “jammed” his right ring finger while trying to catch a ball that was passed to him during a pick-up basketball game. He has rested and iced the finger for a couple of days, but it’s still painful and hard to move. He has no significant medical history and has been taking only acetaminophen for the pain.

Examination reveals that the injured finger has good capillary refill, 2-point discrimination is intact at 5 mm, and the other fingers on his right hand have no deformities and a normal range of motion. On the injured finger, however, the DIP joint is swollen and tender; it cannot be fully extended (FiGURE 3).

WHAT'S YOUR DIAGNOSIS?

Answer: The basketball player has mallet finger (C).

Mallet finger typically occurs on the dominant hand. The key physical finding is that the joint is “stuck” in flexion, which is evident during an exam and on x-ray. Although the DIP joint may be passively fully extended, the patient with mallet finger is unable to actively extend it.

Mallet injuries, which are common in sports and associated with minor trauma, are typically caused by sudden forced flexion of the DIP joint during active extension of the finger. This can either stretch or tear the extensor tendon or lead to avulsion of the tendon insertion from the dorsum of the distal phalanx, with or without a fragment of bone. The injury is called a “soft” mallet finger when there is no bone involvement and a “bony” mallet finger when an avulsion is present, like the one that is evident on the FIGURE 3 x-ray (see arrow).

In some cases, the deformity associated with mallet finger may be delayed by a few hours, or a few days.On clinical examination, the finger may or may not have an obvious deformity; similarly, you won’t always see bruising, swelling, or tenderness over the DIP joint.⁶ The work-up should include posterior/anterior, oblique, and lateral x-rays, followed by an examination of the soft tissue and a range-of-motion evaluation of the metacarpophalangeal and PIP joints. In acute injuries, tenderness is elicited with palpation over the dorsal aspect of the DIP joint. Although most patients develop an extensor lag at the DIP joint immediately after injury, the deformity may be delayed by a few hours or even days.^6,7

Nonsurgical management is the standard of care for most mallet injuries, including mallet fractures involving less than one-third of the articular surface with no associated DIP joint subluxation.⁷

If there is no displacement, round-the-clock splinting to keep the joint in extension for a minimum of 6 weeks is indicated, followed by 2 to 3 weeks of nighttime splinting. It is important that the splinting allow for complete extension of the DIP joint but flexion of the PIP joint. Keeping the PIP in extension for prolonged periods can lead to permanent stiffness of the joint, while failure to provide any immobilization may lead to permanent deformity.

Surgery is indicated for a fracture fragment involving >30% of the joint surface (as demonstrated in the radiograph), volar subluxation, or a swan neck deformity—and when conservative therapy fails.⁷

CASE 4 An 18-year-old high school football player presents with pain and swelling at the tip of his right ring finger from an injury that occurred a week ago. When the player he was trying to tackle broke away, the patient says, he immediately felt pain and a “pop” in the finger.

The DIP joint of his right ring finger is swollen (FIGURE 4), but appears normal otherwise. When you isolate the joint, however, the patient is unable to flex it. You can palpate a stump on the volar surface of the finger.

What’s your next step?

Answer: Order an ultrasound of the football player’s finger and palm (C).

This patient has Jersey finger, caused by a traumatic avulsion of the flexor digitorum profundus (FDP) from the distal phalanx and diagnosed based on the mechanism of injury and the patient’s inability to flex the DIP joint. The injury often does not show on x-rays, and the diagnosis may be missed for several weeks.

Jersey finger, caused by a traumatic avulsion of the flexor digitorum profundus from the distal phalanx, requires surgical reattachment within 10 days.

Jersey finger usually happens in sports like football or rugby, where players tackle each other, and involves forced, passive extension of the DIP joint at a time of active flexion. Management of Jersey finger starts with splinting, with both the DIP and PIP in slight flexion. Surgical reattachment of the flexor tendon is needed, with best results when it is done within 7 to 10 days of injury.⁴

You may be able to palpate the tendon stump in the palm or along the digit; bony avulsions can be trapped at the flexor sheath. Soft tissue swelling can be misleading, however, and the point of maximal tenderness is not an accurate means of identifying the avulsed tendon stump.⁸

Ultrasound is effective in differentiating between a partial and full thickness rupture and in localizing the distal tendon stump.⁸ MRI is usually reserved for precise evaluation of the tendon edges, to aid in operative planning. If the tendon is retracted to the palm, scarring may be irreversible because of the lack of blood supply.

Athletes typically return to play 12 weeks after injury, starting with protected activity and progressing to full gripping/grasping. Physical therapy and/or occupational therapy will be needed after the surgical wound has healed.

CASE 5 A 40-year-old construction worker who smashed his left index finger with a hammer one day ago presents with severe pain in his fingertip, which he is unable to move. On examination, you find that the distal finger is swollen and there is extensive ecchymosis and swelling underneath the nail. The finger has normal sensation, but you are unable to see capillary refill due to a large hematoma.

X-rays (FIGURE 5) reveal a distal tuft fracture. The patient’s main concern is the pain, and he asks what you can do to relieve it.

What’s your next step?

Answer: Perform fenestration of the construction worker’s nail (B).

This patient has a closed fracture of the distal phalanx, called a tuft fracture, and a sub-ungual hematoma, evident from the x-ray and the physical presentation.

In some cases, the deformity associated with mallet finger may be delayed by a few hours, or a few days. Subungual hematoma requires fenestration with a needle to create small holes in the nail. If the nail bed is lacerated, the nail is removed and the injured nail bed repaired with sutures.

