“Counseling is a must with this smoking cessation aid,” stated a PURL published in March 2012 (J Fam Pract. 2012;61:156, 176). “Varenicline [Chantix] is associated with a small but significant harmful effect on CV outcomes.” That statement, and the PURL itself, was based on a meta-analysis published in 2011 by Singh et al.1 The meta-analysis included 14 randomized controlled trials (RCTs) that compared varenicline with placebo for the occurrence of serious cardiovascular disease (CVD) events, including myocardial infarction, coronary artery disease, arrhythmias, stroke, sudden death, and any related coronary death. RCTs that reported no CVD events were excluded.

Using a Peto odds ratio [OR] for analysis, Singh et al reported that varenicline use increased the risk of CVD events compared with placebo (OR=1.72; 95% CI, 1.09-2.71). A more recent meta-analysis by Prochaska et al,² however, challenges the validity of the Singh meta-analysis. As members of the Family Physicians Inquiries Network, which produces the PURLs, we would like to address the questions this newer study raises about varenicline’s actual risk.

The Prochaska meta-analysis included all 14 RCTs analyzed by Singh, and used the same CVD event outcome measures. In addition, Prochaska included 8 trials in which no CVD events were reported, some of which were published after the Singh meta-analysis. And rather than use the Peto OR to estimate the risk, Prochaska calculated the absolute risk (AR). The result? The researchers found no difference in CVD events in the varenicline group compared with placebo (AR=0.27; 95% CI, -0.10 to 0.63; P=.15).

This is a good example of how inclusion criteria, subsequently published clinical trials, and the choice of statistical methods can lead to conflicting conclusions from meta-analyses on the same topic. Including studies that showed no adverse CVD events is more likely to capture the true risk than excluding them, and reporting AR is more meaningful than estimating relative risk based on the Peto OR.

Therefore, the Prochaska findings are more convincing. Given the effectiveness of varenicline and the known benefits of successful smoking cessation, it is important for clinicians to understand that the true risk of CVD adverse events attributable to varenicline is extremely low or even nonexistent.

Dionna Brown, MD
Bernard Ewigman, MD, MSPH
Chicago

“Counseling is a must with this smoking cessation aid,” stated a PURL published in March 2012 (J Fam Pract. 2012;61:156, 176). “Varenicline [Chantix] is associated with a small but significant harmful effect on CV outcomes.” That statement, and the PURL itself, was based on a meta-analysis published in 2011 by Singh et al.1 The meta-analysis included 14 randomized controlled trials (RCTs) that compared varenicline with placebo for the occurrence of serious cardiovascular disease (CVD) events, including myocardial infarction, coronary artery disease, arrhythmias, stroke, sudden death, and any related coronary death. RCTs that reported no CVD events were excluded.

Using a Peto odds ratio [OR] for analysis, Singh et al reported that varenicline use increased the risk of CVD events compared with placebo (OR=1.72; 95% CI, 1.09-2.71). A more recent meta-analysis by Prochaska et al,² however, challenges the validity of the Singh meta-analysis. As members of the Family Physicians Inquiries Network, which produces the PURLs, we would like to address the questions this newer study raises about varenicline’s actual risk.

The Prochaska meta-analysis included all 14 RCTs analyzed by Singh, and used the same CVD event outcome measures. In addition, Prochaska included 8 trials in which no CVD events were reported, some of which were published after the Singh meta-analysis. And rather than use the Peto OR to estimate the risk, Prochaska calculated the absolute risk (AR). The result? The researchers found no difference in CVD events in the varenicline group compared with placebo (AR=0.27; 95% CI, -0.10 to 0.63; P=.15).

This is a good example of how inclusion criteria, subsequently published clinical trials, and the choice of statistical methods can lead to conflicting conclusions from meta-analyses on the same topic. Including studies that showed no adverse CVD events is more likely to capture the true risk than excluding them, and reporting AR is more meaningful than estimating relative risk based on the Peto OR.

Therefore, the Prochaska findings are more convincing. Given the effectiveness of varenicline and the known benefits of successful smoking cessation, it is important for clinicians to understand that the true risk of CVD adverse events attributable to varenicline is extremely low or even nonexistent.

Dionna Brown, MD
Bernard Ewigman, MD, MSPH
Chicago

“Counseling is a must with this smoking cessation aid,” stated a PURL published in March 2012 (J Fam Pract. 2012;61:156, 176). “Varenicline [Chantix] is associated with a small but significant harmful effect on CV outcomes.” That statement, and the PURL itself, was based on a meta-analysis published in 2011 by Singh et al.1 The meta-analysis included 14 randomized controlled trials (RCTs) that compared varenicline with placebo for the occurrence of serious cardiovascular disease (CVD) events, including myocardial infarction, coronary artery disease, arrhythmias, stroke, sudden death, and any related coronary death. RCTs that reported no CVD events were excluded.

Using a Peto odds ratio [OR] for analysis, Singh et al reported that varenicline use increased the risk of CVD events compared with placebo (OR=1.72; 95% CI, 1.09-2.71). A more recent meta-analysis by Prochaska et al,² however, challenges the validity of the Singh meta-analysis. As members of the Family Physicians Inquiries Network, which produces the PURLs, we would like to address the questions this newer study raises about varenicline’s actual risk.

The Prochaska meta-analysis included all 14 RCTs analyzed by Singh, and used the same CVD event outcome measures. In addition, Prochaska included 8 trials in which no CVD events were reported, some of which were published after the Singh meta-analysis. And rather than use the Peto OR to estimate the risk, Prochaska calculated the absolute risk (AR). The result? The researchers found no difference in CVD events in the varenicline group compared with placebo (AR=0.27; 95% CI, -0.10 to 0.63; P=.15).

This is a good example of how inclusion criteria, subsequently published clinical trials, and the choice of statistical methods can lead to conflicting conclusions from meta-analyses on the same topic. Including studies that showed no adverse CVD events is more likely to capture the true risk than excluding them, and reporting AR is more meaningful than estimating relative risk based on the Peto OR.

Therefore, the Prochaska findings are more convincing. Given the effectiveness of varenicline and the known benefits of successful smoking cessation, it is important for clinicians to understand that the true risk of CVD adverse events attributable to varenicline is extremely low or even nonexistent.

Dionna Brown, MD
Bernard Ewigman, MD, MSPH
Chicago

CASE: Worsening insomnia

Mr. Q, age 44, presents for evaluation of altered mental status characterized by disorientation, impaired attention and concentration, paranoid delusions, and prominent auditory and visual hallucinations. His initial Folstein Mini-Mental State Examination (MMSE) score is 7 of 30, indicating severe impairment. He further describes a recent history of nausea, intermittent vomiting, and anorexia. He takes hydrocodone/acetaminophen, 5/500 mg, 4 times daily for lower back and joint pain. Additionally, he has a pacemaker, which was placed when Mr. Q was in his late 30s to treat sinus bradycardia.

Mr. Q’s fiancée describes his 6-month history of worsening sleep disturbance, noting insomnia, fractured sleep, dream enactment, and daytime fatigue. During this time, Mr. Q averaged 3 to 4 hours of sleep nightly without day-time naps. Ten days ago, he stopped sleeping completely and his cognitive function decompensated rapidly. He became increasingly paranoid, believing government agents had been dispatched to kill him. Several days before admission, Mr. Q developed auditory and visual hallucinations. He reports that he hears voices warning him of Armageddon and sees reincarnated spirits of deceased relatives. He describes his mood as “fine” and “okay” and lacks insight into his psychiatric symptoms other than his sleeplessness.

Mr. Q’s family says he has a history of transient mild depression after his older brother died from an unknown neurologic disease 3 years ago. Mr. Q did not receive pharmacotherapy or psychotherapy but his symptoms resolved. His family says that Mr. Q has been using marijuana daily for several years, but they are unaware of other substance use. They deny a family history of psychiatric illness.

On physical examination, Mr. Q appears thin, agitated, and in mild distress. He has a fever of 99.2°F. His blood pressure drops intermittently from a baseline of 120/70 mm Hg to 100/60 mm Hg, at which point he experiences transient normal sinus tachycardia. Neurologic examination reveals psychomotor agitation and diffuse myoclonic tremor.

The authors’ observations

Table 1

Differential diagnosis of insomnia

Medications that can cause or exacerbate insomnia

EVALUATION: Inconclusive results

Routine laboratory studies reveal mild normocytic anemia and mild hypokalemia. Liver panel, renal function, cardiac profile, brain natriuretic peptide level, folate and vitamin B12 levels, thyroid studies, and human immunodeficiency virus serology are negative or within normal limits. Urinalysis reveals the presence of ketones, indicative of Mr. Q’s recent anorexia. Chest radiography and CT imaging of the head, abdomen, and pelvis also are unremarkable. MRI is contraindicated because of Mr. Q’s implanted pacemaker. Pulse oximetry does not suggest apneic events. Mr. Q and his family refuse a lumbar puncture, which precludes cerebrospinal fluid (CSF) analysis. Electroencephalography (EEG) records normal patterns of wakefulness oscillating with transient periods of stage 1 sleep. A detailed family interview reveals that Mr. Q’s older brother had a history of epilepsy and died at age 49 following a prolonged hospitalization for recurrent seizures and similar insomnia symptoms. History from the patient’s paternal lineage is not available.

The authors’ observations

American Psychiatric Association practice guidelines³ do not support first-line use of benzodiazepines for non-alcohol withdrawal-related delirium. Benzodiazepines are ineffective for treating delirium and may exacerbate symptoms.⁴ Laboratory evidence confirmed Mr. Q has no history of alcohol or benzodiazepine use. Although treating the underlying cause of delirium is essential, prescribing a sedative-hypnotic medication such as zolpidem for Mr. Q’s insomnia may worsen his condition. These agents are known to impair cognition and may induce or intensify psychosis.⁵ Melatonin and melatonin receptor agonists, such as ramelteon, promote sleep by regulating the sleep-wake rhythm through their action on melatonin receptors in the hypothalamus.⁶ Recently, a randomized control trial (RCT)⁷ found melatonin protected against delirium in hospitalized patients age ≥65. However, no RCT has examined use of exogenous melatonin or melatonin receptor agonists to treat delirium. In Mr. Q’s case, we chose to administer haloperidol. First- and second-generation antipsychotics have shown efficacy in treating acute delirium. Although more clinical experience has accumulated using first-generation agents such as haloperidol, a 2007 Cochrane meta-analysis⁸ demonstrated equal benefit with second-generation antipsychotics, while noting a decreased incidence of adverse effects.

TREATMENT: Adverse effects

Mr. Q receives an IM injection of haloperidol, 5 mg, for severe agitation, followed 15 hours later by IM aripiprazole, 9.75 mg. Within hours of receiving aripiprazole, Mr. Q develops hyperkinetic perioral and tongue movements. He initially is diagnosed with acute reactionary dystonia, although closer examination reveals myoclonus consistent with his overall presentation. Additionally, his QTc interval increases by 120 ms. Subsequently, all antipsychotics are stopped. We prescribe lorazepam, 1 mg IM every 4 hours as needed, for agitation. Mr. Q receives 2 consecutive doses of lorazepam, although neither effectively reduces his agitation or promotes sleep. Mr. Q is not assessed with positron-emission tomography (PET) or polysomnography.

The authors’ observations

There was no evidence of neurologic disease on Mr. Q’s CT scan and EEG was within normal limits. Other imaging and laboratory studies did not reveal possible infection, malignancy, or cardiovascular disease. Despite its rarity, we considered the possibility of a prion disease, given Mr. Q’s unique presentation and family history. Familial fatal insomnia (FFI) is an autosomal dominant disease caused by a point mutation in the prion protein gene. Prion proteins are theorized to play a role in myelin stability. The aberrant isoform produced in FFI is structurally misfolded so that it resists degradation by proteolytic enzymes. The accumulation of irregular prion proteins in the medial thalamic nucleus results in progressive neurodegeneration. Patients with FFI present with increasingly severe insomnia, mild fever, dysautonomia, spontaneous myoclonus, cognitive dysfunction, and hallucinations.⁹ Generally, patients die from sudden cardiorespiratory failure or ensuing infections 9 to 24 months after symptom onset. In vivo, FFI diagnosis is suggested by a loss of sleep spindles on polysomnogram and by decreased thalamic metabolism on PET scan. Other imaging modalities and testing, including EEG and CSF analysis, lack sensitivity and/or specificity.¹⁰

OUTCOME: Improvement, discharge

On his fourth hospital day, Mr. Q’s symptoms begin to remit spontaneously. His gastrointestinal (GI) upset improves and the following night he sleeps for approximately 4 hours. As his sleep improves, his delusional thinking and hallucinations resolve. Orientation, memory, and concentration gradually improve. Before discharge, his MMSE score is 24 out of 30, indicating improved cognition. His heart rate, blood pressure, and body temperature normalize and his myoclonus improves. Mr. Q is discharged after 6 days in the hospital and returns home. He follows up with his primary care physician, denies any recurrence of sleep disturbance, and reports that his cognition and perception have returned to his baseline.

The authors’ observations

Table 3

DSM-IV-TR diagnostic criteria for opioid withdrawal

• Morin CM, Benca R. Chronic insomnia. Lancet. 2012; 379(9821):1129-1141.
  
• Pressman MR, Orr WC, eds. Understanding sleep: the evolution and treatment of sleep disorders. Washington, DC: American Psychological Association; 1997.
  
• NIH State-of-the-Science Conference Statement on manifestations and management of chronic insomnia in adults. NIH Consens State Sci Statements. 2005;22(2):1-30.
  

