CASE: Disoriented and delusional

Ms. P, a 53-year-old registered nurse, is admitted to the inpatient psychiatric unit with confusion, markedly disorganized thought processes, delayed verbal responsiveness, mood lability, and persecutory delusions. Shortly before hospitalization, Ms. P traveled approximately 360 miles from her daughter’s home with a male companion. Noting changes in her mental status, the man brought Ms. P to the local hospital. She was then transferred to our facility.

At admission, Ms. P is not oriented to time. She denies auditory or visual hallucinations and does not display psychomotor agitation or retardation. She reports her mood as sad and her affect is mildly labile. Insight and judgment are considered poor.

Five years ago, Ms. P and her mother were diagnosed with Fabry’s disease (FD) based on genetic analysis. Both women are carriers for the mutations and Ms. P’s mother was found to have almost absent galactosidase activity.

The authors’ observations

FD is an X-linked recessive glycolipid storage disease caused by deficient activity of the lysosomal storage enzyme α-galactosidase A. The disorder affects both men and women and leads to progressive intracellular accumulation of globotriaosylceramide and other related glycosphingolipids.^1,2 The earliest FD symptoms—burning pain and acroparesthesias—typically appear in childhood (Table 1).² FD often is misdiagnosed in women because women tend to display neurologic symptoms later than men, with typical symptom onset in the teenage years.^3,4 Often, these symptoms are confused with psychiatric disorders or vague neurologic or pain syndromes.⁵ In patients with no family history of FD, accurate diagnosis may not be made until adulthood.

Laboratory, dermatologic, and genetic tests can accurately determine the presence of FD.¹ However, because multiple organ systems are involved, initially attributing symptoms to FD is challenging, particularly in women.^1,3,5 For men, diagnosis can be established by measuring plasma or urinary globotriaosylceramide or plasma α-galactosidase A in addition to genetic analysis. In women, genetic analysis is a better diagnosis strategy because elevations in globotriaosylceramide or α-galactosidase A may not be prominent. An algorithm for diagnosing and assessing patients with FD has been proposed.²

Table 1

Typical signs and symptoms of Fabry’s disease

HISTORY: Cognitive deterioration

Ms. P has had psychiatric symptoms such as depression and anxiety since childhood. However, 3 years ago she started to experience psychological and cognitive deterioration. Medical records indicate that Ms. P described memory and concentration problems over the previous few years. She also reported pain, weakness, and numbness in her left leg after surgery for a work-related back injury, for which she received a financial settlement through workers’ compensation. Shortly thereafter, Ms. P separated from her third husband, moved in with her parents, and found work as a psychiatric nurse. She was dismissed after 6 weeks because she could not learn the electronic medical record system and had difficulty with memory and attention. Her performance on the Mini-Mental State Exam⁶ at that time was 28 out of 30, which was within normal limits.

After her parents died 3 years ago, Ms. P lived with her daughter, who became her primary caregiver and legal guardian. Ms. P’s daughter notes that her mother’s impulsive and risky behaviors grew more pronounced. Ms. P went on shopping sprees and became sexually promiscuous.

Ms. P’s psychiatric history includes childhood sexual abuse, hospitalization for a suicide attempt at age 19, and courses of psychotherapy and pharmacotherapy. In addition to FD, Ms. P’s medical history consists of coronary artery disease, type 2 diabetes mellitus, hypercholesterolemia, obesity, arthritis, back pain, fibromyalgia, and gastroesophageal reflux disease. Her family history is notable for alcohol abuse (both parents and a brother), lung cancer (mother), myocardial infarction (father), and Alzheimer’s disease (father).

The authors’ observations

Because α-galactosidase A is ubiquitous throughout the body, in addition to neurologic symptoms, FD involves multiple organ systems, with possible dermatologic, renal, gastrointestinal, cardiac, and cerebrovascular dysfunction. Despite growth in FD research, including the Fabry Outcomes Survey,³ the psychosocial and neuropsychiatric implications of the disease remain unclear.⁷ Behavioral presentations are idiosyncratic and unstable over time, depending on the structures impacted by progressive glycosphingolipid accumulation. Premature cardiovascular events (onset between age 30 and 40 for women), greater incidence of ischemic stroke or transient ischemic attack (7% to 30%), and frequent evidence of white matter lesions put FD patients at greater risk for developing presenile vascular dementia.^1,3 Nearly all male FD patients with dementia show some evidence of stroke or transient ischemic attack; cognitive functioning has not been well explored in female patients.⁴ In a heterogeneous sample of 15 FD patients age 7 to 61, Segal et al⁸ noted deficits in attention, processing speed, and executive function .75 to 1.95 standard deviations below normative means. No patients in this study had a history of stroke or transient ischemic attack; neuroimaging studies were not reported. Kolodny and Pastores⁹ suggested multiple mechanisms for cognitive disruption, suggesting that mild dementia late in the disease course could be secondary to diffuse leukomalacia, multiple strokes, or possibly to lipid storage in hippocampal and frontal lobe neurons.

Psychiatric comorbidity

Psychiatric illness, such as depression or a personality disorder, may be comorbid with FD, although pathologic mechanisms remain unclear.^7,10,11 Hypothesized mechanisms include:

• psychosocial stress from chronic disease
• white matter changes
• disruption of impaired L-arginine-nitric oxide pathways.^7,12

Crosbie et al¹³ noted that FD patients presented with greater psychological distress as measured by the Minnesota Multiphasic Personality Inventory-2 than patients with Gaucher disease or chronic heart disease. However, no significant differences were found between patients with FD and those diagnosed with a pain disorder. In the Segal et al study, out of 11 adult FD patients, 4 were diagnosed with major depressive disorder, 1 with schizophrenia, 2 with schizotypal personality disorder, and 1 with borderline personality disorder.⁸

EVALUATION: Brain abnormalities

Head CT scans (conducted 2 years ago and 6 months ago) revealed prominent cortical sulci likely caused by underlying volume loss, especially in bifrontal areas. A brain MRI performed 2 months ago indicated a moderate degree of subcortical atrophy in bilateral frontal and parietal regions. These radiology findings suggest mild to moderate frontal atrophy, mild degree of white matter changes, and slightly enlarged ventricles. An EEG showed background slowing and lack of an alpha rhythm, indicative of cerebral cortical dysfunction.

Ms. P’s α-galactosidase A level was within normal limits; however, normal enzyme levels frequently are reported in symptomatic and asymptomatic female FD patients.¹⁴ A dermatology consult confirmed the presence of skin findings characteristic of FD (ie, multiple cherry red papules extensively distributed throughout Ms. P’s chest, abdomen, and back, as well as upper and lower extremities).

Ms. P completed 2 neuropsychological assessments separated by 5 months. For a summary of the results of these tests, see the table titled “Ms. P’s neuropsychological assessment results”. Both assessments revealed grossly impaired intellectual capacity, memory, processing speed, and motor functioning. During the assessment, Ms. P could understand all directions with minimal changes from standardized protocols. Ms. P became insistent that she would not be able to complete memory tasks successfully. She gave up prematurely on tasks, saying they were too difficult. She admitted to guessing on several items because she did not want to continue the task.

Ms. P’s performance on tasks measuring effort and validity of a person’s neuropsychological presentation was consistent with someone exaggerating neurologic symptoms. A person with true dementia may perform as poorly as Ms. P did. However, Ms. P’s scores likely underestimated her level of functioning, even if she was experiencing dementia. Ms. P could not complete tasks individuals with severe dementia complete successfully, such as simple addition and subtraction and digit repetition. Ms. P recalled several recent and remote events, such as her breakfast menu and location of her first assessment, but could not recall words practiced multiple times. Although Ms. P’s scores on a complex card-sorting task were in the impaired range, a detailed review of her pattern indicated that although Ms. P could not generate any correct sorting categories, she made few repetitive responses and errors. This pattern is consistent with someone who understands task requirements, but deliberately avoids answering correctly. This suggests that she retained some ability for hypotheses generation and problem solving; however, because she exaggerated her symptoms, specific deficits could not be determined.

The authors’ observations

Ms. P presented with an interesting manifestation of neuropsychiatric symptoms in the context of FD; however, common cardiac and cerebrovascular features of the disease were not fully developed. Ms. P experienced progressive cognitive and behavioral changes for 2 years before her admission (Table 2), which may represent a prodromal period leading up to what appeared to be a frontally mediated dementia syndrome. Müller et al¹⁵ described a patient with FD who displayed a behavioral profile similar to Ms. P’s that included increasingly unstable mood for at least 3 years, borderline personality disorder features, and rapidly fluctuating mood. A case study reported that risperidone, 1 mg/d, used to treat psychosis in a male FD patient caused extrapyramidal symptoms.¹⁶

Ms. P presented with no evidence of stroke or transient ischemic attacks, which is atypical for FD patients with cognitive impairment. However, neuroimaging did reveal frontal atrophy that may be associated with her impulse control deficits, risk-taking behavior, emotional instability, and poor judgment. Her cognitive testing was notable for impairment and exaggeration of symptoms consistent with personality disorder symptoms. Possible reasons for exaggeration include a desire to maintain the sick role or secondary gain related to obtaining disability income.

Ms. P’s behavior pattern could be caused by dementia with frontal features, possibly secondary to FD, in combination with personality and psychiatric pathology.

The mainstay of FD treatment is enzyme replacement therapy (ERT), which addresses the underlying enzyme deficiency. Available research indicates that ERT may reduce symptom severity and slow disease progression; however, further studies are needed to determine if it will reduce outcomes such as stroke, ischemic heart disease, or renal disease.²

Table 2

Symptoms that preceded Ms. P’s admission

TREATMENT: Persistent deficits

Ms. P is started on risperidone rapidly titrated to 4 mg/d for delusional thinking and behavioral disturbance. After initially improving, she develops delirium when risperidone is increased to 4 mg/d. She has visual hallucinations, marked confusion with disorientation, worsened short-term memory, and an unsteady, shuffling gait. Risperidone is tapered and discontinued and Ms. P’s motor symptoms resolve within 2 days; however, she remains confused and delusional. We start her on quetiapine, 25 mg/d titrated to 50 mg/d, and her agitation and delusional thinking progressively decline. Memantine, titrated to 20 mg/d, and rivastigmine, started at 3 mg/d titrated to 9 mg/d, are added to address her cognitive symptoms.

Over several weeks, Ms. P’s mental status slowly improves and her drug-induced delirium completely resolves. However, she has persistent cognitive impairment characterized by compromised short-term memory and poor insight into her medical and psychological condition. She maintains unrealistic expectations about her ability to live independently and return to the workforce. The treatment team recommends that Ms. P’s daughter pursue guardianship and that she receive around-the-clock supervision after discharge from the hospital.

Table

Ms. P’s neuropsychological assessment results

Related Resources

• National Institute of Neurological Disorders and Stroke. Fabry disease information page. www.ninds.nih.gov/disorders/fabrys/fabrys.htm.
• National Fabry Disease Foundation. www.thenfdf.org.
• Rozenfeld P, Neumann PM. Treatment of Fabry disease: current and emerging strategies. Curr Pharm Biotechnol. 2011;12(6):916-922.

Drug Brand Names

• Donepezil • Aricept
• Memantine • Namenda
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Rivastigmine • Exelon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Disoriented and delusional

Ms. P, a 53-year-old registered nurse, is admitted to the inpatient psychiatric unit with confusion, markedly disorganized thought processes, delayed verbal responsiveness, mood lability, and persecutory delusions. Shortly before hospitalization, Ms. P traveled approximately 360 miles from her daughter’s home with a male companion. Noting changes in her mental status, the man brought Ms. P to the local hospital. She was then transferred to our facility.

At admission, Ms. P is not oriented to time. She denies auditory or visual hallucinations and does not display psychomotor agitation or retardation. She reports her mood as sad and her affect is mildly labile. Insight and judgment are considered poor.

Five years ago, Ms. P and her mother were diagnosed with Fabry’s disease (FD) based on genetic analysis. Both women are carriers for the mutations and Ms. P’s mother was found to have almost absent galactosidase activity.

The authors’ observations

FD is an X-linked recessive glycolipid storage disease caused by deficient activity of the lysosomal storage enzyme α-galactosidase A. The disorder affects both men and women and leads to progressive intracellular accumulation of globotriaosylceramide and other related glycosphingolipids.^1,2 The earliest FD symptoms—burning pain and acroparesthesias—typically appear in childhood (Table 1).² FD often is misdiagnosed in women because women tend to display neurologic symptoms later than men, with typical symptom onset in the teenage years.^3,4 Often, these symptoms are confused with psychiatric disorders or vague neurologic or pain syndromes.⁵ In patients with no family history of FD, accurate diagnosis may not be made until adulthood.

Laboratory, dermatologic, and genetic tests can accurately determine the presence of FD.¹ However, because multiple organ systems are involved, initially attributing symptoms to FD is challenging, particularly in women.^1,3,5 For men, diagnosis can be established by measuring plasma or urinary globotriaosylceramide or plasma α-galactosidase A in addition to genetic analysis. In women, genetic analysis is a better diagnosis strategy because elevations in globotriaosylceramide or α-galactosidase A may not be prominent. An algorithm for diagnosing and assessing patients with FD has been proposed.²

Table 1

Typical signs and symptoms of Fabry’s disease

HISTORY: Cognitive deterioration

Ms. P has had psychiatric symptoms such as depression and anxiety since childhood. However, 3 years ago she started to experience psychological and cognitive deterioration. Medical records indicate that Ms. P described memory and concentration problems over the previous few years. She also reported pain, weakness, and numbness in her left leg after surgery for a work-related back injury, for which she received a financial settlement through workers’ compensation. Shortly thereafter, Ms. P separated from her third husband, moved in with her parents, and found work as a psychiatric nurse. She was dismissed after 6 weeks because she could not learn the electronic medical record system and had difficulty with memory and attention. Her performance on the Mini-Mental State Exam⁶ at that time was 28 out of 30, which was within normal limits.

After her parents died 3 years ago, Ms. P lived with her daughter, who became her primary caregiver and legal guardian. Ms. P’s daughter notes that her mother’s impulsive and risky behaviors grew more pronounced. Ms. P went on shopping sprees and became sexually promiscuous.

Ms. P’s psychiatric history includes childhood sexual abuse, hospitalization for a suicide attempt at age 19, and courses of psychotherapy and pharmacotherapy. In addition to FD, Ms. P’s medical history consists of coronary artery disease, type 2 diabetes mellitus, hypercholesterolemia, obesity, arthritis, back pain, fibromyalgia, and gastroesophageal reflux disease. Her family history is notable for alcohol abuse (both parents and a brother), lung cancer (mother), myocardial infarction (father), and Alzheimer’s disease (father).

The authors’ observations

Because α-galactosidase A is ubiquitous throughout the body, in addition to neurologic symptoms, FD involves multiple organ systems, with possible dermatologic, renal, gastrointestinal, cardiac, and cerebrovascular dysfunction. Despite growth in FD research, including the Fabry Outcomes Survey,³ the psychosocial and neuropsychiatric implications of the disease remain unclear.⁷ Behavioral presentations are idiosyncratic and unstable over time, depending on the structures impacted by progressive glycosphingolipid accumulation. Premature cardiovascular events (onset between age 30 and 40 for women), greater incidence of ischemic stroke or transient ischemic attack (7% to 30%), and frequent evidence of white matter lesions put FD patients at greater risk for developing presenile vascular dementia.^1,3 Nearly all male FD patients with dementia show some evidence of stroke or transient ischemic attack; cognitive functioning has not been well explored in female patients.⁴ In a heterogeneous sample of 15 FD patients age 7 to 61, Segal et al⁸ noted deficits in attention, processing speed, and executive function .75 to 1.95 standard deviations below normative means. No patients in this study had a history of stroke or transient ischemic attack; neuroimaging studies were not reported. Kolodny and Pastores⁹ suggested multiple mechanisms for cognitive disruption, suggesting that mild dementia late in the disease course could be secondary to diffuse leukomalacia, multiple strokes, or possibly to lipid storage in hippocampal and frontal lobe neurons.

Psychiatric comorbidity

Psychiatric illness, such as depression or a personality disorder, may be comorbid with FD, although pathologic mechanisms remain unclear.^7,10,11 Hypothesized mechanisms include:

• psychosocial stress from chronic disease
• white matter changes
• disruption of impaired L-arginine-nitric oxide pathways.^7,12

Crosbie et al¹³ noted that FD patients presented with greater psychological distress as measured by the Minnesota Multiphasic Personality Inventory-2 than patients with Gaucher disease or chronic heart disease. However, no significant differences were found between patients with FD and those diagnosed with a pain disorder. In the Segal et al study, out of 11 adult FD patients, 4 were diagnosed with major depressive disorder, 1 with schizophrenia, 2 with schizotypal personality disorder, and 1 with borderline personality disorder.⁸

EVALUATION: Brain abnormalities

Head CT scans (conducted 2 years ago and 6 months ago) revealed prominent cortical sulci likely caused by underlying volume loss, especially in bifrontal areas. A brain MRI performed 2 months ago indicated a moderate degree of subcortical atrophy in bilateral frontal and parietal regions. These radiology findings suggest mild to moderate frontal atrophy, mild degree of white matter changes, and slightly enlarged ventricles. An EEG showed background slowing and lack of an alpha rhythm, indicative of cerebral cortical dysfunction.

Ms. P’s α-galactosidase A level was within normal limits; however, normal enzyme levels frequently are reported in symptomatic and asymptomatic female FD patients.¹⁴ A dermatology consult confirmed the presence of skin findings characteristic of FD (ie, multiple cherry red papules extensively distributed throughout Ms. P’s chest, abdomen, and back, as well as upper and lower extremities).