Tuft fractures sometimes require reduction. More often, they are stable and minimally displaced and can be managed conservatively, with splinting with a padded aluminum splint or a fingertip guard (Stax splint) for 3 to 4 weeks. Antibiotics are not indicated unless there is suspicion of an overlying or secondary infection. Referral to a hand surgeon is required for severe crush injuries, avulsion of the nail matrix, and open fractures of the distal phalanx.^5,6

A 40-year-old female patient, a childhood immigrant from India, is seeking advice regarding her upcoming 2-week trip to Mumbai. She is taking her 2 children, ages 16 years and 16 months, to visit their grandparents for the first time. She has made this trip alone a few times and has invariably experienced short bouts of self-limited diarrheal illness. She wonders what she might do to prevent travelers’ diarrhea. Her only medical problem is rheumatoid arthritis, which has been well controlled with methotrexate. Her children are healthy. What would you recommend?

Recommendations regarding travelers’ diarrhea (TD) address prevention and management. Prevention encompasses advice about personal behaviors and the use of chemoprophylaxis (antimicrobial and non-antimicrobial) and vaccinations. Since international travelers are known to treat themselves for diarrheal illnesses during their trips,¹ recommendations regarding management should assume self-treatment and include the use of both antibiotics and non-antibiotic remedies. Pretravel recommendations will of course be most effective if they account for the individual’s risk for TD.

Innate patient susceptibility, destination, and dietary choices determine TD risk

TD is generally defined as the passage of 3 of more loose stools in a 24-hour period, with associated symptoms of enteric infection—eg, fever, nausea, vomiting, or abdominal cramping. Defined in this manner, TD is thought to occur in 60% to 70% of individuals who travel from developed countries to less-developed countries.^2,4 Risk of TD is influenced both by intrinsic personal factors and by factors specific to the trip.

Personal risk factorsIndividual variation in susceptibility to TD might result from a genetic predisposition arising from single nucleotide polymorphisms governing various inflammatory marker proteins.⁵ A history of multiple episodes of TD, especially if fellow travelers were spared, can suggest this kind of individual susceptibility. Other factors that increase vulnerability to TD are immunodeficiency, achlorhydric states such as atrophic gastritis, and chronic use of proton pump inhibitors.^6,7 However, the trip itself is much more important in assessing risk for TD.

Trip-related risk factors
The destination. The most salient risk factor for TD is the geographic destination. Regions of the world can be divided into TD risk strata:²

• Very high: South Asia
• High: South America, Sub-Saharan Africa
• Medium: Central America, Mexico, Caribbean, Middle East, North Africa, Southeast Asia, Oceania
• Low: Europe, North America (excluding Mexico), Australasia, Northeast Asia.

Particularly notable countries, in descending order of risk, are Nepal, India, Myanmar, Bolivia, Sri Lanka, Ecuador, Peru, Kenya, and Guatemala.²

Dietary choices. Additionally, since travelers acquire TD by ingesting food or beverages contaminated with pathogenic fecal microbes, dietary behaviors during the trip affect their susceptibility. At least risk are business travelers and tourists who confine their activities to more affluent settings in which food and beverages are prepared and stored hygienically.^1,4,8,9 At greater risk are travelers who immerse themselves in local culture, visiting locations that are more impoverished and not as well equipped with sanitation systems, especially if their stay is at least 2 to 3 weeks.^1,4,8,9

Also, the older a traveler is, the lower his or her risk of TD.^1,9 An exception to this might be infants whose diet consists solely of breast milk or formula prepared under sanitary conditions.

Mandates and options for preventing TD

Emphasize food and beverage precautions
It might be reasonable to expect that travelers who are circumspect about their food and beverage choices on trips will be able to avoid TD. Indeed, this is the basis for the aphorism, “Boil it, peel it, or forget it.” Guidelines routinely recommend that travelers restrict their selection of foods to those that have been well cooked and are served while still very hot, and to fruits and vegetables that they peel themselves. Likewise, they should drink only beverages that have been boiled or are in sealed bottles or under carbonation and served without ice.^10-12 Many travelers might find these recommendations too restrictive to follow faithfully. Moreover, studies suggest it may not be possible for even the most assiduous traveler to fully avoid the risk of TD.^13,14 The hygienic characteristics of the travel destination may be more determinative, as illustrated by the successful reduction of TD rates in Jamaica by improving sanitation in tourist resorts.¹⁵

Antibiotic chemoprophylaxis: A debated practice with limited consensusThe etiologic agents of TD are multiple and vary somewhat in predominance according to geographic region.^3,16,17 TABLE 1 depicts variance by region.¹⁶ The most common pathogens are strains of the bacterium Escherichia coli, particularly enterotoxigenic (ETEC), enteroaggregative (EAEC), and enteropathogenic (EPEC) strains.¹⁶ Other bacteria of importance are Campylobacter, Salmonella, and Shigella. Viruses, particularly norovirus (notably connected with cruise ships), can also cause TD, although it is implicated in no more than 17% of cases.¹⁸ Parasitic pathogens are even less common causes of TD (4%-10%) and mainly involve the protozoa, Giardia lamblia, and, to a lesser extent, Entamoeba histolytica and Cryptosporidium.

Although some pathogens often have a characteristic presentation—such as frothy, greasy diarrhea in the case of G lamblia—they generally cannot be reliably distinguished from one another clinically. Notably, up to 50% of stool samples from TD patients do not yield any pathogen,¹⁶ raising the suspicion that current diagnostic technology is not sufficiently sensitive to routinely identify certain bacteria.

There is no consensus on recommending antibiotic chemoprophylaxis against TD.

