Researchers determined that MRI imaging may predict which persons with cognitive impairment will progress to Alzheimer’s disease in a report published in the April 6 online Radiology. Baseline MRI was obtained for 164 individuals with late-onset Alzheimer’s disease, 317 with mild cognitive impairment, and 203 healthy controls. The investigators then used MRI to measure the thickness and amount of atrophy in the cerebral cortex. “Individualized risk estimates from baseline MRI examinations indicated that the one-year risk of conversion to Alzheimer’s disease ranged from 3% to 40%,” the researchers reported. “Relative to the risk of conversion to Alzheimer’s disease conferred by the clinical diagnosis of mild cognitive impairment alone, MRI measures yield substantially more informative patient-specific risk estimates. Such predictive prognostic information will be critical if disease-modifying therapies become available.”

Cotinine, a compound derived from tobacco, reduced brain plaques associated with dementia and memory loss, according to a study published in the online February 14 Journal of Alzheimer’s Disease. A group of investigators studied the effects of cotinine on b-amyloid plaque aggregation in the brains of mice with Alzheimer’s disease. Mice treated with the compound performed better than untreated mice on tasks measuring working memory and thinking skills; long-term treatment also appeared to prevent spatial memory impairment. Overall, the treated mice showed a 26% reduction in amyloid plaque deposits. “Cotinine, the main metabolite of nicotine, has a long half-life and does not have cardiovascular or addictive side effects in humans,” the authors wrote. “The good safety profile in humans and its beneficial effects suggest that cotinine may be an excellent therapeutic candidate for the treatment of Alzheimer’s disease.”

A study published in the April 13 online Neurology provides evidence that treating certain vascular risk factors helps lower the risk for conversion from mild cognitive impairment to Alzheimer’s disease. Investigators assessed memory and thinking skills of 837 patients with mild cognitive impairment and then reassessed them five years later; 414 participants had at least one vascular risk factor at baseline. “At the end of follow-up 298 subjects converted to Alzheimer’s disease dementia, while 352 remained with mild cognitive impairment,” the investigators reported. “Treatment of individual vascular risk factors including hypertension, diabetes, and hypercholesterolemia was associated with the reduced risk of Alzheimer’s disease conversion.” The findings of the study are observational, the authors concluded, but they suggest that active intervention and treatment of certain risk factors might reduce progression to Alzheimer’s disease.

Researchers have identified mutations of the synapsin 1 gene as a possible common genetic cause for both epilepsy and autism. Their study, published online in the April 12 Human Molecular Genetics, involved members of a large French-Canadian family who had autism spectrum disorders or epilepsy. The severe Q555X mutation appeared in all family members with epilepsy, and in all those who had an autism spectrum disorder. In addition, other mutations in synapsin 1 (A51G, A550T, and T567A) were found in 1% and 3.5% of a separate cohort of French-Canadian individuals with autism and epilepsy, respectively. “These results demonstrate that [synapsin 1] is a novel predisposing gene to [autism spectrum disorders], in addition to epilepsy,” the authors concluded. “[The results also] strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.”

Men who reported chronic ecstasy (MDMA) use were more likely to develop structural brain damage than those who did not use ecstasy, according to a study that was published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry. Using MRI, researchers measured the hippocampal volume of 10 male ecstasy users (average age, 21.3), compared with seven age- and gender-matched subjects who did not use ecstasy. The hippocampal volume of ecstasy users was 10.5% smaller than those of nonusing peers; the overall proportion of gray matter was 4.6% smaller, suggesting that the drug’s effects are not limited to the hippocampus. “These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage,” the authors wrote, adding: “Hippocampal atrophy is a hallmark for disease of progressive cognitive impairment in older patients, such as Alzheimer’s disease.”

In a study published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry, researchers reported that epileptic seizures carry a subsequent risk for brain tumor. “Our study suggests that tumor as an underlying cause for epilepsy may not become apparent for several years after onset, and indicates a need for ongoing vigilance,” the authors stated. In the retrospective cohort study, the investigators examined data regarding individuals with first-time epilepsy admissions and determined that, compared with patients admitted for other common and minor disorders, patients with epilepsy were almost 20 times more likely to develop cerebral tumor. The risk for developing malignant tumors was more than twice the risk for developing benign tumors. “The risk was highest for those aged 15 to 44 years at initial admission for epilepsy,” the authors reported. “The risk of cerebral tumor was still raised several years after initial admission for epilepsy.”

A novel gene transfer vector, NP2, is safe and well tolerated for the treatment of intractable pain, researchers reported in the April 11 online Annals of Neurology. Investigators conducted a multicenter, dose-escalation, phase I clinical trial of intradermal NP2 injection in 10 subjects with persistent pain caused by cancer, despite treatment with morphine or other analgesic. Participants who received the low dose of NP2 reported no substantive change in pain; patients in the middle and high dose cohorts reported pain relief. “There were no placebo controls in this relatively small study,” the authors concluded. “But the dose-responsive analgesic effects suggest that NP2 may be effective in reducing pain and warrants further clinical investigation.”

The FDA has approved DaTscan (ioflupane I 123 injection) for detecting dopamine transporters in the brains of adults with suspected Parkinsonian syndromes. The radiopharmaceutical agent is intended for use with single photon emission CT imaging to evaluate neurodegenerative movement disorders. The injection may be used as an adjunct to other diagnostic evaluation tools to distinguish between essential tremor and tremor due to Parkinson’s disease, as ioflupane I 123 injection alone cannot differentiate between different types of parkinsonian syndromes. The FDA’s approval was based on two phase III clinical trials in which the drug was used to evaluate dopamine transporter distribution in the brains of adult patients. As a new diagnostic adjunct to clinical assessments, ioflupane  I 123 can potentially help physicians select the appropriate treatments for patients with movement disorders.

Persons who are regularly exposed to welding fumes may be at an increased risk for brain damage, specifically in the same areas affected by Parkinson’s disease, researchers reported in the April 12 Neurology. “Welding exposes workers to manganese fumes, but it is unclear if this exposure damages dopaminergic neurons,” the authors stated. “The purpose of this study [was] to determine whether welding exposure is associated with damage to nigrostriatal neurons.” Using PET imaging on 20 welders with no parkinsonian symptoms, 20 individuals with symptoms, and 20 healthy controls, the investigators determined that asymptomatic welders had higher manganese levels in the blood and an average 11.7% reduction in dopamine in certain brain regions. The pattern of reduction seen in welders, however, was distinct from the dysfunction pattern found in symptomatic Parkinson’s disease.

The FDA has approved Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) for the treatment of pseudobulbar affect. The new therapy will help patients manage pseudobulbar affect that occurs secondary to multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), traumatic brain injury, stroke, Parkinson’s disease, and other neurologic diseases. Nuedexta combines dextromethorphan hydrobromide and quinidine sulfate, a metabolic inhibitor that enables therapeutic dextromethorphan concentrations. These components act on NMDA receptors and sigma-1 in the brain, but the mechanism by which it exerts therapeutic effects in patients with pseudobulbar affect is unknown. The drug was tested in patients with ALS and MS and reduced involuntary laughing and crying episodes compared with placebo. 

Virtual reality may be an effective adjunctive therapy for patients experiencing upper arm motor deficits following stroke, according to a study published in the May Stroke. Researchers analyzed seven observational studies and five randomized trials that investigated the effects of virtual reality and video game technology on stroke patients’ upper arm strength and function. Among the observational studies, there was a 14.7% improvement in motor impairment and a 20.1% improvement in motor function; in the randomized trials, patients had an almost five times higher chance of improvement in motor function, compared with those who received traditional therapy. The researchers concluded, “Virtual reality and video game applications are novel and potentially useful technologies that can be combined with conventional rehabilitation for upper arm improvement after stroke.”

Investigators found that surgical revascularization can restore lost brain tissue in patients with cerebrovascular disease that impairs blood flow to the brain, as reported in the online April 14 Stroke. Twenty-nine patients who had undergone vascularization were included in the study. All patients had pre- and postsurgery studies of cerebrovascular reactivity using MRI, and cortical thickness in regions corresponding to steal physiology were measured. “At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere,” the authors stated. “Mean cortical thickness in the revascularized regions increased by 5.1%.” The investigators’ goal was to halt further loss of brain tissue due to strokes, “so it was remarkable to see the loss was actually reversed,” they commented.

Researchers determined that MRI imaging may predict which persons with cognitive impairment will progress to Alzheimer’s disease in a report published in the April 6 online Radiology. Baseline MRI was obtained for 164 individuals with late-onset Alzheimer’s disease, 317 with mild cognitive impairment, and 203 healthy controls. The investigators then used MRI to measure the thickness and amount of atrophy in the cerebral cortex. “Individualized risk estimates from baseline MRI examinations indicated that the one-year risk of conversion to Alzheimer’s disease ranged from 3% to 40%,” the researchers reported. “Relative to the risk of conversion to Alzheimer’s disease conferred by the clinical diagnosis of mild cognitive impairment alone, MRI measures yield substantially more informative patient-specific risk estimates. Such predictive prognostic information will be critical if disease-modifying therapies become available.”

Cotinine, a compound derived from tobacco, reduced brain plaques associated with dementia and memory loss, according to a study published in the online February 14 Journal of Alzheimer’s Disease. A group of investigators studied the effects of cotinine on b-amyloid plaque aggregation in the brains of mice with Alzheimer’s disease. Mice treated with the compound performed better than untreated mice on tasks measuring working memory and thinking skills; long-term treatment also appeared to prevent spatial memory impairment. Overall, the treated mice showed a 26% reduction in amyloid plaque deposits. “Cotinine, the main metabolite of nicotine, has a long half-life and does not have cardiovascular or addictive side effects in humans,” the authors wrote. “The good safety profile in humans and its beneficial effects suggest that cotinine may be an excellent therapeutic candidate for the treatment of Alzheimer’s disease.”

A study published in the April 13 online Neurology provides evidence that treating certain vascular risk factors helps lower the risk for conversion from mild cognitive impairment to Alzheimer’s disease. Investigators assessed memory and thinking skills of 837 patients with mild cognitive impairment and then reassessed them five years later; 414 participants had at least one vascular risk factor at baseline. “At the end of follow-up 298 subjects converted to Alzheimer’s disease dementia, while 352 remained with mild cognitive impairment,” the investigators reported. “Treatment of individual vascular risk factors including hypertension, diabetes, and hypercholesterolemia was associated with the reduced risk of Alzheimer’s disease conversion.” The findings of the study are observational, the authors concluded, but they suggest that active intervention and treatment of certain risk factors might reduce progression to Alzheimer’s disease.

Researchers have identified mutations of the synapsin 1 gene as a possible common genetic cause for both epilepsy and autism. Their study, published online in the April 12 Human Molecular Genetics, involved members of a large French-Canadian family who had autism spectrum disorders or epilepsy. The severe Q555X mutation appeared in all family members with epilepsy, and in all those who had an autism spectrum disorder. In addition, other mutations in synapsin 1 (A51G, A550T, and T567A) were found in 1% and 3.5% of a separate cohort of French-Canadian individuals with autism and epilepsy, respectively. “These results demonstrate that [synapsin 1] is a novel predisposing gene to [autism spectrum disorders], in addition to epilepsy,” the authors concluded. “[The results also] strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.”

Men who reported chronic ecstasy (MDMA) use were more likely to develop structural brain damage than those who did not use ecstasy, according to a study that was published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry. Using MRI, researchers measured the hippocampal volume of 10 male ecstasy users (average age, 21.3), compared with seven age- and gender-matched subjects who did not use ecstasy. The hippocampal volume of ecstasy users was 10.5% smaller than those of nonusing peers; the overall proportion of gray matter was 4.6% smaller, suggesting that the drug’s effects are not limited to the hippocampus. “These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage,” the authors wrote, adding: “Hippocampal atrophy is a hallmark for disease of progressive cognitive impairment in older patients, such as Alzheimer’s disease.”

In a study published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry, researchers reported that epileptic seizures carry a subsequent risk for brain tumor. “Our study suggests that tumor as an underlying cause for epilepsy may not become apparent for several years after onset, and indicates a need for ongoing vigilance,” the authors stated. In the retrospective cohort study, the investigators examined data regarding individuals with first-time epilepsy admissions and determined that, compared with patients admitted for other common and minor disorders, patients with epilepsy were almost 20 times more likely to develop cerebral tumor. The risk for developing malignant tumors was more than twice the risk for developing benign tumors. “The risk was highest for those aged 15 to 44 years at initial admission for epilepsy,” the authors reported. “The risk of cerebral tumor was still raised several years after initial admission for epilepsy.”

A novel gene transfer vector, NP2, is safe and well tolerated for the treatment of intractable pain, researchers reported in the April 11 online Annals of Neurology. Investigators conducted a multicenter, dose-escalation, phase I clinical trial of intradermal NP2 injection in 10 subjects with persistent pain caused by cancer, despite treatment with morphine or other analgesic. Participants who received the low dose of NP2 reported no substantive change in pain; patients in the middle and high dose cohorts reported pain relief. “There were no placebo controls in this relatively small study,” the authors concluded. “But the dose-responsive analgesic effects suggest that NP2 may be effective in reducing pain and warrants further clinical investigation.”

The FDA has approved DaTscan (ioflupane I 123 injection) for detecting dopamine transporters in the brains of adults with suspected Parkinsonian syndromes. The radiopharmaceutical agent is intended for use with single photon emission CT imaging to evaluate neurodegenerative movement disorders. The injection may be used as an adjunct to other diagnostic evaluation tools to distinguish between essential tremor and tremor due to Parkinson’s disease, as ioflupane I 123 injection alone cannot differentiate between different types of parkinsonian syndromes. The FDA’s approval was based on two phase III clinical trials in which the drug was used to evaluate dopamine transporter distribution in the brains of adult patients. As a new diagnostic adjunct to clinical assessments, ioflupane  I 123 can potentially help physicians select the appropriate treatments for patients with movement disorders.

Persons who are regularly exposed to welding fumes may be at an increased risk for brain damage, specifically in the same areas affected by Parkinson’s disease, researchers reported in the April 12 Neurology. “Welding exposes workers to manganese fumes, but it is unclear if this exposure damages dopaminergic neurons,” the authors stated. “The purpose of this study [was] to determine whether welding exposure is associated with damage to nigrostriatal neurons.” Using PET imaging on 20 welders with no parkinsonian symptoms, 20 individuals with symptoms, and 20 healthy controls, the investigators determined that asymptomatic welders had higher manganese levels in the blood and an average 11.7% reduction in dopamine in certain brain regions. The pattern of reduction seen in welders, however, was distinct from the dysfunction pattern found in symptomatic Parkinson’s disease.

The FDA has approved Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) for the treatment of pseudobulbar affect. The new therapy will help patients manage pseudobulbar affect that occurs secondary to multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), traumatic brain injury, stroke, Parkinson’s disease, and other neurologic diseases. Nuedexta combines dextromethorphan hydrobromide and quinidine sulfate, a metabolic inhibitor that enables therapeutic dextromethorphan concentrations. These components act on NMDA receptors and sigma-1 in the brain, but the mechanism by which it exerts therapeutic effects in patients with pseudobulbar affect is unknown. The drug was tested in patients with ALS and MS and reduced involuntary laughing and crying episodes compared with placebo. 

Virtual reality may be an effective adjunctive therapy for patients experiencing upper arm motor deficits following stroke, according to a study published in the May Stroke. Researchers analyzed seven observational studies and five randomized trials that investigated the effects of virtual reality and video game technology on stroke patients’ upper arm strength and function. Among the observational studies, there was a 14.7% improvement in motor impairment and a 20.1% improvement in motor function; in the randomized trials, patients had an almost five times higher chance of improvement in motor function, compared with those who received traditional therapy. The researchers concluded, “Virtual reality and video game applications are novel and potentially useful technologies that can be combined with conventional rehabilitation for upper arm improvement after stroke.”

Investigators found that surgical revascularization can restore lost brain tissue in patients with cerebrovascular disease that impairs blood flow to the brain, as reported in the online April 14 Stroke. Twenty-nine patients who had undergone vascularization were included in the study. All patients had pre- and postsurgery studies of cerebrovascular reactivity using MRI, and cortical thickness in regions corresponding to steal physiology were measured. “At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere,” the authors stated. “Mean cortical thickness in the revascularized regions increased by 5.1%.” The investigators’ goal was to halt further loss of brain tissue due to strokes, “so it was remarkable to see the loss was actually reversed,” they commented.

Researchers determined that MRI imaging may predict which persons with cognitive impairment will progress to Alzheimer’s disease in a report published in the April 6 online Radiology. Baseline MRI was obtained for 164 individuals with late-onset Alzheimer’s disease, 317 with mild cognitive impairment, and 203 healthy controls. The investigators then used MRI to measure the thickness and amount of atrophy in the cerebral cortex. “Individualized risk estimates from baseline MRI examinations indicated that the one-year risk of conversion to Alzheimer’s disease ranged from 3% to 40%,” the researchers reported. “Relative to the risk of conversion to Alzheimer’s disease conferred by the clinical diagnosis of mild cognitive impairment alone, MRI measures yield substantially more informative patient-specific risk estimates. Such predictive prognostic information will be critical if disease-modifying therapies become available.”

Cotinine, a compound derived from tobacco, reduced brain plaques associated with dementia and memory loss, according to a study published in the online February 14 Journal of Alzheimer’s Disease. A group of investigators studied the effects of cotinine on b-amyloid plaque aggregation in the brains of mice with Alzheimer’s disease. Mice treated with the compound performed better than untreated mice on tasks measuring working memory and thinking skills; long-term treatment also appeared to prevent spatial memory impairment. Overall, the treated mice showed a 26% reduction in amyloid plaque deposits. “Cotinine, the main metabolite of nicotine, has a long half-life and does not have cardiovascular or addictive side effects in humans,” the authors wrote. “The good safety profile in humans and its beneficial effects suggest that cotinine may be an excellent therapeutic candidate for the treatment of Alzheimer’s disease.”