Ms. P completed 2 neuropsychological assessments separated by 5 months. For a summary of the results of these tests, see the table titled “Ms. P’s neuropsychological assessment results”. Both assessments revealed grossly impaired intellectual capacity, memory, processing speed, and motor functioning. During the assessment, Ms. P could understand all directions with minimal changes from standardized protocols. Ms. P became insistent that she would not be able to complete memory tasks successfully. She gave up prematurely on tasks, saying they were too difficult. She admitted to guessing on several items because she did not want to continue the task.

Ms. P’s performance on tasks measuring effort and validity of a person’s neuropsychological presentation was consistent with someone exaggerating neurologic symptoms. A person with true dementia may perform as poorly as Ms. P did. However, Ms. P’s scores likely underestimated her level of functioning, even if she was experiencing dementia. Ms. P could not complete tasks individuals with severe dementia complete successfully, such as simple addition and subtraction and digit repetition. Ms. P recalled several recent and remote events, such as her breakfast menu and location of her first assessment, but could not recall words practiced multiple times. Although Ms. P’s scores on a complex card-sorting task were in the impaired range, a detailed review of her pattern indicated that although Ms. P could not generate any correct sorting categories, she made few repetitive responses and errors. This pattern is consistent with someone who understands task requirements, but deliberately avoids answering correctly. This suggests that she retained some ability for hypotheses generation and problem solving; however, because she exaggerated her symptoms, specific deficits could not be determined.

The authors’ observations

Ms. P presented with an interesting manifestation of neuropsychiatric symptoms in the context of FD; however, common cardiac and cerebrovascular features of the disease were not fully developed. Ms. P experienced progressive cognitive and behavioral changes for 2 years before her admission (Table 2), which may represent a prodromal period leading up to what appeared to be a frontally mediated dementia syndrome. Müller et al¹⁵ described a patient with FD who displayed a behavioral profile similar to Ms. P’s that included increasingly unstable mood for at least 3 years, borderline personality disorder features, and rapidly fluctuating mood. A case study reported that risperidone, 1 mg/d, used to treat psychosis in a male FD patient caused extrapyramidal symptoms.¹⁶

Ms. P presented with no evidence of stroke or transient ischemic attacks, which is atypical for FD patients with cognitive impairment. However, neuroimaging did reveal frontal atrophy that may be associated with her impulse control deficits, risk-taking behavior, emotional instability, and poor judgment. Her cognitive testing was notable for impairment and exaggeration of symptoms consistent with personality disorder symptoms. Possible reasons for exaggeration include a desire to maintain the sick role or secondary gain related to obtaining disability income.

Ms. P’s behavior pattern could be caused by dementia with frontal features, possibly secondary to FD, in combination with personality and psychiatric pathology.

The mainstay of FD treatment is enzyme replacement therapy (ERT), which addresses the underlying enzyme deficiency. Available research indicates that ERT may reduce symptom severity and slow disease progression; however, further studies are needed to determine if it will reduce outcomes such as stroke, ischemic heart disease, or renal disease.²

Table 2

Symptoms that preceded Ms. P’s admission

TREATMENT: Persistent deficits

Ms. P is started on risperidone rapidly titrated to 4 mg/d for delusional thinking and behavioral disturbance. After initially improving, she develops delirium when risperidone is increased to 4 mg/d. She has visual hallucinations, marked confusion with disorientation, worsened short-term memory, and an unsteady, shuffling gait. Risperidone is tapered and discontinued and Ms. P’s motor symptoms resolve within 2 days; however, she remains confused and delusional. We start her on quetiapine, 25 mg/d titrated to 50 mg/d, and her agitation and delusional thinking progressively decline. Memantine, titrated to 20 mg/d, and rivastigmine, started at 3 mg/d titrated to 9 mg/d, are added to address her cognitive symptoms.

Over several weeks, Ms. P’s mental status slowly improves and her drug-induced delirium completely resolves. However, she has persistent cognitive impairment characterized by compromised short-term memory and poor insight into her medical and psychological condition. She maintains unrealistic expectations about her ability to live independently and return to the workforce. The treatment team recommends that Ms. P’s daughter pursue guardianship and that she receive around-the-clock supervision after discharge from the hospital.

Table

Ms. P’s neuropsychological assessment results

Related Resources

• National Institute of Neurological Disorders and Stroke. Fabry disease information page. www.ninds.nih.gov/disorders/fabrys/fabrys.htm.
• National Fabry Disease Foundation. www.thenfdf.org.
• Rozenfeld P, Neumann PM. Treatment of Fabry disease: current and emerging strategies. Curr Pharm Biotechnol. 2011;12(6):916-922.

Drug Brand Names

• Donepezil • Aricept
• Memantine • Namenda
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Rivastigmine • Exelon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Disoriented and delusional

Ms. P, a 53-year-old registered nurse, is admitted to the inpatient psychiatric unit with confusion, markedly disorganized thought processes, delayed verbal responsiveness, mood lability, and persecutory delusions. Shortly before hospitalization, Ms. P traveled approximately 360 miles from her daughter’s home with a male companion. Noting changes in her mental status, the man brought Ms. P to the local hospital. She was then transferred to our facility.

At admission, Ms. P is not oriented to time. She denies auditory or visual hallucinations and does not display psychomotor agitation or retardation. She reports her mood as sad and her affect is mildly labile. Insight and judgment are considered poor.

Five years ago, Ms. P and her mother were diagnosed with Fabry’s disease (FD) based on genetic analysis. Both women are carriers for the mutations and Ms. P’s mother was found to have almost absent galactosidase activity.

The authors’ observations

FD is an X-linked recessive glycolipid storage disease caused by deficient activity of the lysosomal storage enzyme α-galactosidase A. The disorder affects both men and women and leads to progressive intracellular accumulation of globotriaosylceramide and other related glycosphingolipids.^1,2 The earliest FD symptoms—burning pain and acroparesthesias—typically appear in childhood (Table 1).² FD often is misdiagnosed in women because women tend to display neurologic symptoms later than men, with typical symptom onset in the teenage years.^3,4 Often, these symptoms are confused with psychiatric disorders or vague neurologic or pain syndromes.⁵ In patients with no family history of FD, accurate diagnosis may not be made until adulthood.

Laboratory, dermatologic, and genetic tests can accurately determine the presence of FD.¹ However, because multiple organ systems are involved, initially attributing symptoms to FD is challenging, particularly in women.^1,3,5 For men, diagnosis can be established by measuring plasma or urinary globotriaosylceramide or plasma α-galactosidase A in addition to genetic analysis. In women, genetic analysis is a better diagnosis strategy because elevations in globotriaosylceramide or α-galactosidase A may not be prominent. An algorithm for diagnosing and assessing patients with FD has been proposed.²

Table 1

Typical signs and symptoms of Fabry’s disease

HISTORY: Cognitive deterioration

Ms. P has had psychiatric symptoms such as depression and anxiety since childhood. However, 3 years ago she started to experience psychological and cognitive deterioration. Medical records indicate that Ms. P described memory and concentration problems over the previous few years. She also reported pain, weakness, and numbness in her left leg after surgery for a work-related back injury, for which she received a financial settlement through workers’ compensation. Shortly thereafter, Ms. P separated from her third husband, moved in with her parents, and found work as a psychiatric nurse. She was dismissed after 6 weeks because she could not learn the electronic medical record system and had difficulty with memory and attention. Her performance on the Mini-Mental State Exam⁶ at that time was 28 out of 30, which was within normal limits.

After her parents died 3 years ago, Ms. P lived with her daughter, who became her primary caregiver and legal guardian. Ms. P’s daughter notes that her mother’s impulsive and risky behaviors grew more pronounced. Ms. P went on shopping sprees and became sexually promiscuous.

Ms. P’s psychiatric history includes childhood sexual abuse, hospitalization for a suicide attempt at age 19, and courses of psychotherapy and pharmacotherapy. In addition to FD, Ms. P’s medical history consists of coronary artery disease, type 2 diabetes mellitus, hypercholesterolemia, obesity, arthritis, back pain, fibromyalgia, and gastroesophageal reflux disease. Her family history is notable for alcohol abuse (both parents and a brother), lung cancer (mother), myocardial infarction (father), and Alzheimer’s disease (father).

The authors’ observations

Because α-galactosidase A is ubiquitous throughout the body, in addition to neurologic symptoms, FD involves multiple organ systems, with possible dermatologic, renal, gastrointestinal, cardiac, and cerebrovascular dysfunction. Despite growth in FD research, including the Fabry Outcomes Survey,³ the psychosocial and neuropsychiatric implications of the disease remain unclear.⁷ Behavioral presentations are idiosyncratic and unstable over time, depending on the structures impacted by progressive glycosphingolipid accumulation. Premature cardiovascular events (onset between age 30 and 40 for women), greater incidence of ischemic stroke or transient ischemic attack (7% to 30%), and frequent evidence of white matter lesions put FD patients at greater risk for developing presenile vascular dementia.^1,3 Nearly all male FD patients with dementia show some evidence of stroke or transient ischemic attack; cognitive functioning has not been well explored in female patients.⁴ In a heterogeneous sample of 15 FD patients age 7 to 61, Segal et al⁸ noted deficits in attention, processing speed, and executive function .75 to 1.95 standard deviations below normative means. No patients in this study had a history of stroke or transient ischemic attack; neuroimaging studies were not reported. Kolodny and Pastores⁹ suggested multiple mechanisms for cognitive disruption, suggesting that mild dementia late in the disease course could be secondary to diffuse leukomalacia, multiple strokes, or possibly to lipid storage in hippocampal and frontal lobe neurons.

Psychiatric comorbidity

Psychiatric illness, such as depression or a personality disorder, may be comorbid with FD, although pathologic mechanisms remain unclear.^7,10,11 Hypothesized mechanisms include:

• psychosocial stress from chronic disease
• white matter changes
• disruption of impaired L-arginine-nitric oxide pathways.^7,12

Crosbie et al¹³ noted that FD patients presented with greater psychological distress as measured by the Minnesota Multiphasic Personality Inventory-2 than patients with Gaucher disease or chronic heart disease. However, no significant differences were found between patients with FD and those diagnosed with a pain disorder. In the Segal et al study, out of 11 adult FD patients, 4 were diagnosed with major depressive disorder, 1 with schizophrenia, 2 with schizotypal personality disorder, and 1 with borderline personality disorder.⁸

EVALUATION: Brain abnormalities

Head CT scans (conducted 2 years ago and 6 months ago) revealed prominent cortical sulci likely caused by underlying volume loss, especially in bifrontal areas. A brain MRI performed 2 months ago indicated a moderate degree of subcortical atrophy in bilateral frontal and parietal regions. These radiology findings suggest mild to moderate frontal atrophy, mild degree of white matter changes, and slightly enlarged ventricles. An EEG showed background slowing and lack of an alpha rhythm, indicative of cerebral cortical dysfunction.

Ms. P’s α-galactosidase A level was within normal limits; however, normal enzyme levels frequently are reported in symptomatic and asymptomatic female FD patients.¹⁴ A dermatology consult confirmed the presence of skin findings characteristic of FD (ie, multiple cherry red papules extensively distributed throughout Ms. P’s chest, abdomen, and back, as well as upper and lower extremities).

Ms. P completed 2 neuropsychological assessments separated by 5 months. For a summary of the results of these tests, see the table titled “Ms. P’s neuropsychological assessment results”. Both assessments revealed grossly impaired intellectual capacity, memory, processing speed, and motor functioning. During the assessment, Ms. P could understand all directions with minimal changes from standardized protocols. Ms. P became insistent that she would not be able to complete memory tasks successfully. She gave up prematurely on tasks, saying they were too difficult. She admitted to guessing on several items because she did not want to continue the task.

Ms. P’s performance on tasks measuring effort and validity of a person’s neuropsychological presentation was consistent with someone exaggerating neurologic symptoms. A person with true dementia may perform as poorly as Ms. P did. However, Ms. P’s scores likely underestimated her level of functioning, even if she was experiencing dementia. Ms. P could not complete tasks individuals with severe dementia complete successfully, such as simple addition and subtraction and digit repetition. Ms. P recalled several recent and remote events, such as her breakfast menu and location of her first assessment, but could not recall words practiced multiple times. Although Ms. P’s scores on a complex card-sorting task were in the impaired range, a detailed review of her pattern indicated that although Ms. P could not generate any correct sorting categories, she made few repetitive responses and errors. This pattern is consistent with someone who understands task requirements, but deliberately avoids answering correctly. This suggests that she retained some ability for hypotheses generation and problem solving; however, because she exaggerated her symptoms, specific deficits could not be determined.

The authors’ observations

Ms. P presented with an interesting manifestation of neuropsychiatric symptoms in the context of FD; however, common cardiac and cerebrovascular features of the disease were not fully developed. Ms. P experienced progressive cognitive and behavioral changes for 2 years before her admission (Table 2), which may represent a prodromal period leading up to what appeared to be a frontally mediated dementia syndrome. Müller et al¹⁵ described a patient with FD who displayed a behavioral profile similar to Ms. P’s that included increasingly unstable mood for at least 3 years, borderline personality disorder features, and rapidly fluctuating mood. A case study reported that risperidone, 1 mg/d, used to treat psychosis in a male FD patient caused extrapyramidal symptoms.¹⁶

Ms. P presented with no evidence of stroke or transient ischemic attacks, which is atypical for FD patients with cognitive impairment. However, neuroimaging did reveal frontal atrophy that may be associated with her impulse control deficits, risk-taking behavior, emotional instability, and poor judgment. Her cognitive testing was notable for impairment and exaggeration of symptoms consistent with personality disorder symptoms. Possible reasons for exaggeration include a desire to maintain the sick role or secondary gain related to obtaining disability income.

Ms. P’s behavior pattern could be caused by dementia with frontal features, possibly secondary to FD, in combination with personality and psychiatric pathology.

The mainstay of FD treatment is enzyme replacement therapy (ERT), which addresses the underlying enzyme deficiency. Available research indicates that ERT may reduce symptom severity and slow disease progression; however, further studies are needed to determine if it will reduce outcomes such as stroke, ischemic heart disease, or renal disease.²

Table 2

Symptoms that preceded Ms. P’s admission

TREATMENT: Persistent deficits

Ms. P is started on risperidone rapidly titrated to 4 mg/d for delusional thinking and behavioral disturbance. After initially improving, she develops delirium when risperidone is increased to 4 mg/d. She has visual hallucinations, marked confusion with disorientation, worsened short-term memory, and an unsteady, shuffling gait. Risperidone is tapered and discontinued and Ms. P’s motor symptoms resolve within 2 days; however, she remains confused and delusional. We start her on quetiapine, 25 mg/d titrated to 50 mg/d, and her agitation and delusional thinking progressively decline. Memantine, titrated to 20 mg/d, and rivastigmine, started at 3 mg/d titrated to 9 mg/d, are added to address her cognitive symptoms.

Over several weeks, Ms. P’s mental status slowly improves and her drug-induced delirium completely resolves. However, she has persistent cognitive impairment characterized by compromised short-term memory and poor insight into her medical and psychological condition. She maintains unrealistic expectations about her ability to live independently and return to the workforce. The treatment team recommends that Ms. P’s daughter pursue guardianship and that she receive around-the-clock supervision after discharge from the hospital.

Table

Ms. P’s neuropsychological assessment results

Related Resources

• National Institute of Neurological Disorders and Stroke. Fabry disease information page. www.ninds.nih.gov/disorders/fabrys/fabrys.htm.
• National Fabry Disease Foundation. www.thenfdf.org.
• Rozenfeld P, Neumann PM. Treatment of Fabry disease: current and emerging strategies. Curr Pharm Biotechnol. 2011;12(6):916-922.

Drug Brand Names

• Donepezil • Aricept
• Memantine • Namenda
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Rivastigmine • Exelon

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Culture results go undiscussed, man suffers stroke

TWO WEEKS AFTER PROSTATE SURGERY, a 76-year-old man went to the ED because he was having trouble urinating. The ED physician catheterized the patient, ordered a urine culture, and discharged him.

The culture results, showing methicillin-resistant Staphylococcus aureus, were sent to a printer in the ED twice, as was the usual practice, but evidently no one saw them.

The patient returned to the ED 2 weeks after his initial visit with the same complaint of difficult urination and was seen by the same physician. The physician again discharged him with a catheter but without mentioning the culture results. Two days later, the patient suffered a stroke, which paralyzed his left side.

PLAINTIFF’S CLAIM The bacteria had spread from the patient’s urine to his bloodstream, sparking a cascade of events that led to the stroke.

THE DEFENSE No information about the defense is available.

VERDICT $2.25 million New Jersey settlement.

COMMENT The repeated missed opportunities to diagnose and treat this patient’s infection were regrettable—and costly.

Inadequate differential proves fatal

SHORTNESS OF BREATH led a 52-year-old woman to visit her medical group, where she was a long-time patient. The family practitioner who saw her noted tachycardia and ordered an electrocardiogram, which was abnormal. The physician also ordered a chest x-ray and, because the woman had a history of anemia, a complete blood count and a number of other blood tests. He subsequently called the patient at home to tell her that the blood tests were normal and she didn’t have anemia.

Three days later, the patient went to an urgent care center complaining of shortness of breath and tightness in her chest. A pulmonary embolism was diagnosed, and she was transferred to a hospital ED. Later that evening, a code blue was called and the patient was resuscitated. She died the following day.

PLAINTIFF’S CLAIM The doctor assumed that the patient had anemia and failed to develop a differential diagnosis. The patient had risk factors for pulmonary embolism—obesity and the use of an ethinyl estradiol-etonogestrel vaginal contraceptive ring—which should have prompted the doctor to consider that possibility. If he had done so, the pulmonary embolism would have been diagnosed and the patient’s death prevented.

THE DEFENSE The patient’s presentation wasn’t typical for pulmonary embolism, and there wasn’t any way to know whether an earlier diagnosis would have resulted in survival.

VERDICT $1.9 million California verdict.

COMMENT Although pulmonary embolism can be a challenging diagnosis to make, it needs to be considered carefully in all patients with shortness of breath, chest pain, or poorly defined pulmonary or cardiac symptoms.