• Albuterol • Proventil, Ventolin
  
• Aripiprazole • Abilify
  
• Bupropion • Wellbutrin, Zyban
  
• Dextroamphetamine • Dexadrine
  
• Haloperidol • Haldol
  
• Hydrocodone/Acetaminophen • Vicodin
  
• Lamotrigine • Lamictal
  
• Lorazepam • Ativan
  
• Methylphenidate • Methylin, Ritalin
  
• Phenylephrine • Neo-Synephrine
  
• Pseudoephedrine • Sudafed
  
• Ramelteon • Rozerem
  
• Theophylline • Elixophyllin, Slo-Phyllin
  
• Zolpidem • Ambien
  

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

CASE: Worsening insomnia

Mr. Q, age 44, presents for evaluation of altered mental status characterized by disorientation, impaired attention and concentration, paranoid delusions, and prominent auditory and visual hallucinations. His initial Folstein Mini-Mental State Examination (MMSE) score is 7 of 30, indicating severe impairment. He further describes a recent history of nausea, intermittent vomiting, and anorexia. He takes hydrocodone/acetaminophen, 5/500 mg, 4 times daily for lower back and joint pain. Additionally, he has a pacemaker, which was placed when Mr. Q was in his late 30s to treat sinus bradycardia.

Mr. Q’s fiancée describes his 6-month history of worsening sleep disturbance, noting insomnia, fractured sleep, dream enactment, and daytime fatigue. During this time, Mr. Q averaged 3 to 4 hours of sleep nightly without day-time naps. Ten days ago, he stopped sleeping completely and his cognitive function decompensated rapidly. He became increasingly paranoid, believing government agents had been dispatched to kill him. Several days before admission, Mr. Q developed auditory and visual hallucinations. He reports that he hears voices warning him of Armageddon and sees reincarnated spirits of deceased relatives. He describes his mood as “fine” and “okay” and lacks insight into his psychiatric symptoms other than his sleeplessness.

Mr. Q’s family says he has a history of transient mild depression after his older brother died from an unknown neurologic disease 3 years ago. Mr. Q did not receive pharmacotherapy or psychotherapy but his symptoms resolved. His family says that Mr. Q has been using marijuana daily for several years, but they are unaware of other substance use. They deny a family history of psychiatric illness.

On physical examination, Mr. Q appears thin, agitated, and in mild distress. He has a fever of 99.2°F. His blood pressure drops intermittently from a baseline of 120/70 mm Hg to 100/60 mm Hg, at which point he experiences transient normal sinus tachycardia. Neurologic examination reveals psychomotor agitation and diffuse myoclonic tremor.

The authors’ observations

Table 1

Differential diagnosis of insomnia

Medications that can cause or exacerbate insomnia

EVALUATION: Inconclusive results

Routine laboratory studies reveal mild normocytic anemia and mild hypokalemia. Liver panel, renal function, cardiac profile, brain natriuretic peptide level, folate and vitamin B12 levels, thyroid studies, and human immunodeficiency virus serology are negative or within normal limits. Urinalysis reveals the presence of ketones, indicative of Mr. Q’s recent anorexia. Chest radiography and CT imaging of the head, abdomen, and pelvis also are unremarkable. MRI is contraindicated because of Mr. Q’s implanted pacemaker. Pulse oximetry does not suggest apneic events. Mr. Q and his family refuse a lumbar puncture, which precludes cerebrospinal fluid (CSF) analysis. Electroencephalography (EEG) records normal patterns of wakefulness oscillating with transient periods of stage 1 sleep. A detailed family interview reveals that Mr. Q’s older brother had a history of epilepsy and died at age 49 following a prolonged hospitalization for recurrent seizures and similar insomnia symptoms. History from the patient’s paternal lineage is not available.

The authors’ observations

American Psychiatric Association practice guidelines³ do not support first-line use of benzodiazepines for non-alcohol withdrawal-related delirium. Benzodiazepines are ineffective for treating delirium and may exacerbate symptoms.⁴ Laboratory evidence confirmed Mr. Q has no history of alcohol or benzodiazepine use. Although treating the underlying cause of delirium is essential, prescribing a sedative-hypnotic medication such as zolpidem for Mr. Q’s insomnia may worsen his condition. These agents are known to impair cognition and may induce or intensify psychosis.⁵ Melatonin and melatonin receptor agonists, such as ramelteon, promote sleep by regulating the sleep-wake rhythm through their action on melatonin receptors in the hypothalamus.⁶ Recently, a randomized control trial (RCT)⁷ found melatonin protected against delirium in hospitalized patients age ≥65. However, no RCT has examined use of exogenous melatonin or melatonin receptor agonists to treat delirium. In Mr. Q’s case, we chose to administer haloperidol. First- and second-generation antipsychotics have shown efficacy in treating acute delirium. Although more clinical experience has accumulated using first-generation agents such as haloperidol, a 2007 Cochrane meta-analysis⁸ demonstrated equal benefit with second-generation antipsychotics, while noting a decreased incidence of adverse effects.

TREATMENT: Adverse effects

Mr. Q receives an IM injection of haloperidol, 5 mg, for severe agitation, followed 15 hours later by IM aripiprazole, 9.75 mg. Within hours of receiving aripiprazole, Mr. Q develops hyperkinetic perioral and tongue movements. He initially is diagnosed with acute reactionary dystonia, although closer examination reveals myoclonus consistent with his overall presentation. Additionally, his QTc interval increases by 120 ms. Subsequently, all antipsychotics are stopped. We prescribe lorazepam, 1 mg IM every 4 hours as needed, for agitation. Mr. Q receives 2 consecutive doses of lorazepam, although neither effectively reduces his agitation or promotes sleep. Mr. Q is not assessed with positron-emission tomography (PET) or polysomnography.

The authors’ observations

There was no evidence of neurologic disease on Mr. Q’s CT scan and EEG was within normal limits. Other imaging and laboratory studies did not reveal possible infection, malignancy, or cardiovascular disease. Despite its rarity, we considered the possibility of a prion disease, given Mr. Q’s unique presentation and family history. Familial fatal insomnia (FFI) is an autosomal dominant disease caused by a point mutation in the prion protein gene. Prion proteins are theorized to play a role in myelin stability. The aberrant isoform produced in FFI is structurally misfolded so that it resists degradation by proteolytic enzymes. The accumulation of irregular prion proteins in the medial thalamic nucleus results in progressive neurodegeneration. Patients with FFI present with increasingly severe insomnia, mild fever, dysautonomia, spontaneous myoclonus, cognitive dysfunction, and hallucinations.⁹ Generally, patients die from sudden cardiorespiratory failure or ensuing infections 9 to 24 months after symptom onset. In vivo, FFI diagnosis is suggested by a loss of sleep spindles on polysomnogram and by decreased thalamic metabolism on PET scan. Other imaging modalities and testing, including EEG and CSF analysis, lack sensitivity and/or specificity.¹⁰

OUTCOME: Improvement, discharge

On his fourth hospital day, Mr. Q’s symptoms begin to remit spontaneously. His gastrointestinal (GI) upset improves and the following night he sleeps for approximately 4 hours. As his sleep improves, his delusional thinking and hallucinations resolve. Orientation, memory, and concentration gradually improve. Before discharge, his MMSE score is 24 out of 30, indicating improved cognition. His heart rate, blood pressure, and body temperature normalize and his myoclonus improves. Mr. Q is discharged after 6 days in the hospital and returns home. He follows up with his primary care physician, denies any recurrence of sleep disturbance, and reports that his cognition and perception have returned to his baseline.

The authors’ observations

Table 3

DSM-IV-TR diagnostic criteria for opioid withdrawal

• Morin CM, Benca R. Chronic insomnia. Lancet. 2012; 379(9821):1129-1141.
  
• Pressman MR, Orr WC, eds. Understanding sleep: the evolution and treatment of sleep disorders. Washington, DC: American Psychological Association; 1997.
  
• NIH State-of-the-Science Conference Statement on manifestations and management of chronic insomnia in adults. NIH Consens State Sci Statements. 2005;22(2):1-30.
  

• Albuterol • Proventil, Ventolin
  
• Aripiprazole • Abilify
  
• Bupropion • Wellbutrin, Zyban
  
• Dextroamphetamine • Dexadrine
  
• Haloperidol • Haldol
  
• Hydrocodone/Acetaminophen • Vicodin
  
• Lamotrigine • Lamictal
  
• Lorazepam • Ativan
  
• Methylphenidate • Methylin, Ritalin
  
• Phenylephrine • Neo-Synephrine
  
• Pseudoephedrine • Sudafed
  
• Ramelteon • Rozerem
  
• Theophylline • Elixophyllin, Slo-Phyllin
  
• Zolpidem • Ambien
  

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

CASE: Worsening insomnia

Mr. Q, age 44, presents for evaluation of altered mental status characterized by disorientation, impaired attention and concentration, paranoid delusions, and prominent auditory and visual hallucinations. His initial Folstein Mini-Mental State Examination (MMSE) score is 7 of 30, indicating severe impairment. He further describes a recent history of nausea, intermittent vomiting, and anorexia. He takes hydrocodone/acetaminophen, 5/500 mg, 4 times daily for lower back and joint pain. Additionally, he has a pacemaker, which was placed when Mr. Q was in his late 30s to treat sinus bradycardia.

Mr. Q’s fiancée describes his 6-month history of worsening sleep disturbance, noting insomnia, fractured sleep, dream enactment, and daytime fatigue. During this time, Mr. Q averaged 3 to 4 hours of sleep nightly without day-time naps. Ten days ago, he stopped sleeping completely and his cognitive function decompensated rapidly. He became increasingly paranoid, believing government agents had been dispatched to kill him. Several days before admission, Mr. Q developed auditory and visual hallucinations. He reports that he hears voices warning him of Armageddon and sees reincarnated spirits of deceased relatives. He describes his mood as “fine” and “okay” and lacks insight into his psychiatric symptoms other than his sleeplessness.

Mr. Q’s family says he has a history of transient mild depression after his older brother died from an unknown neurologic disease 3 years ago. Mr. Q did not receive pharmacotherapy or psychotherapy but his symptoms resolved. His family says that Mr. Q has been using marijuana daily for several years, but they are unaware of other substance use. They deny a family history of psychiatric illness.

On physical examination, Mr. Q appears thin, agitated, and in mild distress. He has a fever of 99.2°F. His blood pressure drops intermittently from a baseline of 120/70 mm Hg to 100/60 mm Hg, at which point he experiences transient normal sinus tachycardia. Neurologic examination reveals psychomotor agitation and diffuse myoclonic tremor.

The authors’ observations

Table 1

Differential diagnosis of insomnia

Medications that can cause or exacerbate insomnia

EVALUATION: Inconclusive results

Routine laboratory studies reveal mild normocytic anemia and mild hypokalemia. Liver panel, renal function, cardiac profile, brain natriuretic peptide level, folate and vitamin B12 levels, thyroid studies, and human immunodeficiency virus serology are negative or within normal limits. Urinalysis reveals the presence of ketones, indicative of Mr. Q’s recent anorexia. Chest radiography and CT imaging of the head, abdomen, and pelvis also are unremarkable. MRI is contraindicated because of Mr. Q’s implanted pacemaker. Pulse oximetry does not suggest apneic events. Mr. Q and his family refuse a lumbar puncture, which precludes cerebrospinal fluid (CSF) analysis. Electroencephalography (EEG) records normal patterns of wakefulness oscillating with transient periods of stage 1 sleep. A detailed family interview reveals that Mr. Q’s older brother had a history of epilepsy and died at age 49 following a prolonged hospitalization for recurrent seizures and similar insomnia symptoms. History from the patient’s paternal lineage is not available.

The authors’ observations

American Psychiatric Association practice guidelines³ do not support first-line use of benzodiazepines for non-alcohol withdrawal-related delirium. Benzodiazepines are ineffective for treating delirium and may exacerbate symptoms.⁴ Laboratory evidence confirmed Mr. Q has no history of alcohol or benzodiazepine use. Although treating the underlying cause of delirium is essential, prescribing a sedative-hypnotic medication such as zolpidem for Mr. Q’s insomnia may worsen his condition. These agents are known to impair cognition and may induce or intensify psychosis.⁵ Melatonin and melatonin receptor agonists, such as ramelteon, promote sleep by regulating the sleep-wake rhythm through their action on melatonin receptors in the hypothalamus.⁶ Recently, a randomized control trial (RCT)⁷ found melatonin protected against delirium in hospitalized patients age ≥65. However, no RCT has examined use of exogenous melatonin or melatonin receptor agonists to treat delirium. In Mr. Q’s case, we chose to administer haloperidol. First- and second-generation antipsychotics have shown efficacy in treating acute delirium. Although more clinical experience has accumulated using first-generation agents such as haloperidol, a 2007 Cochrane meta-analysis⁸ demonstrated equal benefit with second-generation antipsychotics, while noting a decreased incidence of adverse effects.

TREATMENT: Adverse effects

Mr. Q receives an IM injection of haloperidol, 5 mg, for severe agitation, followed 15 hours later by IM aripiprazole, 9.75 mg. Within hours of receiving aripiprazole, Mr. Q develops hyperkinetic perioral and tongue movements. He initially is diagnosed with acute reactionary dystonia, although closer examination reveals myoclonus consistent with his overall presentation. Additionally, his QTc interval increases by 120 ms. Subsequently, all antipsychotics are stopped. We prescribe lorazepam, 1 mg IM every 4 hours as needed, for agitation. Mr. Q receives 2 consecutive doses of lorazepam, although neither effectively reduces his agitation or promotes sleep. Mr. Q is not assessed with positron-emission tomography (PET) or polysomnography.