A study published in the April 13 online Neurology provides evidence that treating certain vascular risk factors helps lower the risk for conversion from mild cognitive impairment to Alzheimer’s disease. Investigators assessed memory and thinking skills of 837 patients with mild cognitive impairment and then reassessed them five years later; 414 participants had at least one vascular risk factor at baseline. “At the end of follow-up 298 subjects converted to Alzheimer’s disease dementia, while 352 remained with mild cognitive impairment,” the investigators reported. “Treatment of individual vascular risk factors including hypertension, diabetes, and hypercholesterolemia was associated with the reduced risk of Alzheimer’s disease conversion.” The findings of the study are observational, the authors concluded, but they suggest that active intervention and treatment of certain risk factors might reduce progression to Alzheimer’s disease.

Researchers have identified mutations of the synapsin 1 gene as a possible common genetic cause for both epilepsy and autism. Their study, published online in the April 12 Human Molecular Genetics, involved members of a large French-Canadian family who had autism spectrum disorders or epilepsy. The severe Q555X mutation appeared in all family members with epilepsy, and in all those who had an autism spectrum disorder. In addition, other mutations in synapsin 1 (A51G, A550T, and T567A) were found in 1% and 3.5% of a separate cohort of French-Canadian individuals with autism and epilepsy, respectively. “These results demonstrate that [synapsin 1] is a novel predisposing gene to [autism spectrum disorders], in addition to epilepsy,” the authors concluded. “[The results also] strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.”

Men who reported chronic ecstasy (MDMA) use were more likely to develop structural brain damage than those who did not use ecstasy, according to a study that was published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry. Using MRI, researchers measured the hippocampal volume of 10 male ecstasy users (average age, 21.3), compared with seven age- and gender-matched subjects who did not use ecstasy. The hippocampal volume of ecstasy users was 10.5% smaller than those of nonusing peers; the overall proportion of gray matter was 4.6% smaller, suggesting that the drug’s effects are not limited to the hippocampus. “These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage,” the authors wrote, adding: “Hippocampal atrophy is a hallmark for disease of progressive cognitive impairment in older patients, such as Alzheimer’s disease.”

In a study published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry, researchers reported that epileptic seizures carry a subsequent risk for brain tumor. “Our study suggests that tumor as an underlying cause for epilepsy may not become apparent for several years after onset, and indicates a need for ongoing vigilance,” the authors stated. In the retrospective cohort study, the investigators examined data regarding individuals with first-time epilepsy admissions and determined that, compared with patients admitted for other common and minor disorders, patients with epilepsy were almost 20 times more likely to develop cerebral tumor. The risk for developing malignant tumors was more than twice the risk for developing benign tumors. “The risk was highest for those aged 15 to 44 years at initial admission for epilepsy,” the authors reported. “The risk of cerebral tumor was still raised several years after initial admission for epilepsy.”

A novel gene transfer vector, NP2, is safe and well tolerated for the treatment of intractable pain, researchers reported in the April 11 online Annals of Neurology. Investigators conducted a multicenter, dose-escalation, phase I clinical trial of intradermal NP2 injection in 10 subjects with persistent pain caused by cancer, despite treatment with morphine or other analgesic. Participants who received the low dose of NP2 reported no substantive change in pain; patients in the middle and high dose cohorts reported pain relief. “There were no placebo controls in this relatively small study,” the authors concluded. “But the dose-responsive analgesic effects suggest that NP2 may be effective in reducing pain and warrants further clinical investigation.”

The FDA has approved DaTscan (ioflupane I 123 injection) for detecting dopamine transporters in the brains of adults with suspected Parkinsonian syndromes. The radiopharmaceutical agent is intended for use with single photon emission CT imaging to evaluate neurodegenerative movement disorders. The injection may be used as an adjunct to other diagnostic evaluation tools to distinguish between essential tremor and tremor due to Parkinson’s disease, as ioflupane I 123 injection alone cannot differentiate between different types of parkinsonian syndromes. The FDA’s approval was based on two phase III clinical trials in which the drug was used to evaluate dopamine transporter distribution in the brains of adult patients. As a new diagnostic adjunct to clinical assessments, ioflupane  I 123 can potentially help physicians select the appropriate treatments for patients with movement disorders.

Persons who are regularly exposed to welding fumes may be at an increased risk for brain damage, specifically in the same areas affected by Parkinson’s disease, researchers reported in the April 12 Neurology. “Welding exposes workers to manganese fumes, but it is unclear if this exposure damages dopaminergic neurons,” the authors stated. “The purpose of this study [was] to determine whether welding exposure is associated with damage to nigrostriatal neurons.” Using PET imaging on 20 welders with no parkinsonian symptoms, 20 individuals with symptoms, and 20 healthy controls, the investigators determined that asymptomatic welders had higher manganese levels in the blood and an average 11.7% reduction in dopamine in certain brain regions. The pattern of reduction seen in welders, however, was distinct from the dysfunction pattern found in symptomatic Parkinson’s disease.

The FDA has approved Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) for the treatment of pseudobulbar affect. The new therapy will help patients manage pseudobulbar affect that occurs secondary to multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), traumatic brain injury, stroke, Parkinson’s disease, and other neurologic diseases. Nuedexta combines dextromethorphan hydrobromide and quinidine sulfate, a metabolic inhibitor that enables therapeutic dextromethorphan concentrations. These components act on NMDA receptors and sigma-1 in the brain, but the mechanism by which it exerts therapeutic effects in patients with pseudobulbar affect is unknown. The drug was tested in patients with ALS and MS and reduced involuntary laughing and crying episodes compared with placebo. 

Virtual reality may be an effective adjunctive therapy for patients experiencing upper arm motor deficits following stroke, according to a study published in the May Stroke. Researchers analyzed seven observational studies and five randomized trials that investigated the effects of virtual reality and video game technology on stroke patients’ upper arm strength and function. Among the observational studies, there was a 14.7% improvement in motor impairment and a 20.1% improvement in motor function; in the randomized trials, patients had an almost five times higher chance of improvement in motor function, compared with those who received traditional therapy. The researchers concluded, “Virtual reality and video game applications are novel and potentially useful technologies that can be combined with conventional rehabilitation for upper arm improvement after stroke.”

Investigators found that surgical revascularization can restore lost brain tissue in patients with cerebrovascular disease that impairs blood flow to the brain, as reported in the online April 14 Stroke. Twenty-nine patients who had undergone vascularization were included in the study. All patients had pre- and postsurgery studies of cerebrovascular reactivity using MRI, and cortical thickness in regions corresponding to steal physiology were measured. “At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere,” the authors stated. “Mean cortical thickness in the revascularized regions increased by 5.1%.” The investigators’ goal was to halt further loss of brain tissue due to strokes, “so it was remarkable to see the loss was actually reversed,” they commented.

A 49-year-old woman presented to urgent care with complaints of worsening dyspnea for the previous two days. She reported that her symptoms had begun gradually; at the time of her presentation, however, she was also experiencing chest tightness, occasional wheezing, and a nonproductive cough. She had experienced similar symptoms in the past and obtained good results by using her albuterol inhaler. During the current episode, however, she had not had the usual response to inhaler treatment.

The patient’s medical history was positive for environmental allergies, asthma, and GERD. Two weeks earlier, she had undergone dilatation and curettage (D&C) for dysfunctional bleeding, with no associated complications.

In the social history, the patient reported drinking four to six caffeine beverages daily and consuming alcohol moderately (two to four glasses of wine per week). She was following no formal dietary regimen. The patient denied current or past history of tobacco use and had not traveled recently. She had no family history of coronary vascular disease.

Her medications included albuterol and desloratadine as needed, pantoprazole 40 mg/d, and drospirenone/ethinyl estradiol. The patient said she used her albuterol inhaler four to six times per month but more often in the summer and fall. Nighttime awakenings due to asthma symptoms occurred no more than twice per month. She denied prior history of acute asthma exacerbations requiring oral systemic corticosteroids. The patient stated that since her D&C, she had been using ibuprofen almost daily for mild abdominal cramping.

A review of systems was positive for mild fatigue since her D&C. The patient denied fever, chills, headache, sore throat, or cough. She did complain of daily nasal congestion but with no unusual drainage. The patient denied orthopnea, chest pain, palpitations, or peripheral edema, as well as nausea, vomiting, diarrhea, constipation, hematochezia, or melena. She admitted to daily heartburn for the previous two weeks that was relieved somewhat with pantoprazole. She had not experienced urinary frequency or urgency, dysuria, or hematuria. She also denied rash, pruritus, weakness, paresthesias, joint pain, or swelling.

Physical examination revealed an alert, oriented female who appeared slightly anxious but was in no acute distress. Specific findings were pulse, 110 beats/min; blood pressure, 138/88 mm Hg; respirations, 24 breaths/min; temperature, 97.7°F; O2 saturation, 92% on room air. Her height measured 5’2” and weight, 150 lb (BMI, 27.43).

Her conjunctiva were slightly injected, and the tympanic membranes were intact bilaterally with a light reflex; the septum was midline. The mucosa was pale, boggy, and moist with clear drainage and no inflammation. The nasopharynx had no erythema, and the tonsils appeared normal, although a cobblestone appearance was noted in the posterior pharynx. The neck was supple with no adenopathy.

The patient’s heart rate, 110 beats/min, was regular with no murmurs, rubs, or gallops. In the lungs, a prolonged expiratory phase was noted, with diffuse wheezing on chest auscultation bilaterally. Neither retractions nor use of accessory muscles with breathing was observed. The abdomen was soft, rounded, and nontender with no organomegaly. Bowel sounds were evident in all four quadrants. The patient’s skin was free of suspicious lesions or rashes. Her extremities were without edema, and no calf tenderness was noted; Homans’ sign was negative. Superficial varicosities were noted bilaterally.

The top differential diagnosis included:

• Acute asthma (risk factors: history of uncontrolled asthma, as evidenced by frequent use of albuterol)

• Acute anemia (risk factors: history of dysfunctional uterine bleeding, recent D&C)

• Pulmonary embolism (risk factors: recent surgery, recent start of oral contraceptive use).

Additional diagnoses to be considered less likely included:

• Acute coronary syndrome/MI (possible causes of chest tightness, dyspnea, dyspepsia; but no chest pain, diaphoresis, or nausea)

• Acute respiratory distress (history of tachycardia, possible dyspnea; but no diaphoresis, cyanosis, retractions, accessory muscle use, or lung crackles)

• Pneumonia (risk factors: recent surgery, possible cause of nonproductive cough; but no evidence of fever, chills, rales, or pleuritic chest pain).

Diagnostic testing included a 12-lead ECG to evaluate the patient for cardiac arrhythmia or injury; on it, tachycardia was noted, with a regular rate of 106 beats/min. The patient’s chest x-ray yielded normal results.

Laboratory testing included a complete blood count to screen for anemia and infection. Results included a white blood cell count of 8,200/mL (normal range, 4,500 to 11,000/mL); hematocrit, 38.2% (normal range for women, 36.1% to 44.3%); hemoglobin, 13.1 g/dL (normal for women, 12.1 to 15.1 g/dL). A comprehensive metabolic panel was performed to assess electrolyte levels and kidney and liver function; findings were normal. Results of a D-dimer assay, which was obtained to exclude pulmonary embolism,¹ were normal at 0.5 mg/L (range, 0.4 to 1.4 mg/L).

In the case of heightened suspicion for MI, the patient would have been transferred to the emergency department (ED) for evaluation, including serial cardiac troponin levels; elevated troponin levels are deemed the standard criterion to define and diagnose MI in a consensus document from the European Society of Cardiology and the American College of Cardiology.² (Troponin-T and troponin-I are more tissue-specific than the MB fraction of creatine kinase [CK-MB] in detecting MI; positive troponin levels are considered virtually diagnostic of MI.² Typically, cardiac troponin levels are measured two to three times over a 12- to 16-hour period.)

Peak expiratory flow (PEF), which was measured to evaluate the patient’s respiratory status, was 150 L/min (compared with personal best for a patient of her height and age, approximately 460 L/min). She was given 2.5 mg/3 mL of inhaled albuterol over 15 minutes. Her PEF increased to 350 L/min. O2 saturation improved to 96% on room air, pulse to 104 beats/min, and respirations 20 breaths/min; her blood pressure reading was now 140/90 mm Hg. A prolonged expiratory phase persisted in the lungs, but diffuse wheezing decreased by 40% on chest auscultation.

A second albuterol treatment was administered 20 minutes later, and the patient’s PEF increased to 380 L/min and O2 saturation to 99%. The lungs presently cleared with no further wheezing noted.

In addition, the patient was given a GI cocktail (ie, liquid antacid combined with an anticholinergic agent and viscous lidocaine). Within 10 minutes, her chest tightness was relieved 100%. Her blood pressure was then measured at 135/84 mm Hg; respirations, 18 breaths/min; and pulse rate, 96 beats/min.

According to the National Asthma Education and Prevention Program (NAEPP) 2007 Guidelines for the Diagnosis and Management of Asthma, Expert Panel Report 3 (EPR-3),³ the patient was classified as having intermittent, not-well-controlled asthma with an acute exacerbation. In addition, she was given a diagnosis of uncontrolled GERD.

DISCUSSION
Asthma Incidence and Risk Factors
Asthma affects approximately 300 million people worldwide and remains a global respiratory concern.⁴ In the United States, this chronic health condition has a prevalence of 8% to 10%. It is estimated that 5% to 10% of asthmatic patients have severe disease that does not respond typically to therapeutic interventions.⁵

Asthma involves bronchial hyperresponsiveness, airflow obstruction, and underlying inflammation. Acute episodes of asthma, arising from bronchospasm, usually manifest with progressively worsening cough, shortness of breath, chest tightness and wheezing (asthma’s hallmark symptoms), or a combination of symptoms.³

Symptoms of asthma or exacerbations of reactive airway disease vary from patient to patient. In addition to the hallmark symptoms noted, subacute or acute episodes of asthma exacerbation are characterized by decreases in expiratory airflow that can be documented by objective measurements of lung function, such as PEF or spirometry; these measures of airflow indicate the severity of an exacerbation more reliably than does perceived symptom severity.³ The EPR-3 panelists recommend determining asthma severity using a combination of objective criteria and clinical symptoms,³ although few clinicians use the objective criteria.⁶

Estimates of the prevalence of GERD among patients with asthma have varied from 34% to 89%.^7-9 Patients with GERD are 1.97 times more likely than patients without GERD to have asthma¹⁰; silent gastroesophageal reflux has been identified in 24% to 62% of patients with asthma, and early studies suggest that treatment for GERD may improve asthma control in patients with severe or difficult-to-control asthma.^8,11,12

The exact link between the two conditions is unclear. However, possible explanations why GERD and asthma coincide are that acid flow causes injury to the lining of the throat, airways, and lungs, making inhalation difficult and often causing a persistent cough; or that when acid enters the esophagus, a nerve reflex is triggered that causes the airways to narrow in order to prevent the acid from entering; this can explain dyspnea.^8,9

Economic Burden
Asthma is costly to treat, and because there is no cure, the expense is ongoing. According to a 2011 report,¹³ the average annual direct cost of care (eg, medications, hospital admissions, nonemergency office visits) for one asthma patient between 2002 and 2007 was $3,259. In 2007, the most current data available, the total cost of asthma in the US was $56 billion, with productivity losses due to mortality accounting for $2.1 billion and morbidity-related losses estimated at $3.8 billion.¹³ The economic consequences of asthma are substantial and can place a considerable burden on affected individuals, their families, the health care system, and society as a whole.³

Current Standard of Care
Based on the scientific literature and the opinions expressed by the NAEPP in the EPR-3,³ clinicians are advised to consider the following general principles and goals for managing asthma: early treatment, special attention to patients at high risk for asthma-related death, and special attention to infants.³ The guidelines emphasize the importance of a clinician/patient partnership to facilitate the asthma patient’s self-management.

Early treatment is a particularly important component for management of asthma exacerbations. Important elements of early treatment include a written asthma action plan, combined with enhanced awareness of the early indicators of an exacerbation (ie, worsening PEF).^3,14 It is believed that if patients are able to monitor their respiratory condition and follow a plan of care based on their PEF and/or signs and symptoms of asthma, they are more likely to achieve optimal management of their disease.¹⁵

Written Asthma Action Plan. The EPR-3³ recommends that health care providers supply all asthmatic patients with a written asthma action plan that will define and support the patient’s efforts at self-management. Written asthma action plans are particularly beneficial for patients with moderate to severe persistent asthma, poorly controlled asthma, or a history of severe exacerbations.^3,14

The written asthma action plan should include instructions for daily management of asthma and ways to recognize and treat worsening asthma, including adjustments to medication dosing. Plans may be based on PEF and/or symptoms. Asthma action plans should be discussed and reevaluated at follow-up visits.³ A sample asthma action plan can be found at www.health.state.ny.us/diseases/asthma/pdf/4850.pdf.¹⁶

Peak Expiratory Flow (PEF). The EPR-3³ recommends PEF monitoring in all asthma patients, regardless of the severity of their exacerbations.¹⁷ PEF-based plans are especially useful for the patient who has difficulty perceiving early signs and symptoms of worsening asthma.^3,18 A PEF-based plan instructs the patient to use quick-relief medications if symptoms occur or if PEF drops below 80% of the patient’s personal or predicted best. (Measured personal best is the patient’s highest PEF in the previous two weeks of good asthma control,^3,19 whereas predicted best is calculated based on findings from a 1983 study by Knudson et al.^3,20)

A PEF between 50% and 79% requires the patient to carefully monitor his or her response to the quick-relief medication and, based on that response, consider whether to contact a health care provider. When PEF falls below 50%, a provider’s immediate intervention is usually recommended.³

In the urgent care or ED setting, according to EPR-3 recommendations,³ the PEF or forced expiratory volume in 1 second (FEV1) is used to indicate the following:

• ≥ 70% predicted PEF or FEV1: goal for discharge

• 40% to 69% predicted PEF or FEV1: incomplete response to treatment, frequent need for treatment in the ED

• 3

Treatment and Management
Asthma management interventions that target the treatment of active disease and predisposing triggers are designed to reduce the severity and/or duration of morbidity associated with asthma—principally, to prevent symptoms and exacerbations (see Table 1³).