The correct diagnosis comes too late

FLU-LIKE SYMPTOMS AND AN IRREGULAR HEART RATE prompted a man to go to the ED, where the physician diagnosed a viral infection, prescribed pain medication, and discharged him. The following day, a laboratory report indicating a staph infection was sent to an ED secretary, but the patient wasn’t told the results.

The patient returned to the hospital 2 days later in a confused state. Tests revealed a staph infection and meningitis, for which the patient received antibiotics. A week later, the patient suffered a stroke, resulting in diminished cognitive ability, impaired vision, and right-sided motor deficits.

PLAINTIFF’S CLAIM The white blood cell count and C-reactive protein level measured at the patient’s first visit to the ED would have led to a diagnosis of bacterial infection. The patient should have been admitted to the hospital and given antibiotics at that time.

THE DEFENSE The original diagnosis was reasonable.

VERDICT Confidential settlement with the hospital. $900,000 net verdict against the physician in New Jersey.

COMMENT Lab reports gone awry and the lack of a fail-safe for abnormal tests result in a $900,000 judgment. Do you have adequate systems in place to avoid a communication failure like this one?

Slow response turns a bad situation into a disaster

A 66-YEAR-OLD MAN on warfarin therapy for chronic atrial fibrillation and a transient ischemic attack underwent lithotripsy for kidney stones. Three days after the lithotripsy, he went to the ED complaining of severe flank pain. A computed tomography (CT) scan of the abdomen showed a large retroperitoneal hematoma and prominent perinephric and pararenal hemorrhages.

The patient remained on a gurney in the hallway of the ED in deteriorating condition until he was admitted to the intensive care unit, by which time his condition was critical. He died the next day.

PLAINTIFF’S CLAIM The ED physician and admitting urologists failed to monitor and treat the patient’s active hemorrhage for 9 hours. They didn’t order coagulation studies or respond to signs of escalating hemorrhagic shock. They failed to seek timely consults from surgery and interventional radiology.

THE DEFENSE No information about the defense is available.

VERDICT $825,000 Virginia settlement.

COMMENT Preventing complications of anticoagulation is hard enough; the lack of a timely response in this case made a bad outcome disastrous.

Were steps taken quickly enough?

SEVERE LOWER ABDOMINAL PAIN prompted a 52-year-old woman to go to the ED. She said she hadn’t had a bowel movement in almost a week. The ED physician, in consultation with the attending physician, admitted her to the hospital and ordered intravenous fluids and a soap suds enema, which didn’t relieve the constipation. The patient’s vital signs deteriorated, and she was crying and restless.

When the attending physician saw the patient almost 3 hours after admission, she had a fever of 101.4°F. He ordered additional tests, a computed tomography (CT) scan, and antibiotics, but didn’t order them STAT.

About 1½ hours later, a house physician examined the patient, and, after speaking with the attending physician, transferred her to a step-down telemetry unit. About 1½ hours after the transfer, a nurse called the house physician to report that the patient’s condition was worsening. The house physician ordered pain relievers and a second enema but didn’t come to the hospital.

Because the patient wasn’t in the intensive care unit, no one checked on her again for 3½ hours. When the nurse did check, she found the patient pale, cold, and turning blue. The nurse called the house physician, who came to the hospital. The patient had a fever of 102.4°F and her blood pressure couldn’t be measured.

After speaking with the attending physician, the house physician had the patient admitted to the ICU and also ordered a STAT surgical consultation and CT scan. In the meantime, the patient went into cardiac arrest and couldn’t be revived. Death was caused by peritonitis with sepsis resulting from a large intestinal obstruction.

PLAINTIFF’S CLAIM The patient showed early signs of sepsis. She should have undergone testing sooner and been transferred to the ICU earlier.

THE DEFENSE The doctors claimed that all their actions were appropriate and that the actions suggested by the plaintiff wouldn’t have resulted in the patient’s survival.

VERDICT $3.8 million Pennsylvania verdict.

COMMENT Prompt evaluation and monitoring of this patient might have prevented death and a substantial verdict.

2 analgesic calamities: Death by fentanyl patch …

AFTER A WEEK OF INCREASING BACK PAIN, which had begun to shoot down his right leg, a 37-year-old man went to the ED. He was examined and given prescriptions for pain killers, including acetaminophen and hydrocodone, and muscle relaxants and discharged with instructions to return in 3 days for magnetic resonance imaging (MRI).

While he was at the hospital for the MRI, the patient returned to the ED because he was still in pain and his acetaminophen-hydrocodone prescription was running out. The ED physician prescribed a 0.75-mg fentanyl transdermal patch and instructed the patient to put it on his chest.

Three days later, the patient filled the prescription and applied the patch. The following day, his girlfriend found him dead in bed. Postmortem toxicology results showed a blood fentanyl level of 9.85 ng/mL, markedly higher than the therapeutic level. Respiratory failure caused by fentanyl toxicity was cited as the cause of death.

PLAINTIFF’S CLAIM The ED physician prescribed an excessive dose of fentanyl.

THE DEFENSE A defective patch or misuse of the patch caused the patient’s death.

VERDICT $1.2 million Indiana verdict.

… and methadone

A 36-YEAR-OLD MAN started treatment with a pain specialist for pain arising from a back problem, for which he had taken pain medication previously. The pain specialist prescribed methadone, 360 10-mg tablets. The prescription limited the patient to 2 tablets every 4 hours for a maximum dosage of 12 tablets (120 mg) per day.

Three days after the patient filled the prescription, he was found dead. An autopsy determined the cause of death to be drug toxicity from methadone. At the time the patient died, the bottle of methadone tablets contained 342 tablets, indicating that he had taken only 18 tablets, well within the maximum dosage authorized by the prescription.

PLAINTIFF’S CLAIM The prescribed methadone dosage was excessive for a patient just beginning to use the drug. A proper initial dosage is between 2.5 and 10 mg every 8 to 12 hours for a maximum of 30 mg per day.

THE DEFENSE No information about the defense is available.

VERDICT Confidential Utah settlement.

COMMENT These 2 cases have a common thread. The effects of opioids are often idiosyncratic. A plan for careful monitoring and follow-up should be prepared at initiation of treatment and when escalating the dosage.

Culture results go undiscussed, man suffers stroke

TWO WEEKS AFTER PROSTATE SURGERY, a 76-year-old man went to the ED because he was having trouble urinating. The ED physician catheterized the patient, ordered a urine culture, and discharged him.

The culture results, showing methicillin-resistant Staphylococcus aureus, were sent to a printer in the ED twice, as was the usual practice, but evidently no one saw them.

The patient returned to the ED 2 weeks after his initial visit with the same complaint of difficult urination and was seen by the same physician. The physician again discharged him with a catheter but without mentioning the culture results. Two days later, the patient suffered a stroke, which paralyzed his left side.

PLAINTIFF’S CLAIM The bacteria had spread from the patient’s urine to his bloodstream, sparking a cascade of events that led to the stroke.

THE DEFENSE No information about the defense is available.

VERDICT $2.25 million New Jersey settlement.

COMMENT The repeated missed opportunities to diagnose and treat this patient’s infection were regrettable—and costly.

Inadequate differential proves fatal

SHORTNESS OF BREATH led a 52-year-old woman to visit her medical group, where she was a long-time patient. The family practitioner who saw her noted tachycardia and ordered an electrocardiogram, which was abnormal. The physician also ordered a chest x-ray and, because the woman had a history of anemia, a complete blood count and a number of other blood tests. He subsequently called the patient at home to tell her that the blood tests were normal and she didn’t have anemia.

Three days later, the patient went to an urgent care center complaining of shortness of breath and tightness in her chest. A pulmonary embolism was diagnosed, and she was transferred to a hospital ED. Later that evening, a code blue was called and the patient was resuscitated. She died the following day.

PLAINTIFF’S CLAIM The doctor assumed that the patient had anemia and failed to develop a differential diagnosis. The patient had risk factors for pulmonary embolism—obesity and the use of an ethinyl estradiol-etonogestrel vaginal contraceptive ring—which should have prompted the doctor to consider that possibility. If he had done so, the pulmonary embolism would have been diagnosed and the patient’s death prevented.

THE DEFENSE The patient’s presentation wasn’t typical for pulmonary embolism, and there wasn’t any way to know whether an earlier diagnosis would have resulted in survival.

VERDICT $1.9 million California verdict.

COMMENT Although pulmonary embolism can be a challenging diagnosis to make, it needs to be considered carefully in all patients with shortness of breath, chest pain, or poorly defined pulmonary or cardiac symptoms.

The correct diagnosis comes too late

FLU-LIKE SYMPTOMS AND AN IRREGULAR HEART RATE prompted a man to go to the ED, where the physician diagnosed a viral infection, prescribed pain medication, and discharged him. The following day, a laboratory report indicating a staph infection was sent to an ED secretary, but the patient wasn’t told the results.

The patient returned to the hospital 2 days later in a confused state. Tests revealed a staph infection and meningitis, for which the patient received antibiotics. A week later, the patient suffered a stroke, resulting in diminished cognitive ability, impaired vision, and right-sided motor deficits.

PLAINTIFF’S CLAIM The white blood cell count and C-reactive protein level measured at the patient’s first visit to the ED would have led to a diagnosis of bacterial infection. The patient should have been admitted to the hospital and given antibiotics at that time.

THE DEFENSE The original diagnosis was reasonable.

VERDICT Confidential settlement with the hospital. $900,000 net verdict against the physician in New Jersey.

COMMENT Lab reports gone awry and the lack of a fail-safe for abnormal tests result in a $900,000 judgment. Do you have adequate systems in place to avoid a communication failure like this one?

Slow response turns a bad situation into a disaster

A 66-YEAR-OLD MAN on warfarin therapy for chronic atrial fibrillation and a transient ischemic attack underwent lithotripsy for kidney stones. Three days after the lithotripsy, he went to the ED complaining of severe flank pain. A computed tomography (CT) scan of the abdomen showed a large retroperitoneal hematoma and prominent perinephric and pararenal hemorrhages.

The patient remained on a gurney in the hallway of the ED in deteriorating condition until he was admitted to the intensive care unit, by which time his condition was critical. He died the next day.

PLAINTIFF’S CLAIM The ED physician and admitting urologists failed to monitor and treat the patient’s active hemorrhage for 9 hours. They didn’t order coagulation studies or respond to signs of escalating hemorrhagic shock. They failed to seek timely consults from surgery and interventional radiology.

THE DEFENSE No information about the defense is available.

VERDICT $825,000 Virginia settlement.

COMMENT Preventing complications of anticoagulation is hard enough; the lack of a timely response in this case made a bad outcome disastrous.

Were steps taken quickly enough?

SEVERE LOWER ABDOMINAL PAIN prompted a 52-year-old woman to go to the ED. She said she hadn’t had a bowel movement in almost a week. The ED physician, in consultation with the attending physician, admitted her to the hospital and ordered intravenous fluids and a soap suds enema, which didn’t relieve the constipation. The patient’s vital signs deteriorated, and she was crying and restless.

When the attending physician saw the patient almost 3 hours after admission, she had a fever of 101.4°F. He ordered additional tests, a computed tomography (CT) scan, and antibiotics, but didn’t order them STAT.

About 1½ hours later, a house physician examined the patient, and, after speaking with the attending physician, transferred her to a step-down telemetry unit. About 1½ hours after the transfer, a nurse called the house physician to report that the patient’s condition was worsening. The house physician ordered pain relievers and a second enema but didn’t come to the hospital.

Because the patient wasn’t in the intensive care unit, no one checked on her again for 3½ hours. When the nurse did check, she found the patient pale, cold, and turning blue. The nurse called the house physician, who came to the hospital. The patient had a fever of 102.4°F and her blood pressure couldn’t be measured.

After speaking with the attending physician, the house physician had the patient admitted to the ICU and also ordered a STAT surgical consultation and CT scan. In the meantime, the patient went into cardiac arrest and couldn’t be revived. Death was caused by peritonitis with sepsis resulting from a large intestinal obstruction.

PLAINTIFF’S CLAIM The patient showed early signs of sepsis. She should have undergone testing sooner and been transferred to the ICU earlier.

THE DEFENSE The doctors claimed that all their actions were appropriate and that the actions suggested by the plaintiff wouldn’t have resulted in the patient’s survival.

VERDICT $3.8 million Pennsylvania verdict.

COMMENT Prompt evaluation and monitoring of this patient might have prevented death and a substantial verdict.

2 analgesic calamities: Death by fentanyl patch …

AFTER A WEEK OF INCREASING BACK PAIN, which had begun to shoot down his right leg, a 37-year-old man went to the ED. He was examined and given prescriptions for pain killers, including acetaminophen and hydrocodone, and muscle relaxants and discharged with instructions to return in 3 days for magnetic resonance imaging (MRI).

While he was at the hospital for the MRI, the patient returned to the ED because he was still in pain and his acetaminophen-hydrocodone prescription was running out. The ED physician prescribed a 0.75-mg fentanyl transdermal patch and instructed the patient to put it on his chest.

Three days later, the patient filled the prescription and applied the patch. The following day, his girlfriend found him dead in bed. Postmortem toxicology results showed a blood fentanyl level of 9.85 ng/mL, markedly higher than the therapeutic level. Respiratory failure caused by fentanyl toxicity was cited as the cause of death.

PLAINTIFF’S CLAIM The ED physician prescribed an excessive dose of fentanyl.

THE DEFENSE A defective patch or misuse of the patch caused the patient’s death.

VERDICT $1.2 million Indiana verdict.

… and methadone

A 36-YEAR-OLD MAN started treatment with a pain specialist for pain arising from a back problem, for which he had taken pain medication previously. The pain specialist prescribed methadone, 360 10-mg tablets. The prescription limited the patient to 2 tablets every 4 hours for a maximum dosage of 12 tablets (120 mg) per day.

Three days after the patient filled the prescription, he was found dead. An autopsy determined the cause of death to be drug toxicity from methadone. At the time the patient died, the bottle of methadone tablets contained 342 tablets, indicating that he had taken only 18 tablets, well within the maximum dosage authorized by the prescription.

PLAINTIFF’S CLAIM The prescribed methadone dosage was excessive for a patient just beginning to use the drug. A proper initial dosage is between 2.5 and 10 mg every 8 to 12 hours for a maximum of 30 mg per day.

THE DEFENSE No information about the defense is available.

VERDICT Confidential Utah settlement.

COMMENT These 2 cases have a common thread. The effects of opioids are often idiosyncratic. A plan for careful monitoring and follow-up should be prepared at initiation of treatment and when escalating the dosage.

Culture results go undiscussed, man suffers stroke

TWO WEEKS AFTER PROSTATE SURGERY, a 76-year-old man went to the ED because he was having trouble urinating. The ED physician catheterized the patient, ordered a urine culture, and discharged him.

The culture results, showing methicillin-resistant Staphylococcus aureus, were sent to a printer in the ED twice, as was the usual practice, but evidently no one saw them.

The patient returned to the ED 2 weeks after his initial visit with the same complaint of difficult urination and was seen by the same physician. The physician again discharged him with a catheter but without mentioning the culture results. Two days later, the patient suffered a stroke, which paralyzed his left side.

PLAINTIFF’S CLAIM The bacteria had spread from the patient’s urine to his bloodstream, sparking a cascade of events that led to the stroke.

THE DEFENSE No information about the defense is available.

VERDICT $2.25 million New Jersey settlement.

COMMENT The repeated missed opportunities to diagnose and treat this patient’s infection were regrettable—and costly.

Inadequate differential proves fatal

SHORTNESS OF BREATH led a 52-year-old woman to visit her medical group, where she was a long-time patient. The family practitioner who saw her noted tachycardia and ordered an electrocardiogram, which was abnormal. The physician also ordered a chest x-ray and, because the woman had a history of anemia, a complete blood count and a number of other blood tests. He subsequently called the patient at home to tell her that the blood tests were normal and she didn’t have anemia.

Three days later, the patient went to an urgent care center complaining of shortness of breath and tightness in her chest. A pulmonary embolism was diagnosed, and she was transferred to a hospital ED. Later that evening, a code blue was called and the patient was resuscitated. She died the following day.

PLAINTIFF’S CLAIM The doctor assumed that the patient had anemia and failed to develop a differential diagnosis. The patient had risk factors for pulmonary embolism—obesity and the use of an ethinyl estradiol-etonogestrel vaginal contraceptive ring—which should have prompted the doctor to consider that possibility. If he had done so, the pulmonary embolism would have been diagnosed and the patient’s death prevented.

THE DEFENSE The patient’s presentation wasn’t typical for pulmonary embolism, and there wasn’t any way to know whether an earlier diagnosis would have resulted in survival.

VERDICT $1.9 million California verdict.

COMMENT Although pulmonary embolism can be a challenging diagnosis to make, it needs to be considered carefully in all patients with shortness of breath, chest pain, or poorly defined pulmonary or cardiac symptoms.

The correct diagnosis comes too late

FLU-LIKE SYMPTOMS AND AN IRREGULAR HEART RATE prompted a man to go to the ED, where the physician diagnosed a viral infection, prescribed pain medication, and discharged him. The following day, a laboratory report indicating a staph infection was sent to an ED secretary, but the patient wasn’t told the results.

The patient returned to the hospital 2 days later in a confused state. Tests revealed a staph infection and meningitis, for which the patient received antibiotics. A week later, the patient suffered a stroke, resulting in diminished cognitive ability, impaired vision, and right-sided motor deficits.

PLAINTIFF’S CLAIM The white blood cell count and C-reactive protein level measured at the patient’s first visit to the ED would have led to a diagnosis of bacterial infection. The patient should have been admitted to the hospital and given antibiotics at that time.

THE DEFENSE The original diagnosis was reasonable.

VERDICT Confidential settlement with the hospital. $900,000 net verdict against the physician in New Jersey.