The authors’ observations

There was no evidence of neurologic disease on Mr. Q’s CT scan and EEG was within normal limits. Other imaging and laboratory studies did not reveal possible infection, malignancy, or cardiovascular disease. Despite its rarity, we considered the possibility of a prion disease, given Mr. Q’s unique presentation and family history. Familial fatal insomnia (FFI) is an autosomal dominant disease caused by a point mutation in the prion protein gene. Prion proteins are theorized to play a role in myelin stability. The aberrant isoform produced in FFI is structurally misfolded so that it resists degradation by proteolytic enzymes. The accumulation of irregular prion proteins in the medial thalamic nucleus results in progressive neurodegeneration. Patients with FFI present with increasingly severe insomnia, mild fever, dysautonomia, spontaneous myoclonus, cognitive dysfunction, and hallucinations.⁹ Generally, patients die from sudden cardiorespiratory failure or ensuing infections 9 to 24 months after symptom onset. In vivo, FFI diagnosis is suggested by a loss of sleep spindles on polysomnogram and by decreased thalamic metabolism on PET scan. Other imaging modalities and testing, including EEG and CSF analysis, lack sensitivity and/or specificity.¹⁰

OUTCOME: Improvement, discharge

On his fourth hospital day, Mr. Q’s symptoms begin to remit spontaneously. His gastrointestinal (GI) upset improves and the following night he sleeps for approximately 4 hours. As his sleep improves, his delusional thinking and hallucinations resolve. Orientation, memory, and concentration gradually improve. Before discharge, his MMSE score is 24 out of 30, indicating improved cognition. His heart rate, blood pressure, and body temperature normalize and his myoclonus improves. Mr. Q is discharged after 6 days in the hospital and returns home. He follows up with his primary care physician, denies any recurrence of sleep disturbance, and reports that his cognition and perception have returned to his baseline.

The authors’ observations

Table 3

DSM-IV-TR diagnostic criteria for opioid withdrawal

• Morin CM, Benca R. Chronic insomnia. Lancet. 2012; 379(9821):1129-1141.
  
• Pressman MR, Orr WC, eds. Understanding sleep: the evolution and treatment of sleep disorders. Washington, DC: American Psychological Association; 1997.
  
• NIH State-of-the-Science Conference Statement on manifestations and management of chronic insomnia in adults. NIH Consens State Sci Statements. 2005;22(2):1-30.
  

• Albuterol • Proventil, Ventolin
  
• Aripiprazole • Abilify
  
• Bupropion • Wellbutrin, Zyban
  
• Dextroamphetamine • Dexadrine
  
• Haloperidol • Haldol
  
• Hydrocodone/Acetaminophen • Vicodin
  
• Lamotrigine • Lamictal
  
• Lorazepam • Ativan
  
• Methylphenidate • Methylin, Ritalin
  
• Phenylephrine • Neo-Synephrine
  
• Pseudoephedrine • Sudafed
  
• Ramelteon • Rozerem
  
• Theophylline • Elixophyllin, Slo-Phyllin
  
• Zolpidem • Ambien
  

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

Postpartum high BP; mother suffers brain damage

HOSPITALIZED TWICE FOR HYPERTENSION in the month before her child was born, a 41-year-old woman gave birth to a healthy baby by cesarean delivery. The mother was discharged 2 days later with a blood pressure (BP) of 130/90 mm Hg.

Three days later, she went to her ObGyn’s office because she was not feeling well and had extreme swelling. Her BP, taken twice by a nurse, read 170/88 mm Hg, and 168/90 mm Hg, but she was not examined by the ObGyn.

That evening, the patient had difficulty breathing and was taken to the emergency department (ED), where she was intubated. She went into cardiac arrest and suffered permanent brain damage after being without a pulse for 15 minutes. She was in a coma for 45 days. She is unable to walk without assistance, is legally blind, and her hands are so contorted that she cannot feed herself. She suffers from short-term memory loss and has difficulty speaking.

PATIENT’S CLAIM The ObGyn should have examined her when she was at the office. Her hypertension would have been properly treated and injuries avoided. She had classic signs of postpartum cardiomyopathy.

PHYSICIAN’S DEFENSE The patient had not come to the office because she was feeling ill, but to show off her baby and have her BP checked. If he had been advised of the BP readings, he would have examined her.

VERDICT A $5 million Georgia verdict was returned.

Cervical biopsy results improperly reported

A 44-YEAR-OLD WOMAN UNDERWENT a cervical biopsy in July 2007 performed by a pathologist. A few days later, the pathologist contacted the patient and reported that the biopsy revealed invasive cervical cancer that required immediate surgery. Several procedures were performed without any cancer ever being found.

A second opinion was sought, and it was determined that the cancer diagnosis was incorrect; another patient’s pathology had been reported as the patient’s.

PATIENT’S CLAIM The pathologist and hospital were negligent in reporting incorrect results of the cervical biopsy, which resulted in the patient’s physical and emotional injuries, including unnecessary surgical procedures and depression and anxiety.

DEFENDANTS’ DEFENSE The defendants did not oppose the patient’s motion for summary judgment on liability; the issue of damages was contested.

VERDICT The patient received summary judgment on liability. She then discontinued claims against the pathologist, and the matter proceeded on damages against the hospital. A $46,000 New York verdict was returned. Stipulated medical expenses were added to the verdict for a total recovery of $60,979.

Brachial plexus injury: child has significant functional disability

AT 38 6/7 WEEKS’ GESTATION, a 23-year-old woman went to the ED with contractions. She had pregestational diabetes mellitus. Her admitting glucose level was 143 mg/dL, and she had gained 25 lb during pregnancy. Her fundal height was 40 cm, and estimated fetal weight was 4000 g (8 lb 13 oz). A pelvic examination determined that she was 3 to 4 cm dilated, 100% effaced, and at minus-1 station. She was given oxytocin to aid labor. The ObGyn noted that overall fetal heart-rate tracings were reassuring, and that a pediatrician would be present for delivery due to suspected macrosomia. Shoulder dystocia occurred during delivery, but it was resolved in 40 seconds. The mother sustained a second-degree perineal laceration.

At birth, the baby’s left arm was limp. Apgar scores were 5 and 9 at 1 and 5 minutes, respectively. Her birth weight was 10 lb 2 oz. A brachial plexus injury was diagnosed, and she underwent surgery in October 2008. Despite successful nerve grafts at C5 and C6, the child has significant functional disability in the left arm.

PARENTS’ CLAIM A cesarean delivery should have been scheduled when a macrosomic fetus was suspected.

PHYSICIAN’S DEFENSE The case was settled during trial.

VERDICT A $1,475,000 Maryland settlement was reached.

Breech position and umbilical cord prolapse: Was everything done that could be done?

DURING A MOTHER’S 38-WEEK PRENATAL VISIT, ultrasonography showed the baby was in breech position. The midwife offered two options: to schedule an external cephalic version procedure at 38 weeks or a cesarean delivery at 39 weeks. The parents agreed to schedule a cesarean delivery for 8 days later. The day before the scheduled birth, the mother awoke to find the umbilical cord between her legs. An emergency cesarean delivery was performed. The newborn required resuscitation and mechanical ventilation and suffered permanent brain damage attributed to hypoxia from umbilical cord prolapse.

PARENTS’ CLAIM The midwife’s negligence caused the baby’s injuries. Breech presentation put the pregnancy at high-risk. She did not have a physician examine the patient before scheduling a cesarean delivery and did not attempt to rotate the child back to a head-first position. She did not warn the parents about the risks of breech presentation and umbilical cord prolapse.

DEFENDANTS’ DEFENSE The choices given the parents were reasonable. Scheduling a cesarean delivery at 39 weeks was proper. A prolapsed cord is not predictable or preventable.

VERDICT A $12.6 million Pennsylvania verdict was returned against the midwife and the hospital; a confidential high/low agreement was reached.

Extensive adhesions result in bowel injury

A 58-YEAR-OLD WOMAN UNDERWENT exploratory laparotomy in May 2009. There were extensive adhesions, and the gynecologist used blind, blunt dissection to resect a large pelvic mass adhered to the sidewall. He had difficulty removing the specimen because it was too large to fit through the incision. A left salpingo-oophorectomy was also performed.

On the second postoperative day, the patient reported shortness of breath, intermittent chest pain, and had a fever of 103° F. The next day, she was unable to ambulate due to shortness of breath. CT results ruled out deep vein thrombosis or pulmonary embolism but revealed significantly decreased lung volume. She continued to experience shortness of breath and temperature spikes for 3 more days. She was discharged on the seventh postoperative day despite shortness of breath.

Two days later, she experienced severe abdominal pain and shortness of breath at home and returned to the ED by ambulance. A CT scan revealed free pelvic air, ascites, and extensive inflammatory changes, likely due to bowel perforation. She was intubated and airlifted to a regional trauma center. During exploratory surgery, the surgeon aspirated a foul-smelling fluid and identified a perforation at the rectosigmoid junction; a colostomy was created. The patient stayed in intensive care for 5 days, developed renal failure, and was transfused due to acute blood loss. She was hospitalized for 19 days. The colostomy was reversed in October 2009.

PATIENT’S CLAIM The ObGyn was negligent in injuring the bowel during surgery and in not recognizing the bowel injury and treating it in a timely manner.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $600,000 Virginia settlement was reached.

Pregnant woman stabbed: mother and baby die

A 20-YEAR-OLD WOMAN AT 30 WEEKS’ gestation was treated in the ED for a stab wound to the shoulder. The emergency medicine (EM) physician noted internal bleeding and a possible collapsed lung on radiographs, and began efforts to have the woman transferred. One facility declined because of her pregnancy. The patient was in pain and her ability to breathe declined. An airlift was finally arranged, but she suffered cardiac arrest as the helicopter arrived. A cesarean delivery was performed, but both the mother and baby died.

ESTATE’S CLAIM The EM physician was negligent in failing to perform a thoracotomy and arrange for a more timely transfer. The physician didn’t contact a hospital that was only 8 miles away.

DEFENDANTS’ DEFENSE The federal government, which operated the facility, admitted fault.

VERDICT A $7,267,390 Mississippi verdict included $5.45 million in noneconomic damages.

What caused child’s brain damage?

DURING LABOR AND DELIVERY, electronic fetal heart-rate monitoring indicated fetal distress. Meconium-stained fluid was present. The child was born with brain damage. It is unlikely that he will walk independently, talk in full sentences, or be able to perform daily activities independently.

PARENTS’ CLAIM The fetal heart-rate monitor indicated a need for emergency cesarean delivery. The quality and quantity of meconium should have alerted the caregivers to fetal distress and caused them to perform a cesarean delivery.

DEFENDANTS’ DEFENSE Fetal heart-rate strips did not indicate a need for emergency delivery until shortly before the delivery occurred. The underlying cause of the child’s injuries was an infection that spread to the brain and was irreversible.

VERDICT A $1.71 million Massachusetts verdict was returned.

When did bladder injury occur?

AN 84-YEAR-OLD WOMAN suffered recurrent bladder cancer. She underwent a cystoscopy, and then chemotherapy. Several weeks later, she was diagnosed with a bladder perforation became septic, and died.

ESTATE’S CLAIM The bladder was lacerated during cystoscopy; she would have survived if the laceration had been treated in a timely manner.

PHYSICIAN’S DEFENSE Bladder perforation during cystoscopy is a known risk of the procedure. However, the bladder was not perforated during cystoscopy; chemotherapy may have caused the perforation.

VERDICT A Michigan defense verdict was returned.

Fetal tracings poor: Why wasn’t an internal lead used?

AT 32 WEEKS’ GESTATION, a woman’s membranes ruptured, and she was admitted. Her ObGyn planned to induce labor at 34 weeks’ gestation. She experienced contractions on the morning of the scheduled induction. Although fetal heart-rate monitoring was reassuring, the fetus was in a compound position, with the chin leading. Labor progressed rapidly to 6-cm dilation. The fetal heart rate began to show recurrent mild variable decelerations that became increasingly deeper. Although the technical quality of the external monitoring was poor, no internal lead was applied.

After 3 hours, the tracing showed severe variable decelerations. The mother was fully dilated and began to push. The tracings were of poor quality, but interpretable portions showed minimal variability and significant decelerations during contractions. The fetal baseline heart rate became tachycardic. The obstetric nurse and resident continued to note abnormalities, but there is no evidence that they called the attending ObGyn. The fetal baseline heart rate reached 190 bpm with ongoing decelerations associated with contractions. Variability remained minimal to absent. After 2 hours of pushing, meconium-stained fluid was noted. The infant was born 1 hour later. The attending ObGyn was present for the last 30 minutes of labor.

The newborn’s Apgar scores were 1, 5, and 7, at 1, 5, and 10 minutes, respectively. His arterial cord pH was significantly low. MRI of the head showed subdural and intraventricular hemorrhage and evolving, profound hypoxic ischemic injury. At 1 year of age, the child suffers from a seizure disorder, cortical blindness, and severe developmental delays.

PARENTS’ CLAIM The nurse and resident failed to respond to fetal heart-rate abnormalities and failed to insert an internal lead to obtain better quality heart-rate tracings. They did not expedite delivery when fetal distress was evident.

DEFENDANTS’ DEFENSE The case was settled during trial.

VERDICT A $4.2 million Massachusetts settlement was reached.

Hypoxic ischemic encephalopathy

DUE TO PREECLAMPSIA, a woman was admitted to the hospital 5 weeks before her due date. Her condition was monitored for 2 weeks when it was decided to induce labor with oxytocin. After 3 hours in labor, the fetal heart-rate tracing began to show significant decelerations. The baby was born at 37 weeks’ gestation with severe hypoxic ischemic encephalopathy. The child died 2 years later from severe brain damage.

PARENTS’ CLAIM The ObGyns failed to respond to signs of fetal distress by performing an emergency cesarean. The brain images would have been different if a stroke-like event had occurred.

DEFENDANTS’ DEFENSE The fetus experienced an embolic process due to a compressed umbilical cord, resulting in a stroke-like vascular event, which led to the hypoxic ischemic encephalopathy.

VERDICT A $450,000 Wisconsin settlement was reached.

Postpartum high BP; mother suffers brain damage

HOSPITALIZED TWICE FOR HYPERTENSION in the month before her child was born, a 41-year-old woman gave birth to a healthy baby by cesarean delivery. The mother was discharged 2 days later with a blood pressure (BP) of 130/90 mm Hg.

Three days later, she went to her ObGyn’s office because she was not feeling well and had extreme swelling. Her BP, taken twice by a nurse, read 170/88 mm Hg, and 168/90 mm Hg, but she was not examined by the ObGyn.