When patients are discharged following an asthma exacerbation, their medications should include an oral corticosteroid burst and a short-acting b2-agonist (SABA); the clinician should also consider prescribing an inhaled corticosteroid (ICS).³

It is no longer recommended that ICS dosing be doubled in place of an oral steroid burst.^3,21 The addition of a leukotriene receptor antagonist (LTRA) may also be considered.^3,22

Patients should be given an action plan, and follow-up with a primary care provider should be scheduled within a few days—or even the following day, depending on the severity of the patient’s condition. The importance of follow-up with a primary care provider, a pulmonologist, or an asthma/allergy specialist should be emphasized.^3,23

For patients who have difficulty recognizing their symptoms, a peak flow meter may be useful. This device is also recommended for patients with moderate to severe asthma or a history of numerous severe exacerbations.³ Additionally, spacers should always be used with metered dose inhalers (MDIs), because they make it easier for medication to reach the lungs and reduce the amount deposited in the mouth and throat, where it can lead to irritation. At each office visit, use of the peak flow meter and inhaler technique should be observed, and the action plan reevaluated and changed if necessary.^3,14

Additional components of patient education include instruction in controlling environmental factors: avoiding environmental tobacco smoke, exposure to insect allergens, and molds. It is also important to stress controlling comorbid conditions that influence asthma, such as allergies or GERD. Patients with symptoms of GERD should be advised to take the steps shown in Table 2.^8,24

Clinical Implications
Assessment of the severity of an asthma exacerbation is an essential component of ambulatory asthma care. Underclassification of asthma severity has been associated with increased morbidity and mortality,⁶ and the NAEPP guidelines recommend that clinicians assess and document asthma severity at each clinic visit.^3,25 Patients who receive care based on evidence-based practice guidelines have been shown to experience 28% better outcomes.²⁶

PATIENT OUTCOME
The case patient was discharged on an oral corticosteroid burst and a low-dose ICS. She was instructed how and when to use her SABA and given a prescription for a spacer; use of a peak flow meter was initiated with an estimated personal best goal of 460 L/min. The patient was given a written asthma action plan to help her recognize early signs and symptoms of worsening asthma and was advised to use quick-relief medications if she experienced symptoms or if her PEF dropped below 80% of her predicted best.

The patient’s clinician emphasized the importance of controlling any asthma-triggering environmental factors and reviewed nonpharmacologic interventions to control GERD. The patient was advised to resume desloratadine 5 mg/d and pantoprazole 40 mg/d. She was also instructed to schedule an appointment with her primary care provider within 48 hours and to return to urgent care or the ED with any further exacerbation of respiratory symptoms not controlled by her SABA.

CONCLUSION
Asthma morbidity is a nationally recognized, major public health problem. Given the sharp rise in health care costs and limited resources, health care providers must factor in the comparative effectiveness, comparative cost, and cost-effectiveness of both new and existing health care interventions when making treatment decisions.

Many asthmatic patients face the challenges of health care access and quality. By promoting their self-care and awareness, clinicians can help asthmatic patients achieve better symptom management and use the health care system less often.

REFERENCES
1. Stein PD, Hull RD, Patel KC, et al. D-Dimer for the exclusion of acute venous thrombosis and pulmonary embolism. Ann Intern Med. 2004;140(8):589-602.

2. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36(3):959-969.

3. National Asthma Education and Prevention Program, National Heart, Lung, and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Heart, Lung, and Blood Institute; 2007. US Department of Health and Human Services publication NIH 07-4051.

4. Lougheed DM. Variability in asthma: symptom perception, care, and outcomes. Can J Physiol Pharmacol. 2007;85(1):149-154.

5. Higgins JC. The ‘crashing asthmatic.’ Am Fam Physician. 2003;67(5):997-1004. 

6. Cowen MK, Wakefield DB, Cloutier MM. Classifying asthma severity: objective versus subjective measures. J Asthma. 2007;44(9):711-715.

7. Takenaka R, Matsuno O, Kitajima K, et al. The use of frequency scale for the symptoms of GERD in assessment of gastro-oesophageal reflux symptoms in asthma. Allergol Immunopathol (Madr). 2010;38(1):20-24.

8. Harding SM, Barnes PJ, Hollingsworth H. Gastroesophageal reflux and asthma (2010). www.uptodate.com/contents/gastroesophageal-reflux-and-asthma. Accessed April 5, 2011.

9. Havemann BD, Henderson CA, El-Serag HB. The association between gastro-oesophageal reflux disease and asthma: a systematic review. Gut. 2007;56(12):1654-1664.

10. Tsai MC, Lin HL, Lin CC, et al. Increased risk of concurrent asthma among patients with gastroesophageal reflux disease: a nationwide population-based study. Eur J Gastroenterol Hepatol. 2010;22(10):1169-1173.

11. Harding SM, Richter JE, Guzzo MR, et al. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med. 1996;100(4):395-405.

12. Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database Syst Rev. 2003;(2):CD001496.

13. Barnett SB, Nurmagambetov TA. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011;127(1):145-152.

14. Walders N, Kercsmar C, Schluchter M, et al. An interdisciplinary intervention for undertreated pediatric asthma. Chest. 2006;129(2):292-299.

15. Morrow R, Fletcher J, Mulvihill M, Park H. The asthma dialogues: a model of interactive education for skills. J Contin Educ Health Prof. 2007;27(1): 49-58.

16. State of New York, Department of Health. Asthma action plan. www.health.state.ny.us/diseases/asthma/pdf/4850.pdf. Accessed April 11, 2011.

17. Picken HA, Greenfield S, Teres D, et al. Effects of local standards on the implementation of national guidelines for asthma: primary care agreement with national asthma guidelines. J Gen Intern Med. 1998;13(10):659-663.

18. Hardie GE, Gold WM, Janson S, et al. Understanding how asthmatics perceive symptom distress during a methacholine challenge. J Asthma. 2002;39(7):611-618.

19. Reddel HK, Marks GB, Jenkins CR. When can personal best peak flow be determined for asthma action plans? Thorax. 2004;59(11):922-924.

20. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127(6):725-734.

21. Ind PW, Dal Negro R, Colman NC, et al. Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma. Respir Med. 2003;97(5):555-562.

22. Price DB, Hernandez D, Magyar P, et al; Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) International Study Group. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax. 2003;58(3):211-216.

23. Schatz M, Zeiger RS, Mosen D, et al. Improved asthma outcomes from allergy specialist care: a population-based cross-sectional analysis. J Allergy Clin Immunol. 2005;116(6):1307-1313.

24. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143(3):199-211.

25. Cabana MD, Bruckman D, Meister K, et al. Documentation of asthma severity in pediatric outpatient clinics. Clin Pediatr (Phila). 2003;42(2):121-125.

26. Heater BS, Becker AM, Olson RK. Nursing interventions and patient outcomes: a meta-analysis of studies. Nurs Res. 1988;37(5):303-307.

A 49-year-old woman presented to urgent care with complaints of worsening dyspnea for the previous two days. She reported that her symptoms had begun gradually; at the time of her presentation, however, she was also experiencing chest tightness, occasional wheezing, and a nonproductive cough. She had experienced similar symptoms in the past and obtained good results by using her albuterol inhaler. During the current episode, however, she had not had the usual response to inhaler treatment.

The patient’s medical history was positive for environmental allergies, asthma, and GERD. Two weeks earlier, she had undergone dilatation and curettage (D&C) for dysfunctional bleeding, with no associated complications.

In the social history, the patient reported drinking four to six caffeine beverages daily and consuming alcohol moderately (two to four glasses of wine per week). She was following no formal dietary regimen. The patient denied current or past history of tobacco use and had not traveled recently. She had no family history of coronary vascular disease.

Her medications included albuterol and desloratadine as needed, pantoprazole 40 mg/d, and drospirenone/ethinyl estradiol. The patient said she used her albuterol inhaler four to six times per month but more often in the summer and fall. Nighttime awakenings due to asthma symptoms occurred no more than twice per month. She denied prior history of acute asthma exacerbations requiring oral systemic corticosteroids. The patient stated that since her D&C, she had been using ibuprofen almost daily for mild abdominal cramping.

A review of systems was positive for mild fatigue since her D&C. The patient denied fever, chills, headache, sore throat, or cough. She did complain of daily nasal congestion but with no unusual drainage. The patient denied orthopnea, chest pain, palpitations, or peripheral edema, as well as nausea, vomiting, diarrhea, constipation, hematochezia, or melena. She admitted to daily heartburn for the previous two weeks that was relieved somewhat with pantoprazole. She had not experienced urinary frequency or urgency, dysuria, or hematuria. She also denied rash, pruritus, weakness, paresthesias, joint pain, or swelling.

Physical examination revealed an alert, oriented female who appeared slightly anxious but was in no acute distress. Specific findings were pulse, 110 beats/min; blood pressure, 138/88 mm Hg; respirations, 24 breaths/min; temperature, 97.7°F; O2 saturation, 92% on room air. Her height measured 5’2” and weight, 150 lb (BMI, 27.43).

Her conjunctiva were slightly injected, and the tympanic membranes were intact bilaterally with a light reflex; the septum was midline. The mucosa was pale, boggy, and moist with clear drainage and no inflammation. The nasopharynx had no erythema, and the tonsils appeared normal, although a cobblestone appearance was noted in the posterior pharynx. The neck was supple with no adenopathy.

The patient’s heart rate, 110 beats/min, was regular with no murmurs, rubs, or gallops. In the lungs, a prolonged expiratory phase was noted, with diffuse wheezing on chest auscultation bilaterally. Neither retractions nor use of accessory muscles with breathing was observed. The abdomen was soft, rounded, and nontender with no organomegaly. Bowel sounds were evident in all four quadrants. The patient’s skin was free of suspicious lesions or rashes. Her extremities were without edema, and no calf tenderness was noted; Homans’ sign was negative. Superficial varicosities were noted bilaterally.

The top differential diagnosis included:

• Acute asthma (risk factors: history of uncontrolled asthma, as evidenced by frequent use of albuterol)

• Acute anemia (risk factors: history of dysfunctional uterine bleeding, recent D&C)

• Pulmonary embolism (risk factors: recent surgery, recent start of oral contraceptive use).

Additional diagnoses to be considered less likely included:

• Acute coronary syndrome/MI (possible causes of chest tightness, dyspnea, dyspepsia; but no chest pain, diaphoresis, or nausea)

• Acute respiratory distress (history of tachycardia, possible dyspnea; but no diaphoresis, cyanosis, retractions, accessory muscle use, or lung crackles)

• Pneumonia (risk factors: recent surgery, possible cause of nonproductive cough; but no evidence of fever, chills, rales, or pleuritic chest pain).

Diagnostic testing included a 12-lead ECG to evaluate the patient for cardiac arrhythmia or injury; on it, tachycardia was noted, with a regular rate of 106 beats/min. The patient’s chest x-ray yielded normal results.

Laboratory testing included a complete blood count to screen for anemia and infection. Results included a white blood cell count of 8,200/mL (normal range, 4,500 to 11,000/mL); hematocrit, 38.2% (normal range for women, 36.1% to 44.3%); hemoglobin, 13.1 g/dL (normal for women, 12.1 to 15.1 g/dL). A comprehensive metabolic panel was performed to assess electrolyte levels and kidney and liver function; findings were normal. Results of a D-dimer assay, which was obtained to exclude pulmonary embolism,¹ were normal at 0.5 mg/L (range, 0.4 to 1.4 mg/L).

In the case of heightened suspicion for MI, the patient would have been transferred to the emergency department (ED) for evaluation, including serial cardiac troponin levels; elevated troponin levels are deemed the standard criterion to define and diagnose MI in a consensus document from the European Society of Cardiology and the American College of Cardiology.² (Troponin-T and troponin-I are more tissue-specific than the MB fraction of creatine kinase [CK-MB] in detecting MI; positive troponin levels are considered virtually diagnostic of MI.² Typically, cardiac troponin levels are measured two to three times over a 12- to 16-hour period.)

Peak expiratory flow (PEF), which was measured to evaluate the patient’s respiratory status, was 150 L/min (compared with personal best for a patient of her height and age, approximately 460 L/min). She was given 2.5 mg/3 mL of inhaled albuterol over 15 minutes. Her PEF increased to 350 L/min. O2 saturation improved to 96% on room air, pulse to 104 beats/min, and respirations 20 breaths/min; her blood pressure reading was now 140/90 mm Hg. A prolonged expiratory phase persisted in the lungs, but diffuse wheezing decreased by 40% on chest auscultation.

A second albuterol treatment was administered 20 minutes later, and the patient’s PEF increased to 380 L/min and O2 saturation to 99%. The lungs presently cleared with no further wheezing noted.

In addition, the patient was given a GI cocktail (ie, liquid antacid combined with an anticholinergic agent and viscous lidocaine). Within 10 minutes, her chest tightness was relieved 100%. Her blood pressure was then measured at 135/84 mm Hg; respirations, 18 breaths/min; and pulse rate, 96 beats/min.

According to the National Asthma Education and Prevention Program (NAEPP) 2007 Guidelines for the Diagnosis and Management of Asthma, Expert Panel Report 3 (EPR-3),³ the patient was classified as having intermittent, not-well-controlled asthma with an acute exacerbation. In addition, she was given a diagnosis of uncontrolled GERD.

DISCUSSION
Asthma Incidence and Risk Factors
Asthma affects approximately 300 million people worldwide and remains a global respiratory concern.⁴ In the United States, this chronic health condition has a prevalence of 8% to 10%. It is estimated that 5% to 10% of asthmatic patients have severe disease that does not respond typically to therapeutic interventions.⁵

Asthma involves bronchial hyperresponsiveness, airflow obstruction, and underlying inflammation. Acute episodes of asthma, arising from bronchospasm, usually manifest with progressively worsening cough, shortness of breath, chest tightness and wheezing (asthma’s hallmark symptoms), or a combination of symptoms.³

Symptoms of asthma or exacerbations of reactive airway disease vary from patient to patient. In addition to the hallmark symptoms noted, subacute or acute episodes of asthma exacerbation are characterized by decreases in expiratory airflow that can be documented by objective measurements of lung function, such as PEF or spirometry; these measures of airflow indicate the severity of an exacerbation more reliably than does perceived symptom severity.³ The EPR-3 panelists recommend determining asthma severity using a combination of objective criteria and clinical symptoms,³ although few clinicians use the objective criteria.⁶

Estimates of the prevalence of GERD among patients with asthma have varied from 34% to 89%.^7-9 Patients with GERD are 1.97 times more likely than patients without GERD to have asthma¹⁰; silent gastroesophageal reflux has been identified in 24% to 62% of patients with asthma, and early studies suggest that treatment for GERD may improve asthma control in patients with severe or difficult-to-control asthma.^8,11,12

The exact link between the two conditions is unclear. However, possible explanations why GERD and asthma coincide are that acid flow causes injury to the lining of the throat, airways, and lungs, making inhalation difficult and often causing a persistent cough; or that when acid enters the esophagus, a nerve reflex is triggered that causes the airways to narrow in order to prevent the acid from entering; this can explain dyspnea.^8,9

Economic Burden
Asthma is costly to treat, and because there is no cure, the expense is ongoing. According to a 2011 report,¹³ the average annual direct cost of care (eg, medications, hospital admissions, nonemergency office visits) for one asthma patient between 2002 and 2007 was $3,259. In 2007, the most current data available, the total cost of asthma in the US was $56 billion, with productivity losses due to mortality accounting for $2.1 billion and morbidity-related losses estimated at $3.8 billion.¹³ The economic consequences of asthma are substantial and can place a considerable burden on affected individuals, their families, the health care system, and society as a whole.³

Current Standard of Care
Based on the scientific literature and the opinions expressed by the NAEPP in the EPR-3,³ clinicians are advised to consider the following general principles and goals for managing asthma: early treatment, special attention to patients at high risk for asthma-related death, and special attention to infants.³ The guidelines emphasize the importance of a clinician/patient partnership to facilitate the asthma patient’s self-management.

Early treatment is a particularly important component for management of asthma exacerbations. Important elements of early treatment include a written asthma action plan, combined with enhanced awareness of the early indicators of an exacerbation (ie, worsening PEF).^3,14 It is believed that if patients are able to monitor their respiratory condition and follow a plan of care based on their PEF and/or signs and symptoms of asthma, they are more likely to achieve optimal management of their disease.¹⁵

Written Asthma Action Plan. The EPR-3³ recommends that health care providers supply all asthmatic patients with a written asthma action plan that will define and support the patient’s efforts at self-management. Written asthma action plans are particularly beneficial for patients with moderate to severe persistent asthma, poorly controlled asthma, or a history of severe exacerbations.^3,14

The written asthma action plan should include instructions for daily management of asthma and ways to recognize and treat worsening asthma, including adjustments to medication dosing. Plans may be based on PEF and/or symptoms. Asthma action plans should be discussed and reevaluated at follow-up visits.³ A sample asthma action plan can be found at www.health.state.ny.us/diseases/asthma/pdf/4850.pdf.¹⁶

Peak Expiratory Flow (PEF). The EPR-3³ recommends PEF monitoring in all asthma patients, regardless of the severity of their exacerbations.¹⁷ PEF-based plans are especially useful for the patient who has difficulty perceiving early signs and symptoms of worsening asthma.^3,18 A PEF-based plan instructs the patient to use quick-relief medications if symptoms occur or if PEF drops below 80% of the patient’s personal or predicted best. (Measured personal best is the patient’s highest PEF in the previous two weeks of good asthma control,^3,19 whereas predicted best is calculated based on findings from a 1983 study by Knudson et al.^3,20)

A PEF between 50% and 79% requires the patient to carefully monitor his or her response to the quick-relief medication and, based on that response, consider whether to contact a health care provider. When PEF falls below 50%, a provider’s immediate intervention is usually recommended.³

In the urgent care or ED setting, according to EPR-3 recommendations,³ the PEF or forced expiratory volume in 1 second (FEV1) is used to indicate the following:

• ≥ 70% predicted PEF or FEV1: goal for discharge

• 40% to 69% predicted PEF or FEV1: incomplete response to treatment, frequent need for treatment in the ED

• 3

Treatment and Management
Asthma management interventions that target the treatment of active disease and predisposing triggers are designed to reduce the severity and/or duration of morbidity associated with asthma—principally, to prevent symptoms and exacerbations (see Table 1³).