COMMENT Lab reports gone awry and the lack of a fail-safe for abnormal tests result in a $900,000 judgment. Do you have adequate systems in place to avoid a communication failure like this one?

Slow response turns a bad situation into a disaster

A 66-YEAR-OLD MAN on warfarin therapy for chronic atrial fibrillation and a transient ischemic attack underwent lithotripsy for kidney stones. Three days after the lithotripsy, he went to the ED complaining of severe flank pain. A computed tomography (CT) scan of the abdomen showed a large retroperitoneal hematoma and prominent perinephric and pararenal hemorrhages.

The patient remained on a gurney in the hallway of the ED in deteriorating condition until he was admitted to the intensive care unit, by which time his condition was critical. He died the next day.

PLAINTIFF’S CLAIM The ED physician and admitting urologists failed to monitor and treat the patient’s active hemorrhage for 9 hours. They didn’t order coagulation studies or respond to signs of escalating hemorrhagic shock. They failed to seek timely consults from surgery and interventional radiology.

THE DEFENSE No information about the defense is available.

VERDICT $825,000 Virginia settlement.

COMMENT Preventing complications of anticoagulation is hard enough; the lack of a timely response in this case made a bad outcome disastrous.

Were steps taken quickly enough?

SEVERE LOWER ABDOMINAL PAIN prompted a 52-year-old woman to go to the ED. She said she hadn’t had a bowel movement in almost a week. The ED physician, in consultation with the attending physician, admitted her to the hospital and ordered intravenous fluids and a soap suds enema, which didn’t relieve the constipation. The patient’s vital signs deteriorated, and she was crying and restless.

When the attending physician saw the patient almost 3 hours after admission, she had a fever of 101.4°F. He ordered additional tests, a computed tomography (CT) scan, and antibiotics, but didn’t order them STAT.

About 1½ hours later, a house physician examined the patient, and, after speaking with the attending physician, transferred her to a step-down telemetry unit. About 1½ hours after the transfer, a nurse called the house physician to report that the patient’s condition was worsening. The house physician ordered pain relievers and a second enema but didn’t come to the hospital.

Because the patient wasn’t in the intensive care unit, no one checked on her again for 3½ hours. When the nurse did check, she found the patient pale, cold, and turning blue. The nurse called the house physician, who came to the hospital. The patient had a fever of 102.4°F and her blood pressure couldn’t be measured.

After speaking with the attending physician, the house physician had the patient admitted to the ICU and also ordered a STAT surgical consultation and CT scan. In the meantime, the patient went into cardiac arrest and couldn’t be revived. Death was caused by peritonitis with sepsis resulting from a large intestinal obstruction.

PLAINTIFF’S CLAIM The patient showed early signs of sepsis. She should have undergone testing sooner and been transferred to the ICU earlier.

THE DEFENSE The doctors claimed that all their actions were appropriate and that the actions suggested by the plaintiff wouldn’t have resulted in the patient’s survival.

VERDICT $3.8 million Pennsylvania verdict.

COMMENT Prompt evaluation and monitoring of this patient might have prevented death and a substantial verdict.

2 analgesic calamities: Death by fentanyl patch …

AFTER A WEEK OF INCREASING BACK PAIN, which had begun to shoot down his right leg, a 37-year-old man went to the ED. He was examined and given prescriptions for pain killers, including acetaminophen and hydrocodone, and muscle relaxants and discharged with instructions to return in 3 days for magnetic resonance imaging (MRI).

While he was at the hospital for the MRI, the patient returned to the ED because he was still in pain and his acetaminophen-hydrocodone prescription was running out. The ED physician prescribed a 0.75-mg fentanyl transdermal patch and instructed the patient to put it on his chest.

Three days later, the patient filled the prescription and applied the patch. The following day, his girlfriend found him dead in bed. Postmortem toxicology results showed a blood fentanyl level of 9.85 ng/mL, markedly higher than the therapeutic level. Respiratory failure caused by fentanyl toxicity was cited as the cause of death.

PLAINTIFF’S CLAIM The ED physician prescribed an excessive dose of fentanyl.

THE DEFENSE A defective patch or misuse of the patch caused the patient’s death.

VERDICT $1.2 million Indiana verdict.

… and methadone

A 36-YEAR-OLD MAN started treatment with a pain specialist for pain arising from a back problem, for which he had taken pain medication previously. The pain specialist prescribed methadone, 360 10-mg tablets. The prescription limited the patient to 2 tablets every 4 hours for a maximum dosage of 12 tablets (120 mg) per day.

Three days after the patient filled the prescription, he was found dead. An autopsy determined the cause of death to be drug toxicity from methadone. At the time the patient died, the bottle of methadone tablets contained 342 tablets, indicating that he had taken only 18 tablets, well within the maximum dosage authorized by the prescription.

PLAINTIFF’S CLAIM The prescribed methadone dosage was excessive for a patient just beginning to use the drug. A proper initial dosage is between 2.5 and 10 mg every 8 to 12 hours for a maximum of 30 mg per day.

THE DEFENSE No information about the defense is available.

VERDICT Confidential Utah settlement.

COMMENT These 2 cases have a common thread. The effects of opioids are often idiosyncratic. A plan for careful monitoring and follow-up should be prepared at initiation of treatment and when escalating the dosage.

ILLUSTRATIVE CASE

Mr. H, age 75, underwent radical prostatectomy for prostate cancer a year ago. Since then, he leaks urine when he coughs and occasionally has complete loss of bladder control. His lack of control has forced him to curtail many of his normal activities and he wants to know what help you can provide.

Routine prostate-specific antigen (PSA) screening has led to an increase in the diagnosis of localized prostate cancer, and prostatectomy is a common treatment. Approximately 90,000 US men undergo radical prostatectomy each year,² and most are left with some degree of incontinence.

Years later, bladder control problems remain
Surgical advances have attempted to minimize nerve and bladder neck damage, but some degree of incontinence is still common after radical prostatectomy. According to the 2000 Prostate Cancer Outcomes Study, 80% of men experienced some incontinence 6 months after radical prostatectomy. After 2 years, 68% of men still had some degree of incontinence,³ and 8% reported frequent or total incontinence. Five years after prostatectomy, only 35% of patients reported complete bladder control vs 87% presurgery.⁴

A 2004 systematic review showed that behavioral therapy (mostly biofeedback) reduced symptoms in patients with all types of urinary incontinence.⁵ Many studies, including a 2010 Cochrane review,⁶ have shown that women with incontinence benefit from pelvic floor muscle training. No randomized trials have assessed the benefit of behavioral therapy for men with incontinence related to postprostatectomy—until now.

STUDY SUMMARY: Behavioral therapy has long-term payoff

The study by Goode et al was an RCT of behavioral therapy for men who had urinary incontinence after radical prostatectomy and whose symptoms persisted more than a year later. It included patients with ≥3 episodes of incontinence per week. Men were excluded if they were undergoing other treatment for prostate cancer, had a high postvoid residual volume or a history of certain bladder surgeries, or were unable to reliably report symptoms. Participants were permitted to continue taking medication for incontinence, with the exception of anticholinergics.

Participants (n=208 from 3 sites) were randomized to one of 3 arms in a blinded fashion with concealed allocation: behavioral therapy alone, behavioral therapy and biofeedback with electrical stimulation, or a control group of men who could elect to try these therapies at a later date.

Behavioral therapy consisted of 4 visits with a physician or nurse practitioner over an 8-week period. At the first visit, patients received instruction in pelvic floor muscle training. Patients then practiced contraction and relaxation exercises and urinary flow control at home. At the second visit, patients learned techniques to avoid episodes of incontinence, such as performing pelvic muscle contractions with stress symptom triggers. During the final 2 visits, patients received advice about control of persistent problems identified in symptom diaries they were required to keep. In addition, continued daily pelvic floor exercises were recommended at the last session.

Men in the group that received biofeedback with electrical stimulation had the same visit schedule, but received additional pelvic floor training—with electrode-mediated feedback and electrical stimulation of pelvic floor muscles during each visit and daily at home. Patients in the control group had the same visit frequency but received no treatment. After 8 weeks, however, the controls were given the opportunity to try behavioral therapy.

Baseline characteristics and attrition rates were similar in all 3 groups. Outcomes were based on an intention-to-treat analysis. At 8 weeks, men receiving behavioral therapy, with or without electrical stimulation and biofeedback, experienced a 55% decrease in incontinence (from 28 episodes per week at baseline to 13 per week); patients in the control group had a 24% decrease (from 25 episodes to 20 per week) (P=.001). More patients in the behavioral groups were completely continent at 8 weeks (16% vs 6% for the controls); the number needed to treat to achieve complete continence was 10. Electrical stimulation and biofeedback provided no added benefit compared with behavioral therapy alone.

Patients in the 2 treatment groups also had clinically significant benefits in some quality-of-life measures (impact of urinary symptoms on travel, emotion, and voiding) and in symptom-specific quality-of-life scores. Patient satisfaction at 8 weeks was higher in the treatment groups: 26 of the 58 men who received behavioral therapy were “delighted, pleased, or mostly satisfied,” vs 9 of 60 in the control group (P=.006 for overall group difference).

Adherence to the behavioral therapy protocol was 100% at 8 weeks and remained high (91%) one year later. Improvement in symptoms continued at one year, with patients in both treatment groups reporting a clinically significant (50%) reduction in incontinence episodes compared with baseline.

WHAT’S NEW: We have evidence-based help for postprostatectomy incontinence

We now have evidence that an 8-week program of pelvic floor training and bladder control strategies reduces the frequency of incontinence in men who have undergone radical prostatectomy.

CAVEATS: The effects of time weren’t factored in

Patients were obviously aware of group assignment, so there is the possibility of treatment bias contributing to the positive self-reported outcomes. While the treatment groups showed both a greater initial improvement and persistent improvement in their symptoms at one year, symptoms of patients in the control group were not measured after a year, so the sustained improvement could reflect resolution of incontinence with time.

CHALLENGES TO IMPLEMENTATION: Locating clinicians who can train patients

The type of behavioral therapy featured in this study may not be easily accessible to all patients. The researchers suggest consulting the National Association for Continence (http://www.nafc.org), a private nonprofit organization whose members include physical therapists, nurses, and physicians. They also cite the Wound Ostomy and Continence Nurses Society (http://www.wocn.org) as a resource in locating nurses who provide these services.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

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ILLUSTRATIVE CASE

Mr. H, age 75, underwent radical prostatectomy for prostate cancer a year ago. Since then, he leaks urine when he coughs and occasionally has complete loss of bladder control. His lack of control has forced him to curtail many of his normal activities and he wants to know what help you can provide.

Routine prostate-specific antigen (PSA) screening has led to an increase in the diagnosis of localized prostate cancer, and prostatectomy is a common treatment. Approximately 90,000 US men undergo radical prostatectomy each year,² and most are left with some degree of incontinence.

Years later, bladder control problems remain
Surgical advances have attempted to minimize nerve and bladder neck damage, but some degree of incontinence is still common after radical prostatectomy. According to the 2000 Prostate Cancer Outcomes Study, 80% of men experienced some incontinence 6 months after radical prostatectomy. After 2 years, 68% of men still had some degree of incontinence,³ and 8% reported frequent or total incontinence. Five years after prostatectomy, only 35% of patients reported complete bladder control vs 87% presurgery.⁴

A 2004 systematic review showed that behavioral therapy (mostly biofeedback) reduced symptoms in patients with all types of urinary incontinence.⁵ Many studies, including a 2010 Cochrane review,⁶ have shown that women with incontinence benefit from pelvic floor muscle training. No randomized trials have assessed the benefit of behavioral therapy for men with incontinence related to postprostatectomy—until now.

STUDY SUMMARY: Behavioral therapy has long-term payoff

The study by Goode et al was an RCT of behavioral therapy for men who had urinary incontinence after radical prostatectomy and whose symptoms persisted more than a year later. It included patients with ≥3 episodes of incontinence per week. Men were excluded if they were undergoing other treatment for prostate cancer, had a high postvoid residual volume or a history of certain bladder surgeries, or were unable to reliably report symptoms. Participants were permitted to continue taking medication for incontinence, with the exception of anticholinergics.

Participants (n=208 from 3 sites) were randomized to one of 3 arms in a blinded fashion with concealed allocation: behavioral therapy alone, behavioral therapy and biofeedback with electrical stimulation, or a control group of men who could elect to try these therapies at a later date.

Behavioral therapy consisted of 4 visits with a physician or nurse practitioner over an 8-week period. At the first visit, patients received instruction in pelvic floor muscle training. Patients then practiced contraction and relaxation exercises and urinary flow control at home. At the second visit, patients learned techniques to avoid episodes of incontinence, such as performing pelvic muscle contractions with stress symptom triggers. During the final 2 visits, patients received advice about control of persistent problems identified in symptom diaries they were required to keep. In addition, continued daily pelvic floor exercises were recommended at the last session.

Men in the group that received biofeedback with electrical stimulation had the same visit schedule, but received additional pelvic floor training—with electrode-mediated feedback and electrical stimulation of pelvic floor muscles during each visit and daily at home. Patients in the control group had the same visit frequency but received no treatment. After 8 weeks, however, the controls were given the opportunity to try behavioral therapy.

Baseline characteristics and attrition rates were similar in all 3 groups. Outcomes were based on an intention-to-treat analysis. At 8 weeks, men receiving behavioral therapy, with or without electrical stimulation and biofeedback, experienced a 55% decrease in incontinence (from 28 episodes per week at baseline to 13 per week); patients in the control group had a 24% decrease (from 25 episodes to 20 per week) (P=.001). More patients in the behavioral groups were completely continent at 8 weeks (16% vs 6% for the controls); the number needed to treat to achieve complete continence was 10. Electrical stimulation and biofeedback provided no added benefit compared with behavioral therapy alone.

Patients in the 2 treatment groups also had clinically significant benefits in some quality-of-life measures (impact of urinary symptoms on travel, emotion, and voiding) and in symptom-specific quality-of-life scores. Patient satisfaction at 8 weeks was higher in the treatment groups: 26 of the 58 men who received behavioral therapy were “delighted, pleased, or mostly satisfied,” vs 9 of 60 in the control group (P=.006 for overall group difference).

Adherence to the behavioral therapy protocol was 100% at 8 weeks and remained high (91%) one year later. Improvement in symptoms continued at one year, with patients in both treatment groups reporting a clinically significant (50%) reduction in incontinence episodes compared with baseline.

WHAT’S NEW: We have evidence-based help for postprostatectomy incontinence

We now have evidence that an 8-week program of pelvic floor training and bladder control strategies reduces the frequency of incontinence in men who have undergone radical prostatectomy.

CAVEATS: The effects of time weren’t factored in

Patients were obviously aware of group assignment, so there is the possibility of treatment bias contributing to the positive self-reported outcomes. While the treatment groups showed both a greater initial improvement and persistent improvement in their symptoms at one year, symptoms of patients in the control group were not measured after a year, so the sustained improvement could reflect resolution of incontinence with time.

CHALLENGES TO IMPLEMENTATION: Locating clinicians who can train patients

The type of behavioral therapy featured in this study may not be easily accessible to all patients. The researchers suggest consulting the National Association for Continence (http://www.nafc.org), a private nonprofit organization whose members include physical therapists, nurses, and physicians. They also cite the Wound Ostomy and Continence Nurses Society (http://www.wocn.org) as a resource in locating nurses who provide these services.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

Mr. H, age 75, underwent radical prostatectomy for prostate cancer a year ago. Since then, he leaks urine when he coughs and occasionally has complete loss of bladder control. His lack of control has forced him to curtail many of his normal activities and he wants to know what help you can provide.

Routine prostate-specific antigen (PSA) screening has led to an increase in the diagnosis of localized prostate cancer, and prostatectomy is a common treatment. Approximately 90,000 US men undergo radical prostatectomy each year,² and most are left with some degree of incontinence.

Years later, bladder control problems remain
Surgical advances have attempted to minimize nerve and bladder neck damage, but some degree of incontinence is still common after radical prostatectomy. According to the 2000 Prostate Cancer Outcomes Study, 80% of men experienced some incontinence 6 months after radical prostatectomy. After 2 years, 68% of men still had some degree of incontinence,³ and 8% reported frequent or total incontinence. Five years after prostatectomy, only 35% of patients reported complete bladder control vs 87% presurgery.⁴

A 2004 systematic review showed that behavioral therapy (mostly biofeedback) reduced symptoms in patients with all types of urinary incontinence.⁵ Many studies, including a 2010 Cochrane review,⁶ have shown that women with incontinence benefit from pelvic floor muscle training. No randomized trials have assessed the benefit of behavioral therapy for men with incontinence related to postprostatectomy—until now.

STUDY SUMMARY: Behavioral therapy has long-term payoff

The study by Goode et al was an RCT of behavioral therapy for men who had urinary incontinence after radical prostatectomy and whose symptoms persisted more than a year later. It included patients with ≥3 episodes of incontinence per week. Men were excluded if they were undergoing other treatment for prostate cancer, had a high postvoid residual volume or a history of certain bladder surgeries, or were unable to reliably report symptoms. Participants were permitted to continue taking medication for incontinence, with the exception of anticholinergics.

Participants (n=208 from 3 sites) were randomized to one of 3 arms in a blinded fashion with concealed allocation: behavioral therapy alone, behavioral therapy and biofeedback with electrical stimulation, or a control group of men who could elect to try these therapies at a later date.

Behavioral therapy consisted of 4 visits with a physician or nurse practitioner over an 8-week period. At the first visit, patients received instruction in pelvic floor muscle training. Patients then practiced contraction and relaxation exercises and urinary flow control at home. At the second visit, patients learned techniques to avoid episodes of incontinence, such as performing pelvic muscle contractions with stress symptom triggers. During the final 2 visits, patients received advice about control of persistent problems identified in symptom diaries they were required to keep. In addition, continued daily pelvic floor exercises were recommended at the last session.