That evening, the patient had difficulty breathing and was taken to the emergency department (ED), where she was intubated. She went into cardiac arrest and suffered permanent brain damage after being without a pulse for 15 minutes. She was in a coma for 45 days. She is unable to walk without assistance, is legally blind, and her hands are so contorted that she cannot feed herself. She suffers from short-term memory loss and has difficulty speaking.

PATIENT’S CLAIM The ObGyn should have examined her when she was at the office. Her hypertension would have been properly treated and injuries avoided. She had classic signs of postpartum cardiomyopathy.

PHYSICIAN’S DEFENSE The patient had not come to the office because she was feeling ill, but to show off her baby and have her BP checked. If he had been advised of the BP readings, he would have examined her.

VERDICT A $5 million Georgia verdict was returned.

Cervical biopsy results improperly reported

A 44-YEAR-OLD WOMAN UNDERWENT a cervical biopsy in July 2007 performed by a pathologist. A few days later, the pathologist contacted the patient and reported that the biopsy revealed invasive cervical cancer that required immediate surgery. Several procedures were performed without any cancer ever being found.

A second opinion was sought, and it was determined that the cancer diagnosis was incorrect; another patient’s pathology had been reported as the patient’s.

PATIENT’S CLAIM The pathologist and hospital were negligent in reporting incorrect results of the cervical biopsy, which resulted in the patient’s physical and emotional injuries, including unnecessary surgical procedures and depression and anxiety.

DEFENDANTS’ DEFENSE The defendants did not oppose the patient’s motion for summary judgment on liability; the issue of damages was contested.

VERDICT The patient received summary judgment on liability. She then discontinued claims against the pathologist, and the matter proceeded on damages against the hospital. A $46,000 New York verdict was returned. Stipulated medical expenses were added to the verdict for a total recovery of $60,979.

Brachial plexus injury: child has significant functional disability

AT 38 6/7 WEEKS’ GESTATION, a 23-year-old woman went to the ED with contractions. She had pregestational diabetes mellitus. Her admitting glucose level was 143 mg/dL, and she had gained 25 lb during pregnancy. Her fundal height was 40 cm, and estimated fetal weight was 4000 g (8 lb 13 oz). A pelvic examination determined that she was 3 to 4 cm dilated, 100% effaced, and at minus-1 station. She was given oxytocin to aid labor. The ObGyn noted that overall fetal heart-rate tracings were reassuring, and that a pediatrician would be present for delivery due to suspected macrosomia. Shoulder dystocia occurred during delivery, but it was resolved in 40 seconds. The mother sustained a second-degree perineal laceration.

At birth, the baby’s left arm was limp. Apgar scores were 5 and 9 at 1 and 5 minutes, respectively. Her birth weight was 10 lb 2 oz. A brachial plexus injury was diagnosed, and she underwent surgery in October 2008. Despite successful nerve grafts at C5 and C6, the child has significant functional disability in the left arm.

PARENTS’ CLAIM A cesarean delivery should have been scheduled when a macrosomic fetus was suspected.

PHYSICIAN’S DEFENSE The case was settled during trial.

VERDICT A $1,475,000 Maryland settlement was reached.

Breech position and umbilical cord prolapse: Was everything done that could be done?

DURING A MOTHER’S 38-WEEK PRENATAL VISIT, ultrasonography showed the baby was in breech position. The midwife offered two options: to schedule an external cephalic version procedure at 38 weeks or a cesarean delivery at 39 weeks. The parents agreed to schedule a cesarean delivery for 8 days later. The day before the scheduled birth, the mother awoke to find the umbilical cord between her legs. An emergency cesarean delivery was performed. The newborn required resuscitation and mechanical ventilation and suffered permanent brain damage attributed to hypoxia from umbilical cord prolapse.

PARENTS’ CLAIM The midwife’s negligence caused the baby’s injuries. Breech presentation put the pregnancy at high-risk. She did not have a physician examine the patient before scheduling a cesarean delivery and did not attempt to rotate the child back to a head-first position. She did not warn the parents about the risks of breech presentation and umbilical cord prolapse.

DEFENDANTS’ DEFENSE The choices given the parents were reasonable. Scheduling a cesarean delivery at 39 weeks was proper. A prolapsed cord is not predictable or preventable.

VERDICT A $12.6 million Pennsylvania verdict was returned against the midwife and the hospital; a confidential high/low agreement was reached.

Extensive adhesions result in bowel injury

A 58-YEAR-OLD WOMAN UNDERWENT exploratory laparotomy in May 2009. There were extensive adhesions, and the gynecologist used blind, blunt dissection to resect a large pelvic mass adhered to the sidewall. He had difficulty removing the specimen because it was too large to fit through the incision. A left salpingo-oophorectomy was also performed.

On the second postoperative day, the patient reported shortness of breath, intermittent chest pain, and had a fever of 103° F. The next day, she was unable to ambulate due to shortness of breath. CT results ruled out deep vein thrombosis or pulmonary embolism but revealed significantly decreased lung volume. She continued to experience shortness of breath and temperature spikes for 3 more days. She was discharged on the seventh postoperative day despite shortness of breath.

Two days later, she experienced severe abdominal pain and shortness of breath at home and returned to the ED by ambulance. A CT scan revealed free pelvic air, ascites, and extensive inflammatory changes, likely due to bowel perforation. She was intubated and airlifted to a regional trauma center. During exploratory surgery, the surgeon aspirated a foul-smelling fluid and identified a perforation at the rectosigmoid junction; a colostomy was created. The patient stayed in intensive care for 5 days, developed renal failure, and was transfused due to acute blood loss. She was hospitalized for 19 days. The colostomy was reversed in October 2009.

PATIENT’S CLAIM The ObGyn was negligent in injuring the bowel during surgery and in not recognizing the bowel injury and treating it in a timely manner.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $600,000 Virginia settlement was reached.

Pregnant woman stabbed: mother and baby die

A 20-YEAR-OLD WOMAN AT 30 WEEKS’ gestation was treated in the ED for a stab wound to the shoulder. The emergency medicine (EM) physician noted internal bleeding and a possible collapsed lung on radiographs, and began efforts to have the woman transferred. One facility declined because of her pregnancy. The patient was in pain and her ability to breathe declined. An airlift was finally arranged, but she suffered cardiac arrest as the helicopter arrived. A cesarean delivery was performed, but both the mother and baby died.

ESTATE’S CLAIM The EM physician was negligent in failing to perform a thoracotomy and arrange for a more timely transfer. The physician didn’t contact a hospital that was only 8 miles away.

DEFENDANTS’ DEFENSE The federal government, which operated the facility, admitted fault.

VERDICT A $7,267,390 Mississippi verdict included $5.45 million in noneconomic damages.

What caused child’s brain damage?

DURING LABOR AND DELIVERY, electronic fetal heart-rate monitoring indicated fetal distress. Meconium-stained fluid was present. The child was born with brain damage. It is unlikely that he will walk independently, talk in full sentences, or be able to perform daily activities independently.

PARENTS’ CLAIM The fetal heart-rate monitor indicated a need for emergency cesarean delivery. The quality and quantity of meconium should have alerted the caregivers to fetal distress and caused them to perform a cesarean delivery.

DEFENDANTS’ DEFENSE Fetal heart-rate strips did not indicate a need for emergency delivery until shortly before the delivery occurred. The underlying cause of the child’s injuries was an infection that spread to the brain and was irreversible.

VERDICT A $1.71 million Massachusetts verdict was returned.

When did bladder injury occur?

AN 84-YEAR-OLD WOMAN suffered recurrent bladder cancer. She underwent a cystoscopy, and then chemotherapy. Several weeks later, she was diagnosed with a bladder perforation became septic, and died.

ESTATE’S CLAIM The bladder was lacerated during cystoscopy; she would have survived if the laceration had been treated in a timely manner.

PHYSICIAN’S DEFENSE Bladder perforation during cystoscopy is a known risk of the procedure. However, the bladder was not perforated during cystoscopy; chemotherapy may have caused the perforation.

VERDICT A Michigan defense verdict was returned.

Fetal tracings poor: Why wasn’t an internal lead used?

AT 32 WEEKS’ GESTATION, a woman’s membranes ruptured, and she was admitted. Her ObGyn planned to induce labor at 34 weeks’ gestation. She experienced contractions on the morning of the scheduled induction. Although fetal heart-rate monitoring was reassuring, the fetus was in a compound position, with the chin leading. Labor progressed rapidly to 6-cm dilation. The fetal heart rate began to show recurrent mild variable decelerations that became increasingly deeper. Although the technical quality of the external monitoring was poor, no internal lead was applied.

After 3 hours, the tracing showed severe variable decelerations. The mother was fully dilated and began to push. The tracings were of poor quality, but interpretable portions showed minimal variability and significant decelerations during contractions. The fetal baseline heart rate became tachycardic. The obstetric nurse and resident continued to note abnormalities, but there is no evidence that they called the attending ObGyn. The fetal baseline heart rate reached 190 bpm with ongoing decelerations associated with contractions. Variability remained minimal to absent. After 2 hours of pushing, meconium-stained fluid was noted. The infant was born 1 hour later. The attending ObGyn was present for the last 30 minutes of labor.

The newborn’s Apgar scores were 1, 5, and 7, at 1, 5, and 10 minutes, respectively. His arterial cord pH was significantly low. MRI of the head showed subdural and intraventricular hemorrhage and evolving, profound hypoxic ischemic injury. At 1 year of age, the child suffers from a seizure disorder, cortical blindness, and severe developmental delays.

PARENTS’ CLAIM The nurse and resident failed to respond to fetal heart-rate abnormalities and failed to insert an internal lead to obtain better quality heart-rate tracings. They did not expedite delivery when fetal distress was evident.

DEFENDANTS’ DEFENSE The case was settled during trial.

VERDICT A $4.2 million Massachusetts settlement was reached.

Hypoxic ischemic encephalopathy

DUE TO PREECLAMPSIA, a woman was admitted to the hospital 5 weeks before her due date. Her condition was monitored for 2 weeks when it was decided to induce labor with oxytocin. After 3 hours in labor, the fetal heart-rate tracing began to show significant decelerations. The baby was born at 37 weeks’ gestation with severe hypoxic ischemic encephalopathy. The child died 2 years later from severe brain damage.

PARENTS’ CLAIM The ObGyns failed to respond to signs of fetal distress by performing an emergency cesarean. The brain images would have been different if a stroke-like event had occurred.

DEFENDANTS’ DEFENSE The fetus experienced an embolic process due to a compressed umbilical cord, resulting in a stroke-like vascular event, which led to the hypoxic ischemic encephalopathy.

VERDICT A $450,000 Wisconsin settlement was reached.

Postpartum high BP; mother suffers brain damage

HOSPITALIZED TWICE FOR HYPERTENSION in the month before her child was born, a 41-year-old woman gave birth to a healthy baby by cesarean delivery. The mother was discharged 2 days later with a blood pressure (BP) of 130/90 mm Hg.

Three days later, she went to her ObGyn’s office because she was not feeling well and had extreme swelling. Her BP, taken twice by a nurse, read 170/88 mm Hg, and 168/90 mm Hg, but she was not examined by the ObGyn.

That evening, the patient had difficulty breathing and was taken to the emergency department (ED), where she was intubated. She went into cardiac arrest and suffered permanent brain damage after being without a pulse for 15 minutes. She was in a coma for 45 days. She is unable to walk without assistance, is legally blind, and her hands are so contorted that she cannot feed herself. She suffers from short-term memory loss and has difficulty speaking.

PATIENT’S CLAIM The ObGyn should have examined her when she was at the office. Her hypertension would have been properly treated and injuries avoided. She had classic signs of postpartum cardiomyopathy.

PHYSICIAN’S DEFENSE The patient had not come to the office because she was feeling ill, but to show off her baby and have her BP checked. If he had been advised of the BP readings, he would have examined her.

VERDICT A $5 million Georgia verdict was returned.

Cervical biopsy results improperly reported

A 44-YEAR-OLD WOMAN UNDERWENT a cervical biopsy in July 2007 performed by a pathologist. A few days later, the pathologist contacted the patient and reported that the biopsy revealed invasive cervical cancer that required immediate surgery. Several procedures were performed without any cancer ever being found.

A second opinion was sought, and it was determined that the cancer diagnosis was incorrect; another patient’s pathology had been reported as the patient’s.

PATIENT’S CLAIM The pathologist and hospital were negligent in reporting incorrect results of the cervical biopsy, which resulted in the patient’s physical and emotional injuries, including unnecessary surgical procedures and depression and anxiety.

DEFENDANTS’ DEFENSE The defendants did not oppose the patient’s motion for summary judgment on liability; the issue of damages was contested.

VERDICT The patient received summary judgment on liability. She then discontinued claims against the pathologist, and the matter proceeded on damages against the hospital. A $46,000 New York verdict was returned. Stipulated medical expenses were added to the verdict for a total recovery of $60,979.

Brachial plexus injury: child has significant functional disability

AT 38 6/7 WEEKS’ GESTATION, a 23-year-old woman went to the ED with contractions. She had pregestational diabetes mellitus. Her admitting glucose level was 143 mg/dL, and she had gained 25 lb during pregnancy. Her fundal height was 40 cm, and estimated fetal weight was 4000 g (8 lb 13 oz). A pelvic examination determined that she was 3 to 4 cm dilated, 100% effaced, and at minus-1 station. She was given oxytocin to aid labor. The ObGyn noted that overall fetal heart-rate tracings were reassuring, and that a pediatrician would be present for delivery due to suspected macrosomia. Shoulder dystocia occurred during delivery, but it was resolved in 40 seconds. The mother sustained a second-degree perineal laceration.

At birth, the baby’s left arm was limp. Apgar scores were 5 and 9 at 1 and 5 minutes, respectively. Her birth weight was 10 lb 2 oz. A brachial plexus injury was diagnosed, and she underwent surgery in October 2008. Despite successful nerve grafts at C5 and C6, the child has significant functional disability in the left arm.