When patients are discharged following an asthma exacerbation, their medications should include an oral corticosteroid burst and a short-acting b2-agonist (SABA); the clinician should also consider prescribing an inhaled corticosteroid (ICS).³

It is no longer recommended that ICS dosing be doubled in place of an oral steroid burst.^3,21 The addition of a leukotriene receptor antagonist (LTRA) may also be considered.^3,22

Patients should be given an action plan, and follow-up with a primary care provider should be scheduled within a few days—or even the following day, depending on the severity of the patient’s condition. The importance of follow-up with a primary care provider, a pulmonologist, or an asthma/allergy specialist should be emphasized.^3,23

For patients who have difficulty recognizing their symptoms, a peak flow meter may be useful. This device is also recommended for patients with moderate to severe asthma or a history of numerous severe exacerbations.³ Additionally, spacers should always be used with metered dose inhalers (MDIs), because they make it easier for medication to reach the lungs and reduce the amount deposited in the mouth and throat, where it can lead to irritation. At each office visit, use of the peak flow meter and inhaler technique should be observed, and the action plan reevaluated and changed if necessary.^3,14

Additional components of patient education include instruction in controlling environmental factors: avoiding environmental tobacco smoke, exposure to insect allergens, and molds. It is also important to stress controlling comorbid conditions that influence asthma, such as allergies or GERD. Patients with symptoms of GERD should be advised to take the steps shown in Table 2.^8,24

Clinical Implications
Assessment of the severity of an asthma exacerbation is an essential component of ambulatory asthma care. Underclassification of asthma severity has been associated with increased morbidity and mortality,⁶ and the NAEPP guidelines recommend that clinicians assess and document asthma severity at each clinic visit.^3,25 Patients who receive care based on evidence-based practice guidelines have been shown to experience 28% better outcomes.²⁶

PATIENT OUTCOME
The case patient was discharged on an oral corticosteroid burst and a low-dose ICS. She was instructed how and when to use her SABA and given a prescription for a spacer; use of a peak flow meter was initiated with an estimated personal best goal of 460 L/min. The patient was given a written asthma action plan to help her recognize early signs and symptoms of worsening asthma and was advised to use quick-relief medications if she experienced symptoms or if her PEF dropped below 80% of her predicted best.

The patient’s clinician emphasized the importance of controlling any asthma-triggering environmental factors and reviewed nonpharmacologic interventions to control GERD. The patient was advised to resume desloratadine 5 mg/d and pantoprazole 40 mg/d. She was also instructed to schedule an appointment with her primary care provider within 48 hours and to return to urgent care or the ED with any further exacerbation of respiratory symptoms not controlled by her SABA.

CONCLUSION
Asthma morbidity is a nationally recognized, major public health problem. Given the sharp rise in health care costs and limited resources, health care providers must factor in the comparative effectiveness, comparative cost, and cost-effectiveness of both new and existing health care interventions when making treatment decisions.

Many asthmatic patients face the challenges of health care access and quality. By promoting their self-care and awareness, clinicians can help asthmatic patients achieve better symptom management and use the health care system less often.

REFERENCES
1. Stein PD, Hull RD, Patel KC, et al. D-Dimer for the exclusion of acute venous thrombosis and pulmonary embolism. Ann Intern Med. 2004;140(8):589-602.

2. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36(3):959-969.

3. National Asthma Education and Prevention Program, National Heart, Lung, and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Heart, Lung, and Blood Institute; 2007. US Department of Health and Human Services publication NIH 07-4051.

4. Lougheed DM. Variability in asthma: symptom perception, care, and outcomes. Can J Physiol Pharmacol. 2007;85(1):149-154.

5. Higgins JC. The ‘crashing asthmatic.’ Am Fam Physician. 2003;67(5):997-1004. 

6. Cowen MK, Wakefield DB, Cloutier MM. Classifying asthma severity: objective versus subjective measures. J Asthma. 2007;44(9):711-715.

7. Takenaka R, Matsuno O, Kitajima K, et al. The use of frequency scale for the symptoms of GERD in assessment of gastro-oesophageal reflux symptoms in asthma. Allergol Immunopathol (Madr). 2010;38(1):20-24.

8. Harding SM, Barnes PJ, Hollingsworth H. Gastroesophageal reflux and asthma (2010). www.uptodate.com/contents/gastroesophageal-reflux-and-asthma. Accessed April 5, 2011.

9. Havemann BD, Henderson CA, El-Serag HB. The association between gastro-oesophageal reflux disease and asthma: a systematic review. Gut. 2007;56(12):1654-1664.

10. Tsai MC, Lin HL, Lin CC, et al. Increased risk of concurrent asthma among patients with gastroesophageal reflux disease: a nationwide population-based study. Eur J Gastroenterol Hepatol. 2010;22(10):1169-1173.

11. Harding SM, Richter JE, Guzzo MR, et al. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med. 1996;100(4):395-405.

12. Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database Syst Rev. 2003;(2):CD001496.

13. Barnett SB, Nurmagambetov TA. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011;127(1):145-152.

14. Walders N, Kercsmar C, Schluchter M, et al. An interdisciplinary intervention for undertreated pediatric asthma. Chest. 2006;129(2):292-299.

15. Morrow R, Fletcher J, Mulvihill M, Park H. The asthma dialogues: a model of interactive education for skills. J Contin Educ Health Prof. 2007;27(1): 49-58.

16. State of New York, Department of Health. Asthma action plan. www.health.state.ny.us/diseases/asthma/pdf/4850.pdf. Accessed April 11, 2011.

17. Picken HA, Greenfield S, Teres D, et al. Effects of local standards on the implementation of national guidelines for asthma: primary care agreement with national asthma guidelines. J Gen Intern Med. 1998;13(10):659-663.

18. Hardie GE, Gold WM, Janson S, et al. Understanding how asthmatics perceive symptom distress during a methacholine challenge. J Asthma. 2002;39(7):611-618.

19. Reddel HK, Marks GB, Jenkins CR. When can personal best peak flow be determined for asthma action plans? Thorax. 2004;59(11):922-924.

20. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127(6):725-734.

21. Ind PW, Dal Negro R, Colman NC, et al. Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma. Respir Med. 2003;97(5):555-562.

22. Price DB, Hernandez D, Magyar P, et al; Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) International Study Group. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax. 2003;58(3):211-216.

23. Schatz M, Zeiger RS, Mosen D, et al. Improved asthma outcomes from allergy specialist care: a population-based cross-sectional analysis. J Allergy Clin Immunol. 2005;116(6):1307-1313.

24. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143(3):199-211.

25. Cabana MD, Bruckman D, Meister K, et al. Documentation of asthma severity in pediatric outpatient clinics. Clin Pediatr (Phila). 2003;42(2):121-125.

26. Heater BS, Becker AM, Olson RK. Nursing interventions and patient outcomes: a meta-analysis of studies. Nurs Res. 1988;37(5):303-307.

A 49-year-old woman presented to urgent care with complaints of worsening dyspnea for the previous two days. She reported that her symptoms had begun gradually; at the time of her presentation, however, she was also experiencing chest tightness, occasional wheezing, and a nonproductive cough. She had experienced similar symptoms in the past and obtained good results by using her albuterol inhaler. During the current episode, however, she had not had the usual response to inhaler treatment.

The patient’s medical history was positive for environmental allergies, asthma, and GERD. Two weeks earlier, she had undergone dilatation and curettage (D&C) for dysfunctional bleeding, with no associated complications.

In the social history, the patient reported drinking four to six caffeine beverages daily and consuming alcohol moderately (two to four glasses of wine per week). She was following no formal dietary regimen. The patient denied current or past history of tobacco use and had not traveled recently. She had no family history of coronary vascular disease.

Her medications included albuterol and desloratadine as needed, pantoprazole 40 mg/d, and drospirenone/ethinyl estradiol. The patient said she used her albuterol inhaler four to six times per month but more often in the summer and fall. Nighttime awakenings due to asthma symptoms occurred no more than twice per month. She denied prior history of acute asthma exacerbations requiring oral systemic corticosteroids. The patient stated that since her D&C, she had been using ibuprofen almost daily for mild abdominal cramping.

A review of systems was positive for mild fatigue since her D&C. The patient denied fever, chills, headache, sore throat, or cough. She did complain of daily nasal congestion but with no unusual drainage. The patient denied orthopnea, chest pain, palpitations, or peripheral edema, as well as nausea, vomiting, diarrhea, constipation, hematochezia, or melena. She admitted to daily heartburn for the previous two weeks that was relieved somewhat with pantoprazole. She had not experienced urinary frequency or urgency, dysuria, or hematuria. She also denied rash, pruritus, weakness, paresthesias, joint pain, or swelling.

Physical examination revealed an alert, oriented female who appeared slightly anxious but was in no acute distress. Specific findings were pulse, 110 beats/min; blood pressure, 138/88 mm Hg; respirations, 24 breaths/min; temperature, 97.7°F; O2 saturation, 92% on room air. Her height measured 5’2” and weight, 150 lb (BMI, 27.43).

Her conjunctiva were slightly injected, and the tympanic membranes were intact bilaterally with a light reflex; the septum was midline. The mucosa was pale, boggy, and moist with clear drainage and no inflammation. The nasopharynx had no erythema, and the tonsils appeared normal, although a cobblestone appearance was noted in the posterior pharynx. The neck was supple with no adenopathy.

The patient’s heart rate, 110 beats/min, was regular with no murmurs, rubs, or gallops. In the lungs, a prolonged expiratory phase was noted, with diffuse wheezing on chest auscultation bilaterally. Neither retractions nor use of accessory muscles with breathing was observed. The abdomen was soft, rounded, and nontender with no organomegaly. Bowel sounds were evident in all four quadrants. The patient’s skin was free of suspicious lesions or rashes. Her extremities were without edema, and no calf tenderness was noted; Homans’ sign was negative. Superficial varicosities were noted bilaterally.

The top differential diagnosis included:

• Acute asthma (risk factors: history of uncontrolled asthma, as evidenced by frequent use of albuterol)

• Acute anemia (risk factors: history of dysfunctional uterine bleeding, recent D&C)

• Pulmonary embolism (risk factors: recent surgery, recent start of oral contraceptive use).

Additional diagnoses to be considered less likely included:

• Acute coronary syndrome/MI (possible causes of chest tightness, dyspnea, dyspepsia; but no chest pain, diaphoresis, or nausea)

• Acute respiratory distress (history of tachycardia, possible dyspnea; but no diaphoresis, cyanosis, retractions, accessory muscle use, or lung crackles)

• Pneumonia (risk factors: recent surgery, possible cause of nonproductive cough; but no evidence of fever, chills, rales, or pleuritic chest pain).

Diagnostic testing included a 12-lead ECG to evaluate the patient for cardiac arrhythmia or injury; on it, tachycardia was noted, with a regular rate of 106 beats/min. The patient’s chest x-ray yielded normal results.

Laboratory testing included a complete blood count to screen for anemia and infection. Results included a white blood cell count of 8,200/mL (normal range, 4,500 to 11,000/mL); hematocrit, 38.2% (normal range for women, 36.1% to 44.3%); hemoglobin, 13.1 g/dL (normal for women, 12.1 to 15.1 g/dL). A comprehensive metabolic panel was performed to assess electrolyte levels and kidney and liver function; findings were normal. Results of a D-dimer assay, which was obtained to exclude pulmonary embolism,¹ were normal at 0.5 mg/L (range, 0.4 to 1.4 mg/L).

In the case of heightened suspicion for MI, the patient would have been transferred to the emergency department (ED) for evaluation, including serial cardiac troponin levels; elevated troponin levels are deemed the standard criterion to define and diagnose MI in a consensus document from the European Society of Cardiology and the American College of Cardiology.² (Troponin-T and troponin-I are more tissue-specific than the MB fraction of creatine kinase [CK-MB] in detecting MI; positive troponin levels are considered virtually diagnostic of MI.² Typically, cardiac troponin levels are measured two to three times over a 12- to 16-hour period.)

Peak expiratory flow (PEF), which was measured to evaluate the patient’s respiratory status, was 150 L/min (compared with personal best for a patient of her height and age, approximately 460 L/min). She was given 2.5 mg/3 mL of inhaled albuterol over 15 minutes. Her PEF increased to 350 L/min. O2 saturation improved to 96% on room air, pulse to 104 beats/min, and respirations 20 breaths/min; her blood pressure reading was now 140/90 mm Hg. A prolonged expiratory phase persisted in the lungs, but diffuse wheezing decreased by 40% on chest auscultation.

A second albuterol treatment was administered 20 minutes later, and the patient’s PEF increased to 380 L/min and O2 saturation to 99%. The lungs presently cleared with no further wheezing noted.

In addition, the patient was given a GI cocktail (ie, liquid antacid combined with an anticholinergic agent and viscous lidocaine). Within 10 minutes, her chest tightness was relieved 100%. Her blood pressure was then measured at 135/84 mm Hg; respirations, 18 breaths/min; and pulse rate, 96 beats/min.

According to the National Asthma Education and Prevention Program (NAEPP) 2007 Guidelines for the Diagnosis and Management of Asthma, Expert Panel Report 3 (EPR-3),³ the patient was classified as having intermittent, not-well-controlled asthma with an acute exacerbation. In addition, she was given a diagnosis of uncontrolled GERD.

DISCUSSION
Asthma Incidence and Risk Factors
Asthma affects approximately 300 million people worldwide and remains a global respiratory concern.⁴ In the United States, this chronic health condition has a prevalence of 8% to 10%. It is estimated that 5% to 10% of asthmatic patients have severe disease that does not respond typically to therapeutic interventions.⁵

Asthma involves bronchial hyperresponsiveness, airflow obstruction, and underlying inflammation. Acute episodes of asthma, arising from bronchospasm, usually manifest with progressively worsening cough, shortness of breath, chest tightness and wheezing (asthma’s hallmark symptoms), or a combination of symptoms.³

Symptoms of asthma or exacerbations of reactive airway disease vary from patient to patient. In addition to the hallmark symptoms noted, subacute or acute episodes of asthma exacerbation are characterized by decreases in expiratory airflow that can be documented by objective measurements of lung function, such as PEF or spirometry; these measures of airflow indicate the severity of an exacerbation more reliably than does perceived symptom severity.³ The EPR-3 panelists recommend determining asthma severity using a combination of objective criteria and clinical symptoms,³ although few clinicians use the objective criteria.⁶

Estimates of the prevalence of GERD among patients with asthma have varied from 34% to 89%.^7-9 Patients with GERD are 1.97 times more likely than patients without GERD to have asthma¹⁰; silent gastroesophageal reflux has been identified in 24% to 62% of patients with asthma, and early studies suggest that treatment for GERD may improve asthma control in patients with severe or difficult-to-control asthma.^8,11,12

The exact link between the two conditions is unclear. However, possible explanations why GERD and asthma coincide are that acid flow causes injury to the lining of the throat, airways, and lungs, making inhalation difficult and often causing a persistent cough; or that when acid enters the esophagus, a nerve reflex is triggered that causes the airways to narrow in order to prevent the acid from entering; this can explain dyspnea.^8,9

Economic Burden
Asthma is costly to treat, and because there is no cure, the expense is ongoing. According to a 2011 report,¹³ the average annual direct cost of care (eg, medications, hospital admissions, nonemergency office visits) for one asthma patient between 2002 and 2007 was $3,259. In 2007, the most current data available, the total cost of asthma in the US was $56 billion, with productivity losses due to mortality accounting for $2.1 billion and morbidity-related losses estimated at $3.8 billion.¹³ The economic consequences of asthma are substantial and can place a considerable burden on affected individuals, their families, the health care system, and society as a whole.³

Current Standard of Care
Based on the scientific literature and the opinions expressed by the NAEPP in the EPR-3,³ clinicians are advised to consider the following general principles and goals for managing asthma: early treatment, special attention to patients at high risk for asthma-related death, and special attention to infants.³ The guidelines emphasize the importance of a clinician/patient partnership to facilitate the asthma patient’s self-management.

Early treatment is a particularly important component for management of asthma exacerbations. Important elements of early treatment include a written asthma action plan, combined with enhanced awareness of the early indicators of an exacerbation (ie, worsening PEF).^3,14 It is believed that if patients are able to monitor their respiratory condition and follow a plan of care based on their PEF and/or signs and symptoms of asthma, they are more likely to achieve optimal management of their disease.¹⁵

Written Asthma Action Plan. The EPR-3³ recommends that health care providers supply all asthmatic patients with a written asthma action plan that will define and support the patient’s efforts at self-management. Written asthma action plans are particularly beneficial for patients with moderate to severe persistent asthma, poorly controlled asthma, or a history of severe exacerbations.^3,14

The written asthma action plan should include instructions for daily management of asthma and ways to recognize and treat worsening asthma, including adjustments to medication dosing. Plans may be based on PEF and/or symptoms. Asthma action plans should be discussed and reevaluated at follow-up visits.³ A sample asthma action plan can be found at www.health.state.ny.us/diseases/asthma/pdf/4850.pdf.¹⁶

Peak Expiratory Flow (PEF). The EPR-3³ recommends PEF monitoring in all asthma patients, regardless of the severity of their exacerbations.¹⁷ PEF-based plans are especially useful for the patient who has difficulty perceiving early signs and symptoms of worsening asthma.^3,18 A PEF-based plan instructs the patient to use quick-relief medications if symptoms occur or if PEF drops below 80% of the patient’s personal or predicted best. (Measured personal best is the patient’s highest PEF in the previous two weeks of good asthma control,^3,19 whereas predicted best is calculated based on findings from a 1983 study by Knudson et al.^3,20)

A PEF between 50% and 79% requires the patient to carefully monitor his or her response to the quick-relief medication and, based on that response, consider whether to contact a health care provider. When PEF falls below 50%, a provider’s immediate intervention is usually recommended.³

In the urgent care or ED setting, according to EPR-3 recommendations,³ the PEF or forced expiratory volume in 1 second (FEV1) is used to indicate the following:

• ≥ 70% predicted PEF or FEV1: goal for discharge

• 40% to 69% predicted PEF or FEV1: incomplete response to treatment, frequent need for treatment in the ED

• 3

Treatment and Management
Asthma management interventions that target the treatment of active disease and predisposing triggers are designed to reduce the severity and/or duration of morbidity associated with asthma—principally, to prevent symptoms and exacerbations (see Table 1³).