Opponents of this practice^10-12,19,20 point out that TD is generally a brief (3-5 days), self-limited illness. Moreover, concerns about antibiotic resistance have come to pass. Previously used agents, trimethoprim-sulfamethoxazole and doxycycline, are no longer effective in preventing or treating TD. In addition, antibiotic use carries the risk of allergic reactions as well as other adverse effects including, ironically, the development of antibiotic-associated diarrhea and Clostridium difficile diarrhea.

Proponents of antibiotic chemoprophylaxis^21,22 point to its demonstrated efficacy in reducing the risk of TD by 4% to 40%.¹¹ They also argue that at least 20% to 25% of travelers who get TD must significantly curtail their activities for a day or more.^1,23 This change in travel plans is associated not only with significant personal loss but also imposes a financial burden.²³ Furthermore, TD is known to have longer-term effects. Up to 10% of sufferers develop postinfectious irritable bowel syndrome (PI-IBS) that can last for 5 or 6 years.^21,22,24,25 It is not known, however, whether the use of antibiotic chemoprophylaxis significantly reduces the incidence of PI-IBS.

Finally, the luminal antibiotic, rifaximin, nonabsorbable as it is, is very well-tolerated and holds promise for not inciting antibiotic resistance.²² However, while its efficacy in preventing TD has been demonstrated in various settings,^22,26,27 it is not approved by the US Food and Drug Administration for this indication. Also, concerns persist that it might not be effective in preventing TD caused by invasive pathogens.¹⁹

Indications on which all agree. Even opponents of antibiotic chemoprophylaxis grant that it is probably warranted for 2 groups of travelers.^10-12 The first is those whose trip schedule is of such importance that any deviation would be intolerable. The second is travelers with comorbidities that would render them at high risk for serious inconvenience or illness if they developed TD. Examples of the latter include patients with enterostomies, mobility impairments, immune suppression, inflammatory bowel disease, and renal or metabolic diseases.

Chemoprophylaxis regimens. If you prescribe an antibiotic prophylactically, consider daily doses of a fluoroquinolone (eg, ciprofloxacin 500 mg orally once daily, not twice daily as for treatment) or rifaximin 200 mg orally once or twice a day, for no longer than 2 to 3 weeks.¹⁰

Non-antimicrobial chemoprophylaxis
Bismuth subsalicylate has reduced the incidence of TD from 40% to just 14% when taken in doses of 2 chewable tablets or 60 mL of liquid 4 times daily. ^11,19,22 However, the dosing frequency can hinder adherence. Moreover, the relatively high doses required raise the risk of adverse drug reactions such as blackening of the tongue and stool, nausea, constipation, Reye syndrome (in children under 12 years), and possibly tinnitus. The salicylate component of the drug poses a threat to patients with aspirin allergy, renal disease, and those taking anticoagulants. Drug interactions with probenecid and methotrexate are also possible. Bismuth is not recommended for use for longer than 3 weeks, or for children younger than 3 years or pregnant women in their third trimester.

Other non-antimicrobial chemoprophylaxis agents include probiotics such as Lactobacillus andSaccharomyces. These preparations of bacteria and fungi are marketed either singly or in blends of varying composition and proportion. The evidence is divided on their efficacy, and even though some meta-analyses have concluded probiotics such as Saccharomyces boulardii are useful in preventing TD, endorsement in clinical guidelines is muted.^10-12,28-30

Immunizations have limited value so farNatural immunity to E coli gastrointestinal infection among indigenous people in less developed countries has raised the possibility of a role for vaccines in preventing TD. Some strains of ETEC produce a heat-labile toxin (LT) that bears significant resemblance to the toxin produced by Vibrio cholerae. Therefore, the oral cholera vaccine, Dukoral, has been marketed outside the United States for the prevention of TD.^19,22 However, only ≤7% of TD cases worldwide would be prevented by routine use of this vaccine.³¹ A transdermal LT vaccine, which involves the antigen-presenting Langerhans cells in the superficial skin layers, is promising but not yet available for routine use.^19,22

Treating TD and associated symptoms

Antibiotic treatment
Given that most cases of TD are caused by bacterial pathogens, antibiotics are considered the mainstay of treatment. Concerns about the ill effects of antibiotic use in the case of enterohemorrhagic E coli(EHEC O157:H7) can be allayed because this strain is rarely a  cause of TD.⁹Patient factors that increase vulnerability to TD are immunodeficiency, achlorhydric states such as atrophic gastritis, and chronic use of proton pump inhibitors. 

Consider local resistance patterns and risk of invasive infection. Which antibiotic to recommend is governed by the antibiotic resistance patterns prevalent in the travel destinations and by the risk of infection by invasive pathogens. Invasive TD is generally caused by Campylobacter, Shigella, or Salmonella and manifests clinically with bloody diarrhea, fever, or both. Rifaximin at a dose of 200 mg orally 3 times daily is effective for noninvasive TD.^31,32 However, travelers who develop invasive TD need an alternative to rifaximin. (Those who advocate reserving antibiotic treatment only for invasive diarrhea will not see a role for rifaximin in the first place.) In most invasive cases, a fluoroquinolone will suffice.^10-12,19,32 However, increasing prevalence of fluoroquinolone-resistantCampylobacter species has been reported in South and Southeast Asia. In those locations, azithromycin is an effective alternative, albeit with risk of nausea.³³TABLE 2¹² provides details of recommended antibiotic dosages for adults and children. The duration of treatment is generally 1 day unless symptoms persist, in which case a 3-day course is recommended.^10-12,19,32 If the traveler experiences persistent, new, or worsening symptoms beyond this point, immediate evaluation by a physician is required.