PARENTS’ CLAIM A cesarean delivery should have been scheduled when a macrosomic fetus was suspected.

PHYSICIAN’S DEFENSE The case was settled during trial.

VERDICT A $1,475,000 Maryland settlement was reached.

Breech position and umbilical cord prolapse: Was everything done that could be done?

DURING A MOTHER’S 38-WEEK PRENATAL VISIT, ultrasonography showed the baby was in breech position. The midwife offered two options: to schedule an external cephalic version procedure at 38 weeks or a cesarean delivery at 39 weeks. The parents agreed to schedule a cesarean delivery for 8 days later. The day before the scheduled birth, the mother awoke to find the umbilical cord between her legs. An emergency cesarean delivery was performed. The newborn required resuscitation and mechanical ventilation and suffered permanent brain damage attributed to hypoxia from umbilical cord prolapse.

PARENTS’ CLAIM The midwife’s negligence caused the baby’s injuries. Breech presentation put the pregnancy at high-risk. She did not have a physician examine the patient before scheduling a cesarean delivery and did not attempt to rotate the child back to a head-first position. She did not warn the parents about the risks of breech presentation and umbilical cord prolapse.

DEFENDANTS’ DEFENSE The choices given the parents were reasonable. Scheduling a cesarean delivery at 39 weeks was proper. A prolapsed cord is not predictable or preventable.

VERDICT A $12.6 million Pennsylvania verdict was returned against the midwife and the hospital; a confidential high/low agreement was reached.

Extensive adhesions result in bowel injury

A 58-YEAR-OLD WOMAN UNDERWENT exploratory laparotomy in May 2009. There were extensive adhesions, and the gynecologist used blind, blunt dissection to resect a large pelvic mass adhered to the sidewall. He had difficulty removing the specimen because it was too large to fit through the incision. A left salpingo-oophorectomy was also performed.

On the second postoperative day, the patient reported shortness of breath, intermittent chest pain, and had a fever of 103° F. The next day, she was unable to ambulate due to shortness of breath. CT results ruled out deep vein thrombosis or pulmonary embolism but revealed significantly decreased lung volume. She continued to experience shortness of breath and temperature spikes for 3 more days. She was discharged on the seventh postoperative day despite shortness of breath.

Two days later, she experienced severe abdominal pain and shortness of breath at home and returned to the ED by ambulance. A CT scan revealed free pelvic air, ascites, and extensive inflammatory changes, likely due to bowel perforation. She was intubated and airlifted to a regional trauma center. During exploratory surgery, the surgeon aspirated a foul-smelling fluid and identified a perforation at the rectosigmoid junction; a colostomy was created. The patient stayed in intensive care for 5 days, developed renal failure, and was transfused due to acute blood loss. She was hospitalized for 19 days. The colostomy was reversed in October 2009.

PATIENT’S CLAIM The ObGyn was negligent in injuring the bowel during surgery and in not recognizing the bowel injury and treating it in a timely manner.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $600,000 Virginia settlement was reached.

Pregnant woman stabbed: mother and baby die

A 20-YEAR-OLD WOMAN AT 30 WEEKS’ gestation was treated in the ED for a stab wound to the shoulder. The emergency medicine (EM) physician noted internal bleeding and a possible collapsed lung on radiographs, and began efforts to have the woman transferred. One facility declined because of her pregnancy. The patient was in pain and her ability to breathe declined. An airlift was finally arranged, but she suffered cardiac arrest as the helicopter arrived. A cesarean delivery was performed, but both the mother and baby died.

ESTATE’S CLAIM The EM physician was negligent in failing to perform a thoracotomy and arrange for a more timely transfer. The physician didn’t contact a hospital that was only 8 miles away.

DEFENDANTS’ DEFENSE The federal government, which operated the facility, admitted fault.

VERDICT A $7,267,390 Mississippi verdict included $5.45 million in noneconomic damages.

What caused child’s brain damage?

DURING LABOR AND DELIVERY, electronic fetal heart-rate monitoring indicated fetal distress. Meconium-stained fluid was present. The child was born with brain damage. It is unlikely that he will walk independently, talk in full sentences, or be able to perform daily activities independently.

PARENTS’ CLAIM The fetal heart-rate monitor indicated a need for emergency cesarean delivery. The quality and quantity of meconium should have alerted the caregivers to fetal distress and caused them to perform a cesarean delivery.

DEFENDANTS’ DEFENSE Fetal heart-rate strips did not indicate a need for emergency delivery until shortly before the delivery occurred. The underlying cause of the child’s injuries was an infection that spread to the brain and was irreversible.

VERDICT A $1.71 million Massachusetts verdict was returned.

When did bladder injury occur?

AN 84-YEAR-OLD WOMAN suffered recurrent bladder cancer. She underwent a cystoscopy, and then chemotherapy. Several weeks later, she was diagnosed with a bladder perforation became septic, and died.

ESTATE’S CLAIM The bladder was lacerated during cystoscopy; she would have survived if the laceration had been treated in a timely manner.

PHYSICIAN’S DEFENSE Bladder perforation during cystoscopy is a known risk of the procedure. However, the bladder was not perforated during cystoscopy; chemotherapy may have caused the perforation.

VERDICT A Michigan defense verdict was returned.

Fetal tracings poor: Why wasn’t an internal lead used?

AT 32 WEEKS’ GESTATION, a woman’s membranes ruptured, and she was admitted. Her ObGyn planned to induce labor at 34 weeks’ gestation. She experienced contractions on the morning of the scheduled induction. Although fetal heart-rate monitoring was reassuring, the fetus was in a compound position, with the chin leading. Labor progressed rapidly to 6-cm dilation. The fetal heart rate began to show recurrent mild variable decelerations that became increasingly deeper. Although the technical quality of the external monitoring was poor, no internal lead was applied.

After 3 hours, the tracing showed severe variable decelerations. The mother was fully dilated and began to push. The tracings were of poor quality, but interpretable portions showed minimal variability and significant decelerations during contractions. The fetal baseline heart rate became tachycardic. The obstetric nurse and resident continued to note abnormalities, but there is no evidence that they called the attending ObGyn. The fetal baseline heart rate reached 190 bpm with ongoing decelerations associated with contractions. Variability remained minimal to absent. After 2 hours of pushing, meconium-stained fluid was noted. The infant was born 1 hour later. The attending ObGyn was present for the last 30 minutes of labor.

The newborn’s Apgar scores were 1, 5, and 7, at 1, 5, and 10 minutes, respectively. His arterial cord pH was significantly low. MRI of the head showed subdural and intraventricular hemorrhage and evolving, profound hypoxic ischemic injury. At 1 year of age, the child suffers from a seizure disorder, cortical blindness, and severe developmental delays.

PARENTS’ CLAIM The nurse and resident failed to respond to fetal heart-rate abnormalities and failed to insert an internal lead to obtain better quality heart-rate tracings. They did not expedite delivery when fetal distress was evident.

DEFENDANTS’ DEFENSE The case was settled during trial.

VERDICT A $4.2 million Massachusetts settlement was reached.

Hypoxic ischemic encephalopathy

DUE TO PREECLAMPSIA, a woman was admitted to the hospital 5 weeks before her due date. Her condition was monitored for 2 weeks when it was decided to induce labor with oxytocin. After 3 hours in labor, the fetal heart-rate tracing began to show significant decelerations. The baby was born at 37 weeks’ gestation with severe hypoxic ischemic encephalopathy. The child died 2 years later from severe brain damage.

PARENTS’ CLAIM The ObGyns failed to respond to signs of fetal distress by performing an emergency cesarean. The brain images would have been different if a stroke-like event had occurred.

DEFENDANTS’ DEFENSE The fetus experienced an embolic process due to a compressed umbilical cord, resulting in a stroke-like vascular event, which led to the hypoxic ischemic encephalopathy.

VERDICT A $450,000 Wisconsin settlement was reached.

CASE: Stage 2 prolapse to the hymenal ring

A 54-year-old Para 3 woman presents with stage 2 prolapse to the hymenal ring. The prolapse predominantly involves the anterior vagina, with her cervix prolapsing to 2 cm within the hymenal ring. The patient is bothered by the bulge and stress urinary leakage. She does not want to use a pessary and prefers to have definitive surgical correction, including hysterectomy.

The first surgeon she consulted recommended a vaginal hysterectomy, anterior colporrhaphy, anterior synthetic mesh vaginal colpopexy, and synthetic midurethral sling. The patient was concerned about mesh placement for prolapse and the sling after seeing ads on the Internet about vaginal mesh. She presents for a second opinion about surgical alternatives.

Stop routinely offering synthetic vaginal mesh for prolapse

Advantages to the use of synthetic vaginal mesh include improved subjective and objective cure rates for prolapse (especially for the anterior compartment) and fewer repeat surgeries for recurrent prolapse. However, disadvantages include:

• mesh exposure and extrusion through the vaginal epithelium
• overall higher reoperation for mesh-related complications and de novo stress urinary incontinence.¹

Synthetic vaginal mesh should be reserved for special situations. Currently, experts agree that synthetic vaginal mesh is appropriate in cases of recurrent prolapse, advanced-stage prolapse, collagen deficiency, or in cases with relative contraindications to longer endoscopic or abdominal surgery, such as medical comorbidities or adhesions.^2,3 Other indications for synthetic vaginal mesh include vaginal hysteropexy procedures.

Mesh is likely not necessary in:

• primary repairs
• prolapse < POPQ (pelvic organ prolapse quantification system) stage 2
• posterior prolapse
• patients with chronic pelvic pain.

Start offering, learning, and mastering native tissue repairs

For the patient in the opening case, who has symptomatic stage 2 uterovaginal prolapse and stress urinary incontinence, surgery, including a transvaginal hysterectomy, anterior colporrhaphy, uterosacral ligament suspension, and synthetic midurethral sling, is a reasonable alternative and has a high subjective and objective cure rate—81.2% rate for anterior prolapse and 98.3% rate for apical prolapse. Better outcomes are noted with stage 2 compared with stage 3 prolapse (92.4% vs 66.8%, respectively).⁴

Final note

If you are offering selective transvaginal synthetic mesh for prolapse repairs:

• Undergo training specific to each device.
• Track your outcomes—including objective, subjective, quality of life, and reoperation for complications and recurrence.
• Enroll in the national pelvic floor disorders registry, which is scheduled to debut in Fall 2013.

We want to hear from you! Tell us what you think.

CASE: Stage 2 prolapse to the hymenal ring

A 54-year-old Para 3 woman presents with stage 2 prolapse to the hymenal ring. The prolapse predominantly involves the anterior vagina, with her cervix prolapsing to 2 cm within the hymenal ring. The patient is bothered by the bulge and stress urinary leakage. She does not want to use a pessary and prefers to have definitive surgical correction, including hysterectomy.

The first surgeon she consulted recommended a vaginal hysterectomy, anterior colporrhaphy, anterior synthetic mesh vaginal colpopexy, and synthetic midurethral sling. The patient was concerned about mesh placement for prolapse and the sling after seeing ads on the Internet about vaginal mesh. She presents for a second opinion about surgical alternatives.

Stop routinely offering synthetic vaginal mesh for prolapse

Advantages to the use of synthetic vaginal mesh include improved subjective and objective cure rates for prolapse (especially for the anterior compartment) and fewer repeat surgeries for recurrent prolapse. However, disadvantages include:

• mesh exposure and extrusion through the vaginal epithelium
• overall higher reoperation for mesh-related complications and de novo stress urinary incontinence.¹

Synthetic vaginal mesh should be reserved for special situations. Currently, experts agree that synthetic vaginal mesh is appropriate in cases of recurrent prolapse, advanced-stage prolapse, collagen deficiency, or in cases with relative contraindications to longer endoscopic or abdominal surgery, such as medical comorbidities or adhesions.^2,3 Other indications for synthetic vaginal mesh include vaginal hysteropexy procedures.

Mesh is likely not necessary in:

• primary repairs
• prolapse < POPQ (pelvic organ prolapse quantification system) stage 2
• posterior prolapse
• patients with chronic pelvic pain.

Start offering, learning, and mastering native tissue repairs

For the patient in the opening case, who has symptomatic stage 2 uterovaginal prolapse and stress urinary incontinence, surgery, including a transvaginal hysterectomy, anterior colporrhaphy, uterosacral ligament suspension, and synthetic midurethral sling, is a reasonable alternative and has a high subjective and objective cure rate—81.2% rate for anterior prolapse and 98.3% rate for apical prolapse. Better outcomes are noted with stage 2 compared with stage 3 prolapse (92.4% vs 66.8%, respectively).⁴

Final note

If you are offering selective transvaginal synthetic mesh for prolapse repairs:

• Undergo training specific to each device.
• Track your outcomes—including objective, subjective, quality of life, and reoperation for complications and recurrence.
• Enroll in the national pelvic floor disorders registry, which is scheduled to debut in Fall 2013.

We want to hear from you! Tell us what you think.

CASE: Stage 2 prolapse to the hymenal ring

A 54-year-old Para 3 woman presents with stage 2 prolapse to the hymenal ring. The prolapse predominantly involves the anterior vagina, with her cervix prolapsing to 2 cm within the hymenal ring. The patient is bothered by the bulge and stress urinary leakage. She does not want to use a pessary and prefers to have definitive surgical correction, including hysterectomy.

The first surgeon she consulted recommended a vaginal hysterectomy, anterior colporrhaphy, anterior synthetic mesh vaginal colpopexy, and synthetic midurethral sling. The patient was concerned about mesh placement for prolapse and the sling after seeing ads on the Internet about vaginal mesh. She presents for a second opinion about surgical alternatives.