When patients are discharged following an asthma exacerbation, their medications should include an oral corticosteroid burst and a short-acting b2-agonist (SABA); the clinician should also consider prescribing an inhaled corticosteroid (ICS).³

It is no longer recommended that ICS dosing be doubled in place of an oral steroid burst.^3,21 The addition of a leukotriene receptor antagonist (LTRA) may also be considered.^3,22

Patients should be given an action plan, and follow-up with a primary care provider should be scheduled within a few days—or even the following day, depending on the severity of the patient’s condition. The importance of follow-up with a primary care provider, a pulmonologist, or an asthma/allergy specialist should be emphasized.^3,23

For patients who have difficulty recognizing their symptoms, a peak flow meter may be useful. This device is also recommended for patients with moderate to severe asthma or a history of numerous severe exacerbations.³ Additionally, spacers should always be used with metered dose inhalers (MDIs), because they make it easier for medication to reach the lungs and reduce the amount deposited in the mouth and throat, where it can lead to irritation. At each office visit, use of the peak flow meter and inhaler technique should be observed, and the action plan reevaluated and changed if necessary.^3,14

Additional components of patient education include instruction in controlling environmental factors: avoiding environmental tobacco smoke, exposure to insect allergens, and molds. It is also important to stress controlling comorbid conditions that influence asthma, such as allergies or GERD. Patients with symptoms of GERD should be advised to take the steps shown in Table 2.^8,24

Clinical Implications
Assessment of the severity of an asthma exacerbation is an essential component of ambulatory asthma care. Underclassification of asthma severity has been associated with increased morbidity and mortality,⁶ and the NAEPP guidelines recommend that clinicians assess and document asthma severity at each clinic visit.^3,25 Patients who receive care based on evidence-based practice guidelines have been shown to experience 28% better outcomes.²⁶

PATIENT OUTCOME
The case patient was discharged on an oral corticosteroid burst and a low-dose ICS. She was instructed how and when to use her SABA and given a prescription for a spacer; use of a peak flow meter was initiated with an estimated personal best goal of 460 L/min. The patient was given a written asthma action plan to help her recognize early signs and symptoms of worsening asthma and was advised to use quick-relief medications if she experienced symptoms or if her PEF dropped below 80% of her predicted best.

The patient’s clinician emphasized the importance of controlling any asthma-triggering environmental factors and reviewed nonpharmacologic interventions to control GERD. The patient was advised to resume desloratadine 5 mg/d and pantoprazole 40 mg/d. She was also instructed to schedule an appointment with her primary care provider within 48 hours and to return to urgent care or the ED with any further exacerbation of respiratory symptoms not controlled by her SABA.

CONCLUSION
Asthma morbidity is a nationally recognized, major public health problem. Given the sharp rise in health care costs and limited resources, health care providers must factor in the comparative effectiveness, comparative cost, and cost-effectiveness of both new and existing health care interventions when making treatment decisions.

Many asthmatic patients face the challenges of health care access and quality. By promoting their self-care and awareness, clinicians can help asthmatic patients achieve better symptom management and use the health care system less often.

REFERENCES
1. Stein PD, Hull RD, Patel KC, et al. D-Dimer for the exclusion of acute venous thrombosis and pulmonary embolism. Ann Intern Med. 2004;140(8):589-602.

2. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36(3):959-969.

3. National Asthma Education and Prevention Program, National Heart, Lung, and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Heart, Lung, and Blood Institute; 2007. US Department of Health and Human Services publication NIH 07-4051.

4. Lougheed DM. Variability in asthma: symptom perception, care, and outcomes. Can J Physiol Pharmacol. 2007;85(1):149-154.

5. Higgins JC. The ‘crashing asthmatic.’ Am Fam Physician. 2003;67(5):997-1004. 

6. Cowen MK, Wakefield DB, Cloutier MM. Classifying asthma severity: objective versus subjective measures. J Asthma. 2007;44(9):711-715.

7. Takenaka R, Matsuno O, Kitajima K, et al. The use of frequency scale for the symptoms of GERD in assessment of gastro-oesophageal reflux symptoms in asthma. Allergol Immunopathol (Madr). 2010;38(1):20-24.

8. Harding SM, Barnes PJ, Hollingsworth H. Gastroesophageal reflux and asthma (2010). www.uptodate.com/contents/gastroesophageal-reflux-and-asthma. Accessed April 5, 2011.

9. Havemann BD, Henderson CA, El-Serag HB. The association between gastro-oesophageal reflux disease and asthma: a systematic review. Gut. 2007;56(12):1654-1664.

10. Tsai MC, Lin HL, Lin CC, et al. Increased risk of concurrent asthma among patients with gastroesophageal reflux disease: a nationwide population-based study. Eur J Gastroenterol Hepatol. 2010;22(10):1169-1173.

11. Harding SM, Richter JE, Guzzo MR, et al. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med. 1996;100(4):395-405.

12. Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database Syst Rev. 2003;(2):CD001496.

13. Barnett SB, Nurmagambetov TA. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011;127(1):145-152.

14. Walders N, Kercsmar C, Schluchter M, et al. An interdisciplinary intervention for undertreated pediatric asthma. Chest. 2006;129(2):292-299.

15. Morrow R, Fletcher J, Mulvihill M, Park H. The asthma dialogues: a model of interactive education for skills. J Contin Educ Health Prof. 2007;27(1): 49-58.

16. State of New York, Department of Health. Asthma action plan. www.health.state.ny.us/diseases/asthma/pdf/4850.pdf. Accessed April 11, 2011.

17. Picken HA, Greenfield S, Teres D, et al. Effects of local standards on the implementation of national guidelines for asthma: primary care agreement with national asthma guidelines. J Gen Intern Med. 1998;13(10):659-663.

18. Hardie GE, Gold WM, Janson S, et al. Understanding how asthmatics perceive symptom distress during a methacholine challenge. J Asthma. 2002;39(7):611-618.

19. Reddel HK, Marks GB, Jenkins CR. When can personal best peak flow be determined for asthma action plans? Thorax. 2004;59(11):922-924.

20. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127(6):725-734.

21. Ind PW, Dal Negro R, Colman NC, et al. Addition of salmeterol to fluticasone propionate treatment in moderate-to-severe asthma. Respir Med. 2003;97(5):555-562.

22. Price DB, Hernandez D, Magyar P, et al; Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) International Study Group. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax. 2003;58(3):211-216.

23. Schatz M, Zeiger RS, Mosen D, et al. Improved asthma outcomes from allergy specialist care: a population-based cross-sectional analysis. J Allergy Clin Immunol. 2005;116(6):1307-1313.

24. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143(3):199-211.

25. Cabana MD, Bruckman D, Meister K, et al. Documentation of asthma severity in pediatric outpatient clinics. Clin Pediatr (Phila). 2003;42(2):121-125.

26. Heater BS, Becker AM, Olson RK. Nursing interventions and patient outcomes: a meta-analysis of studies. Nurs Res. 1988;37(5):303-307.

In response to “Traumatic brain injury: Pharmacotherapy options for cognitive deficits” (Med/Psych Update, Current Psychiatry, February 2011, p. 21-37), traumatic brain injury (TBI) has been recognized as a risk factor for cognitive impairment, but TBI also has been shown to be a risk factor for hypopituitarism, presenting most frequently with growth hormone deficiency (GHD). GHD is associated not only with changes in body composition but also with impaired quality of life, cognitive dysfunctions, and psychiatric sequelae, usually classified as “depression.”

In a case study we evaluated the impact of GH therapy on the mental status of TBI patients.¹ Psychiatric and cognitive functions were tested in 6 GHD patients at baseline (minimum 3 years after TBI) and reassessed after 6 months of GH therapy and 12 months after discontinuing GH therapy. Psychiatric and cognitive examinations included semi-structured interviews and 3 instruments: Symptom Checklist-90-Revised, Zung Depression Inventory, and a standard composite neuropsychological battery.

Our results showed that 6 months of GH therapy in GHD TBI patients improved cognitive abilities (particularly verbal and nonverbal memory) and significantly improved psychiatric functioning. Depression severity decreased, as did intensity of interpersonal sensitivity, hostility, paranoid ideation, anxiety, and psychoticism. Somatization, obsessive-compulsive symptoms, and phobic anxiety decreased in all but 1 patient. In 3 GHD patients who stopped GH therapy for 12 months, we observed worsening verbal and nonverbal memory, interpersonal sensitivity, anxiety, and paranoid ideation. Thus, GHD might be associated with affective and cognitive symptoms in TBI patients and GH replacement therapy could be beneficial. Screening for pituitary dysfunction in TBI patients is strongly recommended, particularly in presence of cognitive and affective symptoms.

Nadja Maric, MD, PhD
Associate Professor
Head of Department for Research and Early
Interventions in Psychiatry
Clinic for Psychiatry, Clinical Centre of Serbia
University of Belgrade School of Medicine
Belgrade, Serbia

In response to “Traumatic brain injury: Pharmacotherapy options for cognitive deficits” (Med/Psych Update, Current Psychiatry, February 2011, p. 21-37), traumatic brain injury (TBI) has been recognized as a risk factor for cognitive impairment, but TBI also has been shown to be a risk factor for hypopituitarism, presenting most frequently with growth hormone deficiency (GHD). GHD is associated not only with changes in body composition but also with impaired quality of life, cognitive dysfunctions, and psychiatric sequelae, usually classified as “depression.”

In a case study we evaluated the impact of GH therapy on the mental status of TBI patients.¹ Psychiatric and cognitive functions were tested in 6 GHD patients at baseline (minimum 3 years after TBI) and reassessed after 6 months of GH therapy and 12 months after discontinuing GH therapy. Psychiatric and cognitive examinations included semi-structured interviews and 3 instruments: Symptom Checklist-90-Revised, Zung Depression Inventory, and a standard composite neuropsychological battery.

Our results showed that 6 months of GH therapy in GHD TBI patients improved cognitive abilities (particularly verbal and nonverbal memory) and significantly improved psychiatric functioning. Depression severity decreased, as did intensity of interpersonal sensitivity, hostility, paranoid ideation, anxiety, and psychoticism. Somatization, obsessive-compulsive symptoms, and phobic anxiety decreased in all but 1 patient. In 3 GHD patients who stopped GH therapy for 12 months, we observed worsening verbal and nonverbal memory, interpersonal sensitivity, anxiety, and paranoid ideation. Thus, GHD might be associated with affective and cognitive symptoms in TBI patients and GH replacement therapy could be beneficial. Screening for pituitary dysfunction in TBI patients is strongly recommended, particularly in presence of cognitive and affective symptoms.

Nadja Maric, MD, PhD
Associate Professor
Head of Department for Research and Early
Interventions in Psychiatry
Clinic for Psychiatry, Clinical Centre of Serbia
University of Belgrade School of Medicine
Belgrade, Serbia

In response to “Traumatic brain injury: Pharmacotherapy options for cognitive deficits” (Med/Psych Update, Current Psychiatry, February 2011, p. 21-37), traumatic brain injury (TBI) has been recognized as a risk factor for cognitive impairment, but TBI also has been shown to be a risk factor for hypopituitarism, presenting most frequently with growth hormone deficiency (GHD). GHD is associated not only with changes in body composition but also with impaired quality of life, cognitive dysfunctions, and psychiatric sequelae, usually classified as “depression.”

In a case study we evaluated the impact of GH therapy on the mental status of TBI patients.¹ Psychiatric and cognitive functions were tested in 6 GHD patients at baseline (minimum 3 years after TBI) and reassessed after 6 months of GH therapy and 12 months after discontinuing GH therapy. Psychiatric and cognitive examinations included semi-structured interviews and 3 instruments: Symptom Checklist-90-Revised, Zung Depression Inventory, and a standard composite neuropsychological battery.

Our results showed that 6 months of GH therapy in GHD TBI patients improved cognitive abilities (particularly verbal and nonverbal memory) and significantly improved psychiatric functioning. Depression severity decreased, as did intensity of interpersonal sensitivity, hostility, paranoid ideation, anxiety, and psychoticism. Somatization, obsessive-compulsive symptoms, and phobic anxiety decreased in all but 1 patient. In 3 GHD patients who stopped GH therapy for 12 months, we observed worsening verbal and nonverbal memory, interpersonal sensitivity, anxiety, and paranoid ideation. Thus, GHD might be associated with affective and cognitive symptoms in TBI patients and GH replacement therapy could be beneficial. Screening for pituitary dysfunction in TBI patients is strongly recommended, particularly in presence of cognitive and affective symptoms.

Nadja Maric, MD, PhD
Associate Professor
Head of Department for Research and Early
Interventions in Psychiatry
Clinic for Psychiatry, Clinical Centre of Serbia
University of Belgrade School of Medicine
Belgrade, Serbia

Some of patients’ most common complaints involve sleep: too little, too late, never enough. Although sleep disruptions often are related to the psychiatric disorder for which the person seeks treatment, cognitive and behavioral factors play significant roles.¹ Unfortunately, quite often patients expect to be given “something” to foster sleep.

Before writing a prescription, be prepared to evaluate sleep disturbances and educate patients about sleep and how it can be facilitated without medication. The mnemonic SLEEP can help you readily access a basic set of nonpharmacologic aids to assess and treat uncomplicated sleep disturbances.

Schedule. Ask patients about their sleep-wake schedule. Is their pattern routine and regular, or unpredictable? Are they “in synch” with the sleep/activity patterns of those with whom they live, or is their schedule “off track” and disrupted by household noise and activities? Consistency is key to normalizing sleep.

Limit. Sensible limits on caffeinated beverages need to be addressed. Strongly encourage patients to limit nicotine and alcohol in-take. Assess the amount as well as timing of their use of these substances. Remind your patient that alcohol and smoking have a direct impact on sleep initiation and can disrupt sleep because of nocturnal withdrawal.

Eliminate. Removing noxious environmental stimuli is critical. Ask patients about the level of nighttime noise, excessive light, and ventilation and temperature of their sleeping area (cooler is better). Eliminate factors that create a “hostile” sleep environment.

Exercise. Regular exercise performed during the day (but not immediately before going to bed) may be an effective antidote to the psychic stress and physical tension that often contribute to insomnia.² A several-times-per-week routine of brisk walking, riding a bicycle, swimming, or yoga can reduce sleep-onset latency and improve sleep maintenance. An exercise routine can enhance a patient’s overall health and knock out a daytime sleep habit.

Psychotherapy. Cognitive-behavioral therapy for insomnia has demonstrated efficacy in treating sleep disorders.³ Learning how to “catch, check, and change” distorted and negative cognitions regarding sleep onset can be a valuable tool for persons who are motivated to alter their thoughts and behaviors that contribute to sleep complaints, and may simultaneously improve associated anxiety and/or depression.

Disclosure

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

Some of patients’ most common complaints involve sleep: too little, too late, never enough. Although sleep disruptions often are related to the psychiatric disorder for which the person seeks treatment, cognitive and behavioral factors play significant roles.¹ Unfortunately, quite often patients expect to be given “something” to foster sleep.

Before writing a prescription, be prepared to evaluate sleep disturbances and educate patients about sleep and how it can be facilitated without medication. The mnemonic SLEEP can help you readily access a basic set of nonpharmacologic aids to assess and treat uncomplicated sleep disturbances.

Schedule. Ask patients about their sleep-wake schedule. Is their pattern routine and regular, or unpredictable? Are they “in synch” with the sleep/activity patterns of those with whom they live, or is their schedule “off track” and disrupted by household noise and activities? Consistency is key to normalizing sleep.

Limit. Sensible limits on caffeinated beverages need to be addressed. Strongly encourage patients to limit nicotine and alcohol in-take. Assess the amount as well as timing of their use of these substances. Remind your patient that alcohol and smoking have a direct impact on sleep initiation and can disrupt sleep because of nocturnal withdrawal.

Eliminate. Removing noxious environmental stimuli is critical. Ask patients about the level of nighttime noise, excessive light, and ventilation and temperature of their sleeping area (cooler is better). Eliminate factors that create a “hostile” sleep environment.

Exercise. Regular exercise performed during the day (but not immediately before going to bed) may be an effective antidote to the psychic stress and physical tension that often contribute to insomnia.² A several-times-per-week routine of brisk walking, riding a bicycle, swimming, or yoga can reduce sleep-onset latency and improve sleep maintenance. An exercise routine can enhance a patient’s overall health and knock out a daytime sleep habit.

Psychotherapy. Cognitive-behavioral therapy for insomnia has demonstrated efficacy in treating sleep disorders.³ Learning how to “catch, check, and change” distorted and negative cognitions regarding sleep onset can be a valuable tool for persons who are motivated to alter their thoughts and behaviors that contribute to sleep complaints, and may simultaneously improve associated anxiety and/or depression.

Disclosure

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

Some of patients’ most common complaints involve sleep: too little, too late, never enough. Although sleep disruptions often are related to the psychiatric disorder for which the person seeks treatment, cognitive and behavioral factors play significant roles.¹ Unfortunately, quite often patients expect to be given “something” to foster sleep.

Before writing a prescription, be prepared to evaluate sleep disturbances and educate patients about sleep and how it can be facilitated without medication. The mnemonic SLEEP can help you readily access a basic set of nonpharmacologic aids to assess and treat uncomplicated sleep disturbances.

Schedule. Ask patients about their sleep-wake schedule. Is their pattern routine and regular, or unpredictable? Are they “in synch” with the sleep/activity patterns of those with whom they live, or is their schedule “off track” and disrupted by household noise and activities? Consistency is key to normalizing sleep.

Limit. Sensible limits on caffeinated beverages need to be addressed. Strongly encourage patients to limit nicotine and alcohol in-take. Assess the amount as well as timing of their use of these substances. Remind your patient that alcohol and smoking have a direct impact on sleep initiation and can disrupt sleep because of nocturnal withdrawal.

Eliminate. Removing noxious environmental stimuli is critical. Ask patients about the level of nighttime noise, excessive light, and ventilation and temperature of their sleeping area (cooler is better). Eliminate factors that create a “hostile” sleep environment.

Exercise. Regular exercise performed during the day (but not immediately before going to bed) may be an effective antidote to the psychic stress and physical tension that often contribute to insomnia.² A several-times-per-week routine of brisk walking, riding a bicycle, swimming, or yoga can reduce sleep-onset latency and improve sleep maintenance. An exercise routine can enhance a patient’s overall health and knock out a daytime sleep habit.