Men in the group that received biofeedback with electrical stimulation had the same visit schedule, but received additional pelvic floor training—with electrode-mediated feedback and electrical stimulation of pelvic floor muscles during each visit and daily at home. Patients in the control group had the same visit frequency but received no treatment. After 8 weeks, however, the controls were given the opportunity to try behavioral therapy.

Baseline characteristics and attrition rates were similar in all 3 groups. Outcomes were based on an intention-to-treat analysis. At 8 weeks, men receiving behavioral therapy, with or without electrical stimulation and biofeedback, experienced a 55% decrease in incontinence (from 28 episodes per week at baseline to 13 per week); patients in the control group had a 24% decrease (from 25 episodes to 20 per week) (P=.001). More patients in the behavioral groups were completely continent at 8 weeks (16% vs 6% for the controls); the number needed to treat to achieve complete continence was 10. Electrical stimulation and biofeedback provided no added benefit compared with behavioral therapy alone.

Patients in the 2 treatment groups also had clinically significant benefits in some quality-of-life measures (impact of urinary symptoms on travel, emotion, and voiding) and in symptom-specific quality-of-life scores. Patient satisfaction at 8 weeks was higher in the treatment groups: 26 of the 58 men who received behavioral therapy were “delighted, pleased, or mostly satisfied,” vs 9 of 60 in the control group (P=.006 for overall group difference).

Adherence to the behavioral therapy protocol was 100% at 8 weeks and remained high (91%) one year later. Improvement in symptoms continued at one year, with patients in both treatment groups reporting a clinically significant (50%) reduction in incontinence episodes compared with baseline.

WHAT’S NEW: We have evidence-based help for postprostatectomy incontinence

We now have evidence that an 8-week program of pelvic floor training and bladder control strategies reduces the frequency of incontinence in men who have undergone radical prostatectomy.

CAVEATS: The effects of time weren’t factored in

Patients were obviously aware of group assignment, so there is the possibility of treatment bias contributing to the positive self-reported outcomes. While the treatment groups showed both a greater initial improvement and persistent improvement in their symptoms at one year, symptoms of patients in the control group were not measured after a year, so the sustained improvement could reflect resolution of incontinence with time.

CHALLENGES TO IMPLEMENTATION: Locating clinicians who can train patients

The type of behavioral therapy featured in this study may not be easily accessible to all patients. The researchers suggest consulting the National Association for Continence (http://www.nafc.org), a private nonprofit organization whose members include physical therapists, nurses, and physicians. They also cite the Wound Ostomy and Continence Nurses Society (http://www.wocn.org) as a resource in locating nurses who provide these services.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

Nausea, Vomiting, and Weakness for 4 days prompted a 76-year-old woman to seek care at our hospital. She was admitted for possible large bowel obstruction and severe dehydration. Her medical history was significant for a metastatic lung cancer to the mediastinal lymph nodes and to the left hip (for which she underwent a hip replacement 4 months earlier), anemia, and diverticulosis.

On Day 1 of her hospital stay, the patient became hypotensive and developed labored breathing. She also had mottled skin and cool fingertips with poor capillary refill. Her abdomen was distended, firm, and diffusely tympanic with diffuse pain to deep palpation and absent bowel sounds.

Her laboratory values revealed leukocytosis (with a significant left shift), metabolic acidosis, and an elevated lactic acid level. Her upright chest x-ray (FIGURE) is shown. The patient was transferred to the intensive care unit for further management.

FIGURE
Upright chest x-ray

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Pneumoperitoneum

This patient had free air under her diaphragm (due to a viscus perforation) and concomitant septic shock. Free air in the peritoneal cavity—pneumoperitoneum— indicates visceral perforation in 85% to 95% of cases.^1,2 A ruptured intra-abdominal viscus is considered a surgical emergency. Pneumoperitoneum is often linked to peptic ulcer disease and is seen in 50% of cases of bowel perforations.³ This condition has a higher prevalence in the elderly and carries a higher mortality rate (up to 30% compared with 19% in a younger population).⁴

A picture that shifts according to the patient’s age
Physical findings suggestive of visceral perforation include sharp abdominal pain with a rigid abdominal wall. Patients will usually lie still because of the peritoneal irritation. Tachycardia and tachypnea are seen early in the disease process, while hypotension and fever usually develop within 4 to 6 hours.⁵

Elderly patients, however, can present with milder or nonspecific symptoms. Rather than pain, they may complain of the urge to defecate. Physical exam findings such as tachycardia or fever can also be absent due to autonomic dysregulation or medication. Furthermore, laboratory analysis is commonly within normal limits, making the diagnosis even more challenging in this population.^5,6

Imaging confirms the Dx

The standard imaging test used to confirm pneumoperitoneum is a standing chest x-ray that will detect free air in almost 80% of cases.⁷ The sensitivity is influenced by the location of the perforation: Free air will be seen in 69% of gastroduodenal perforations, 30% to 41% of distal small bowel perforations, and 37% to 46% of large bowel perforations.¹ Abdominal computed tomography scans have been reported to be more sensitive (up to 100%), especially in identifying small pneumoperitoneum.^8,9

Surgery is the next step

Management of pneumoperitoneum includes a prompt surgical consult for a possible emergent laparotomy, nasogastric suctioning, supportive measures for blood pressure, and broad-spectrum antibiotics such as a fourth-generation penicillin or a third-generation cephalosporin plus metronidazole.¹⁰

The end of the fight
Given the high mortality rate and the atypical presentation of perforated viscus in the elderly, it is important to maintain a high index of suspicion in this population and to intervene rapidly to improve the outcome.

In the case of our patient, the family followed her wishes and declined surgery. She was aggressively managed with broad-spectrum antibiotics, IV fluids, and vasopressors—but unfortunately died 2 days later.

CORRESPONDENCE Balaji Yegneswaran, MD, University of Pittsburgh Medical Center, 651, Scaife Hall, Pittsburgh, PA 15261; [email protected]

Nausea, Vomiting, and Weakness for 4 days prompted a 76-year-old woman to seek care at our hospital. She was admitted for possible large bowel obstruction and severe dehydration. Her medical history was significant for a metastatic lung cancer to the mediastinal lymph nodes and to the left hip (for which she underwent a hip replacement 4 months earlier), anemia, and diverticulosis.

On Day 1 of her hospital stay, the patient became hypotensive and developed labored breathing. She also had mottled skin and cool fingertips with poor capillary refill. Her abdomen was distended, firm, and diffusely tympanic with diffuse pain to deep palpation and absent bowel sounds.

Her laboratory values revealed leukocytosis (with a significant left shift), metabolic acidosis, and an elevated lactic acid level. Her upright chest x-ray (FIGURE) is shown. The patient was transferred to the intensive care unit for further management.

FIGURE
Upright chest x-ray

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Pneumoperitoneum

This patient had free air under her diaphragm (due to a viscus perforation) and concomitant septic shock. Free air in the peritoneal cavity—pneumoperitoneum— indicates visceral perforation in 85% to 95% of cases.^1,2 A ruptured intra-abdominal viscus is considered a surgical emergency. Pneumoperitoneum is often linked to peptic ulcer disease and is seen in 50% of cases of bowel perforations.³ This condition has a higher prevalence in the elderly and carries a higher mortality rate (up to 30% compared with 19% in a younger population).⁴

A picture that shifts according to the patient’s age
Physical findings suggestive of visceral perforation include sharp abdominal pain with a rigid abdominal wall. Patients will usually lie still because of the peritoneal irritation. Tachycardia and tachypnea are seen early in the disease process, while hypotension and fever usually develop within 4 to 6 hours.⁵

Elderly patients, however, can present with milder or nonspecific symptoms. Rather than pain, they may complain of the urge to defecate. Physical exam findings such as tachycardia or fever can also be absent due to autonomic dysregulation or medication. Furthermore, laboratory analysis is commonly within normal limits, making the diagnosis even more challenging in this population.^5,6

Imaging confirms the Dx

The standard imaging test used to confirm pneumoperitoneum is a standing chest x-ray that will detect free air in almost 80% of cases.⁷ The sensitivity is influenced by the location of the perforation: Free air will be seen in 69% of gastroduodenal perforations, 30% to 41% of distal small bowel perforations, and 37% to 46% of large bowel perforations.¹ Abdominal computed tomography scans have been reported to be more sensitive (up to 100%), especially in identifying small pneumoperitoneum.^8,9

Surgery is the next step

Management of pneumoperitoneum includes a prompt surgical consult for a possible emergent laparotomy, nasogastric suctioning, supportive measures for blood pressure, and broad-spectrum antibiotics such as a fourth-generation penicillin or a third-generation cephalosporin plus metronidazole.¹⁰

The end of the fight
Given the high mortality rate and the atypical presentation of perforated viscus in the elderly, it is important to maintain a high index of suspicion in this population and to intervene rapidly to improve the outcome.

In the case of our patient, the family followed her wishes and declined surgery. She was aggressively managed with broad-spectrum antibiotics, IV fluids, and vasopressors—but unfortunately died 2 days later.

CORRESPONDENCE Balaji Yegneswaran, MD, University of Pittsburgh Medical Center, 651, Scaife Hall, Pittsburgh, PA 15261; [email protected]

Nausea, Vomiting, and Weakness for 4 days prompted a 76-year-old woman to seek care at our hospital. She was admitted for possible large bowel obstruction and severe dehydration. Her medical history was significant for a metastatic lung cancer to the mediastinal lymph nodes and to the left hip (for which she underwent a hip replacement 4 months earlier), anemia, and diverticulosis.

On Day 1 of her hospital stay, the patient became hypotensive and developed labored breathing. She also had mottled skin and cool fingertips with poor capillary refill. Her abdomen was distended, firm, and diffusely tympanic with diffuse pain to deep palpation and absent bowel sounds.

Her laboratory values revealed leukocytosis (with a significant left shift), metabolic acidosis, and an elevated lactic acid level. Her upright chest x-ray (FIGURE) is shown. The patient was transferred to the intensive care unit for further management.

FIGURE
Upright chest x-ray

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Pneumoperitoneum

This patient had free air under her diaphragm (due to a viscus perforation) and concomitant septic shock. Free air in the peritoneal cavity—pneumoperitoneum— indicates visceral perforation in 85% to 95% of cases.^1,2 A ruptured intra-abdominal viscus is considered a surgical emergency. Pneumoperitoneum is often linked to peptic ulcer disease and is seen in 50% of cases of bowel perforations.³ This condition has a higher prevalence in the elderly and carries a higher mortality rate (up to 30% compared with 19% in a younger population).⁴

A picture that shifts according to the patient’s age
Physical findings suggestive of visceral perforation include sharp abdominal pain with a rigid abdominal wall. Patients will usually lie still because of the peritoneal irritation. Tachycardia and tachypnea are seen early in the disease process, while hypotension and fever usually develop within 4 to 6 hours.⁵

Elderly patients, however, can present with milder or nonspecific symptoms. Rather than pain, they may complain of the urge to defecate. Physical exam findings such as tachycardia or fever can also be absent due to autonomic dysregulation or medication. Furthermore, laboratory analysis is commonly within normal limits, making the diagnosis even more challenging in this population.^5,6

Imaging confirms the Dx

The standard imaging test used to confirm pneumoperitoneum is a standing chest x-ray that will detect free air in almost 80% of cases.⁷ The sensitivity is influenced by the location of the perforation: Free air will be seen in 69% of gastroduodenal perforations, 30% to 41% of distal small bowel perforations, and 37% to 46% of large bowel perforations.¹ Abdominal computed tomography scans have been reported to be more sensitive (up to 100%), especially in identifying small pneumoperitoneum.^8,9

Surgery is the next step

Management of pneumoperitoneum includes a prompt surgical consult for a possible emergent laparotomy, nasogastric suctioning, supportive measures for blood pressure, and broad-spectrum antibiotics such as a fourth-generation penicillin or a third-generation cephalosporin plus metronidazole.¹⁰

The end of the fight
Given the high mortality rate and the atypical presentation of perforated viscus in the elderly, it is important to maintain a high index of suspicion in this population and to intervene rapidly to improve the outcome.

In the case of our patient, the family followed her wishes and declined surgery. She was aggressively managed with broad-spectrum antibiotics, IV fluids, and vasopressors—but unfortunately died 2 days later.

CORRESPONDENCE Balaji Yegneswaran, MD, University of Pittsburgh Medical Center, 651, Scaife Hall, Pittsburgh, PA 15261; [email protected]

Various media outlets have sensationalized your article on colon cleansing, “The dangers of colon cleansing” (J Fam Pract. 2011;60:454-457). The article has been perceived by many as a generic criticism of many forms of colon cleansing, with some inappropriate conclusions about widespread harm.

The article included 2 case reports that were incomplete and unclear; no specific diagnosis was made in either case. Authors Mishori et al tried to ascribe negative outcomes to colon cleansing, but the co-mingling of different treatments is apparent in their writing. In other words, colonic hydrotherapy and laxative agents are 2 quite distinct treatments used to facilitate the passage of stool, with different mechanisms of action and potential outcomes, beneficial or otherwise. The authors, in effect, compared apples and oranges, then reached conclusions about colon cleansing that were potentially misleading, generalized, or even naïve.

The first case report described an alleged negative outcome of colon hydrotherapy (colonic irrigation), which may or may not have been directly attributable to the procedure. Furthermore, the procedure was undertaken in an individual with Crohn’s disease, a clear contraindication. To conclude from this case report that colon hydrotherapy is harmful overall has no scientific basis.

The second case report involved the consumption of some form of herbal laxative formula that is not disclosed by the authors. The gastroenterologist who performed a colonoscopy and biopsy on this patient reached a “diagnosis” of “herbal intoxication,” in the presence of some histological evidence of both acute and chronic inflammation.

In both case reports, the actual underlying diagnosis is not clear. One could construct a differential diagnosis that could explain the complaints of these patients as a consequence of events unrelated to the act of colon cleansing.

While I agree that a clear evidence base to support the widespread practice of colonic irrigation is not available in current scientific literature, the procedure should not be summarily condemned. Many individuals report beneficial outcomes of colon hydrotherapy, even if such data are anecdotal and not archived with consistency.

My principal criticism of this article is that it did not present a complete or balanced perspective on the alleged dangers of the procedures in question. The authors failed to acknowledge that the frequency of reported complications of colon hydrotherapy may be significantly less than those reported with various diagnostic tests, such as barium enema examination, sigmoidoscopy, or colonoscopy.

I encourage your readers not to summarily reject “colon cleansing.” I submit that Mishori et al failed to fulfill the criteria for concluding that the act of colon cleansing is overly dangerous or ineffective when applied in an appropriate or medically indicated manner.

Stephen Holt, MD, DSc
Little Falls, NJ

Various media outlets have sensationalized your article on colon cleansing, “The dangers of colon cleansing” (J Fam Pract. 2011;60:454-457). The article has been perceived by many as a generic criticism of many forms of colon cleansing, with some inappropriate conclusions about widespread harm.

The article included 2 case reports that were incomplete and unclear; no specific diagnosis was made in either case. Authors Mishori et al tried to ascribe negative outcomes to colon cleansing, but the co-mingling of different treatments is apparent in their writing. In other words, colonic hydrotherapy and laxative agents are 2 quite distinct treatments used to facilitate the passage of stool, with different mechanisms of action and potential outcomes, beneficial or otherwise. The authors, in effect, compared apples and oranges, then reached conclusions about colon cleansing that were potentially misleading, generalized, or even naïve.

The first case report described an alleged negative outcome of colon hydrotherapy (colonic irrigation), which may or may not have been directly attributable to the procedure. Furthermore, the procedure was undertaken in an individual with Crohn’s disease, a clear contraindication. To conclude from this case report that colon hydrotherapy is harmful overall has no scientific basis.

The second case report involved the consumption of some form of herbal laxative formula that is not disclosed by the authors. The gastroenterologist who performed a colonoscopy and biopsy on this patient reached a “diagnosis” of “herbal intoxication,” in the presence of some histological evidence of both acute and chronic inflammation.

In both case reports, the actual underlying diagnosis is not clear. One could construct a differential diagnosis that could explain the complaints of these patients as a consequence of events unrelated to the act of colon cleansing.

While I agree that a clear evidence base to support the widespread practice of colonic irrigation is not available in current scientific literature, the procedure should not be summarily condemned. Many individuals report beneficial outcomes of colon hydrotherapy, even if such data are anecdotal and not archived with consistency.

My principal criticism of this article is that it did not present a complete or balanced perspective on the alleged dangers of the procedures in question. The authors failed to acknowledge that the frequency of reported complications of colon hydrotherapy may be significantly less than those reported with various diagnostic tests, such as barium enema examination, sigmoidoscopy, or colonoscopy.

I encourage your readers not to summarily reject “colon cleansing.” I submit that Mishori et al failed to fulfill the criteria for concluding that the act of colon cleansing is overly dangerous or ineffective when applied in an appropriate or medically indicated manner.

Stephen Holt, MD, DSc
Little Falls, NJ

Various media outlets have sensationalized your article on colon cleansing, “The dangers of colon cleansing” (J Fam Pract. 2011;60:454-457). The article has been perceived by many as a generic criticism of many forms of colon cleansing, with some inappropriate conclusions about widespread harm.

The article included 2 case reports that were incomplete and unclear; no specific diagnosis was made in either case. Authors Mishori et al tried to ascribe negative outcomes to colon cleansing, but the co-mingling of different treatments is apparent in their writing. In other words, colonic hydrotherapy and laxative agents are 2 quite distinct treatments used to facilitate the passage of stool, with different mechanisms of action and potential outcomes, beneficial or otherwise. The authors, in effect, compared apples and oranges, then reached conclusions about colon cleansing that were potentially misleading, generalized, or even naïve.

The first case report described an alleged negative outcome of colon hydrotherapy (colonic irrigation), which may or may not have been directly attributable to the procedure. Furthermore, the procedure was undertaken in an individual with Crohn’s disease, a clear contraindication. To conclude from this case report that colon hydrotherapy is harmful overall has no scientific basis.