Stop routinely offering synthetic vaginal mesh for prolapse

Advantages to the use of synthetic vaginal mesh include improved subjective and objective cure rates for prolapse (especially for the anterior compartment) and fewer repeat surgeries for recurrent prolapse. However, disadvantages include:

• mesh exposure and extrusion through the vaginal epithelium
• overall higher reoperation for mesh-related complications and de novo stress urinary incontinence.¹

Synthetic vaginal mesh should be reserved for special situations. Currently, experts agree that synthetic vaginal mesh is appropriate in cases of recurrent prolapse, advanced-stage prolapse, collagen deficiency, or in cases with relative contraindications to longer endoscopic or abdominal surgery, such as medical comorbidities or adhesions.^2,3 Other indications for synthetic vaginal mesh include vaginal hysteropexy procedures.

Mesh is likely not necessary in:

• primary repairs
• prolapse < POPQ (pelvic organ prolapse quantification system) stage 2
• posterior prolapse
• patients with chronic pelvic pain.

Start offering, learning, and mastering native tissue repairs

For the patient in the opening case, who has symptomatic stage 2 uterovaginal prolapse and stress urinary incontinence, surgery, including a transvaginal hysterectomy, anterior colporrhaphy, uterosacral ligament suspension, and synthetic midurethral sling, is a reasonable alternative and has a high subjective and objective cure rate—81.2% rate for anterior prolapse and 98.3% rate for apical prolapse. Better outcomes are noted with stage 2 compared with stage 3 prolapse (92.4% vs 66.8%, respectively).⁴

Final note

If you are offering selective transvaginal synthetic mesh for prolapse repairs:

• Undergo training specific to each device.
• Track your outcomes—including objective, subjective, quality of life, and reoperation for complications and recurrence.
• Enroll in the national pelvic floor disorders registry, which is scheduled to debut in Fall 2013.

We want to hear from you! Tell us what you think.

• Michele Jonsson Funk, PhD, and colleagues from University of North Carolina (UNC) at Chapel Hill concluded that using vaginal mesh versus native tissue for anterior prolapse repair is associated with 5-year increased risk of any repeat surgery, especially surgery for mesh removal.¹
  
• Shunaha Kim-Fine, MD, and colleagues from Mayo Clinic, Rochester, Minnesota, believe that traditional native tissue repair is the best procedure for most women undergoing vaginal POP repair.²
  

UNC study details

Investigators from the Gillings School of Global Public Health at UNC studied health-care claims from 2005 to 2010. They identified women who, after undergoing anterior wall prolapse repair, experienced repeat surgery for recurrent prolapse or mesh removal. Of the initial 27,809 anterior prolapse surgeries, 6,871 (24.7%) included the use of vaginal mesh.¹

5-year risk of repeat surgery. The authors determined that¹:

• the 5-year cumulative risk of any repeat surgery was significantly higher with the use of vaginal mesh than with the use of native tissue (15.2% vs 9.8%, respectively; P <.0001 with a risk of mesh revision or removal>
• the 5-year risk for recurrent prolapse surgery between both groups was comparable (10.4% vs 9.3%, P = .70).
  

Mayo Clinic study details

Researchers from Female Pelvic Medicine and Reconstructive Surgery, Division of Gynecologic Surgery at Mayo Clinic reviewed the literature and compared vaginal native tissue repair with vaginal mesh–augmented repair of pelvic organ prolapse. Their report was published online ahead of print on January 17, 2013, in Current Bladder Dysfunction Reports.

The authors discuss POP; the procedures available to treat symptomatic POP; the Public Heath Notifications issued in 2008 and 2011 from U.S. Food and Drug Administration (FDA) regarding the use of transvaginal mesh in POP repair; and success, failure, and complication rates from both techniques.²

“Given the lack of robust and long-term data in these relatively new procedures for [mesh-augmentation] repair, we agree with the caution and prudence communication in the recent FDA warning,” state the authors.² However, a caveat is offered that native tissue repair must utilize best principles of surgical technique and incorporate a multicompartment repair to achieve optimal outcome. The authors strongly advise that appropriate surgical technique, obtained only through adequate surgical training, can be improved for both repair procedures.²

Risks and complications from mesh. Mesh introduces unique risks related to the mesh itself, including mesh erosion, and complications, including new onset pain and dyspareunia following mesh-augmented repair. Complications are possibly related to the intrinsic properties of the mesh, (ie, shrinkage); to the patient (ie, scarring); or to the operative technique (ie, the placement/location of the mesh and increased tension on the mesh). The authors conclude that additional studies are needed, given the lack of robust and long-term data on mesh-augmentation repair of POP.²

“The evidence thus far has not shown that the benefits of mesh outweigh the added risks in vaginal prolapse repairs,” write the authors.² Therefore, although patient-centered success rates for both techniques of POP repair are equivalent, the authors conclude: “there does not appear to be a clear advantage of mesh augmentation repair over native tissue in terms of anatomic success.”²

To access the Jonsson Funk abstract, click here.

To access the Kim-Fine abstract, click here.

We want to hear from you! Tell us what you think.

• Michele Jonsson Funk, PhD, and colleagues from University of North Carolina (UNC) at Chapel Hill concluded that using vaginal mesh versus native tissue for anterior prolapse repair is associated with 5-year increased risk of any repeat surgery, especially surgery for mesh removal.¹
  
• Shunaha Kim-Fine, MD, and colleagues from Mayo Clinic, Rochester, Minnesota, believe that traditional native tissue repair is the best procedure for most women undergoing vaginal POP repair.²
  

UNC study details

Investigators from the Gillings School of Global Public Health at UNC studied health-care claims from 2005 to 2010. They identified women who, after undergoing anterior wall prolapse repair, experienced repeat surgery for recurrent prolapse or mesh removal. Of the initial 27,809 anterior prolapse surgeries, 6,871 (24.7%) included the use of vaginal mesh.¹

5-year risk of repeat surgery. The authors determined that¹:

• the 5-year cumulative risk of any repeat surgery was significantly higher with the use of vaginal mesh than with the use of native tissue (15.2% vs 9.8%, respectively; P <.0001 with a risk of mesh revision or removal>
• the 5-year risk for recurrent prolapse surgery between both groups was comparable (10.4% vs 9.3%, P = .70).
  

Mayo Clinic study details

Researchers from Female Pelvic Medicine and Reconstructive Surgery, Division of Gynecologic Surgery at Mayo Clinic reviewed the literature and compared vaginal native tissue repair with vaginal mesh–augmented repair of pelvic organ prolapse. Their report was published online ahead of print on January 17, 2013, in Current Bladder Dysfunction Reports.

The authors discuss POP; the procedures available to treat symptomatic POP; the Public Heath Notifications issued in 2008 and 2011 from U.S. Food and Drug Administration (FDA) regarding the use of transvaginal mesh in POP repair; and success, failure, and complication rates from both techniques.²

“Given the lack of robust and long-term data in these relatively new procedures for [mesh-augmentation] repair, we agree with the caution and prudence communication in the recent FDA warning,” state the authors.² However, a caveat is offered that native tissue repair must utilize best principles of surgical technique and incorporate a multicompartment repair to achieve optimal outcome. The authors strongly advise that appropriate surgical technique, obtained only through adequate surgical training, can be improved for both repair procedures.²

Risks and complications from mesh. Mesh introduces unique risks related to the mesh itself, including mesh erosion, and complications, including new onset pain and dyspareunia following mesh-augmented repair. Complications are possibly related to the intrinsic properties of the mesh, (ie, shrinkage); to the patient (ie, scarring); or to the operative technique (ie, the placement/location of the mesh and increased tension on the mesh). The authors conclude that additional studies are needed, given the lack of robust and long-term data on mesh-augmentation repair of POP.²

“The evidence thus far has not shown that the benefits of mesh outweigh the added risks in vaginal prolapse repairs,” write the authors.² Therefore, although patient-centered success rates for both techniques of POP repair are equivalent, the authors conclude: “there does not appear to be a clear advantage of mesh augmentation repair over native tissue in terms of anatomic success.”²

To access the Jonsson Funk abstract, click here.

To access the Kim-Fine abstract, click here.

We want to hear from you! Tell us what you think.

• Michele Jonsson Funk, PhD, and colleagues from University of North Carolina (UNC) at Chapel Hill concluded that using vaginal mesh versus native tissue for anterior prolapse repair is associated with 5-year increased risk of any repeat surgery, especially surgery for mesh removal.¹
  
• Shunaha Kim-Fine, MD, and colleagues from Mayo Clinic, Rochester, Minnesota, believe that traditional native tissue repair is the best procedure for most women undergoing vaginal POP repair.²
  

UNC study details

Investigators from the Gillings School of Global Public Health at UNC studied health-care claims from 2005 to 2010. They identified women who, after undergoing anterior wall prolapse repair, experienced repeat surgery for recurrent prolapse or mesh removal. Of the initial 27,809 anterior prolapse surgeries, 6,871 (24.7%) included the use of vaginal mesh.¹

5-year risk of repeat surgery. The authors determined that¹:

• the 5-year cumulative risk of any repeat surgery was significantly higher with the use of vaginal mesh than with the use of native tissue (15.2% vs 9.8%, respectively; P <.0001 with a risk of mesh revision or removal>
• the 5-year risk for recurrent prolapse surgery between both groups was comparable (10.4% vs 9.3%, P = .70).
  

Mayo Clinic study details

Researchers from Female Pelvic Medicine and Reconstructive Surgery, Division of Gynecologic Surgery at Mayo Clinic reviewed the literature and compared vaginal native tissue repair with vaginal mesh–augmented repair of pelvic organ prolapse. Their report was published online ahead of print on January 17, 2013, in Current Bladder Dysfunction Reports.

The authors discuss POP; the procedures available to treat symptomatic POP; the Public Heath Notifications issued in 2008 and 2011 from U.S. Food and Drug Administration (FDA) regarding the use of transvaginal mesh in POP repair; and success, failure, and complication rates from both techniques.²

“Given the lack of robust and long-term data in these relatively new procedures for [mesh-augmentation] repair, we agree with the caution and prudence communication in the recent FDA warning,” state the authors.² However, a caveat is offered that native tissue repair must utilize best principles of surgical technique and incorporate a multicompartment repair to achieve optimal outcome. The authors strongly advise that appropriate surgical technique, obtained only through adequate surgical training, can be improved for both repair procedures.²

Risks and complications from mesh. Mesh introduces unique risks related to the mesh itself, including mesh erosion, and complications, including new onset pain and dyspareunia following mesh-augmented repair. Complications are possibly related to the intrinsic properties of the mesh, (ie, shrinkage); to the patient (ie, scarring); or to the operative technique (ie, the placement/location of the mesh and increased tension on the mesh). The authors conclude that additional studies are needed, given the lack of robust and long-term data on mesh-augmentation repair of POP.²

“The evidence thus far has not shown that the benefits of mesh outweigh the added risks in vaginal prolapse repairs,” write the authors.² Therefore, although patient-centered success rates for both techniques of POP repair are equivalent, the authors conclude: “there does not appear to be a clear advantage of mesh augmentation repair over native tissue in terms of anatomic success.”²

To access the Jonsson Funk abstract, click here.

To access the Kim-Fine abstract, click here.

We want to hear from you! Tell us what you think.

CASE Angela D, a 34-year-old patient, has asthma with recurrent exacerbations. She uses a low-dose inhaled corticosteroid (ICS) daily and an albuterol inhaler, as needed, for shortness of breath or wheezing. She also has allergic rhinitis, for which she uses nasal fluticasone. Yet despite this regimen, Ms. D reports she still experiences wheezing, chest tightness, and shortness of breath 3 to 4 times a week and is awak-ened by coughing at least twice a week. In the past 6 months, she has had one emergency department (ED) visit and completed 2 courses of oral steroids.

Ms. D has gained weight since her last visit 3 months ago; her body mass index has gone from 27.5 to 29 kg/m². And, while she has always been somewhat anxious, Ms. D notes that her anxiety has gotten progressively worse, as well.

About 25 million Americans—approximately one in 12—suffer from asthma¹ and, despite improvements in asthma guidelines and treatment in the last 20 years,² many still struggle with uncontrolled symptoms.³ The consequences can be severe.

Suboptimal control of asthma is associated with a significant decrease in quality of life, a greater likelihood of absence from work or school, and an increased risk for life-threatening events, trips to the ED, hospital admissions, and death.¹ A multifaceted approach, including regular assessment, aggressive medication management, and attention to comorbidities, is needed to alleviate the suffering of patients with persistent asthma. This evidence-based review can help you provide such broad-based treatment.

Diagnosis and classification go hand in hand

The cornerstones of asthma management are accurate diagnosis and assessment of disease severity, based on both qualitative and quantitative measures. Start with a patient history, eliciting information about symptoms, triggers, risk factors, and most importantly, how often symptoms occur. Classic high-pitched wheezing sounds during exhalation, a cough that often worsens at night, shortness of breath, and chest tightness should raise suspicion for an asthma diagnosis.² But frequency (and timing) of symptoms and exacerbations, as well as changes in the patient’s ability to function normally, help to determine whether asthma is classified as mild intermittent, mild persistent, moderate persistent, or severe persistent (TABLE).²

TABLE
Classifying asthma severity²

Because asthma treatment should be based on its classification, an accurate assessment of disease severity is especially important for patients like Ms. D, who have been treated for asthma but continue to have unresolved symptoms. Keep in mind that asthma classification should be based on the worst symptom a patient has, not necessarily the symptom that occurs most frequently. Thus, a patient who has daytime symptoms requiring use of a rescue inhaler 2 to 3 times a week but is awakened at night with shortness of breath 2 times a week would receive a diagnosis of moderate persistent asthma on the basis of the night-time symptoms.