Non-antibiotic treatment
The antimotility agent loperamide is a well-established antidiarrheal agent. Its effective and safe use as an adjunct to antibiotics in the treatment of TD has been demonstrated in several studies.^{10-12,19,32,34} It is generally not used to treat children with TD⁹

No other non-antibiotic treatment for TD has significant guideline or clinical trial support. Bismuth subsalicylate can be helpful as an antidiarrheal agent,³⁵ but is not often recommended because the regimen makes adherence difficult and because antibiotics and loperamide are effective.

Oral rehydration is usually a mainstay of treating gastrointestinal disease among infants and children. However, it, too, has a limited role in cases of TD because dehydration is not usually a significant part of the clinical presentation, perhaps because vomiting is not often prominent.

CASE Advice regarding safe food and beverage choices is essential for the patient and her children. Despite the increased risk for TD due to her history and her use of the immunosuppressant methotrexate, she decides not to pursue antibiotic prophylaxis. Bismuth is also contraindicated because of the methotrexate. Her teenage daughter declines bismuth prophylaxis, and her toddler is too young for it.

The patient does accept a prescription for azithromycin for her and her daughters in case they experience TD. This choice is appropriate given the destination of India and concern about Campylobacterresistance to fluoroquinolones. You also recommend loperamide for use by the mother and older child, in conjunction with the antibiotic.

Two weeks after their trip abroad, the travelers return for an office visit. On the trip, the mother and toddler suffered diarrhea, which responded well to your recommended management. The older child was well during the trip, but she developed diarrhea, abdominal pain, and anorexia one week after returning to the United States. These symptoms have persisted despite a 3-day course of azithromycin and loperamide.

Post-travel evaluation

TD generally occurs within one to 2 weeks of arrival at the travel destination and usually lasts no longer than 4 to 5 days.¹⁹ This scenario is typical of a bacterial infection. When it occurs later or lasts longer, or both, consider several alternative possibilities.^19,36 First, the likelihood of a protozoal parasitic infection is increased. Although giardiasis is most likely, other protozoa such as Entamoeba, Cyclospora, Isospora, and Cryptosporidium are also possibilities. Second, if diarrhea persists, it might be due, not to continued infection, but to a self-limited post-infectious enteropathy or to PI-IBS. Third, TD is known to precipitate the clinical manifestation of underlying gastrointestinal disorders such as inflammatory bowel disease (IBD), celiac disease, or even cancer.³⁷

With an atypical disease course, it’s advisable to send 3 stool samples for laboratory evaluation for ova and parasites and for antigen assays for Giardia. If results of these tests are negative, given the difficulty inherent in diagnosing Giardia, consider empiric treatment with metronidazole in lieu of duodenal sampling.³⁶ If the diarrhea persists, investigate serologic markers for celiac disease and IBD. If these are not revealing, referral for colonoscopy is prudent.

CASE The teenager’s 3 stool samples were negative for ova and parasites and for Giardia antigen. Following empirical treatment with oral metronidazole 250 mg, 3 times daily for 7 days, the diarrhea resolved.

CORRESPONDENCE Dilip Nair, MD, Joan C. Edwards School of Medicine at Marshall University, 1600 Medical Center Drive, Suite 1500, Huntington, WV 25701; [email protected]

A 40-year-old female patient, a childhood immigrant from India, is seeking advice regarding her upcoming 2-week trip to Mumbai. She is taking her 2 children, ages 16 years and 16 months, to visit their grandparents for the first time. She has made this trip alone a few times and has invariably experienced short bouts of self-limited diarrheal illness. She wonders what she might do to prevent travelers’ diarrhea. Her only medical problem is rheumatoid arthritis, which has been well controlled with methotrexate. Her children are healthy. What would you recommend?

Recommendations regarding travelers’ diarrhea (TD) address prevention and management. Prevention encompasses advice about personal behaviors and the use of chemoprophylaxis (antimicrobial and non-antimicrobial) and vaccinations. Since international travelers are known to treat themselves for diarrheal illnesses during their trips,¹ recommendations regarding management should assume self-treatment and include the use of both antibiotics and non-antibiotic remedies. Pretravel recommendations will of course be most effective if they account for the individual’s risk for TD.

Innate patient susceptibility, destination, and dietary choices determine TD risk

TD is generally defined as the passage of 3 of more loose stools in a 24-hour period, with associated symptoms of enteric infection—eg, fever, nausea, vomiting, or abdominal cramping. Defined in this manner, TD is thought to occur in 60% to 70% of individuals who travel from developed countries to less-developed countries.^2,4 Risk of TD is influenced both by intrinsic personal factors and by factors specific to the trip.

Personal risk factorsIndividual variation in susceptibility to TD might result from a genetic predisposition arising from single nucleotide polymorphisms governing various inflammatory marker proteins.⁵ A history of multiple episodes of TD, especially if fellow travelers were spared, can suggest this kind of individual susceptibility. Other factors that increase vulnerability to TD are immunodeficiency, achlorhydric states such as atrophic gastritis, and chronic use of proton pump inhibitors.^6,7 However, the trip itself is much more important in assessing risk for TD.

Trip-related risk factors
The destination. The most salient risk factor for TD is the geographic destination. Regions of the world can be divided into TD risk strata:²

• Very high: South Asia
• High: South America, Sub-Saharan Africa
• Medium: Central America, Mexico, Caribbean, Middle East, North Africa, Southeast Asia, Oceania
• Low: Europe, North America (excluding Mexico), Australasia, Northeast Asia.