Psychotherapy. Cognitive-behavioral therapy for insomnia has demonstrated efficacy in treating sleep disorders.³ Learning how to “catch, check, and change” distorted and negative cognitions regarding sleep onset can be a valuable tool for persons who are motivated to alter their thoughts and behaviors that contribute to sleep complaints, and may simultaneously improve associated anxiety and/or depression.

Disclosure

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

“An alternative to oral NSAIDs for acute musculoskeletal injuries,” (PURLs, J Fam Pract. 2011;60:147-148) promotes an unreasonable conclusion. The Cochrane review on which it is based found a 50% response rate to topical diclofenac for ankle sprains, compared with a 25% response to placebo. (A response was defined as ≥50% reduction in pain.) The authors of the Cochrane review seem to think this is adequate, and the authors of this PURL apparently agree.

First, they overstate the benefit. If we consider that 1 in 4 patients respond to placebo, we find that only 1 in 4 patients actually have what the authors describe as an adequate response to topical diclofenac. That still means that half the patients I see for ankle sprain could be calling at 11:00 PM to complain about inadequate pain relief.

Second, the Cochrane reviewers did not use an active control group with oral NSAIDs, leaving us to guess whether oral NSAIDs are equally effective, worse, or better than topical agents. The great majority of people I treat for ankle sprains obtain adequate pain relief with oral therapy. Studies have compared topical and oral NSAIDs, but the authors make no mention of these comparisons.

I trust and rely on the Cochrane reviews, but they are not the word of God. This review did not provide useful information. The space would have been better devoted to a topic I can put into practice.

Dean M. Center, MD
Bozeman, MT

I find it difficult to believe that these ivory tower researchers used topical diclofenac as their base. I’ve used topical agents for acute musculoskeletal pain for 40 years, costing one-tenth (or less) of the price of diclofenac. Only a few patients have complained of skin reactions. For more severe cases, capsaicin is a good choice; otherwise, a methyl salicylate product is very effective, at a concentration of 30% or more. Both are available as generics and do not require a prescription.

Robert Migliorino, DO
Lake Preston, SD

The authors respond:

We appreciate the issues raised by the letter writers. Dr. Center notes that there are few head-to-head trials with other therapy options, such as oral NSAIDs or acetaminophen. We agree. This Cochrane review demonstrates another possible option for pain relief for patients who cannot tolerate oral NSAIDs or prefer not to take them. The body of literature comparing topical to oral NSAIDs is small, but we could not find any high-quality evidence to suggest that oral NSAIDs are more effective.

Dr. Center also questions the clinical utility of a medication that must be given to 4 patients in order for 1 to have a 50% reduction in pain (number needed to treat [NNT]=4). The NNT for topical NSAIDs is about the same.¹ For acute musculoskeletal injuries, 1 patient in 4 will respond to placebo, 1 in 4 will respond to active topical or oral therapy, and 2 in 4 will fail treatment. Whether these response rates are acceptable is an individual clinical decision to be made with the patient. We believe they are acceptable to most patients.

We thank Dr. Migliorino for bringing to light other topical pain medications. Diclofenac is the only topical NSAID available in the United States, which is why we chose to highlight it. The Cochrane review did not include salicylates because they are no longer classified as topical NSAIDS, and capsaicin was not included as it is not an NSAID. Both may very well offer pain relief.

The purpose of PURLs (Priority Updates from the Research Literature) is to identify and disseminate evidence that should change the practice of family medicine. We believe that this Cochrane review demonstrates that topical NSAIDs are effective options for acute musculoskeletal injuries and that many primary care physicians would be unfamiliar with this option.

Nina V. Rogers, MD
Kate Rowland, MD
Chicago

“An alternative to oral NSAIDs for acute musculoskeletal injuries,” (PURLs, J Fam Pract. 2011;60:147-148) promotes an unreasonable conclusion. The Cochrane review on which it is based found a 50% response rate to topical diclofenac for ankle sprains, compared with a 25% response to placebo. (A response was defined as ≥50% reduction in pain.) The authors of the Cochrane review seem to think this is adequate, and the authors of this PURL apparently agree.

First, they overstate the benefit. If we consider that 1 in 4 patients respond to placebo, we find that only 1 in 4 patients actually have what the authors describe as an adequate response to topical diclofenac. That still means that half the patients I see for ankle sprain could be calling at 11:00 PM to complain about inadequate pain relief.

Second, the Cochrane reviewers did not use an active control group with oral NSAIDs, leaving us to guess whether oral NSAIDs are equally effective, worse, or better than topical agents. The great majority of people I treat for ankle sprains obtain adequate pain relief with oral therapy. Studies have compared topical and oral NSAIDs, but the authors make no mention of these comparisons.

I trust and rely on the Cochrane reviews, but they are not the word of God. This review did not provide useful information. The space would have been better devoted to a topic I can put into practice.

Dean M. Center, MD
Bozeman, MT

I find it difficult to believe that these ivory tower researchers used topical diclofenac as their base. I’ve used topical agents for acute musculoskeletal pain for 40 years, costing one-tenth (or less) of the price of diclofenac. Only a few patients have complained of skin reactions. For more severe cases, capsaicin is a good choice; otherwise, a methyl salicylate product is very effective, at a concentration of 30% or more. Both are available as generics and do not require a prescription.

Robert Migliorino, DO
Lake Preston, SD

The authors respond:

We appreciate the issues raised by the letter writers. Dr. Center notes that there are few head-to-head trials with other therapy options, such as oral NSAIDs or acetaminophen. We agree. This Cochrane review demonstrates another possible option for pain relief for patients who cannot tolerate oral NSAIDs or prefer not to take them. The body of literature comparing topical to oral NSAIDs is small, but we could not find any high-quality evidence to suggest that oral NSAIDs are more effective.

Dr. Center also questions the clinical utility of a medication that must be given to 4 patients in order for 1 to have a 50% reduction in pain (number needed to treat [NNT]=4). The NNT for topical NSAIDs is about the same.¹ For acute musculoskeletal injuries, 1 patient in 4 will respond to placebo, 1 in 4 will respond to active topical or oral therapy, and 2 in 4 will fail treatment. Whether these response rates are acceptable is an individual clinical decision to be made with the patient. We believe they are acceptable to most patients.

We thank Dr. Migliorino for bringing to light other topical pain medications. Diclofenac is the only topical NSAID available in the United States, which is why we chose to highlight it. The Cochrane review did not include salicylates because they are no longer classified as topical NSAIDS, and capsaicin was not included as it is not an NSAID. Both may very well offer pain relief.

The purpose of PURLs (Priority Updates from the Research Literature) is to identify and disseminate evidence that should change the practice of family medicine. We believe that this Cochrane review demonstrates that topical NSAIDs are effective options for acute musculoskeletal injuries and that many primary care physicians would be unfamiliar with this option.

Nina V. Rogers, MD
Kate Rowland, MD
Chicago

“An alternative to oral NSAIDs for acute musculoskeletal injuries,” (PURLs, J Fam Pract. 2011;60:147-148) promotes an unreasonable conclusion. The Cochrane review on which it is based found a 50% response rate to topical diclofenac for ankle sprains, compared with a 25% response to placebo. (A response was defined as ≥50% reduction in pain.) The authors of the Cochrane review seem to think this is adequate, and the authors of this PURL apparently agree.

First, they overstate the benefit. If we consider that 1 in 4 patients respond to placebo, we find that only 1 in 4 patients actually have what the authors describe as an adequate response to topical diclofenac. That still means that half the patients I see for ankle sprain could be calling at 11:00 PM to complain about inadequate pain relief.

Second, the Cochrane reviewers did not use an active control group with oral NSAIDs, leaving us to guess whether oral NSAIDs are equally effective, worse, or better than topical agents. The great majority of people I treat for ankle sprains obtain adequate pain relief with oral therapy. Studies have compared topical and oral NSAIDs, but the authors make no mention of these comparisons.

I trust and rely on the Cochrane reviews, but they are not the word of God. This review did not provide useful information. The space would have been better devoted to a topic I can put into practice.

Dean M. Center, MD
Bozeman, MT

I find it difficult to believe that these ivory tower researchers used topical diclofenac as their base. I’ve used topical agents for acute musculoskeletal pain for 40 years, costing one-tenth (or less) of the price of diclofenac. Only a few patients have complained of skin reactions. For more severe cases, capsaicin is a good choice; otherwise, a methyl salicylate product is very effective, at a concentration of 30% or more. Both are available as generics and do not require a prescription.

Robert Migliorino, DO
Lake Preston, SD

The authors respond:

We appreciate the issues raised by the letter writers. Dr. Center notes that there are few head-to-head trials with other therapy options, such as oral NSAIDs or acetaminophen. We agree. This Cochrane review demonstrates another possible option for pain relief for patients who cannot tolerate oral NSAIDs or prefer not to take them. The body of literature comparing topical to oral NSAIDs is small, but we could not find any high-quality evidence to suggest that oral NSAIDs are more effective.

Dr. Center also questions the clinical utility of a medication that must be given to 4 patients in order for 1 to have a 50% reduction in pain (number needed to treat [NNT]=4). The NNT for topical NSAIDs is about the same.¹ For acute musculoskeletal injuries, 1 patient in 4 will respond to placebo, 1 in 4 will respond to active topical or oral therapy, and 2 in 4 will fail treatment. Whether these response rates are acceptable is an individual clinical decision to be made with the patient. We believe they are acceptable to most patients.

We thank Dr. Migliorino for bringing to light other topical pain medications. Diclofenac is the only topical NSAID available in the United States, which is why we chose to highlight it. The Cochrane review did not include salicylates because they are no longer classified as topical NSAIDS, and capsaicin was not included as it is not an NSAID. Both may very well offer pain relief.

The purpose of PURLs (Priority Updates from the Research Literature) is to identify and disseminate evidence that should change the practice of family medicine. We believe that this Cochrane review demonstrates that topical NSAIDs are effective options for acute musculoskeletal injuries and that many primary care physicians would be unfamiliar with this option.

Nina V. Rogers, MD
Kate Rowland, MD
Chicago

My wife was diagnosed with Alzheimer’s disease (AD) at age 63. Unfortunately, her AD went misdiagnosed for several years while I repeatedly tried to convince her doctors that she was experiencing dementia. For 3 years, doctors administered the Mini-Mental State Exam (MMSE) and other cognitive tests, but she consistently did very well (on one occasion scoring 29 out of a possible 30 on the same day that she couldn’t remember our granddaughters’ names). An MRI of her brain showed no definitive signs of AD. Thus, she was treated for stress, anxiety, and depression, although I told both our primary care physician (PCP) and a neurologist that her symptoms couldn’t possibly be due to any of these conditions.

I documented my wife’s behaviors in weekly logs and brought copies to each visit, but invariably my notes went unread or were quickly dismissed. When I told the PCP I thought the medications prescribed by the neurologist weren’t working because she was declining further, he deferred to the specialist, who advised us to “stay the course.” Finally, I convinced my wife to see a psychiatrist affiliated with a major medical center who requested copies of my logs even before our first visit.

At that visit, the psychiatrist interviewed us at length, reviewed previous tests, and administered his own cognitive, physical, and neurological tests. He then ordered a new battery of tests and referred us to his facility’s AD center, where my wife finally received a diagnosis of early-onset Alzheimer’s.

Doctors can improve their chance of accurate diagnosis simply by listening to the spouse or significant other. One recent study found that the AD8, an 8-question, 2-minute screening test given to a close friend or family member, was superior to conventional testing in its ability to detect signs of early dementia.¹

Although doctors can’t identify the cause of AD or offer hope for a cure, early diagnosis is important. The sooner the patient starts taking medication designed to help slow the degenerative progression, the more effective the drugs may be.

So please, doctors, if a family member or loved one reports worrisome symptoms of possible dementia, listen carefully. The observations of someone close to the patient just may be more accurate than any screening test you could give.

Allan Vann
Commack, NY

My wife was diagnosed with Alzheimer’s disease (AD) at age 63. Unfortunately, her AD went misdiagnosed for several years while I repeatedly tried to convince her doctors that she was experiencing dementia. For 3 years, doctors administered the Mini-Mental State Exam (MMSE) and other cognitive tests, but she consistently did very well (on one occasion scoring 29 out of a possible 30 on the same day that she couldn’t remember our granddaughters’ names). An MRI of her brain showed no definitive signs of AD. Thus, she was treated for stress, anxiety, and depression, although I told both our primary care physician (PCP) and a neurologist that her symptoms couldn’t possibly be due to any of these conditions.

I documented my wife’s behaviors in weekly logs and brought copies to each visit, but invariably my notes went unread or were quickly dismissed. When I told the PCP I thought the medications prescribed by the neurologist weren’t working because she was declining further, he deferred to the specialist, who advised us to “stay the course.” Finally, I convinced my wife to see a psychiatrist affiliated with a major medical center who requested copies of my logs even before our first visit.

At that visit, the psychiatrist interviewed us at length, reviewed previous tests, and administered his own cognitive, physical, and neurological tests. He then ordered a new battery of tests and referred us to his facility’s AD center, where my wife finally received a diagnosis of early-onset Alzheimer’s.

Doctors can improve their chance of accurate diagnosis simply by listening to the spouse or significant other. One recent study found that the AD8, an 8-question, 2-minute screening test given to a close friend or family member, was superior to conventional testing in its ability to detect signs of early dementia.¹

Although doctors can’t identify the cause of AD or offer hope for a cure, early diagnosis is important. The sooner the patient starts taking medication designed to help slow the degenerative progression, the more effective the drugs may be.

So please, doctors, if a family member or loved one reports worrisome symptoms of possible dementia, listen carefully. The observations of someone close to the patient just may be more accurate than any screening test you could give.

Allan Vann
Commack, NY

My wife was diagnosed with Alzheimer’s disease (AD) at age 63. Unfortunately, her AD went misdiagnosed for several years while I repeatedly tried to convince her doctors that she was experiencing dementia. For 3 years, doctors administered the Mini-Mental State Exam (MMSE) and other cognitive tests, but she consistently did very well (on one occasion scoring 29 out of a possible 30 on the same day that she couldn’t remember our granddaughters’ names). An MRI of her brain showed no definitive signs of AD. Thus, she was treated for stress, anxiety, and depression, although I told both our primary care physician (PCP) and a neurologist that her symptoms couldn’t possibly be due to any of these conditions.

I documented my wife’s behaviors in weekly logs and brought copies to each visit, but invariably my notes went unread or were quickly dismissed. When I told the PCP I thought the medications prescribed by the neurologist weren’t working because she was declining further, he deferred to the specialist, who advised us to “stay the course.” Finally, I convinced my wife to see a psychiatrist affiliated with a major medical center who requested copies of my logs even before our first visit.

At that visit, the psychiatrist interviewed us at length, reviewed previous tests, and administered his own cognitive, physical, and neurological tests. He then ordered a new battery of tests and referred us to his facility’s AD center, where my wife finally received a diagnosis of early-onset Alzheimer’s.

Doctors can improve their chance of accurate diagnosis simply by listening to the spouse or significant other. One recent study found that the AD8, an 8-question, 2-minute screening test given to a close friend or family member, was superior to conventional testing in its ability to detect signs of early dementia.¹

Although doctors can’t identify the cause of AD or offer hope for a cure, early diagnosis is important. The sooner the patient starts taking medication designed to help slow the degenerative progression, the more effective the drugs may be.

So please, doctors, if a family member or loved one reports worrisome symptoms of possible dementia, listen carefully. The observations of someone close to the patient just may be more accurate than any screening test you could give.

Allan Vann
Commack, NY

Rotavirus is the most common cause of severe gastroenteritis in infants and children younger than 5 years of age, and it accounts for approximately 5% of childhood deaths worldwide.1 In the United States, rotavirus causes numerous cases of dehydrating diarrhea and vomiting, and is responsible for direct and indirect healthcare costs of approximately $1 billion per year. Infection during childhood is almost universal.2

Improved personal hygiene and community sanitation have steadily reduced the prevalence of bacterial and parasitic disease. But these measures have had little effect on the spread of rotavirus and its potential complications of severe dehydration, hospitalization, and even death.¹ Importantly, we now have the means to vaccinate against rotavirus infection and dramatically reduce the incidence of disease. In this article, I describe the available vaccines and the vaccination recommendations endorsed by the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). I also review supportive treatment for rotavirus infection, which entails both do’s and don’ts.

Who is at risk of rotavirus disease?

For most term neonates, rotavirus disease is mild, perhaps because of partial protection from maternal antibodies.³ However, premature infants lacking full maternal antibody protection often suffer from more serious gastroenteritis. The most severe infections usually strike children between the ages of 4 months, when maternally derived antibody protection wanes, and 23 months, when dehydration risk lessens.^4-6

The virus spreads from person to person via the fecal–oral route.^6,7 Thirty percent to 50% of family members of an infected child may also become infected, but disease in older children and adults is usually subclinical or mild.⁶ Outbreaks of rotavirus are common in childcare centers and in children’s hospitals.^7,8

How the disease presents

Rotavirus gastroenteritis peaks during the winter. With mild cases, a watery diarrhea will last a few days. In severe cases, onset is usually abrupt with fever, abdominal pain, and vomiting, which can precede diarrhea. A third of patients have a temperature higher than 102°F (38.9°C).⁶ There is a risk of dehydration, shock, and even, occasionally, infant death.⁹

Typically, the incubation period is 1 to 4 days, and the infection lasts 3 to 7 days. However, damage to the brush border of the intestinal villi can produce persistent disaccharide malabsorption, resulting in prolonged diarrhea even after resolution of infection.^10,11 Stools generally do not contain blood or leukocytes. Ultrasound examination during rotavirus infections has shown thickening of the distal ileum and lymphadenopathy, which may predispose to intussusception.¹² Other problems possibly linked to wild-type rotavirus infection are Kawasaki disease and sudden infant death syndrome. Recurrent rotavirus infection with one of the many different serotypes is common during childhood.