In assessing asthma severity, it is also important to ask specifically about recent events, including ED visits, hospitalizations, and intubations. This information, as well as answers to questions about smoking status, mental health problems, quality of life, and treatment compliance—and whether the patient can afford to purchase the asthma medications you’ve prescribed—can be used to assess the likelihood of poor outcomes.²

Factor in spirometry findings
History and physical examination alone cannot adequately diagnose and classify asthma severity.^4,5 Spirometry, a reimbursable office test that can be administered by trained staff members, can be beneficial for any patient older than 5 years for whom a diagnosis of asthma is being considered or disease severity being determined.² Other objective measures, such as the Mini Asthma Quality of Life questionnaire (http://erj.ersjournals.com/content/14/1/32.full.pdf+html) and peak expiratory flow measurement, may be helpful, as well.^2,6

Spirometry measures forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) and calculates the FEV₁/FVC ratio. Reference spirometry values vary according to patient characteristics, such as age, height, sex, and race, as well as the positioning of the patient during the test.⁷ (A seated position is optimal to reduce the risk of falls as a result of the light-headedness some patients may experience.) The American Thoracic Society provides a set of criteria (available at http://www.gp-training.net/protocol/respiratory/copd/spirometry.htm) that should be considered in interpreting test results.⁸

The 3 main spirometry patterns you’ll see are:

• Normal (FEV₁ >80% predicted; FVC >80% predicted; FEV₁/FVC >70%)
• Obstructive (FEV₁ <80% predicted; FVC normal or mildly reduced; FEV₁/FVC <70%)
• Restrictive (FEV₁ normal or mildly reduced; FVC <80% predicted; FEV₁/FVC >70%).

Because asthma is a chronic disease with fluctuating symptomatology and severity, spirometry testing should be repeated and results compared on several occasions as a guide to treatment.⁹ When an obstructive pattern is found, the patient should receive a bronchodilator treatment, then undergo spirometry 15 to 20 minutes later to determine reversibility. A reversible obstructive pattern, defined as an increase in FEV₁ by 12% (≥200 mL), is consistent with an asthma diagnosis. If spirometry results are consistently normal but a high clinical suspicion for obstructive disease remains, the patient should be evaluated with a methacholine or histamine challenge test to definitively rule out asthma.¹⁰

Rule out asthma mimics. Many medical conditions can mimic symptoms of asthma and result in misdiagnosis or incorrect severity classification and unnecessary treatment. Patients should be evaluated for alternate or coexisting pulmonary conditions, including restrictive lung disease, vocal cord dysfunction, cough-variant asthma, malignancy, and allergies. For a patient whose asthma diagnosis is in doubt or who has a restrictive pattern on spirometry, additional evaluation based on signs and symptoms may require comprehensive pulmonary function testing, chest x-ray, bronchoscopy, laryngoscopy, computed tomography, and/or allergy testing.²

Peak expiratory flow (PEF). While measuring PEF should not replace spirometry or formal pulmonary function testing, it can be helpful for evaluating disease severity and monitoring treatment. Patients should use their own peak flow meters, and results compared with their personal best measurements. An improvement of 60 L/min or >20% after treatment with a bronchodilator is suggestive of asthma.⁹ There are a number of free or low-cost apps that patients can use to track their PEF measurements and response to treatment, such as Asthma MD, Huff and Puff (for children), and the Peak Flow Calculator.^11-13

An evidence-based approach to asthma treatment

The first step in treating newly diagnosed asthma is to advise the patient to avoid known triggers, such as allergens, stressors, and particular odors or activities, to the extent possible, and, most importantly, to avoid exposure to smoke. If the patient smokes—cigarettes, marijuana, hookah, or pipe—stress the importance of quitting and living in a home that is smoke free. The link between asthma exacerbations and cockroaches is also well documented, particularly affecting those in urban areas. Avoidance of cockroaches and their droppings is critical, and may require the use of pest control services.^14,15

A general principle of asthma management is to treat it aggressively initially to help the patient achieve quick control, then gradually cut back to the fewest medications and lowest effective doses required to maintain control.² The National Heart, Lung, and Blood Institute (NHLBI)’s 2007 Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma (FIGURE)² call for a stepwise approach.

Short-acting beta-agonists (SABAs) and ICS—first-line asthma therapy—have minimal risks or adverse effects. SABAs help reverse acute shortness of breath and wheezing, and ICS can reduce the frequency of exacerbations.²

FIGURE
Stepwise approach to asthma management for patients ≥12 years

*Consult with an asthma specialist if Step 4 care or higher is required; consider consultation at Step 3.
^†Consider subcutaneous allergen immunotherapy for patients with allergic asthma.
ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LTRA, leukotriene receptor agonist; SABA, short-acting beta-agonist.
Adapted from: National Asthma Education and Prevention Program. J Allergy Clin Immunol. 2007.²

Second-line therapy is less clearcut
There are several options for patients whose symptoms are not well controlled with first-line treatment: (1) Add a long-acting beta-agonist (LABA); (2) add a leukotriene receptor antagonist (LTRA); or (3) increase the ICS dose, the most straightforward approach.

A dose increase avoids both the additional risk of adverse drug reactions and the added cost associated with another medication. But the easiest solution is not necessarily the best. Consider the evidence detailed below, which includes findings from studies published after the NHLBI’s guidelines.

The research on LABAs
LABAs have been widely used as adjunctive therapy for adults with asthma. However, a 2006 study raised safety concerns.¹⁶

The Salmeterol Multicenter Asthma Research Trial (SMART) compared the safety of the LABA salmeterol with a placebo added to usual asthma care over a 28-week treatment period. Overall, the primary composite end point—the number of respiratory-related deaths or life-threatening events—was low, and not statistically significant for salmeterol (50 vs 36; relative risk [RR]=1.40; 95% confidence interval [CI], 0.91-2.14).¹⁶ However, individual outcomes—respiratory-related deaths, asthma-related deaths, and asthma-related deaths or life-threatening episodes—were significantly more likely in the salmeterol group compared with the placebo group. In subgroup analysis, African American patients were found to be at greatest risk.¹⁶

It is hard to draw general conclusions from these data because the study was terminated early and poor outcomes were limited to a particular study year. Nonetheless, many physicians remain wary of LABAs as adjunctive therapy because of these findings and the media publicity they generated.

A 2010 Cochrane review provided additional data on the safety and efficacy of the combination of a LABA and ICS compared with a higher dose of ICS.¹⁷ The review, which included 48 randomized controlled trials, found that combination therapy had a lower risk of exacerbations for which oral corticosteroids were required than a higher dose of ICS (RR=0.88; 95% CI, 0.78-0.98; P=.02). The median number needed to treat (NNT) was 73. No significant difference in the risk of overall adverse events (RR=0.99; 95% CI, 0.95-1.03) was found, but there was an increase in the risk of tremor (RR=1.84; 95% CI, 1.20-2.82) and a decrease in risk for oral thrush (RR=0.58; 95% CI, 0.40-0.86) in the combination therapy group.

While the Cochrane review did not show a combination of LABA and ICS to be less safe overall than higher doses of ICS alone, the findings were less favorable for children and patients with higher baseline lung function, in circumstances in which the combination therapy was taken for a longer duration, and when the LABA being studied was formoterol.¹⁷

Overall, it is when a LABA is delivered via separate inhaler that adverse outcomes have been reported. Findings have been positive when the LABA is combined with ICS, and this combination is recommended as maintenance therapy for moderate to severe asthma.

Two new studies, published in March 2013, reported successful use of a LABA-ICS combination not only for maintenance via scheduled dosing, but also for early phases of exacerbation via extra dosing—an approach called Single inhaler Maintenance and Reliever Therapy (SMART).^18,19 In both studies, SMART resulted in less excessive use of SABAs and less need for oral steroids, fewer hospitalizations for asthma, and fewer cases of progression to a full-blown exacerbation.

The takeaway: LABAs should be reserved for use as an adjunct to ICS in adults with poor baseline pulmonary function tests or severe asthma, and delivered as a combination product with ICS, not as a separate inhaled medication. SMART is a safe and effective means of administering LABA-ICS therapy for some patients at risk for frequent severe exacerbations.

When to consider LTRAs
LTRAs can be valuable medications in asthma management and there are extensive data on their use, particularly in the treatment of children with asthma. A Cochrane review published in 2012, however, supported current guideline recommendations, finding that as monotherapy, ICS are superior to LTRAs.²⁰

When LTRAs as an adjunctive therapy to ICS were compared with ICS monotherapy, researchers found a modest improvement in PEF (weighted mean difference [WMD] =7.7 L/min; 95% CI, 3.6-11.8) in the group receiving combination therapy and a decrease in the need for a SABA as rescue therapy (WMD=1 puff/week; 95% CI, 0.5-2.0).²¹ There was no significant reduction in the risk of exacerbations requiring systemic steroids (RR=0.64; 95% CI, 0.38-1.07).

LABAs and LTRAs go head to head. A 2010 Cochrane review compared the efficacy and safety of a daily LABA vs a LTRA as add-on therapy for patients whose asthma was not well controlled with ICS monotherapy.²² The LABA/ICS combination was significantly better at reducing the risk of exacerbations requiring systemic corticosteroids than monotherapy with either a LTRA or ICS, reducing the risk from 11% to 9% (RR=0.83; 95% CI, 0.71-0.97). The NNT to prevent one exacerbation over 48 weeks was 38 (95% CI, 22-244).²²

The safety of LABAs continues to be a concern, however, as serious adverse events were more common in the LABA group. The number needed to harm (NNH) with LABA therapy vs LTRA over 48 weeks was 78; 95% CI, 33 to infinity.²² (The width of the CI indicates that while harm is possible in as few as 33 patients, it is also possible that an infinite number of patients would need to be treated for one individual to incur harm.) Overall, the evidence suggests that LABAs are superior add-on therapy to ICS for the treatment of uncontrolled asthma compared with LTRAs, but their use nonetheless requires caution and close monitoring in African American and pediatric patients.¹⁷

Is there a role for a long-acting anticholinergic inhaler?

Long-acting anticholinergic medication (LAAM)—tiotropium is the only drug in this class on the market, but there are others in clinical trials—is the mainstay of therapy for chronic obstructive pulmonary disease. This drug class was not widely available or studied as an asthma treatment when the NHLBI guidelines were drafted.

A 2010 study of tiotropium challenged the notion that there is no place for LAAMs in asthma therapy. Using a 3-way crossover design, the study compared the addition of tiotropium to ICS with a double dose of ICS or a LABA/ICS combination.²³

The results suggest that LAAMs could be useful in treating uncontrolled asthma. Compared with the double dose of ICS, the tiotropium/ICS combination increased PEF by a mean difference of 25.8 L/min (P<.001) and resulted in a statistically significant improvement in the proportion of asthma control days, FEV₁, and daily symptom scores.²³ As an adjunctive treatment to ICS, tiotropium was not inferior to a LABA.

CASE After a detailed history, physical exam, and diagnostic testing, Ms. D was given a diagnosis of moderate persistent asthma. We recognized the need to step up her treatment. Prior to making any changes in her medication regimen, however, our team, which included a clinical pharmacist, observed her use of inhaled medications and verified that she was using the inhaler properly. We then initiated combination therapy, pairing a LABA and ICS.

Comorbidities complicate asthma management

Asthma management is often complicated by other uncontrolled coexisting medical problems. Common comorbidities that can affect asthma severity include allergic rhinitis, chronic sinusitis, gastroesophageal reflux disease (GERD), obesity, obstructive sleep apnea (OSA), mental health disorders, tobacco use, and hormonal disturbances.²

Allergic rhinitis. Allergic rhinitis has been associated with worse asthma control and a negative impact on quality of life, and the upper airway inflammation associated with it should be treated.²⁴

Antihistamines and nasal steroids are the most effective medical management. Some patients with allergic rhinitis benefit from blood or skin allergy testing for confirmation or to aid in avoidance. Referral to an allergist may be necessary if symptoms are recalcitrant, a food allergy is in question, or the diagnosis is unclear.

GERD. Compared with the general population, patients with asthma have a much higher risk of GERD, although it is not always symptomatic. While results are inconsistent and difficult to predict, treating symptomatic GERD with acid-blocking medications can result in better asthma control for some patients. However, proton pump inhibitors should not be used to treat asthma symptoms in patients with asymptomatic GERD.^25,26

Obesity and OSA. Weight loss can significantly improve asthma control, decrease medication use, and improve quality of life.^27,28 Obese patients are less likely to respond to treatment with ICS.² Weight loss also benefits those who suffer from OSA, which may contribute to airway hyperresponsiveness.²⁹

Mental health disorders. Compared with the general population, patients with asthma are more likely to have depression, anxiety, and panic disorders.³⁰ Diagnosis and treatment of these comorbid conditions can lead to better asthma management, increased medication adherence, decreased health care utilization—including fewer ED visits and hospitalizations—and a better quality of life.³⁰

CASE We also addressed our patient’s comorbidities—weight gain, allergic rhinitis, and anxiety. The allergic rhinitis was already well-controlled with a nasal steroid, but we suspected a relationship between Ms. D’s weight gain and increasing anxiety associated with some recent life events. We suggested she see a counselor, and she agreed.

When the patient returned in 12 weeks, she reported that she hardly needed her rescue inhaler anymore and that she was managing her anxiety more effectively. She also told us that she had begun a low-fat dietary regimen, and we confirmed that she had already lost 5 pounds.

CORRESPONDENCE 
Stephen A. Wilson, MD, MPH, FAAFP, UPMC St. Margaret, 815 Freeport Road, Pittsburgh, PA 15215; wilsons2@upmc.edu

CASE Angela D, a 34-year-old patient, has asthma with recurrent exacerbations. She uses a low-dose inhaled corticosteroid (ICS) daily and an albuterol inhaler, as needed, for shortness of breath or wheezing. She also has allergic rhinitis, for which she uses nasal fluticasone. Yet despite this regimen, Ms. D reports she still experiences wheezing, chest tightness, and shortness of breath 3 to 4 times a week and is awak-ened by coughing at least twice a week. In the past 6 months, she has had one emergency department (ED) visit and completed 2 courses of oral steroids.

Ms. D has gained weight since her last visit 3 months ago; her body mass index has gone from 27.5 to 29 kg/m². And, while she has always been somewhat anxious, Ms. D notes that her anxiety has gotten progressively worse, as well.

About 25 million Americans—approximately one in 12—suffer from asthma¹ and, despite improvements in asthma guidelines and treatment in the last 20 years,² many still struggle with uncontrolled symptoms.³ The consequences can be severe.