The second case report involved the consumption of some form of herbal laxative formula that is not disclosed by the authors. The gastroenterologist who performed a colonoscopy and biopsy on this patient reached a “diagnosis” of “herbal intoxication,” in the presence of some histological evidence of both acute and chronic inflammation.

In both case reports, the actual underlying diagnosis is not clear. One could construct a differential diagnosis that could explain the complaints of these patients as a consequence of events unrelated to the act of colon cleansing.

While I agree that a clear evidence base to support the widespread practice of colonic irrigation is not available in current scientific literature, the procedure should not be summarily condemned. Many individuals report beneficial outcomes of colon hydrotherapy, even if such data are anecdotal and not archived with consistency.

My principal criticism of this article is that it did not present a complete or balanced perspective on the alleged dangers of the procedures in question. The authors failed to acknowledge that the frequency of reported complications of colon hydrotherapy may be significantly less than those reported with various diagnostic tests, such as barium enema examination, sigmoidoscopy, or colonoscopy.

I encourage your readers not to summarily reject “colon cleansing.” I submit that Mishori et al failed to fulfill the criteria for concluding that the act of colon cleansing is overly dangerous or ineffective when applied in an appropriate or medically indicated manner.

Stephen Holt, MD, DSc
Little Falls, NJ

Evidence summary

A Cochrane review of 14 randomized and quasi-randomized trials concluded that patients who used external ankle supports, such as semi-rigid orthotics or air cast braces, suffered significantly fewer ankle sprains than controls (relative risk [RR]=0.53; 95% confidence interval [CI], 0.40-0.69; number needed to treat [NNT]=22).¹ Participants in the trials ranged in age from adolescence to middle age and were either at risk of injury or had suffered a previous ligament injury.

The benefits of ankle supports were most apparent in patients with previous injuries but still evident in patients who hadn’t been injured. External ankle support is recommended for sports with a high risk of ankle injury, such as soccer and basketball, but the decision to use it should be based on perceived risk of injury as opposed to perceived loss of performance.¹

Research is insufficient to support wearing high-top shoes to prevent primary and secondary ankle sprains.

Also helpful: Balance and proprioceptive training
A systematic review of 2 RCTs with 703 and 1057 patients concluded that completing a minimum of 6 weeks of balance and coordination training after an acute injury substantially reduced the risk of recurrent ankle sprains for as long as a year (NNT=22; absolute risk reduction=4.5%).²

Proprioceptive training appears to effectively prevent primary and secondary ankle injuries but is more beneficial for patients with a previous ankle injury. A recent RCT that enrolled 522 active sports participants with recent ankle injuries found that those who completed an 8-week, self-guided, proprioceptive training program suffered significantly fewer recurrent sprains at 1 year than the control group (22% vs 33%; relative risk reduction=35%; NNT=9).³

Recommendations

The American Orthopaedic Society for Sports Medicine continues to endorse rest, ice, compression, and elevation for optimal initial care of ankle sprains.⁴ The American College of Sports Medicine suggests that rehabilitation after an ankle injury should include guided stretching and strengthening of the ankle joint as well as balance training to prevent future injuries.⁵ Both groups also recommend external ankle supports instead of taping to prevent ankle reinjury.^4,5

Evidence summary

A Cochrane review of 14 randomized and quasi-randomized trials concluded that patients who used external ankle supports, such as semi-rigid orthotics or air cast braces, suffered significantly fewer ankle sprains than controls (relative risk [RR]=0.53; 95% confidence interval [CI], 0.40-0.69; number needed to treat [NNT]=22).¹ Participants in the trials ranged in age from adolescence to middle age and were either at risk of injury or had suffered a previous ligament injury.

The benefits of ankle supports were most apparent in patients with previous injuries but still evident in patients who hadn’t been injured. External ankle support is recommended for sports with a high risk of ankle injury, such as soccer and basketball, but the decision to use it should be based on perceived risk of injury as opposed to perceived loss of performance.¹

Research is insufficient to support wearing high-top shoes to prevent primary and secondary ankle sprains.

Also helpful: Balance and proprioceptive training
A systematic review of 2 RCTs with 703 and 1057 patients concluded that completing a minimum of 6 weeks of balance and coordination training after an acute injury substantially reduced the risk of recurrent ankle sprains for as long as a year (NNT=22; absolute risk reduction=4.5%).²

Proprioceptive training appears to effectively prevent primary and secondary ankle injuries but is more beneficial for patients with a previous ankle injury. A recent RCT that enrolled 522 active sports participants with recent ankle injuries found that those who completed an 8-week, self-guided, proprioceptive training program suffered significantly fewer recurrent sprains at 1 year than the control group (22% vs 33%; relative risk reduction=35%; NNT=9).³

Recommendations

The American Orthopaedic Society for Sports Medicine continues to endorse rest, ice, compression, and elevation for optimal initial care of ankle sprains.⁴ The American College of Sports Medicine suggests that rehabilitation after an ankle injury should include guided stretching and strengthening of the ankle joint as well as balance training to prevent future injuries.⁵ Both groups also recommend external ankle supports instead of taping to prevent ankle reinjury.^4,5

Evidence summary

A Cochrane review of 14 randomized and quasi-randomized trials concluded that patients who used external ankle supports, such as semi-rigid orthotics or air cast braces, suffered significantly fewer ankle sprains than controls (relative risk [RR]=0.53; 95% confidence interval [CI], 0.40-0.69; number needed to treat [NNT]=22).¹ Participants in the trials ranged in age from adolescence to middle age and were either at risk of injury or had suffered a previous ligament injury.

The benefits of ankle supports were most apparent in patients with previous injuries but still evident in patients who hadn’t been injured. External ankle support is recommended for sports with a high risk of ankle injury, such as soccer and basketball, but the decision to use it should be based on perceived risk of injury as opposed to perceived loss of performance.¹

Research is insufficient to support wearing high-top shoes to prevent primary and secondary ankle sprains.

Also helpful: Balance and proprioceptive training
A systematic review of 2 RCTs with 703 and 1057 patients concluded that completing a minimum of 6 weeks of balance and coordination training after an acute injury substantially reduced the risk of recurrent ankle sprains for as long as a year (NNT=22; absolute risk reduction=4.5%).²

Proprioceptive training appears to effectively prevent primary and secondary ankle injuries but is more beneficial for patients with a previous ankle injury. A recent RCT that enrolled 522 active sports participants with recent ankle injuries found that those who completed an 8-week, self-guided, proprioceptive training program suffered significantly fewer recurrent sprains at 1 year than the control group (22% vs 33%; relative risk reduction=35%; NNT=9).³

Recommendations

The American Orthopaedic Society for Sports Medicine continues to endorse rest, ice, compression, and elevation for optimal initial care of ankle sprains.⁴ The American College of Sports Medicine suggests that rehabilitation after an ankle injury should include guided stretching and strengthening of the ankle joint as well as balance training to prevent future injuries.⁵ Both groups also recommend external ankle supports instead of taping to prevent ankle reinjury.^4,5

There are enough challenges in controlling diabetes mellitus without the hindrance of undetected problematic alcohol use. The good news is that asking a single nonthreatening question can help you detect at-risk drinking—defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as 5 or more drinks on one occasion or more than 14 drinks per week for men; and 4 or more drinks on one occasion or more than 7 drinks per week for women.^1,2 And, for patients who may be compromising their diabetes care and overall health through problem drinking, brief intervention techniques used in the office can enable them to reduce alcohol consumption significantly.

When alcohol becomes a problem in diabetes care

Several studies have explored the long-term benefits of moderate alcohol use on glycemic control—with mixed results. A 2007 study found that diabetes patients who drink 1 glass of wine per day exhibited a lower fasting glucose level than abstainers after 3 months.³ There was no difference, however, on postprandial glucose levels. A 2008 study found that individuals who drank one to 2 glasses of wine per day for a month had lower fasting serum insulin levels relative to when they have abstained for a month,⁴ although levels of fasting plasma cholesterol, HDL cholesterol, glucose, and hemoglobin A1c (HbA_1c) remained unchanged relative to periods of abstinence.⁴

Furthermore, rates of coronary heart disease and CHD mortality in a meta-analysis were significantly lower in 3 categories of alcohol consumption (<6 g/d, 6 to <18 g/d, and ≥18 g/d) compared with abstinence.⁵ Nondrinkers also had a greater risk of total mortality compared with the lightest drinking group. Notably, however, the lower limit of the highest drinking category was only 1.5 drinks per day.

How big is the problem? In a study of insulin-treated patients seen for severe hypoglycemia, 17% had been drinking before the episode.⁶ In a primary care sample, 28% of randomly selected patients with type 2 diabetes met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a lifetime incidence of alcohol abuse and 13% met either current or lifetime criteria for alcohol dependence.⁷ Another study of primary care patients with diabetes⁸ found that 13.4% met NIAAA criteria for at-risk drinking; 11.1% of these at-risk drinkers met criteria for current alcohol dependence. (According to the NIAAA, the rate of at-risk/heavy drinking among US adults is 30%, and about one in 4 heavy drinkers meets the criteria for alcohol abuse or dependence.¹)

Detrimental effects with immoderate drinking. Individuals who engage in at-risk drinking, as defined by the NIAAA, are at increased risk for alcohol dependence⁹ and associated complications such as diabetic neuropathy and retinopathy,¹⁰ atherosclerosis,¹¹ and total and CHD mortality.^3,12 Heavy drinking also interferes with neuroendocrine, gastrointestinal, and sexual function,¹³ and its interaction with diabetes increases the risk for hepatocellular carcinoma after controlling for hepatitis B and C serology.¹⁴

Interference with diabetes control. Research examining the short-term effect of alcohol use has produced contradictory results, partly due to differences among studies, such as whether alcohol is administered with a meal and whether a fasting glucose level is measured.¹⁵ However, alcohol affects glycemic control and, when used excessively, can impair glucose production.^16,17 Alcohol may induce hypoglycemia,^10,18 and even small amounts may jeopardize diabetes control.¹³ In a study of patients with insulin-treated diabetes, alcohol use in the presence of mild hypoglycemia increased diastolic blood pressure or exacerbated hypoglycemia-related cognitive deficits.¹⁹ Another concern—in both the short and long term—is that alcohol interacts negatively with certain diabetes medications. It is more likely to induce hypoglycemia in the presence of sulfonylurea medications.¹⁰ Chlorpropamide decreases the rate of ethanol elimination from the blood.²⁰ And, in those taking metformin, excessive alcohol use elevates risk for lactic acidosis. ²¹

Diminished self-care. Alcohol use can interfere with self-care,^22,23 which is a crucial component of diabetes treatment.²⁴ It may lead to reduced eating¹⁶ or to decreased willingness to adhere to prescribed dietary regimens.¹³ It also impairs other self-care behaviors^13,15,25 such as self-monitoring blood glucose and showing up for medical appointments.²⁶ In a large, diverse sample of patients with diabetes,²⁴ heavy drinkers had the highest rates of morbidity. Importantly, alcohol and diabetes self-care behavior were significantly negatively associated. Studies of ethnic minority samples have yielded comparable results.²⁷

Assessing alcohol use: Obstacles and solutions

Although alcohol use can be readily evaluated during routine primary care appointments, it is often neglected, perhaps due to a lack of awareness about its impact on diabetes.¹⁵ Those who are most often assessed tend to have a psychiatric diagnosis or other condition raising a red flag for physicians.²⁸ When internists, general practitioners, and psychiatrists were questioned in a study regarding patients’ alcohol and drug use, all 3 groups were misinformed about which substance-use treatments were empirically supported²⁹ and did not believe that treatment for alcohol abuse held much promise. Another study showed that physicians can be reluctant to screen for alcohol use because of the difficulty in recognizing a problem, the perceived unimportance of alcohol use as a health risk, a supposed lack of adequate intervention tools, and a fear of stigmatizing patients.³⁰ Physicians are more likely to discuss alcohol use under certain extreme conditions such as when a patient smells of alcohol.

Multiple opportunities to ask in the VA system. In the Veterans Health Administration, primary care VA providers have reported that prompts for alcohol screening embedded in computerized progress notes, clinical reminder lists, and annual health evaluation forms encourage them to assess alcohol use. Other useful materials include manual checklists and reference cards.³¹ These providers also report that education, feedback on rates of alcohol screening, and increased supervision facilitate assessment. Finally, providers indicate that asking nurses or clerical staff to administer the screen improves completion rates.

Ask a simple question

“How often have you had a drink containing alcohol in the last year?” or “How many drinks containing alcohol did you have on a typical day when you were drinking in the last year?” are questions that can help you compare a patient’s alcohol use to the at-risk drinking cutoffs established by the NIAAA.^1,2

Recent research has also validated the use of a single question in identifying NIAAA-defined at-risk drinking.³² Simply ask patients, “How many times in the past year have you had X or more drinks in a day?” (X=5 for men or 4 for women). The screen is positive when a patient acknowledges having done so at least once in the past year. This question was 81.8% sensitive and 79.3% specific for unhealthy alcohol use, and 87.9% sensitive and 66.8% specific for current alcohol abuse or dependence.³² Advantages of this method are its brevity, ease of scoring, validity in the primary care setting,³² and ease of recollection for treatment providers (TABLE 1).^1,2

TABLE 1
Ask these simple questions to assess alcohol use^1,2

Brief intervention works in primary care

Brief interventions for drinking have strong empirical support. In a review of treatments for alcohol abuse and dependence,³³ brief intervention was one of only 2 “efficacious” treatments.

Although some individual studies of brief alcohol interventions in primary care have not shown favorable results, several systematic reviews have demonstrated the efficacy of such interventions in this setting. General practitioner–delivered brief interventions led to significantly better patient outcomes compared with standard care, and “very brief advice” resulted in reductions in alcohol consumption overall and in the percentage of “excessive drinkers.”³⁴ In a review of health behavior interventions,³⁵ brief interventions reduced risky or harmful drinking. In one of 2 meta-analyses that support this finding, brief interventions with primary care patients not seeking treatment for alcohol abuse yielded small-to-medium effect sizes relative to control conditions.³⁶ In the other study, brief interventions significantly reduced longer term alcohol use in primary care patients.³⁷

The US Preventive Services Task Force conducted a systematic review of behavioral counseling interventions and recommends screening and brief interventions for unhealthy drinking in primary care.^38,39 Its findings indicate that alcohol use declines significantly after brief interventions containing at least 2 of the following elements: feedback regarding drinking, advice to reduce drinking, or goal setting.

Brief advice is a form of intervention that shows considerable promise in primary care.^40-42 Two 10- to 15-minute sessions have led to significant reductions in the mean number of drinks and frequency of excessive drinking in the 7 days before a follow-up interview, as well as a reduction in binge drinking episodes in the previous 30 days.^41,42

One study produced positive results with just a 5- to 10-minute counseling session involving advice for drinking goals delivered by primary care providers as part of a routine medical visit.⁴³ This intervention led to significant decreases in alcohol use at a 6-month follow-up for high-risk drinkers compared with controls.⁴³ Brief interventions additionally work within the time constraints of a busy primary care practice and are cost effective.

Some primary care providers think a specialist should conduct interventions and suggest that having a specialist immediately available would enable intervention.³¹ In fact, some research has supported the idea of special training. In a European study, primary care providers reported that more practical training, information about brief intervention studies, personal training, and lectures would facilitate interventions.⁴⁴

Applying brief alcohol interventions to diabetes patients

Newer research has tested the efficacy of alcohol interventions with diabetes patients in the primary care setting. In one study,⁴⁵ brief advice was given in 2 15-minute sessions and 2 5-minute follow-up telephone calls. Compared with controls, significantly more participants who received the intervention reduced heavy drinking from baseline to follow-up. One caveat is that patients with hypertension were included in the sample, making it difficult to determine the impact of the intervention on diabetes patients specifically.

In a small study of patients with diabetes exhibiting at-risk drinking,⁸ a single-session intervention based on motivational interviewing (MI) principles⁴⁶ gave participants personalized feedback in relation to sex-based norms of drinking rates and HbA1c and triglyceride laboratory results. Patients were given information on the physiologic effects of alcohol on diabetes, the potential interactions between alcohol and diabetes medications, and the effect of alcohol on diabetes self-care behavior. They were asked to identify pros and cons of their drinking and to develop personal change goals. One of 2 PhD-level clinical psychologists trained in MI administered the single 50-minute intervention. By 1 month and continuing through to the 6-month follow-up, participants had reduced the proportion of drinking days, mean number of daily drinks, and proportion of heavy drinking days.

Ramsey and colleagues⁴⁷ extended this work by comparatively examining a group of patients exhibiting at-risk drinking who received no intervention. The results favored the intervention group, with a medium-to-large effect size for the proportion of drinking days, a medium effect size for the reduction of mean number of daily drinks, and a small-to-medium effect size in the reduction of heavy drinking days. Furthermore, in the intervention group there was a trend toward better diabetes adherence behavior.

Implementing brief intervention in practice. Despite differences among interventions, the elements of brief interventions tend to be similar.⁴⁸ Incorporating these elements in the primary care setting provides a useful framework that will likely prove beneficial. Specifically, brief interventions typically contain elements of the FRAMES (TABLE 2)⁴⁶ acronym:

• Feedback about one’s drinking relative to others
• Responsibility for deciding to change
• Advice to change drinking
• Menu of options for implementing a change strategy
• Empathic listening
• Self-efficacy enhancement.

Decision-making models indicate that expectations about the effects of behavior change play a significant role in determining whether a decision to change is made.⁴⁹ The perceived costs and benefits of changing drinking^50,51 and positive⁵² and negative alcohol expectancies^53,54 predict future alcohol use. For patients with diabetes who are at-risk drinkers, primary care appointments may provide “teachable moments” in which brief advice can have a significant impact—particularly when patients are told laboratory test results; advised about the sugar and carbohydrate content of alcohol; or given information regarding the effect of alcohol on diabetes, medications, and self-care behavior. Finally, primary care providers will also likely have knowledge of a patient’s comorbid conditions (eg, depression) that may relate to diabetes or alcohol use.