More than 25 different assays can detect rotavirus in stool, but the most reliable method is direct electron microscopy. A suitable clinically available alternative is enzyme immunoassay testing of stool samples. In mild cases, testing to detect rotavirus is not necessary. But for bloody, severe, or persistent diarrhea, stool testing for rotavirus and other entities is warranted.

Supportive treatment: Do’s and don’ts

No specific antiviral treatment is available for rotavirus infection. That said, the do’s and don’ts that follow will help guide your care.

DO administer oral, enteral, or intravenous (IV) fluids to prevent or correct dehydration. Oral rehydration therapy is the standard treatment for dehydration in anyone with acute gastroenteritis, including that caused by rotavirus. The recommended World Health Organization (WHO) oral rehydration solution contains sodium, chloride, and electrolytes (TABLE 1).¹³ Rice-based oral rehydration solution is an easily metabolized carbohydrate formulation that helps repair damaged tissues and enhances electrolyte absorption.⁹ WHO has endorsed guidelines that base fluid replacement on the patient’s age and weight, and that recommend oral zinc intake (10 mg/d for 10-14 days up to age 6 months; 20 mg/d for 10-14 days for older children) for all episodes of diarrhea (http://hetv.org/pdf/diarrhoea-guidelines.pdf). Oral glucose electrolyte solutions containing less sodium and chloride are also effective treatments.

DO recommend frequent small doses of oral rehydration solution, even if the patient is vomiting.¹⁴ Rehydration volumes are suggested in TABLE 1. Alternatively, give 10 to 20 mL/kg for each diarrheal episode, and 2 mL/kg for each bout of emesis. Feeding frequent small volumes (30 mL every 5-10 minutes) reduces the risk of emesis.

Although oral rehydration solutions are contraindicated for infants and young children with depressed consciousness, vomiting is not a contraindication to oral intake. About half of the oral intake stays in the stomach, even after vomiting. A single dose of ondansetron may safely reduce vomiting.¹⁵

Patients with mainly diarrhea can take fluids or feed at will. With children who refuse to drink, oral rehydration solutions can be administered via nasogastric tube at approximately 5 mL/min to limit vomiting and maintain hydration.¹⁴ In dehydrated infants and toddlers with collapsed veins, nasogastric intubation has been shown to be less traumatic than repetitive attempts at placing IV catheters.

DO encourage nursing mothers to con tinue breastfeeding during rehydration treatments. If a mother is bottle feeding, keep this in mind: Rotavirus can cause temporary lactase deficiency for some non-breastfeeding infants; lactose-free formulas may help.

DON’T assume that parents know how to provide proper supplementation. Tell them to avoid fluids containing mostly sugar that lack significant electrolyte supplementation (eg, cola) unless no other fluid alternative is available. Advise caregivers to avoid juices and other liquids high in complex or simple sugars because the osmotic load may worsen diarrhea.¹⁴

DON’T give antidiarrheal agents for acute treatment in infants and young children. Such treatment has resulted in death.¹⁴

TABLE 1
Prevent or correct dehydration using the WHO-recommended oral rehydration salts solution¹³

KEEP IN MIND

Hospitalization may be needed to replace fluids via IV or interosseous supplementation. For the severely dehydrated child, 20 mL/kg isotonic fluid can be administered as a rapid bolus.¹⁴ It may be necessary to repeat a rapid fluid infusion of 10 to 20 mL/kg every 20 to 30 minutes. For less severely ill infants who require IV rehydration, standard references such as the Harriet Lane Handbook¹⁶ provide excellent guidance.

Probiotics may help. Consider probiotics with Lactobacillus or Bifida bacterium to reduce the severity of diarrhea in infants and children who are mildly to moderately ill.^17,18 Their usefulness in the severely ill patient has not been demonstrated.

Available vaccines and clinical recommendations

In February 2006, the US Food and Drug Administration (FDA) licensed a 3-dose, oral pentavalent rotavirus vaccine (RV5, RotaTeq) for use among infants. The vaccine contains live reassortant rotaviruses¹⁹—4 human rotavirus G outer-surface proteins and 1 human P attachment protein reassorted into a bovine rotavirus not infectious to humans.

In February 2008, the FDA approved a 2-dose, oral monovalent rotavirus vaccine (RV1, Rotarix), an attenuated live human rotavirus containing 1 G protein and 1 P protein. Both vaccines have proven to be clinically effective in rotavirus prevention trials, but effectiveness may depend on which rotavirus serotypes circulate each season.

ACIP, AAP, and AAFP recommend that all infants be routinely vaccinated with either RV5 or RV1.^6,20–22 Vaccination should be complete by the time infants reach the age of 8 months (TABLE 2). Guidelines for vaccination emphasize the following points:

Timing. According to the ACIP, the first dose of either vaccine must be administered between the ages of 6 weeks and 14 weeks 6 days (the RV5 manufacturer [Merck] states a maximum age of 12 weeks). Give subsequent doses at 4- to 10-week intervals, as long as all doses are administered by 8 months of age. The RV1 manufacturer (GlaxoSmithKline) suggests completing the second (final) dose of its vaccine by age 24 weeks.

If an infant 15 weeks of age or older accidentally receives a first dose of RV vaccine, the series should be continued, as long as the last dose can be given by 8 months of age. Either vaccine can be administered concurrently with all other vaccines.

Contraindications. The only absolute contraindications to RV5 administration are a demonstrated hypersensitivity to any component of the vaccine and severe combined immunodeficiency disease (SCID). Contraindications to RV1 vaccine are vaccine component hypersensitivity, SCID, latex-induced allergy (anaphylaxis), and uncorrected malformation of the gastrointestinal (GI) tract that might predispose to intussusception.

Precautions. Precautions for vaccines include other forms of primary or secondary immunocompromised or immunodeficiency states, including cancer and acute or chronic GI disorders such as ongoing gastroenteritis or intussusception. Infants with transient mild illness with or without low-grade fever and infants who are breastfeeding can receive either vaccine. RV5 is shed in 9% of recipients and RV1 in 26% of recipients after Dose 1, but transmission of vaccine virus is not known to occur. Likewise, reversion of vaccine virus to more virulent pathogens is not known to occur. A household member with an immuno-compromised condition does not preclude giving either RV vaccine to an infant. The risk of transmitting vaccine virus is much smaller than the risk of acquiring infectious wild-type rotavirus.

Regurgitation of a vaccine dose is uncommon. When it does occur, the RV5 vaccine should not be repeated; some of the vaccine dose is retained and the safety of the additional vaccine from a second dose is unknown. Readministration of a dose of RV1 is not recommended, although not contraindicated.

TABLE 2
Recommended rotavirus live virus vaccine dosing⁶

Vaccine efficacy
The safety and efficacy of live rotavirus vaccines were demonstrated in large studies that enrolled 71,725 children in RV5 vaccine trials²³ and 24,163 children in RV1 vaccine trials.²¹ The pivotal RV5 study included a nested substudy to evaluate efficacy against any G1–G4 rotavirus gastroenteritis.

RV5 (RotaTeq) vaccine. In double-blind, placebo-controlled clinical trials, for the first rotavirus season, live RV5 vaccine effectively prevented severe rotavirus infection in 98% of cases, and reduced hospitalization by 95%, emergency department visits by 94%, physician office visits by 86%, and all rotavirus cases by 74% for infants who received all 3 doses of vaccine according to protocol.²³ Hospitalization for any-cause gastroenteritis was reduced by 63%. Second-season data showed persistence of antibody protection. All 3 doses of vaccine are required for maximum protection.²³

Both preterm and term infants received their first dose of vaccine between 6 and 12 weeks of life. For preterm infants who are experiencing medical difficulties, the first dose of vaccine may be delayed until the patient is stable, if it can be given before 15 weeks of age.

RV1 (Rotarix) vaccine. In double-blind, placebo-controlled clinical trials, for the first rotavirus season, live RV1 vaccine was 85% (Latin America) to 96% (Europe) effective in preventing severe rotavirus infection. It reduced hospitalization due to rotavirus by 85% (Latin America) to 100% (Europe), and all rotavirus cases by 87% (Europe) for infants who received both doses of the vaccine according to protocol. For the second season, the vaccine reduced severe rotavirus disease by 70% to 96%, and any rotavirus disease by 73% to 89%, showing persistence of antibody protection.⁶

Adverse events
With both vaccines, common side effects include irritability, flatulence, fever, vomiting, diarrhea, cough, runny nose, and loss of appetite. The RV5 vaccine has been shown not to increase the risk of intussusception compared with placebo.^24,25 The RV1 vaccine should not be used in children with an uncorrected bowel malformation, due to unproven increased risk of intussusception. Risk of death from complications after administration of either vaccine did not differ from that among children receiving placebo.

Postmarketing surveillance of vaccination outcomes
Even though rotavirus vaccine coverage with RV5 RotaTeq in the 2007-2008 and 2008-2009 seasons was far less than that with other childhood immunizations, the number of rotavirus infections dropped by >60% in both 2008 and 2009.²⁶ The number of stool tests for rotavirus and the percentage of positive results also dropped dramatically.

Additionally, the rotavirus peak incidence was delayed 2 to 4 months until April 2008 and March 2009.²⁶ Incidence was reduced in all age groups, suggesting the possibility of herd immunity despite a low vaccine coverage rate (estimates are 57% for ≥1 dose) that would not be expected to provide herd immunity.²⁷ Hospitalizations in the United States for rotavirus gastroenteritis dropped by as much as 85%,²⁸ markedly reducing costs for gastroenteritis.

In a 2010 report from an emergency department in Houston, a complete RV5 vaccine series conferred 82% protection against acute gastroenteritis, 96% against severe rotavirus disease requiring IV rehydration, and 100% against hospitalization.²⁹ For more on the vaccine, see the report by Yen et al.³⁰

Reports of the effectiveness of Rotarix in postmarketing surveillance are limited, but the vaccine does seem to provide broad coverage.³¹

Incorporating rotavirus vaccine into a family medicine practice
Given inadequately reimbursed costs including the cost of stocking RV vaccine (see “Costs of RV vaccines” above), family physicians who treat relatively few infants must determine whether offering RV vaccine fits within their practices.

For family physicians who do treat infants, offering RV vaccination makes sense. These oral vaccines are highly effective, safe, and easy to administer, and will prevent a great deal of worry and calls regarding infants who have a fever or diarrhea or are vomiting. Due to the costs of stocking all vaccines, private practitioners are wise to purchase vaccine loss insurance. Many insurance agencies provide a rider on office insurance policies to cover vaccine supplies.

CORRESPONDENCE
Donald B. Middleton, MD, UPMC St. Margaret, 815 Freeport Road, Pittsburgh, PA 15215; [email protected]

Rotavirus is the most common cause of severe gastroenteritis in infants and children younger than 5 years of age, and it accounts for approximately 5% of childhood deaths worldwide.1 In the United States, rotavirus causes numerous cases of dehydrating diarrhea and vomiting, and is responsible for direct and indirect healthcare costs of approximately $1 billion per year. Infection during childhood is almost universal.2

Improved personal hygiene and community sanitation have steadily reduced the prevalence of bacterial and parasitic disease. But these measures have had little effect on the spread of rotavirus and its potential complications of severe dehydration, hospitalization, and even death.¹ Importantly, we now have the means to vaccinate against rotavirus infection and dramatically reduce the incidence of disease. In this article, I describe the available vaccines and the vaccination recommendations endorsed by the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). I also review supportive treatment for rotavirus infection, which entails both do’s and don’ts.

Who is at risk of rotavirus disease?

For most term neonates, rotavirus disease is mild, perhaps because of partial protection from maternal antibodies.³ However, premature infants lacking full maternal antibody protection often suffer from more serious gastroenteritis. The most severe infections usually strike children between the ages of 4 months, when maternally derived antibody protection wanes, and 23 months, when dehydration risk lessens.^4-6

The virus spreads from person to person via the fecal–oral route.^6,7 Thirty percent to 50% of family members of an infected child may also become infected, but disease in older children and adults is usually subclinical or mild.⁶ Outbreaks of rotavirus are common in childcare centers and in children’s hospitals.^7,8

How the disease presents

Rotavirus gastroenteritis peaks during the winter. With mild cases, a watery diarrhea will last a few days. In severe cases, onset is usually abrupt with fever, abdominal pain, and vomiting, which can precede diarrhea. A third of patients have a temperature higher than 102°F (38.9°C).⁶ There is a risk of dehydration, shock, and even, occasionally, infant death.⁹

Typically, the incubation period is 1 to 4 days, and the infection lasts 3 to 7 days. However, damage to the brush border of the intestinal villi can produce persistent disaccharide malabsorption, resulting in prolonged diarrhea even after resolution of infection.^10,11 Stools generally do not contain blood or leukocytes. Ultrasound examination during rotavirus infections has shown thickening of the distal ileum and lymphadenopathy, which may predispose to intussusception.¹² Other problems possibly linked to wild-type rotavirus infection are Kawasaki disease and sudden infant death syndrome. Recurrent rotavirus infection with one of the many different serotypes is common during childhood.

More than 25 different assays can detect rotavirus in stool, but the most reliable method is direct electron microscopy. A suitable clinically available alternative is enzyme immunoassay testing of stool samples. In mild cases, testing to detect rotavirus is not necessary. But for bloody, severe, or persistent diarrhea, stool testing for rotavirus and other entities is warranted.

Supportive treatment: Do’s and don’ts

No specific antiviral treatment is available for rotavirus infection. That said, the do’s and don’ts that follow will help guide your care.

DO administer oral, enteral, or intravenous (IV) fluids to prevent or correct dehydration. Oral rehydration therapy is the standard treatment for dehydration in anyone with acute gastroenteritis, including that caused by rotavirus. The recommended World Health Organization (WHO) oral rehydration solution contains sodium, chloride, and electrolytes (TABLE 1).¹³ Rice-based oral rehydration solution is an easily metabolized carbohydrate formulation that helps repair damaged tissues and enhances electrolyte absorption.⁹ WHO has endorsed guidelines that base fluid replacement on the patient’s age and weight, and that recommend oral zinc intake (10 mg/d for 10-14 days up to age 6 months; 20 mg/d for 10-14 days for older children) for all episodes of diarrhea (http://hetv.org/pdf/diarrhoea-guidelines.pdf). Oral glucose electrolyte solutions containing less sodium and chloride are also effective treatments.

DO recommend frequent small doses of oral rehydration solution, even if the patient is vomiting.¹⁴ Rehydration volumes are suggested in TABLE 1. Alternatively, give 10 to 20 mL/kg for each diarrheal episode, and 2 mL/kg for each bout of emesis. Feeding frequent small volumes (30 mL every 5-10 minutes) reduces the risk of emesis.

Although oral rehydration solutions are contraindicated for infants and young children with depressed consciousness, vomiting is not a contraindication to oral intake. About half of the oral intake stays in the stomach, even after vomiting. A single dose of ondansetron may safely reduce vomiting.¹⁵

Patients with mainly diarrhea can take fluids or feed at will. With children who refuse to drink, oral rehydration solutions can be administered via nasogastric tube at approximately 5 mL/min to limit vomiting and maintain hydration.¹⁴ In dehydrated infants and toddlers with collapsed veins, nasogastric intubation has been shown to be less traumatic than repetitive attempts at placing IV catheters.

DO encourage nursing mothers to con tinue breastfeeding during rehydration treatments. If a mother is bottle feeding, keep this in mind: Rotavirus can cause temporary lactase deficiency for some non-breastfeeding infants; lactose-free formulas may help.

DON’T assume that parents know how to provide proper supplementation. Tell them to avoid fluids containing mostly sugar that lack significant electrolyte supplementation (eg, cola) unless no other fluid alternative is available. Advise caregivers to avoid juices and other liquids high in complex or simple sugars because the osmotic load may worsen diarrhea.¹⁴

DON’T give antidiarrheal agents for acute treatment in infants and young children. Such treatment has resulted in death.¹⁴

TABLE 1
Prevent or correct dehydration using the WHO-recommended oral rehydration salts solution¹³

KEEP IN MIND

Hospitalization may be needed to replace fluids via IV or interosseous supplementation. For the severely dehydrated child, 20 mL/kg isotonic fluid can be administered as a rapid bolus.¹⁴ It may be necessary to repeat a rapid fluid infusion of 10 to 20 mL/kg every 20 to 30 minutes. For less severely ill infants who require IV rehydration, standard references such as the Harriet Lane Handbook¹⁶ provide excellent guidance.

Probiotics may help. Consider probiotics with Lactobacillus or Bifida bacterium to reduce the severity of diarrhea in infants and children who are mildly to moderately ill.^17,18 Their usefulness in the severely ill patient has not been demonstrated.

Available vaccines and clinical recommendations

In February 2006, the US Food and Drug Administration (FDA) licensed a 3-dose, oral pentavalent rotavirus vaccine (RV5, RotaTeq) for use among infants. The vaccine contains live reassortant rotaviruses¹⁹—4 human rotavirus G outer-surface proteins and 1 human P attachment protein reassorted into a bovine rotavirus not infectious to humans.

In February 2008, the FDA approved a 2-dose, oral monovalent rotavirus vaccine (RV1, Rotarix), an attenuated live human rotavirus containing 1 G protein and 1 P protein. Both vaccines have proven to be clinically effective in rotavirus prevention trials, but effectiveness may depend on which rotavirus serotypes circulate each season.

ACIP, AAP, and AAFP recommend that all infants be routinely vaccinated with either RV5 or RV1.^6,20–22 Vaccination should be complete by the time infants reach the age of 8 months (TABLE 2). Guidelines for vaccination emphasize the following points:

Timing. According to the ACIP, the first dose of either vaccine must be administered between the ages of 6 weeks and 14 weeks 6 days (the RV5 manufacturer [Merck] states a maximum age of 12 weeks). Give subsequent doses at 4- to 10-week intervals, as long as all doses are administered by 8 months of age. The RV1 manufacturer (GlaxoSmithKline) suggests completing the second (final) dose of its vaccine by age 24 weeks.

If an infant 15 weeks of age or older accidentally receives a first dose of RV vaccine, the series should be continued, as long as the last dose can be given by 8 months of age. Either vaccine can be administered concurrently with all other vaccines.