Particularly notable countries, in descending order of risk, are Nepal, India, Myanmar, Bolivia, Sri Lanka, Ecuador, Peru, Kenya, and Guatemala.²

Dietary choices. Additionally, since travelers acquire TD by ingesting food or beverages contaminated with pathogenic fecal microbes, dietary behaviors during the trip affect their susceptibility. At least risk are business travelers and tourists who confine their activities to more affluent settings in which food and beverages are prepared and stored hygienically.^1,4,8,9 At greater risk are travelers who immerse themselves in local culture, visiting locations that are more impoverished and not as well equipped with sanitation systems, especially if their stay is at least 2 to 3 weeks.^1,4,8,9

Also, the older a traveler is, the lower his or her risk of TD.^1,9 An exception to this might be infants whose diet consists solely of breast milk or formula prepared under sanitary conditions.

Mandates and options for preventing TD

Emphasize food and beverage precautions
It might be reasonable to expect that travelers who are circumspect about their food and beverage choices on trips will be able to avoid TD. Indeed, this is the basis for the aphorism, “Boil it, peel it, or forget it.” Guidelines routinely recommend that travelers restrict their selection of foods to those that have been well cooked and are served while still very hot, and to fruits and vegetables that they peel themselves. Likewise, they should drink only beverages that have been boiled or are in sealed bottles or under carbonation and served without ice.^10-12 Many travelers might find these recommendations too restrictive to follow faithfully. Moreover, studies suggest it may not be possible for even the most assiduous traveler to fully avoid the risk of TD.^13,14 The hygienic characteristics of the travel destination may be more determinative, as illustrated by the successful reduction of TD rates in Jamaica by improving sanitation in tourist resorts.¹⁵

Antibiotic chemoprophylaxis: A debated practice with limited consensusThe etiologic agents of TD are multiple and vary somewhat in predominance according to geographic region.^3,16,17 TABLE 1 depicts variance by region.¹⁶ The most common pathogens are strains of the bacterium Escherichia coli, particularly enterotoxigenic (ETEC), enteroaggregative (EAEC), and enteropathogenic (EPEC) strains.¹⁶ Other bacteria of importance are Campylobacter, Salmonella, and Shigella. Viruses, particularly norovirus (notably connected with cruise ships), can also cause TD, although it is implicated in no more than 17% of cases.¹⁸ Parasitic pathogens are even less common causes of TD (4%-10%) and mainly involve the protozoa, Giardia lamblia, and, to a lesser extent, Entamoeba histolytica and Cryptosporidium.

Although some pathogens often have a characteristic presentation—such as frothy, greasy diarrhea in the case of G lamblia—they generally cannot be reliably distinguished from one another clinically. Notably, up to 50% of stool samples from TD patients do not yield any pathogen,¹⁶ raising the suspicion that current diagnostic technology is not sufficiently sensitive to routinely identify certain bacteria.

There is no consensus on recommending antibiotic chemoprophylaxis against TD.

Opponents of this practice^10-12,19,20 point out that TD is generally a brief (3-5 days), self-limited illness. Moreover, concerns about antibiotic resistance have come to pass. Previously used agents, trimethoprim-sulfamethoxazole and doxycycline, are no longer effective in preventing or treating TD. In addition, antibiotic use carries the risk of allergic reactions as well as other adverse effects including, ironically, the development of antibiotic-associated diarrhea and Clostridium difficile diarrhea.

Proponents of antibiotic chemoprophylaxis^21,22 point to its demonstrated efficacy in reducing the risk of TD by 4% to 40%.¹¹ They also argue that at least 20% to 25% of travelers who get TD must significantly curtail their activities for a day or more.^1,23 This change in travel plans is associated not only with significant personal loss but also imposes a financial burden.²³ Furthermore, TD is known to have longer-term effects. Up to 10% of sufferers develop postinfectious irritable bowel syndrome (PI-IBS) that can last for 5 or 6 years.^21,22,24,25 It is not known, however, whether the use of antibiotic chemoprophylaxis significantly reduces the incidence of PI-IBS.

Finally, the luminal antibiotic, rifaximin, nonabsorbable as it is, is very well-tolerated and holds promise for not inciting antibiotic resistance.²² However, while its efficacy in preventing TD has been demonstrated in various settings,^22,26,27 it is not approved by the US Food and Drug Administration for this indication. Also, concerns persist that it might not be effective in preventing TD caused by invasive pathogens.¹⁹

Indications on which all agree. Even opponents of antibiotic chemoprophylaxis grant that it is probably warranted for 2 groups of travelers.^10-12 The first is those whose trip schedule is of such importance that any deviation would be intolerable. The second is travelers with comorbidities that would render them at high risk for serious inconvenience or illness if they developed TD. Examples of the latter include patients with enterostomies, mobility impairments, immune suppression, inflammatory bowel disease, and renal or metabolic diseases.

Chemoprophylaxis regimens. If you prescribe an antibiotic prophylactically, consider daily doses of a fluoroquinolone (eg, ciprofloxacin 500 mg orally once daily, not twice daily as for treatment) or rifaximin 200 mg orally once or twice a day, for no longer than 2 to 3 weeks.¹⁰

Non-antimicrobial chemoprophylaxis
Bismuth subsalicylate has reduced the incidence of TD from 40% to just 14% when taken in doses of 2 chewable tablets or 60 mL of liquid 4 times daily. ^11,19,22 However, the dosing frequency can hinder adherence. Moreover, the relatively high doses required raise the risk of adverse drug reactions such as blackening of the tongue and stool, nausea, constipation, Reye syndrome (in children under 12 years), and possibly tinnitus. The salicylate component of the drug poses a threat to patients with aspirin allergy, renal disease, and those taking anticoagulants. Drug interactions with probenecid and methotrexate are also possible. Bismuth is not recommended for use for longer than 3 weeks, or for children younger than 3 years or pregnant women in their third trimester.