TABLE 2
How to implement the FRAMES approach in brief interventions⁴⁶

CORRESPONDENCE Patricia A. Engler, PhD, DGIM, 111 Plain Street Building, Providence, RI 02903; [email protected]

There are enough challenges in controlling diabetes mellitus without the hindrance of undetected problematic alcohol use. The good news is that asking a single nonthreatening question can help you detect at-risk drinking—defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as 5 or more drinks on one occasion or more than 14 drinks per week for men; and 4 or more drinks on one occasion or more than 7 drinks per week for women.^1,2 And, for patients who may be compromising their diabetes care and overall health through problem drinking, brief intervention techniques used in the office can enable them to reduce alcohol consumption significantly.

When alcohol becomes a problem in diabetes care

Several studies have explored the long-term benefits of moderate alcohol use on glycemic control—with mixed results. A 2007 study found that diabetes patients who drink 1 glass of wine per day exhibited a lower fasting glucose level than abstainers after 3 months.³ There was no difference, however, on postprandial glucose levels. A 2008 study found that individuals who drank one to 2 glasses of wine per day for a month had lower fasting serum insulin levels relative to when they have abstained for a month,⁴ although levels of fasting plasma cholesterol, HDL cholesterol, glucose, and hemoglobin A1c (HbA_1c) remained unchanged relative to periods of abstinence.⁴

Furthermore, rates of coronary heart disease and CHD mortality in a meta-analysis were significantly lower in 3 categories of alcohol consumption (<6 g/d, 6 to <18 g/d, and ≥18 g/d) compared with abstinence.⁵ Nondrinkers also had a greater risk of total mortality compared with the lightest drinking group. Notably, however, the lower limit of the highest drinking category was only 1.5 drinks per day.

How big is the problem? In a study of insulin-treated patients seen for severe hypoglycemia, 17% had been drinking before the episode.⁶ In a primary care sample, 28% of randomly selected patients with type 2 diabetes met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a lifetime incidence of alcohol abuse and 13% met either current or lifetime criteria for alcohol dependence.⁷ Another study of primary care patients with diabetes⁸ found that 13.4% met NIAAA criteria for at-risk drinking; 11.1% of these at-risk drinkers met criteria for current alcohol dependence. (According to the NIAAA, the rate of at-risk/heavy drinking among US adults is 30%, and about one in 4 heavy drinkers meets the criteria for alcohol abuse or dependence.¹)

Detrimental effects with immoderate drinking. Individuals who engage in at-risk drinking, as defined by the NIAAA, are at increased risk for alcohol dependence⁹ and associated complications such as diabetic neuropathy and retinopathy,¹⁰ atherosclerosis,¹¹ and total and CHD mortality.^3,12 Heavy drinking also interferes with neuroendocrine, gastrointestinal, and sexual function,¹³ and its interaction with diabetes increases the risk for hepatocellular carcinoma after controlling for hepatitis B and C serology.¹⁴

Interference with diabetes control. Research examining the short-term effect of alcohol use has produced contradictory results, partly due to differences among studies, such as whether alcohol is administered with a meal and whether a fasting glucose level is measured.¹⁵ However, alcohol affects glycemic control and, when used excessively, can impair glucose production.^16,17 Alcohol may induce hypoglycemia,^10,18 and even small amounts may jeopardize diabetes control.¹³ In a study of patients with insulin-treated diabetes, alcohol use in the presence of mild hypoglycemia increased diastolic blood pressure or exacerbated hypoglycemia-related cognitive deficits.¹⁹ Another concern—in both the short and long term—is that alcohol interacts negatively with certain diabetes medications. It is more likely to induce hypoglycemia in the presence of sulfonylurea medications.¹⁰ Chlorpropamide decreases the rate of ethanol elimination from the blood.²⁰ And, in those taking metformin, excessive alcohol use elevates risk for lactic acidosis. ²¹

Diminished self-care. Alcohol use can interfere with self-care,^22,23 which is a crucial component of diabetes treatment.²⁴ It may lead to reduced eating¹⁶ or to decreased willingness to adhere to prescribed dietary regimens.¹³ It also impairs other self-care behaviors^13,15,25 such as self-monitoring blood glucose and showing up for medical appointments.²⁶ In a large, diverse sample of patients with diabetes,²⁴ heavy drinkers had the highest rates of morbidity. Importantly, alcohol and diabetes self-care behavior were significantly negatively associated. Studies of ethnic minority samples have yielded comparable results.²⁷

Assessing alcohol use: Obstacles and solutions

Although alcohol use can be readily evaluated during routine primary care appointments, it is often neglected, perhaps due to a lack of awareness about its impact on diabetes.¹⁵ Those who are most often assessed tend to have a psychiatric diagnosis or other condition raising a red flag for physicians.²⁸ When internists, general practitioners, and psychiatrists were questioned in a study regarding patients’ alcohol and drug use, all 3 groups were misinformed about which substance-use treatments were empirically supported²⁹ and did not believe that treatment for alcohol abuse held much promise. Another study showed that physicians can be reluctant to screen for alcohol use because of the difficulty in recognizing a problem, the perceived unimportance of alcohol use as a health risk, a supposed lack of adequate intervention tools, and a fear of stigmatizing patients.³⁰ Physicians are more likely to discuss alcohol use under certain extreme conditions such as when a patient smells of alcohol.

Multiple opportunities to ask in the VA system. In the Veterans Health Administration, primary care VA providers have reported that prompts for alcohol screening embedded in computerized progress notes, clinical reminder lists, and annual health evaluation forms encourage them to assess alcohol use. Other useful materials include manual checklists and reference cards.³¹ These providers also report that education, feedback on rates of alcohol screening, and increased supervision facilitate assessment. Finally, providers indicate that asking nurses or clerical staff to administer the screen improves completion rates.

Ask a simple question

“How often have you had a drink containing alcohol in the last year?” or “How many drinks containing alcohol did you have on a typical day when you were drinking in the last year?” are questions that can help you compare a patient’s alcohol use to the at-risk drinking cutoffs established by the NIAAA.^1,2

Recent research has also validated the use of a single question in identifying NIAAA-defined at-risk drinking.³² Simply ask patients, “How many times in the past year have you had X or more drinks in a day?” (X=5 for men or 4 for women). The screen is positive when a patient acknowledges having done so at least once in the past year. This question was 81.8% sensitive and 79.3% specific for unhealthy alcohol use, and 87.9% sensitive and 66.8% specific for current alcohol abuse or dependence.³² Advantages of this method are its brevity, ease of scoring, validity in the primary care setting,³² and ease of recollection for treatment providers (TABLE 1).^1,2

TABLE 1
Ask these simple questions to assess alcohol use^1,2

Brief intervention works in primary care

Brief interventions for drinking have strong empirical support. In a review of treatments for alcohol abuse and dependence,³³ brief intervention was one of only 2 “efficacious” treatments.

Although some individual studies of brief alcohol interventions in primary care have not shown favorable results, several systematic reviews have demonstrated the efficacy of such interventions in this setting. General practitioner–delivered brief interventions led to significantly better patient outcomes compared with standard care, and “very brief advice” resulted in reductions in alcohol consumption overall and in the percentage of “excessive drinkers.”³⁴ In a review of health behavior interventions,³⁵ brief interventions reduced risky or harmful drinking. In one of 2 meta-analyses that support this finding, brief interventions with primary care patients not seeking treatment for alcohol abuse yielded small-to-medium effect sizes relative to control conditions.³⁶ In the other study, brief interventions significantly reduced longer term alcohol use in primary care patients.³⁷

The US Preventive Services Task Force conducted a systematic review of behavioral counseling interventions and recommends screening and brief interventions for unhealthy drinking in primary care.^38,39 Its findings indicate that alcohol use declines significantly after brief interventions containing at least 2 of the following elements: feedback regarding drinking, advice to reduce drinking, or goal setting.

Brief advice is a form of intervention that shows considerable promise in primary care.^40-42 Two 10- to 15-minute sessions have led to significant reductions in the mean number of drinks and frequency of excessive drinking in the 7 days before a follow-up interview, as well as a reduction in binge drinking episodes in the previous 30 days.^41,42

One study produced positive results with just a 5- to 10-minute counseling session involving advice for drinking goals delivered by primary care providers as part of a routine medical visit.⁴³ This intervention led to significant decreases in alcohol use at a 6-month follow-up for high-risk drinkers compared with controls.⁴³ Brief interventions additionally work within the time constraints of a busy primary care practice and are cost effective.

Some primary care providers think a specialist should conduct interventions and suggest that having a specialist immediately available would enable intervention.³¹ In fact, some research has supported the idea of special training. In a European study, primary care providers reported that more practical training, information about brief intervention studies, personal training, and lectures would facilitate interventions.⁴⁴

Applying brief alcohol interventions to diabetes patients

Newer research has tested the efficacy of alcohol interventions with diabetes patients in the primary care setting. In one study,⁴⁵ brief advice was given in 2 15-minute sessions and 2 5-minute follow-up telephone calls. Compared with controls, significantly more participants who received the intervention reduced heavy drinking from baseline to follow-up. One caveat is that patients with hypertension were included in the sample, making it difficult to determine the impact of the intervention on diabetes patients specifically.

In a small study of patients with diabetes exhibiting at-risk drinking,⁸ a single-session intervention based on motivational interviewing (MI) principles⁴⁶ gave participants personalized feedback in relation to sex-based norms of drinking rates and HbA1c and triglyceride laboratory results. Patients were given information on the physiologic effects of alcohol on diabetes, the potential interactions between alcohol and diabetes medications, and the effect of alcohol on diabetes self-care behavior. They were asked to identify pros and cons of their drinking and to develop personal change goals. One of 2 PhD-level clinical psychologists trained in MI administered the single 50-minute intervention. By 1 month and continuing through to the 6-month follow-up, participants had reduced the proportion of drinking days, mean number of daily drinks, and proportion of heavy drinking days.

Ramsey and colleagues⁴⁷ extended this work by comparatively examining a group of patients exhibiting at-risk drinking who received no intervention. The results favored the intervention group, with a medium-to-large effect size for the proportion of drinking days, a medium effect size for the reduction of mean number of daily drinks, and a small-to-medium effect size in the reduction of heavy drinking days. Furthermore, in the intervention group there was a trend toward better diabetes adherence behavior.

Implementing brief intervention in practice. Despite differences among interventions, the elements of brief interventions tend to be similar.⁴⁸ Incorporating these elements in the primary care setting provides a useful framework that will likely prove beneficial. Specifically, brief interventions typically contain elements of the FRAMES (TABLE 2)⁴⁶ acronym:

• Feedback about one’s drinking relative to others
• Responsibility for deciding to change
• Advice to change drinking
• Menu of options for implementing a change strategy
• Empathic listening
• Self-efficacy enhancement.

Decision-making models indicate that expectations about the effects of behavior change play a significant role in determining whether a decision to change is made.⁴⁹ The perceived costs and benefits of changing drinking^50,51 and positive⁵² and negative alcohol expectancies^53,54 predict future alcohol use. For patients with diabetes who are at-risk drinkers, primary care appointments may provide “teachable moments” in which brief advice can have a significant impact—particularly when patients are told laboratory test results; advised about the sugar and carbohydrate content of alcohol; or given information regarding the effect of alcohol on diabetes, medications, and self-care behavior. Finally, primary care providers will also likely have knowledge of a patient’s comorbid conditions (eg, depression) that may relate to diabetes or alcohol use.

TABLE 2
How to implement the FRAMES approach in brief interventions⁴⁶

CORRESPONDENCE Patricia A. Engler, PhD, DGIM, 111 Plain Street Building, Providence, RI 02903; [email protected]

There are enough challenges in controlling diabetes mellitus without the hindrance of undetected problematic alcohol use. The good news is that asking a single nonthreatening question can help you detect at-risk drinking—defined by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) as 5 or more drinks on one occasion or more than 14 drinks per week for men; and 4 or more drinks on one occasion or more than 7 drinks per week for women.^1,2 And, for patients who may be compromising their diabetes care and overall health through problem drinking, brief intervention techniques used in the office can enable them to reduce alcohol consumption significantly.

When alcohol becomes a problem in diabetes care

Several studies have explored the long-term benefits of moderate alcohol use on glycemic control—with mixed results. A 2007 study found that diabetes patients who drink 1 glass of wine per day exhibited a lower fasting glucose level than abstainers after 3 months.³ There was no difference, however, on postprandial glucose levels. A 2008 study found that individuals who drank one to 2 glasses of wine per day for a month had lower fasting serum insulin levels relative to when they have abstained for a month,⁴ although levels of fasting plasma cholesterol, HDL cholesterol, glucose, and hemoglobin A1c (HbA_1c) remained unchanged relative to periods of abstinence.⁴

Furthermore, rates of coronary heart disease and CHD mortality in a meta-analysis were significantly lower in 3 categories of alcohol consumption (<6 g/d, 6 to <18 g/d, and ≥18 g/d) compared with abstinence.⁵ Nondrinkers also had a greater risk of total mortality compared with the lightest drinking group. Notably, however, the lower limit of the highest drinking category was only 1.5 drinks per day.

How big is the problem? In a study of insulin-treated patients seen for severe hypoglycemia, 17% had been drinking before the episode.⁶ In a primary care sample, 28% of randomly selected patients with type 2 diabetes met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a lifetime incidence of alcohol abuse and 13% met either current or lifetime criteria for alcohol dependence.⁷ Another study of primary care patients with diabetes⁸ found that 13.4% met NIAAA criteria for at-risk drinking; 11.1% of these at-risk drinkers met criteria for current alcohol dependence. (According to the NIAAA, the rate of at-risk/heavy drinking among US adults is 30%, and about one in 4 heavy drinkers meets the criteria for alcohol abuse or dependence.¹)

Detrimental effects with immoderate drinking. Individuals who engage in at-risk drinking, as defined by the NIAAA, are at increased risk for alcohol dependence⁹ and associated complications such as diabetic neuropathy and retinopathy,¹⁰ atherosclerosis,¹¹ and total and CHD mortality.^3,12 Heavy drinking also interferes with neuroendocrine, gastrointestinal, and sexual function,¹³ and its interaction with diabetes increases the risk for hepatocellular carcinoma after controlling for hepatitis B and C serology.¹⁴

Interference with diabetes control. Research examining the short-term effect of alcohol use has produced contradictory results, partly due to differences among studies, such as whether alcohol is administered with a meal and whether a fasting glucose level is measured.¹⁵ However, alcohol affects glycemic control and, when used excessively, can impair glucose production.^16,17 Alcohol may induce hypoglycemia,^10,18 and even small amounts may jeopardize diabetes control.¹³ In a study of patients with insulin-treated diabetes, alcohol use in the presence of mild hypoglycemia increased diastolic blood pressure or exacerbated hypoglycemia-related cognitive deficits.¹⁹ Another concern—in both the short and long term—is that alcohol interacts negatively with certain diabetes medications. It is more likely to induce hypoglycemia in the presence of sulfonylurea medications.¹⁰ Chlorpropamide decreases the rate of ethanol elimination from the blood.²⁰ And, in those taking metformin, excessive alcohol use elevates risk for lactic acidosis. ²¹

Diminished self-care. Alcohol use can interfere with self-care,^22,23 which is a crucial component of diabetes treatment.²⁴ It may lead to reduced eating¹⁶ or to decreased willingness to adhere to prescribed dietary regimens.¹³ It also impairs other self-care behaviors^13,15,25 such as self-monitoring blood glucose and showing up for medical appointments.²⁶ In a large, diverse sample of patients with diabetes,²⁴ heavy drinkers had the highest rates of morbidity. Importantly, alcohol and diabetes self-care behavior were significantly negatively associated. Studies of ethnic minority samples have yielded comparable results.²⁷

Assessing alcohol use: Obstacles and solutions

Although alcohol use can be readily evaluated during routine primary care appointments, it is often neglected, perhaps due to a lack of awareness about its impact on diabetes.¹⁵ Those who are most often assessed tend to have a psychiatric diagnosis or other condition raising a red flag for physicians.²⁸ When internists, general practitioners, and psychiatrists were questioned in a study regarding patients’ alcohol and drug use, all 3 groups were misinformed about which substance-use treatments were empirically supported²⁹ and did not believe that treatment for alcohol abuse held much promise. Another study showed that physicians can be reluctant to screen for alcohol use because of the difficulty in recognizing a problem, the perceived unimportance of alcohol use as a health risk, a supposed lack of adequate intervention tools, and a fear of stigmatizing patients.³⁰ Physicians are more likely to discuss alcohol use under certain extreme conditions such as when a patient smells of alcohol.

Multiple opportunities to ask in the VA system. In the Veterans Health Administration, primary care VA providers have reported that prompts for alcohol screening embedded in computerized progress notes, clinical reminder lists, and annual health evaluation forms encourage them to assess alcohol use. Other useful materials include manual checklists and reference cards.³¹ These providers also report that education, feedback on rates of alcohol screening, and increased supervision facilitate assessment. Finally, providers indicate that asking nurses or clerical staff to administer the screen improves completion rates.

Ask a simple question

“How often have you had a drink containing alcohol in the last year?” or “How many drinks containing alcohol did you have on a typical day when you were drinking in the last year?” are questions that can help you compare a patient’s alcohol use to the at-risk drinking cutoffs established by the NIAAA.^1,2

Recent research has also validated the use of a single question in identifying NIAAA-defined at-risk drinking.³² Simply ask patients, “How many times in the past year have you had X or more drinks in a day?” (X=5 for men or 4 for women). The screen is positive when a patient acknowledges having done so at least once in the past year. This question was 81.8% sensitive and 79.3% specific for unhealthy alcohol use, and 87.9% sensitive and 66.8% specific for current alcohol abuse or dependence.³² Advantages of this method are its brevity, ease of scoring, validity in the primary care setting,³² and ease of recollection for treatment providers (TABLE 1).^1,2

TABLE 1
Ask these simple questions to assess alcohol use^1,2

Brief intervention works in primary care

Brief interventions for drinking have strong empirical support. In a review of treatments for alcohol abuse and dependence,³³ brief intervention was one of only 2 “efficacious” treatments.