Contraindications. The only absolute contraindications to RV5 administration are a demonstrated hypersensitivity to any component of the vaccine and severe combined immunodeficiency disease (SCID). Contraindications to RV1 vaccine are vaccine component hypersensitivity, SCID, latex-induced allergy (anaphylaxis), and uncorrected malformation of the gastrointestinal (GI) tract that might predispose to intussusception.

Precautions. Precautions for vaccines include other forms of primary or secondary immunocompromised or immunodeficiency states, including cancer and acute or chronic GI disorders such as ongoing gastroenteritis or intussusception. Infants with transient mild illness with or without low-grade fever and infants who are breastfeeding can receive either vaccine. RV5 is shed in 9% of recipients and RV1 in 26% of recipients after Dose 1, but transmission of vaccine virus is not known to occur. Likewise, reversion of vaccine virus to more virulent pathogens is not known to occur. A household member with an immuno-compromised condition does not preclude giving either RV vaccine to an infant. The risk of transmitting vaccine virus is much smaller than the risk of acquiring infectious wild-type rotavirus.

Regurgitation of a vaccine dose is uncommon. When it does occur, the RV5 vaccine should not be repeated; some of the vaccine dose is retained and the safety of the additional vaccine from a second dose is unknown. Readministration of a dose of RV1 is not recommended, although not contraindicated.

TABLE 2
Recommended rotavirus live virus vaccine dosing⁶

Vaccine efficacy
The safety and efficacy of live rotavirus vaccines were demonstrated in large studies that enrolled 71,725 children in RV5 vaccine trials²³ and 24,163 children in RV1 vaccine trials.²¹ The pivotal RV5 study included a nested substudy to evaluate efficacy against any G1–G4 rotavirus gastroenteritis.

RV5 (RotaTeq) vaccine. In double-blind, placebo-controlled clinical trials, for the first rotavirus season, live RV5 vaccine effectively prevented severe rotavirus infection in 98% of cases, and reduced hospitalization by 95%, emergency department visits by 94%, physician office visits by 86%, and all rotavirus cases by 74% for infants who received all 3 doses of vaccine according to protocol.²³ Hospitalization for any-cause gastroenteritis was reduced by 63%. Second-season data showed persistence of antibody protection. All 3 doses of vaccine are required for maximum protection.²³

Both preterm and term infants received their first dose of vaccine between 6 and 12 weeks of life. For preterm infants who are experiencing medical difficulties, the first dose of vaccine may be delayed until the patient is stable, if it can be given before 15 weeks of age.

RV1 (Rotarix) vaccine. In double-blind, placebo-controlled clinical trials, for the first rotavirus season, live RV1 vaccine was 85% (Latin America) to 96% (Europe) effective in preventing severe rotavirus infection. It reduced hospitalization due to rotavirus by 85% (Latin America) to 100% (Europe), and all rotavirus cases by 87% (Europe) for infants who received both doses of the vaccine according to protocol. For the second season, the vaccine reduced severe rotavirus disease by 70% to 96%, and any rotavirus disease by 73% to 89%, showing persistence of antibody protection.⁶

Adverse events
With both vaccines, common side effects include irritability, flatulence, fever, vomiting, diarrhea, cough, runny nose, and loss of appetite. The RV5 vaccine has been shown not to increase the risk of intussusception compared with placebo.^24,25 The RV1 vaccine should not be used in children with an uncorrected bowel malformation, due to unproven increased risk of intussusception. Risk of death from complications after administration of either vaccine did not differ from that among children receiving placebo.

Postmarketing surveillance of vaccination outcomes
Even though rotavirus vaccine coverage with RV5 RotaTeq in the 2007-2008 and 2008-2009 seasons was far less than that with other childhood immunizations, the number of rotavirus infections dropped by >60% in both 2008 and 2009.²⁶ The number of stool tests for rotavirus and the percentage of positive results also dropped dramatically.

Additionally, the rotavirus peak incidence was delayed 2 to 4 months until April 2008 and March 2009.²⁶ Incidence was reduced in all age groups, suggesting the possibility of herd immunity despite a low vaccine coverage rate (estimates are 57% for ≥1 dose) that would not be expected to provide herd immunity.²⁷ Hospitalizations in the United States for rotavirus gastroenteritis dropped by as much as 85%,²⁸ markedly reducing costs for gastroenteritis.

In a 2010 report from an emergency department in Houston, a complete RV5 vaccine series conferred 82% protection against acute gastroenteritis, 96% against severe rotavirus disease requiring IV rehydration, and 100% against hospitalization.²⁹ For more on the vaccine, see the report by Yen et al.³⁰

Reports of the effectiveness of Rotarix in postmarketing surveillance are limited, but the vaccine does seem to provide broad coverage.³¹

Incorporating rotavirus vaccine into a family medicine practice
Given inadequately reimbursed costs including the cost of stocking RV vaccine (see “Costs of RV vaccines” above), family physicians who treat relatively few infants must determine whether offering RV vaccine fits within their practices.

For family physicians who do treat infants, offering RV vaccination makes sense. These oral vaccines are highly effective, safe, and easy to administer, and will prevent a great deal of worry and calls regarding infants who have a fever or diarrhea or are vomiting. Due to the costs of stocking all vaccines, private practitioners are wise to purchase vaccine loss insurance. Many insurance agencies provide a rider on office insurance policies to cover vaccine supplies.

CORRESPONDENCE
Donald B. Middleton, MD, UPMC St. Margaret, 815 Freeport Road, Pittsburgh, PA 15215; [email protected]

Rotavirus is the most common cause of severe gastroenteritis in infants and children younger than 5 years of age, and it accounts for approximately 5% of childhood deaths worldwide.1 In the United States, rotavirus causes numerous cases of dehydrating diarrhea and vomiting, and is responsible for direct and indirect healthcare costs of approximately $1 billion per year. Infection during childhood is almost universal.2

Improved personal hygiene and community sanitation have steadily reduced the prevalence of bacterial and parasitic disease. But these measures have had little effect on the spread of rotavirus and its potential complications of severe dehydration, hospitalization, and even death.¹ Importantly, we now have the means to vaccinate against rotavirus infection and dramatically reduce the incidence of disease. In this article, I describe the available vaccines and the vaccination recommendations endorsed by the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). I also review supportive treatment for rotavirus infection, which entails both do’s and don’ts.

Who is at risk of rotavirus disease?

For most term neonates, rotavirus disease is mild, perhaps because of partial protection from maternal antibodies.³ However, premature infants lacking full maternal antibody protection often suffer from more serious gastroenteritis. The most severe infections usually strike children between the ages of 4 months, when maternally derived antibody protection wanes, and 23 months, when dehydration risk lessens.^4-6

The virus spreads from person to person via the fecal–oral route.^6,7 Thirty percent to 50% of family members of an infected child may also become infected, but disease in older children and adults is usually subclinical or mild.⁶ Outbreaks of rotavirus are common in childcare centers and in children’s hospitals.^7,8

How the disease presents

Rotavirus gastroenteritis peaks during the winter. With mild cases, a watery diarrhea will last a few days. In severe cases, onset is usually abrupt with fever, abdominal pain, and vomiting, which can precede diarrhea. A third of patients have a temperature higher than 102°F (38.9°C).⁶ There is a risk of dehydration, shock, and even, occasionally, infant death.⁹

Typically, the incubation period is 1 to 4 days, and the infection lasts 3 to 7 days. However, damage to the brush border of the intestinal villi can produce persistent disaccharide malabsorption, resulting in prolonged diarrhea even after resolution of infection.^10,11 Stools generally do not contain blood or leukocytes. Ultrasound examination during rotavirus infections has shown thickening of the distal ileum and lymphadenopathy, which may predispose to intussusception.¹² Other problems possibly linked to wild-type rotavirus infection are Kawasaki disease and sudden infant death syndrome. Recurrent rotavirus infection with one of the many different serotypes is common during childhood.

More than 25 different assays can detect rotavirus in stool, but the most reliable method is direct electron microscopy. A suitable clinically available alternative is enzyme immunoassay testing of stool samples. In mild cases, testing to detect rotavirus is not necessary. But for bloody, severe, or persistent diarrhea, stool testing for rotavirus and other entities is warranted.

Supportive treatment: Do’s and don’ts

No specific antiviral treatment is available for rotavirus infection. That said, the do’s and don’ts that follow will help guide your care.

DO administer oral, enteral, or intravenous (IV) fluids to prevent or correct dehydration. Oral rehydration therapy is the standard treatment for dehydration in anyone with acute gastroenteritis, including that caused by rotavirus. The recommended World Health Organization (WHO) oral rehydration solution contains sodium, chloride, and electrolytes (TABLE 1).¹³ Rice-based oral rehydration solution is an easily metabolized carbohydrate formulation that helps repair damaged tissues and enhances electrolyte absorption.⁹ WHO has endorsed guidelines that base fluid replacement on the patient’s age and weight, and that recommend oral zinc intake (10 mg/d for 10-14 days up to age 6 months; 20 mg/d for 10-14 days for older children) for all episodes of diarrhea (http://hetv.org/pdf/diarrhoea-guidelines.pdf). Oral glucose electrolyte solutions containing less sodium and chloride are also effective treatments.

DO recommend frequent small doses of oral rehydration solution, even if the patient is vomiting.¹⁴ Rehydration volumes are suggested in TABLE 1. Alternatively, give 10 to 20 mL/kg for each diarrheal episode, and 2 mL/kg for each bout of emesis. Feeding frequent small volumes (30 mL every 5-10 minutes) reduces the risk of emesis.

Although oral rehydration solutions are contraindicated for infants and young children with depressed consciousness, vomiting is not a contraindication to oral intake. About half of the oral intake stays in the stomach, even after vomiting. A single dose of ondansetron may safely reduce vomiting.¹⁵

Patients with mainly diarrhea can take fluids or feed at will. With children who refuse to drink, oral rehydration solutions can be administered via nasogastric tube at approximately 5 mL/min to limit vomiting and maintain hydration.¹⁴ In dehydrated infants and toddlers with collapsed veins, nasogastric intubation has been shown to be less traumatic than repetitive attempts at placing IV catheters.

DO encourage nursing mothers to con tinue breastfeeding during rehydration treatments. If a mother is bottle feeding, keep this in mind: Rotavirus can cause temporary lactase deficiency for some non-breastfeeding infants; lactose-free formulas may help.

DON’T assume that parents know how to provide proper supplementation. Tell them to avoid fluids containing mostly sugar that lack significant electrolyte supplementation (eg, cola) unless no other fluid alternative is available. Advise caregivers to avoid juices and other liquids high in complex or simple sugars because the osmotic load may worsen diarrhea.¹⁴

DON’T give antidiarrheal agents for acute treatment in infants and young children. Such treatment has resulted in death.¹⁴

TABLE 1
Prevent or correct dehydration using the WHO-recommended oral rehydration salts solution¹³

KEEP IN MIND

Hospitalization may be needed to replace fluids via IV or interosseous supplementation. For the severely dehydrated child, 20 mL/kg isotonic fluid can be administered as a rapid bolus.¹⁴ It may be necessary to repeat a rapid fluid infusion of 10 to 20 mL/kg every 20 to 30 minutes. For less severely ill infants who require IV rehydration, standard references such as the Harriet Lane Handbook¹⁶ provide excellent guidance.

Probiotics may help. Consider probiotics with Lactobacillus or Bifida bacterium to reduce the severity of diarrhea in infants and children who are mildly to moderately ill.^17,18 Their usefulness in the severely ill patient has not been demonstrated.

Available vaccines and clinical recommendations

In February 2006, the US Food and Drug Administration (FDA) licensed a 3-dose, oral pentavalent rotavirus vaccine (RV5, RotaTeq) for use among infants. The vaccine contains live reassortant rotaviruses¹⁹—4 human rotavirus G outer-surface proteins and 1 human P attachment protein reassorted into a bovine rotavirus not infectious to humans.

In February 2008, the FDA approved a 2-dose, oral monovalent rotavirus vaccine (RV1, Rotarix), an attenuated live human rotavirus containing 1 G protein and 1 P protein. Both vaccines have proven to be clinically effective in rotavirus prevention trials, but effectiveness may depend on which rotavirus serotypes circulate each season.

ACIP, AAP, and AAFP recommend that all infants be routinely vaccinated with either RV5 or RV1.^6,20–22 Vaccination should be complete by the time infants reach the age of 8 months (TABLE 2). Guidelines for vaccination emphasize the following points:

Timing. According to the ACIP, the first dose of either vaccine must be administered between the ages of 6 weeks and 14 weeks 6 days (the RV5 manufacturer [Merck] states a maximum age of 12 weeks). Give subsequent doses at 4- to 10-week intervals, as long as all doses are administered by 8 months of age. The RV1 manufacturer (GlaxoSmithKline) suggests completing the second (final) dose of its vaccine by age 24 weeks.

If an infant 15 weeks of age or older accidentally receives a first dose of RV vaccine, the series should be continued, as long as the last dose can be given by 8 months of age. Either vaccine can be administered concurrently with all other vaccines.

Contraindications. The only absolute contraindications to RV5 administration are a demonstrated hypersensitivity to any component of the vaccine and severe combined immunodeficiency disease (SCID). Contraindications to RV1 vaccine are vaccine component hypersensitivity, SCID, latex-induced allergy (anaphylaxis), and uncorrected malformation of the gastrointestinal (GI) tract that might predispose to intussusception.

Precautions. Precautions for vaccines include other forms of primary or secondary immunocompromised or immunodeficiency states, including cancer and acute or chronic GI disorders such as ongoing gastroenteritis or intussusception. Infants with transient mild illness with or without low-grade fever and infants who are breastfeeding can receive either vaccine. RV5 is shed in 9% of recipients and RV1 in 26% of recipients after Dose 1, but transmission of vaccine virus is not known to occur. Likewise, reversion of vaccine virus to more virulent pathogens is not known to occur. A household member with an immuno-compromised condition does not preclude giving either RV vaccine to an infant. The risk of transmitting vaccine virus is much smaller than the risk of acquiring infectious wild-type rotavirus.

Regurgitation of a vaccine dose is uncommon. When it does occur, the RV5 vaccine should not be repeated; some of the vaccine dose is retained and the safety of the additional vaccine from a second dose is unknown. Readministration of a dose of RV1 is not recommended, although not contraindicated.

TABLE 2
Recommended rotavirus live virus vaccine dosing⁶

Vaccine efficacy
The safety and efficacy of live rotavirus vaccines were demonstrated in large studies that enrolled 71,725 children in RV5 vaccine trials²³ and 24,163 children in RV1 vaccine trials.²¹ The pivotal RV5 study included a nested substudy to evaluate efficacy against any G1–G4 rotavirus gastroenteritis.

RV5 (RotaTeq) vaccine. In double-blind, placebo-controlled clinical trials, for the first rotavirus season, live RV5 vaccine effectively prevented severe rotavirus infection in 98% of cases, and reduced hospitalization by 95%, emergency department visits by 94%, physician office visits by 86%, and all rotavirus cases by 74% for infants who received all 3 doses of vaccine according to protocol.²³ Hospitalization for any-cause gastroenteritis was reduced by 63%. Second-season data showed persistence of antibody protection. All 3 doses of vaccine are required for maximum protection.²³

Both preterm and term infants received their first dose of vaccine between 6 and 12 weeks of life. For preterm infants who are experiencing medical difficulties, the first dose of vaccine may be delayed until the patient is stable, if it can be given before 15 weeks of age.

RV1 (Rotarix) vaccine. In double-blind, placebo-controlled clinical trials, for the first rotavirus season, live RV1 vaccine was 85% (Latin America) to 96% (Europe) effective in preventing severe rotavirus infection. It reduced hospitalization due to rotavirus by 85% (Latin America) to 100% (Europe), and all rotavirus cases by 87% (Europe) for infants who received both doses of the vaccine according to protocol. For the second season, the vaccine reduced severe rotavirus disease by 70% to 96%, and any rotavirus disease by 73% to 89%, showing persistence of antibody protection.⁶

Adverse events
With both vaccines, common side effects include irritability, flatulence, fever, vomiting, diarrhea, cough, runny nose, and loss of appetite. The RV5 vaccine has been shown not to increase the risk of intussusception compared with placebo.^24,25 The RV1 vaccine should not be used in children with an uncorrected bowel malformation, due to unproven increased risk of intussusception. Risk of death from complications after administration of either vaccine did not differ from that among children receiving placebo.

Postmarketing surveillance of vaccination outcomes
Even though rotavirus vaccine coverage with RV5 RotaTeq in the 2007-2008 and 2008-2009 seasons was far less than that with other childhood immunizations, the number of rotavirus infections dropped by >60% in both 2008 and 2009.²⁶ The number of stool tests for rotavirus and the percentage of positive results also dropped dramatically.

Additionally, the rotavirus peak incidence was delayed 2 to 4 months until April 2008 and March 2009.²⁶ Incidence was reduced in all age groups, suggesting the possibility of herd immunity despite a low vaccine coverage rate (estimates are 57% for ≥1 dose) that would not be expected to provide herd immunity.²⁷ Hospitalizations in the United States for rotavirus gastroenteritis dropped by as much as 85%,²⁸ markedly reducing costs for gastroenteritis.

In a 2010 report from an emergency department in Houston, a complete RV5 vaccine series conferred 82% protection against acute gastroenteritis, 96% against severe rotavirus disease requiring IV rehydration, and 100% against hospitalization.²⁹ For more on the vaccine, see the report by Yen et al.³⁰

Reports of the effectiveness of Rotarix in postmarketing surveillance are limited, but the vaccine does seem to provide broad coverage.³¹

Incorporating rotavirus vaccine into a family medicine practice
Given inadequately reimbursed costs including the cost of stocking RV vaccine (see “Costs of RV vaccines” above), family physicians who treat relatively few infants must determine whether offering RV vaccine fits within their practices.

For family physicians who do treat infants, offering RV vaccination makes sense. These oral vaccines are highly effective, safe, and easy to administer, and will prevent a great deal of worry and calls regarding infants who have a fever or diarrhea or are vomiting. Due to the costs of stocking all vaccines, private practitioners are wise to purchase vaccine loss insurance. Many insurance agencies provide a rider on office insurance policies to cover vaccine supplies.

CORRESPONDENCE
Donald B. Middleton, MD, UPMC St. Margaret, 815 Freeport Road, Pittsburgh, PA 15215; [email protected]