Other non-antimicrobial chemoprophylaxis agents include probiotics such as Lactobacillus andSaccharomyces. These preparations of bacteria and fungi are marketed either singly or in blends of varying composition and proportion. The evidence is divided on their efficacy, and even though some meta-analyses have concluded probiotics such as Saccharomyces boulardii are useful in preventing TD, endorsement in clinical guidelines is muted.^10-12,28-30

Immunizations have limited value so farNatural immunity to E coli gastrointestinal infection among indigenous people in less developed countries has raised the possibility of a role for vaccines in preventing TD. Some strains of ETEC produce a heat-labile toxin (LT) that bears significant resemblance to the toxin produced by Vibrio cholerae. Therefore, the oral cholera vaccine, Dukoral, has been marketed outside the United States for the prevention of TD.^19,22 However, only ≤7% of TD cases worldwide would be prevented by routine use of this vaccine.³¹ A transdermal LT vaccine, which involves the antigen-presenting Langerhans cells in the superficial skin layers, is promising but not yet available for routine use.^19,22

Treating TD and associated symptoms

Antibiotic treatment
Given that most cases of TD are caused by bacterial pathogens, antibiotics are considered the mainstay of treatment. Concerns about the ill effects of antibiotic use in the case of enterohemorrhagic E coli(EHEC O157:H7) can be allayed because this strain is rarely a  cause of TD.⁹Patient factors that increase vulnerability to TD are immunodeficiency, achlorhydric states such as atrophic gastritis, and chronic use of proton pump inhibitors. 

Consider local resistance patterns and risk of invasive infection. Which antibiotic to recommend is governed by the antibiotic resistance patterns prevalent in the travel destinations and by the risk of infection by invasive pathogens. Invasive TD is generally caused by Campylobacter, Shigella, or Salmonella and manifests clinically with bloody diarrhea, fever, or both. Rifaximin at a dose of 200 mg orally 3 times daily is effective for noninvasive TD.^31,32 However, travelers who develop invasive TD need an alternative to rifaximin. (Those who advocate reserving antibiotic treatment only for invasive diarrhea will not see a role for rifaximin in the first place.) In most invasive cases, a fluoroquinolone will suffice.^10-12,19,32 However, increasing prevalence of fluoroquinolone-resistantCampylobacter species has been reported in South and Southeast Asia. In those locations, azithromycin is an effective alternative, albeit with risk of nausea.³³TABLE 2¹² provides details of recommended antibiotic dosages for adults and children. The duration of treatment is generally 1 day unless symptoms persist, in which case a 3-day course is recommended.^10-12,19,32 If the traveler experiences persistent, new, or worsening symptoms beyond this point, immediate evaluation by a physician is required.

Non-antibiotic treatment
The antimotility agent loperamide is a well-established antidiarrheal agent. Its effective and safe use as an adjunct to antibiotics in the treatment of TD has been demonstrated in several studies.^{10-12,19,32,34} It is generally not used to treat children with TD⁹

No other non-antibiotic treatment for TD has significant guideline or clinical trial support. Bismuth subsalicylate can be helpful as an antidiarrheal agent,³⁵ but is not often recommended because the regimen makes adherence difficult and because antibiotics and loperamide are effective.

Oral rehydration is usually a mainstay of treating gastrointestinal disease among infants and children. However, it, too, has a limited role in cases of TD because dehydration is not usually a significant part of the clinical presentation, perhaps because vomiting is not often prominent.

CASE Advice regarding safe food and beverage choices is essential for the patient and her children. Despite the increased risk for TD due to her history and her use of the immunosuppressant methotrexate, she decides not to pursue antibiotic prophylaxis. Bismuth is also contraindicated because of the methotrexate. Her teenage daughter declines bismuth prophylaxis, and her toddler is too young for it.

The patient does accept a prescription for azithromycin for her and her daughters in case they experience TD. This choice is appropriate given the destination of India and concern about Campylobacterresistance to fluoroquinolones. You also recommend loperamide for use by the mother and older child, in conjunction with the antibiotic.

Two weeks after their trip abroad, the travelers return for an office visit. On the trip, the mother and toddler suffered diarrhea, which responded well to your recommended management. The older child was well during the trip, but she developed diarrhea, abdominal pain, and anorexia one week after returning to the United States. These symptoms have persisted despite a 3-day course of azithromycin and loperamide.

Post-travel evaluation

TD generally occurs within one to 2 weeks of arrival at the travel destination and usually lasts no longer than 4 to 5 days.¹⁹ This scenario is typical of a bacterial infection. When it occurs later or lasts longer, or both, consider several alternative possibilities.^19,36 First, the likelihood of a protozoal parasitic infection is increased. Although giardiasis is most likely, other protozoa such as Entamoeba, Cyclospora, Isospora, and Cryptosporidium are also possibilities. Second, if diarrhea persists, it might be due, not to continued infection, but to a self-limited post-infectious enteropathy or to PI-IBS. Third, TD is known to precipitate the clinical manifestation of underlying gastrointestinal disorders such as inflammatory bowel disease (IBD), celiac disease, or even cancer.³⁷

With an atypical disease course, it’s advisable to send 3 stool samples for laboratory evaluation for ova and parasites and for antigen assays for Giardia. If results of these tests are negative, given the difficulty inherent in diagnosing Giardia, consider empiric treatment with metronidazole in lieu of duodenal sampling.³⁶ If the diarrhea persists, investigate serologic markers for celiac disease and IBD. If these are not revealing, referral for colonoscopy is prudent.