Although some individual studies of brief alcohol interventions in primary care have not shown favorable results, several systematic reviews have demonstrated the efficacy of such interventions in this setting. General practitioner–delivered brief interventions led to significantly better patient outcomes compared with standard care, and “very brief advice” resulted in reductions in alcohol consumption overall and in the percentage of “excessive drinkers.”³⁴ In a review of health behavior interventions,³⁵ brief interventions reduced risky or harmful drinking. In one of 2 meta-analyses that support this finding, brief interventions with primary care patients not seeking treatment for alcohol abuse yielded small-to-medium effect sizes relative to control conditions.³⁶ In the other study, brief interventions significantly reduced longer term alcohol use in primary care patients.³⁷

The US Preventive Services Task Force conducted a systematic review of behavioral counseling interventions and recommends screening and brief interventions for unhealthy drinking in primary care.^38,39 Its findings indicate that alcohol use declines significantly after brief interventions containing at least 2 of the following elements: feedback regarding drinking, advice to reduce drinking, or goal setting.

Brief advice is a form of intervention that shows considerable promise in primary care.^40-42 Two 10- to 15-minute sessions have led to significant reductions in the mean number of drinks and frequency of excessive drinking in the 7 days before a follow-up interview, as well as a reduction in binge drinking episodes in the previous 30 days.^41,42

One study produced positive results with just a 5- to 10-minute counseling session involving advice for drinking goals delivered by primary care providers as part of a routine medical visit.⁴³ This intervention led to significant decreases in alcohol use at a 6-month follow-up for high-risk drinkers compared with controls.⁴³ Brief interventions additionally work within the time constraints of a busy primary care practice and are cost effective.

Some primary care providers think a specialist should conduct interventions and suggest that having a specialist immediately available would enable intervention.³¹ In fact, some research has supported the idea of special training. In a European study, primary care providers reported that more practical training, information about brief intervention studies, personal training, and lectures would facilitate interventions.⁴⁴

Applying brief alcohol interventions to diabetes patients

Newer research has tested the efficacy of alcohol interventions with diabetes patients in the primary care setting. In one study,⁴⁵ brief advice was given in 2 15-minute sessions and 2 5-minute follow-up telephone calls. Compared with controls, significantly more participants who received the intervention reduced heavy drinking from baseline to follow-up. One caveat is that patients with hypertension were included in the sample, making it difficult to determine the impact of the intervention on diabetes patients specifically.

In a small study of patients with diabetes exhibiting at-risk drinking,⁸ a single-session intervention based on motivational interviewing (MI) principles⁴⁶ gave participants personalized feedback in relation to sex-based norms of drinking rates and HbA1c and triglyceride laboratory results. Patients were given information on the physiologic effects of alcohol on diabetes, the potential interactions between alcohol and diabetes medications, and the effect of alcohol on diabetes self-care behavior. They were asked to identify pros and cons of their drinking and to develop personal change goals. One of 2 PhD-level clinical psychologists trained in MI administered the single 50-minute intervention. By 1 month and continuing through to the 6-month follow-up, participants had reduced the proportion of drinking days, mean number of daily drinks, and proportion of heavy drinking days.

Ramsey and colleagues⁴⁷ extended this work by comparatively examining a group of patients exhibiting at-risk drinking who received no intervention. The results favored the intervention group, with a medium-to-large effect size for the proportion of drinking days, a medium effect size for the reduction of mean number of daily drinks, and a small-to-medium effect size in the reduction of heavy drinking days. Furthermore, in the intervention group there was a trend toward better diabetes adherence behavior.

Implementing brief intervention in practice. Despite differences among interventions, the elements of brief interventions tend to be similar.⁴⁸ Incorporating these elements in the primary care setting provides a useful framework that will likely prove beneficial. Specifically, brief interventions typically contain elements of the FRAMES (TABLE 2)⁴⁶ acronym:

• Feedback about one’s drinking relative to others
• Responsibility for deciding to change
• Advice to change drinking
• Menu of options for implementing a change strategy
• Empathic listening
• Self-efficacy enhancement.

Decision-making models indicate that expectations about the effects of behavior change play a significant role in determining whether a decision to change is made.⁴⁹ The perceived costs and benefits of changing drinking^50,51 and positive⁵² and negative alcohol expectancies^53,54 predict future alcohol use. For patients with diabetes who are at-risk drinkers, primary care appointments may provide “teachable moments” in which brief advice can have a significant impact—particularly when patients are told laboratory test results; advised about the sugar and carbohydrate content of alcohol; or given information regarding the effect of alcohol on diabetes, medications, and self-care behavior. Finally, primary care providers will also likely have knowledge of a patient’s comorbid conditions (eg, depression) that may relate to diabetes or alcohol use.

TABLE 2
How to implement the FRAMES approach in brief interventions⁴⁶

CORRESPONDENCE Patricia A. Engler, PhD, DGIM, 111 Plain Street Building, Providence, RI 02903; [email protected]

Public health efforts have decreased the incidence of gonorrhea over the past several decades, but this progress is threatened by emergent bacteria resistance to the few remaining antibiotics available to treat it.

Gonococcal resistance to penicillin and tetracycline began in the 1970s and was widespread by the 1980s. Resistance to fluoroquinolones developed during the last decade and led the Centers for Disease Control and Prevention (CDC) in 2007 to stop recommending this class of antibiotics for treatment of gonorrhea.¹ (See “The decline of gonorrhea: A success story now threatened by antibiotic resistance”.)

Given the speed with which gonococci developed resistance to fluoroquinolones, the CDC sees as inevitable the eventual development of resistance to cephalosporins—the currently favored agents for gonorrhea.² This is the main reason behind the new recommendations for treating all cases of gonorrhea with both a cephalosporin and azithromycin, whether or not co-infection with Chlamydia trachomatis is documented or suspected.³

FIGURE 1
A decline in gonorrhea that began in the mid-1970s*

FIGURE 2
Gonorrhea prevalence, 2010

FIGURE 3
Gonorrhea prevalence by age and sex, 2010

Augment therapy, follow up thoroughly

Family physicians can assist with public health efforts to control gonorrhea and delay the development of cephalosporin resistance by screening for and detecting the infection, diagnosing those with symptoms, and treating according to newer recommendations. It’s also essential to report cases to local public health departments, assist with finding and treating sexual contacts of infected individuals, and immediately report suspected treatment failures.

A 2-drug regimen is imperative. The latest recommendation for treating gonorrhea is ceftriaxone 250 mg IM in a single dose and azithromycin 1 g orally in a single dose. Until 2010, the dose of ceftriaxone had been 125 mg. This dual drug regimen is recommended for several reasons: As with using multiple drugs to treat tuberculosis, it is hoped dual drug therapy will slow development of resistance to both cephalosporins and azithromycin; co-infection with C trachomatis remains a significant problem; and the combination may be more effective against pharyngeal gonorrhea, which is hard to detect.

Alternative regimens. Cefixime 400 mg orally as a single dose is an option in lieu of ceftriaxone, but is not preferred because of the higher number of reported failures of treatment with oral cephalosporins and less efficacy against pharyngeal disease.³ Other injectable cephalosporins are also an option, but less is known about their effectiveness in treating pharyngeal infection. Injectable options include ceftizoxime 500 mg IM, cefoxitin 2 g IM with probenecid 1 g orally, and cefotaxime 500 mg IM.

Regardless of the cephalosporin chosen, always administer azithromycin. If necessary, an alternative to azithromycin is doxycycline 100 mg orally twice a day. But doxycycline is not preferred because it has a multiple daily dosing requirement and higher levels of gonococcal resistance than is seen with azithromycin.

Necessary follow-up. Although routine testing for cure is not advocated for those treated with a recommended antibiotic regimen, a gonococcal culture and testing for antibiotic susceptibility should be done for any patient whose symptoms persist after treatment. Rapid tests using nucleic acid amplification are unsuitable for testing antibiotic susceptibility. The CDC does recommend retesting patients 3 months after treatment is completed because of a high prevalence of reinfection.³ If cephalosporin resistance becomes prevalent, routine tests of cure might become a recommended standard.

Report all patients with gonorrhea to the local public health department so that sexual contacts within the past 60 days can be notified, tested, and treated presumptively with the dual drug regimen. Recommend simultaneous treatment for all current sex partners, and discourage sexual intercourse until symptoms have resolved. Promptly report any patient with suspected treatment failure to the local health department, and consult the local or state health department for recommendations on subsequent treatment regimens.

The US Preventive Services Task Force (USPSTF) recommends routine screening for asymptomatic infection in women at risk, as per the details in the TABLE.⁴ While the USPSTF found insufficient evidence to recommend screening of high-risk men, physicians might still consider screening men who have sex with multiple male partners.

TABLE
USPSTF recommendations on screening for gonorrhea⁴

Doing our best in the face of uncertainty
Although evidence is lacking that dual drug therapy will delay the progression of resistance, the strategy makes empirical sense. If gonorrhea develops resistance to cephalosporins, it will seriously challenge public health efforts to control this infection. Family physicians have an important role in controlling this sexually transmitted infection and helping to prevent drug resistance.

Public health efforts have decreased the incidence of gonorrhea over the past several decades, but this progress is threatened by emergent bacteria resistance to the few remaining antibiotics available to treat it.

Gonococcal resistance to penicillin and tetracycline began in the 1970s and was widespread by the 1980s. Resistance to fluoroquinolones developed during the last decade and led the Centers for Disease Control and Prevention (CDC) in 2007 to stop recommending this class of antibiotics for treatment of gonorrhea.¹ (See “The decline of gonorrhea: A success story now threatened by antibiotic resistance”.)

Given the speed with which gonococci developed resistance to fluoroquinolones, the CDC sees as inevitable the eventual development of resistance to cephalosporins—the currently favored agents for gonorrhea.² This is the main reason behind the new recommendations for treating all cases of gonorrhea with both a cephalosporin and azithromycin, whether or not co-infection with Chlamydia trachomatis is documented or suspected.³

FIGURE 1
A decline in gonorrhea that began in the mid-1970s*

FIGURE 2
Gonorrhea prevalence, 2010

FIGURE 3
Gonorrhea prevalence by age and sex, 2010

Augment therapy, follow up thoroughly

Family physicians can assist with public health efforts to control gonorrhea and delay the development of cephalosporin resistance by screening for and detecting the infection, diagnosing those with symptoms, and treating according to newer recommendations. It’s also essential to report cases to local public health departments, assist with finding and treating sexual contacts of infected individuals, and immediately report suspected treatment failures.

A 2-drug regimen is imperative. The latest recommendation for treating gonorrhea is ceftriaxone 250 mg IM in a single dose and azithromycin 1 g orally in a single dose. Until 2010, the dose of ceftriaxone had been 125 mg. This dual drug regimen is recommended for several reasons: As with using multiple drugs to treat tuberculosis, it is hoped dual drug therapy will slow development of resistance to both cephalosporins and azithromycin; co-infection with C trachomatis remains a significant problem; and the combination may be more effective against pharyngeal gonorrhea, which is hard to detect.

Alternative regimens. Cefixime 400 mg orally as a single dose is an option in lieu of ceftriaxone, but is not preferred because of the higher number of reported failures of treatment with oral cephalosporins and less efficacy against pharyngeal disease.³ Other injectable cephalosporins are also an option, but less is known about their effectiveness in treating pharyngeal infection. Injectable options include ceftizoxime 500 mg IM, cefoxitin 2 g IM with probenecid 1 g orally, and cefotaxime 500 mg IM.

Regardless of the cephalosporin chosen, always administer azithromycin. If necessary, an alternative to azithromycin is doxycycline 100 mg orally twice a day. But doxycycline is not preferred because it has a multiple daily dosing requirement and higher levels of gonococcal resistance than is seen with azithromycin.

Necessary follow-up. Although routine testing for cure is not advocated for those treated with a recommended antibiotic regimen, a gonococcal culture and testing for antibiotic susceptibility should be done for any patient whose symptoms persist after treatment. Rapid tests using nucleic acid amplification are unsuitable for testing antibiotic susceptibility. The CDC does recommend retesting patients 3 months after treatment is completed because of a high prevalence of reinfection.³ If cephalosporin resistance becomes prevalent, routine tests of cure might become a recommended standard.

Report all patients with gonorrhea to the local public health department so that sexual contacts within the past 60 days can be notified, tested, and treated presumptively with the dual drug regimen. Recommend simultaneous treatment for all current sex partners, and discourage sexual intercourse until symptoms have resolved. Promptly report any patient with suspected treatment failure to the local health department, and consult the local or state health department for recommendations on subsequent treatment regimens.

The US Preventive Services Task Force (USPSTF) recommends routine screening for asymptomatic infection in women at risk, as per the details in the TABLE.⁴ While the USPSTF found insufficient evidence to recommend screening of high-risk men, physicians might still consider screening men who have sex with multiple male partners.

TABLE
USPSTF recommendations on screening for gonorrhea⁴

Doing our best in the face of uncertainty
Although evidence is lacking that dual drug therapy will delay the progression of resistance, the strategy makes empirical sense. If gonorrhea develops resistance to cephalosporins, it will seriously challenge public health efforts to control this infection. Family physicians have an important role in controlling this sexually transmitted infection and helping to prevent drug resistance.

Public health efforts have decreased the incidence of gonorrhea over the past several decades, but this progress is threatened by emergent bacteria resistance to the few remaining antibiotics available to treat it.

Gonococcal resistance to penicillin and tetracycline began in the 1970s and was widespread by the 1980s. Resistance to fluoroquinolones developed during the last decade and led the Centers for Disease Control and Prevention (CDC) in 2007 to stop recommending this class of antibiotics for treatment of gonorrhea.¹ (See “The decline of gonorrhea: A success story now threatened by antibiotic resistance”.)

Given the speed with which gonococci developed resistance to fluoroquinolones, the CDC sees as inevitable the eventual development of resistance to cephalosporins—the currently favored agents for gonorrhea.² This is the main reason behind the new recommendations for treating all cases of gonorrhea with both a cephalosporin and azithromycin, whether or not co-infection with Chlamydia trachomatis is documented or suspected.³

FIGURE 1
A decline in gonorrhea that began in the mid-1970s*

FIGURE 2
Gonorrhea prevalence, 2010

FIGURE 3
Gonorrhea prevalence by age and sex, 2010

Augment therapy, follow up thoroughly

Family physicians can assist with public health efforts to control gonorrhea and delay the development of cephalosporin resistance by screening for and detecting the infection, diagnosing those with symptoms, and treating according to newer recommendations. It’s also essential to report cases to local public health departments, assist with finding and treating sexual contacts of infected individuals, and immediately report suspected treatment failures.

A 2-drug regimen is imperative. The latest recommendation for treating gonorrhea is ceftriaxone 250 mg IM in a single dose and azithromycin 1 g orally in a single dose. Until 2010, the dose of ceftriaxone had been 125 mg. This dual drug regimen is recommended for several reasons: As with using multiple drugs to treat tuberculosis, it is hoped dual drug therapy will slow development of resistance to both cephalosporins and azithromycin; co-infection with C trachomatis remains a significant problem; and the combination may be more effective against pharyngeal gonorrhea, which is hard to detect.

Alternative regimens. Cefixime 400 mg orally as a single dose is an option in lieu of ceftriaxone, but is not preferred because of the higher number of reported failures of treatment with oral cephalosporins and less efficacy against pharyngeal disease.³ Other injectable cephalosporins are also an option, but less is known about their effectiveness in treating pharyngeal infection. Injectable options include ceftizoxime 500 mg IM, cefoxitin 2 g IM with probenecid 1 g orally, and cefotaxime 500 mg IM.

Regardless of the cephalosporin chosen, always administer azithromycin. If necessary, an alternative to azithromycin is doxycycline 100 mg orally twice a day. But doxycycline is not preferred because it has a multiple daily dosing requirement and higher levels of gonococcal resistance than is seen with azithromycin.

Necessary follow-up. Although routine testing for cure is not advocated for those treated with a recommended antibiotic regimen, a gonococcal culture and testing for antibiotic susceptibility should be done for any patient whose symptoms persist after treatment. Rapid tests using nucleic acid amplification are unsuitable for testing antibiotic susceptibility. The CDC does recommend retesting patients 3 months after treatment is completed because of a high prevalence of reinfection.³ If cephalosporin resistance becomes prevalent, routine tests of cure might become a recommended standard.

Report all patients with gonorrhea to the local public health department so that sexual contacts within the past 60 days can be notified, tested, and treated presumptively with the dual drug regimen. Recommend simultaneous treatment for all current sex partners, and discourage sexual intercourse until symptoms have resolved. Promptly report any patient with suspected treatment failure to the local health department, and consult the local or state health department for recommendations on subsequent treatment regimens.

The US Preventive Services Task Force (USPSTF) recommends routine screening for asymptomatic infection in women at risk, as per the details in the TABLE.⁴ While the USPSTF found insufficient evidence to recommend screening of high-risk men, physicians might still consider screening men who have sex with multiple male partners.

TABLE
USPSTF recommendations on screening for gonorrhea⁴

Doing our best in the face of uncertainty
Although evidence is lacking that dual drug therapy will delay the progression of resistance, the strategy makes empirical sense. If gonorrhea develops resistance to cephalosporins, it will seriously challenge public health efforts to control this infection. Family physicians have an important role in controlling this sexually transmitted infection and helping to prevent drug resistance.