CASE The teenager’s 3 stool samples were negative for ova and parasites and for Giardia antigen. Following empirical treatment with oral metronidazole 250 mg, 3 times daily for 7 days, the diarrhea resolved.

CORRESPONDENCE Dilip Nair, MD, Joan C. Edwards School of Medicine at Marshall University, 1600 Medical Center Drive, Suite 1500, Huntington, WV 25701; [email protected]

A 40-year-old female patient, a childhood immigrant from India, is seeking advice regarding her upcoming 2-week trip to Mumbai. She is taking her 2 children, ages 16 years and 16 months, to visit their grandparents for the first time. She has made this trip alone a few times and has invariably experienced short bouts of self-limited diarrheal illness. She wonders what she might do to prevent travelers’ diarrhea. Her only medical problem is rheumatoid arthritis, which has been well controlled with methotrexate. Her children are healthy. What would you recommend?

Recommendations regarding travelers’ diarrhea (TD) address prevention and management. Prevention encompasses advice about personal behaviors and the use of chemoprophylaxis (antimicrobial and non-antimicrobial) and vaccinations. Since international travelers are known to treat themselves for diarrheal illnesses during their trips,¹ recommendations regarding management should assume self-treatment and include the use of both antibiotics and non-antibiotic remedies. Pretravel recommendations will of course be most effective if they account for the individual’s risk for TD.

Innate patient susceptibility, destination, and dietary choices determine TD risk

TD is generally defined as the passage of 3 of more loose stools in a 24-hour period, with associated symptoms of enteric infection—eg, fever, nausea, vomiting, or abdominal cramping. Defined in this manner, TD is thought to occur in 60% to 70% of individuals who travel from developed countries to less-developed countries.^2,4 Risk of TD is influenced both by intrinsic personal factors and by factors specific to the trip.

Personal risk factorsIndividual variation in susceptibility to TD might result from a genetic predisposition arising from single nucleotide polymorphisms governing various inflammatory marker proteins.⁵ A history of multiple episodes of TD, especially if fellow travelers were spared, can suggest this kind of individual susceptibility. Other factors that increase vulnerability to TD are immunodeficiency, achlorhydric states such as atrophic gastritis, and chronic use of proton pump inhibitors.^6,7 However, the trip itself is much more important in assessing risk for TD.

Trip-related risk factors
The destination. The most salient risk factor for TD is the geographic destination. Regions of the world can be divided into TD risk strata:²

• Very high: South Asia
• High: South America, Sub-Saharan Africa
• Medium: Central America, Mexico, Caribbean, Middle East, North Africa, Southeast Asia, Oceania
• Low: Europe, North America (excluding Mexico), Australasia, Northeast Asia.

Particularly notable countries, in descending order of risk, are Nepal, India, Myanmar, Bolivia, Sri Lanka, Ecuador, Peru, Kenya, and Guatemala.²

Dietary choices. Additionally, since travelers acquire TD by ingesting food or beverages contaminated with pathogenic fecal microbes, dietary behaviors during the trip affect their susceptibility. At least risk are business travelers and tourists who confine their activities to more affluent settings in which food and beverages are prepared and stored hygienically.^1,4,8,9 At greater risk are travelers who immerse themselves in local culture, visiting locations that are more impoverished and not as well equipped with sanitation systems, especially if their stay is at least 2 to 3 weeks.^1,4,8,9

Also, the older a traveler is, the lower his or her risk of TD.^1,9 An exception to this might be infants whose diet consists solely of breast milk or formula prepared under sanitary conditions.

Mandates and options for preventing TD

Emphasize food and beverage precautions
It might be reasonable to expect that travelers who are circumspect about their food and beverage choices on trips will be able to avoid TD. Indeed, this is the basis for the aphorism, “Boil it, peel it, or forget it.” Guidelines routinely recommend that travelers restrict their selection of foods to those that have been well cooked and are served while still very hot, and to fruits and vegetables that they peel themselves. Likewise, they should drink only beverages that have been boiled or are in sealed bottles or under carbonation and served without ice.^10-12 Many travelers might find these recommendations too restrictive to follow faithfully. Moreover, studies suggest it may not be possible for even the most assiduous traveler to fully avoid the risk of TD.^13,14 The hygienic characteristics of the travel destination may be more determinative, as illustrated by the successful reduction of TD rates in Jamaica by improving sanitation in tourist resorts.¹⁵

Antibiotic chemoprophylaxis: A debated practice with limited consensusThe etiologic agents of TD are multiple and vary somewhat in predominance according to geographic region.^3,16,17 TABLE 1 depicts variance by region.¹⁶ The most common pathogens are strains of the bacterium Escherichia coli, particularly enterotoxigenic (ETEC), enteroaggregative (EAEC), and enteropathogenic (EPEC) strains.¹⁶ Other bacteria of importance are Campylobacter, Salmonella, and Shigella. Viruses, particularly norovirus (notably connected with cruise ships), can also cause TD, although it is implicated in no more than 17% of cases.¹⁸ Parasitic pathogens are even less common causes of TD (4%-10%) and mainly involve the protozoa, Giardia lamblia, and, to a lesser extent, Entamoeba histolytica and Cryptosporidium.

Although some pathogens often have a characteristic presentation—such as frothy, greasy diarrhea in the case of G lamblia—they generally cannot be reliably distinguished from one another clinically. Notably, up to 50% of stool samples from TD patients do not yield any pathogen,¹⁶ raising the suspicion that current diagnostic technology is not sufficiently sensitive to routinely identify certain bacteria.

There is no consensus on recommending antibiotic chemoprophylaxis against TD.

Opponents of this practice^10-12,19,20 point out that TD is generally a brief (3-5 days), self-limited illness. Moreover, concerns about antibiotic resistance have come to pass. Previously used agents, trimethoprim-sulfamethoxazole and doxycycline, are no longer effective in preventing or treating TD. In addition, antibiotic use carries the risk of allergic reactions as well as other adverse effects including, ironically, the development of antibiotic-associated diarrhea and Clostridium difficile diarrhea.

Proponents of antibiotic chemoprophylaxis^21,22 point to its demonstrated efficacy in reducing the risk of TD by 4% to 40%.¹¹ They also argue that at least 20% to 25% of travelers who get TD must significantly curtail their activities for a day or more.^1,23 This change in travel plans is associated not only with significant personal loss but also imposes a financial burden.²³ Furthermore, TD is known to have longer-term effects. Up to 10% of sufferers develop postinfectious irritable bowel syndrome (PI-IBS) that can last for 5 or 6 years.^21,22,24,25 It is not known, however, whether the use of antibiotic chemoprophylaxis significantly reduces the incidence of PI-IBS.

Finally, the luminal antibiotic, rifaximin, nonabsorbable as it is, is very well-tolerated and holds promise for not inciting antibiotic resistance.²² However, while its efficacy in preventing TD has been demonstrated in various settings,^22,26,27 it is not approved by the US Food and Drug Administration for this indication. Also, concerns persist that it might not be effective in preventing TD caused by invasive pathogens.¹⁹

Indications on which all agree. Even opponents of antibiotic chemoprophylaxis grant that it is probably warranted for 2 groups of travelers.^10-12 The first is those whose trip schedule is of such importance that any deviation would be intolerable. The second is travelers with comorbidities that would render them at high risk for serious inconvenience or illness if they developed TD. Examples of the latter include patients with enterostomies, mobility impairments, immune suppression, inflammatory bowel disease, and renal or metabolic diseases.

Chemoprophylaxis regimens. If you prescribe an antibiotic prophylactically, consider daily doses of a fluoroquinolone (eg, ciprofloxacin 500 mg orally once daily, not twice daily as for treatment) or rifaximin 200 mg orally once or twice a day, for no longer than 2 to 3 weeks.¹⁰

Non-antimicrobial chemoprophylaxis
Bismuth subsalicylate has reduced the incidence of TD from 40% to just 14% when taken in doses of 2 chewable tablets or 60 mL of liquid 4 times daily. ^11,19,22 However, the dosing frequency can hinder adherence. Moreover, the relatively high doses required raise the risk of adverse drug reactions such as blackening of the tongue and stool, nausea, constipation, Reye syndrome (in children under 12 years), and possibly tinnitus. The salicylate component of the drug poses a threat to patients with aspirin allergy, renal disease, and those taking anticoagulants. Drug interactions with probenecid and methotrexate are also possible. Bismuth is not recommended for use for longer than 3 weeks, or for children younger than 3 years or pregnant women in their third trimester.

Other non-antimicrobial chemoprophylaxis agents include probiotics such as Lactobacillus andSaccharomyces. These preparations of bacteria and fungi are marketed either singly or in blends of varying composition and proportion. The evidence is divided on their efficacy, and even though some meta-analyses have concluded probiotics such as Saccharomyces boulardii are useful in preventing TD, endorsement in clinical guidelines is muted.^10-12,28-30

Immunizations have limited value so farNatural immunity to E coli gastrointestinal infection among indigenous people in less developed countries has raised the possibility of a role for vaccines in preventing TD. Some strains of ETEC produce a heat-labile toxin (LT) that bears significant resemblance to the toxin produced by Vibrio cholerae. Therefore, the oral cholera vaccine, Dukoral, has been marketed outside the United States for the prevention of TD.^19,22 However, only ≤7% of TD cases worldwide would be prevented by routine use of this vaccine.³¹ A transdermal LT vaccine, which involves the antigen-presenting Langerhans cells in the superficial skin layers, is promising but not yet available for routine use.^19,22

Treating TD and associated symptoms

Antibiotic treatment
Given that most cases of TD are caused by bacterial pathogens, antibiotics are considered the mainstay of treatment. Concerns about the ill effects of antibiotic use in the case of enterohemorrhagic E coli(EHEC O157:H7) can be allayed because this strain is rarely a  cause of TD.⁹Patient factors that increase vulnerability to TD are immunodeficiency, achlorhydric states such as atrophic gastritis, and chronic use of proton pump inhibitors. 

Consider local resistance patterns and risk of invasive infection. Which antibiotic to recommend is governed by the antibiotic resistance patterns prevalent in the travel destinations and by the risk of infection by invasive pathogens. Invasive TD is generally caused by Campylobacter, Shigella, or Salmonella and manifests clinically with bloody diarrhea, fever, or both. Rifaximin at a dose of 200 mg orally 3 times daily is effective for noninvasive TD.^31,32 However, travelers who develop invasive TD need an alternative to rifaximin. (Those who advocate reserving antibiotic treatment only for invasive diarrhea will not see a role for rifaximin in the first place.) In most invasive cases, a fluoroquinolone will suffice.^10-12,19,32 However, increasing prevalence of fluoroquinolone-resistantCampylobacter species has been reported in South and Southeast Asia. In those locations, azithromycin is an effective alternative, albeit with risk of nausea.³³TABLE 2¹² provides details of recommended antibiotic dosages for adults and children. The duration of treatment is generally 1 day unless symptoms persist, in which case a 3-day course is recommended.^10-12,19,32 If the traveler experiences persistent, new, or worsening symptoms beyond this point, immediate evaluation by a physician is required.