Suboptimal control of asthma is associated with a significant decrease in quality of life, a greater likelihood of absence from work or school, and an increased risk for life-threatening events, trips to the ED, hospital admissions, and death.¹ A multifaceted approach, including regular assessment, aggressive medication management, and attention to comorbidities, is needed to alleviate the suffering of patients with persistent asthma. This evidence-based review can help you provide such broad-based treatment.

Diagnosis and classification go hand in hand

The cornerstones of asthma management are accurate diagnosis and assessment of disease severity, based on both qualitative and quantitative measures. Start with a patient history, eliciting information about symptoms, triggers, risk factors, and most importantly, how often symptoms occur. Classic high-pitched wheezing sounds during exhalation, a cough that often worsens at night, shortness of breath, and chest tightness should raise suspicion for an asthma diagnosis.² But frequency (and timing) of symptoms and exacerbations, as well as changes in the patient’s ability to function normally, help to determine whether asthma is classified as mild intermittent, mild persistent, moderate persistent, or severe persistent (TABLE).²

TABLE
Classifying asthma severity²

Because asthma treatment should be based on its classification, an accurate assessment of disease severity is especially important for patients like Ms. D, who have been treated for asthma but continue to have unresolved symptoms. Keep in mind that asthma classification should be based on the worst symptom a patient has, not necessarily the symptom that occurs most frequently. Thus, a patient who has daytime symptoms requiring use of a rescue inhaler 2 to 3 times a week but is awakened at night with shortness of breath 2 times a week would receive a diagnosis of moderate persistent asthma on the basis of the night-time symptoms.

In assessing asthma severity, it is also important to ask specifically about recent events, including ED visits, hospitalizations, and intubations. This information, as well as answers to questions about smoking status, mental health problems, quality of life, and treatment compliance—and whether the patient can afford to purchase the asthma medications you’ve prescribed—can be used to assess the likelihood of poor outcomes.²

Factor in spirometry findings
History and physical examination alone cannot adequately diagnose and classify asthma severity.^4,5 Spirometry, a reimbursable office test that can be administered by trained staff members, can be beneficial for any patient older than 5 years for whom a diagnosis of asthma is being considered or disease severity being determined.² Other objective measures, such as the Mini Asthma Quality of Life questionnaire (http://erj.ersjournals.com/content/14/1/32.full.pdf+html) and peak expiratory flow measurement, may be helpful, as well.^2,6

Spirometry measures forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) and calculates the FEV₁/FVC ratio. Reference spirometry values vary according to patient characteristics, such as age, height, sex, and race, as well as the positioning of the patient during the test.⁷ (A seated position is optimal to reduce the risk of falls as a result of the light-headedness some patients may experience.) The American Thoracic Society provides a set of criteria (available at http://www.gp-training.net/protocol/respiratory/copd/spirometry.htm) that should be considered in interpreting test results.⁸

The 3 main spirometry patterns you’ll see are:

• Normal (FEV₁ >80% predicted; FVC >80% predicted; FEV₁/FVC >70%)
• Obstructive (FEV₁ <80% predicted; FVC normal or mildly reduced; FEV₁/FVC <70%)
• Restrictive (FEV₁ normal or mildly reduced; FVC <80% predicted; FEV₁/FVC >70%).

Because asthma is a chronic disease with fluctuating symptomatology and severity, spirometry testing should be repeated and results compared on several occasions as a guide to treatment.⁹ When an obstructive pattern is found, the patient should receive a bronchodilator treatment, then undergo spirometry 15 to 20 minutes later to determine reversibility. A reversible obstructive pattern, defined as an increase in FEV₁ by 12% (≥200 mL), is consistent with an asthma diagnosis. If spirometry results are consistently normal but a high clinical suspicion for obstructive disease remains, the patient should be evaluated with a methacholine or histamine challenge test to definitively rule out asthma.¹⁰

Rule out asthma mimics. Many medical conditions can mimic symptoms of asthma and result in misdiagnosis or incorrect severity classification and unnecessary treatment. Patients should be evaluated for alternate or coexisting pulmonary conditions, including restrictive lung disease, vocal cord dysfunction, cough-variant asthma, malignancy, and allergies. For a patient whose asthma diagnosis is in doubt or who has a restrictive pattern on spirometry, additional evaluation based on signs and symptoms may require comprehensive pulmonary function testing, chest x-ray, bronchoscopy, laryngoscopy, computed tomography, and/or allergy testing.²

Peak expiratory flow (PEF). While measuring PEF should not replace spirometry or formal pulmonary function testing, it can be helpful for evaluating disease severity and monitoring treatment. Patients should use their own peak flow meters, and results compared with their personal best measurements. An improvement of 60 L/min or >20% after treatment with a bronchodilator is suggestive of asthma.⁹ There are a number of free or low-cost apps that patients can use to track their PEF measurements and response to treatment, such as Asthma MD, Huff and Puff (for children), and the Peak Flow Calculator.^11-13

An evidence-based approach to asthma treatment

The first step in treating newly diagnosed asthma is to advise the patient to avoid known triggers, such as allergens, stressors, and particular odors or activities, to the extent possible, and, most importantly, to avoid exposure to smoke. If the patient smokes—cigarettes, marijuana, hookah, or pipe—stress the importance of quitting and living in a home that is smoke free. The link between asthma exacerbations and cockroaches is also well documented, particularly affecting those in urban areas. Avoidance of cockroaches and their droppings is critical, and may require the use of pest control services.^14,15

A general principle of asthma management is to treat it aggressively initially to help the patient achieve quick control, then gradually cut back to the fewest medications and lowest effective doses required to maintain control.² The National Heart, Lung, and Blood Institute (NHLBI)’s 2007 Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma (FIGURE)² call for a stepwise approach.

Short-acting beta-agonists (SABAs) and ICS—first-line asthma therapy—have minimal risks or adverse effects. SABAs help reverse acute shortness of breath and wheezing, and ICS can reduce the frequency of exacerbations.²

FIGURE
Stepwise approach to asthma management for patients ≥12 years

*Consult with an asthma specialist if Step 4 care or higher is required; consider consultation at Step 3.
^†Consider subcutaneous allergen immunotherapy for patients with allergic asthma.
ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LTRA, leukotriene receptor agonist; SABA, short-acting beta-agonist.
Adapted from: National Asthma Education and Prevention Program. J Allergy Clin Immunol. 2007.²

Second-line therapy is less clearcut
There are several options for patients whose symptoms are not well controlled with first-line treatment: (1) Add a long-acting beta-agonist (LABA); (2) add a leukotriene receptor antagonist (LTRA); or (3) increase the ICS dose, the most straightforward approach.

A dose increase avoids both the additional risk of adverse drug reactions and the added cost associated with another medication. But the easiest solution is not necessarily the best. Consider the evidence detailed below, which includes findings from studies published after the NHLBI’s guidelines.

The research on LABAs
LABAs have been widely used as adjunctive therapy for adults with asthma. However, a 2006 study raised safety concerns.¹⁶

The Salmeterol Multicenter Asthma Research Trial (SMART) compared the safety of the LABA salmeterol with a placebo added to usual asthma care over a 28-week treatment period. Overall, the primary composite end point—the number of respiratory-related deaths or life-threatening events—was low, and not statistically significant for salmeterol (50 vs 36; relative risk [RR]=1.40; 95% confidence interval [CI], 0.91-2.14).¹⁶ However, individual outcomes—respiratory-related deaths, asthma-related deaths, and asthma-related deaths or life-threatening episodes—were significantly more likely in the salmeterol group compared with the placebo group. In subgroup analysis, African American patients were found to be at greatest risk.¹⁶

It is hard to draw general conclusions from these data because the study was terminated early and poor outcomes were limited to a particular study year. Nonetheless, many physicians remain wary of LABAs as adjunctive therapy because of these findings and the media publicity they generated.

A 2010 Cochrane review provided additional data on the safety and efficacy of the combination of a LABA and ICS compared with a higher dose of ICS.¹⁷ The review, which included 48 randomized controlled trials, found that combination therapy had a lower risk of exacerbations for which oral corticosteroids were required than a higher dose of ICS (RR=0.88; 95% CI, 0.78-0.98; P=.02). The median number needed to treat (NNT) was 73. No significant difference in the risk of overall adverse events (RR=0.99; 95% CI, 0.95-1.03) was found, but there was an increase in the risk of tremor (RR=1.84; 95% CI, 1.20-2.82) and a decrease in risk for oral thrush (RR=0.58; 95% CI, 0.40-0.86) in the combination therapy group.

While the Cochrane review did not show a combination of LABA and ICS to be less safe overall than higher doses of ICS alone, the findings were less favorable for children and patients with higher baseline lung function, in circumstances in which the combination therapy was taken for a longer duration, and when the LABA being studied was formoterol.¹⁷

Overall, it is when a LABA is delivered via separate inhaler that adverse outcomes have been reported. Findings have been positive when the LABA is combined with ICS, and this combination is recommended as maintenance therapy for moderate to severe asthma.

Two new studies, published in March 2013, reported successful use of a LABA-ICS combination not only for maintenance via scheduled dosing, but also for early phases of exacerbation via extra dosing—an approach called Single inhaler Maintenance and Reliever Therapy (SMART).^18,19 In both studies, SMART resulted in less excessive use of SABAs and less need for oral steroids, fewer hospitalizations for asthma, and fewer cases of progression to a full-blown exacerbation.

The takeaway: LABAs should be reserved for use as an adjunct to ICS in adults with poor baseline pulmonary function tests or severe asthma, and delivered as a combination product with ICS, not as a separate inhaled medication. SMART is a safe and effective means of administering LABA-ICS therapy for some patients at risk for frequent severe exacerbations.

When to consider LTRAs
LTRAs can be valuable medications in asthma management and there are extensive data on their use, particularly in the treatment of children with asthma. A Cochrane review published in 2012, however, supported current guideline recommendations, finding that as monotherapy, ICS are superior to LTRAs.²⁰

When LTRAs as an adjunctive therapy to ICS were compared with ICS monotherapy, researchers found a modest improvement in PEF (weighted mean difference [WMD] =7.7 L/min; 95% CI, 3.6-11.8) in the group receiving combination therapy and a decrease in the need for a SABA as rescue therapy (WMD=1 puff/week; 95% CI, 0.5-2.0).²¹ There was no significant reduction in the risk of exacerbations requiring systemic steroids (RR=0.64; 95% CI, 0.38-1.07).

LABAs and LTRAs go head to head. A 2010 Cochrane review compared the efficacy and safety of a daily LABA vs a LTRA as add-on therapy for patients whose asthma was not well controlled with ICS monotherapy.²² The LABA/ICS combination was significantly better at reducing the risk of exacerbations requiring systemic corticosteroids than monotherapy with either a LTRA or ICS, reducing the risk from 11% to 9% (RR=0.83; 95% CI, 0.71-0.97). The NNT to prevent one exacerbation over 48 weeks was 38 (95% CI, 22-244).²²

The safety of LABAs continues to be a concern, however, as serious adverse events were more common in the LABA group. The number needed to harm (NNH) with LABA therapy vs LTRA over 48 weeks was 78; 95% CI, 33 to infinity.²² (The width of the CI indicates that while harm is possible in as few as 33 patients, it is also possible that an infinite number of patients would need to be treated for one individual to incur harm.) Overall, the evidence suggests that LABAs are superior add-on therapy to ICS for the treatment of uncontrolled asthma compared with LTRAs, but their use nonetheless requires caution and close monitoring in African American and pediatric patients.¹⁷

Is there a role for a long-acting anticholinergic inhaler?

Long-acting anticholinergic medication (LAAM)—tiotropium is the only drug in this class on the market, but there are others in clinical trials—is the mainstay of therapy for chronic obstructive pulmonary disease. This drug class was not widely available or studied as an asthma treatment when the NHLBI guidelines were drafted.

A 2010 study of tiotropium challenged the notion that there is no place for LAAMs in asthma therapy. Using a 3-way crossover design, the study compared the addition of tiotropium to ICS with a double dose of ICS or a LABA/ICS combination.²³

The results suggest that LAAMs could be useful in treating uncontrolled asthma. Compared with the double dose of ICS, the tiotropium/ICS combination increased PEF by a mean difference of 25.8 L/min (P<.001) and resulted in a statistically significant improvement in the proportion of asthma control days, FEV₁, and daily symptom scores.²³ As an adjunctive treatment to ICS, tiotropium was not inferior to a LABA.

CASE After a detailed history, physical exam, and diagnostic testing, Ms. D was given a diagnosis of moderate persistent asthma. We recognized the need to step up her treatment. Prior to making any changes in her medication regimen, however, our team, which included a clinical pharmacist, observed her use of inhaled medications and verified that she was using the inhaler properly. We then initiated combination therapy, pairing a LABA and ICS.

Comorbidities complicate asthma management

Asthma management is often complicated by other uncontrolled coexisting medical problems. Common comorbidities that can affect asthma severity include allergic rhinitis, chronic sinusitis, gastroesophageal reflux disease (GERD), obesity, obstructive sleep apnea (OSA), mental health disorders, tobacco use, and hormonal disturbances.²

Allergic rhinitis. Allergic rhinitis has been associated with worse asthma control and a negative impact on quality of life, and the upper airway inflammation associated with it should be treated.²⁴

Antihistamines and nasal steroids are the most effective medical management. Some patients with allergic rhinitis benefit from blood or skin allergy testing for confirmation or to aid in avoidance. Referral to an allergist may be necessary if symptoms are recalcitrant, a food allergy is in question, or the diagnosis is unclear.

GERD. Compared with the general population, patients with asthma have a much higher risk of GERD, although it is not always symptomatic. While results are inconsistent and difficult to predict, treating symptomatic GERD with acid-blocking medications can result in better asthma control for some patients. However, proton pump inhibitors should not be used to treat asthma symptoms in patients with asymptomatic GERD.^25,26

Obesity and OSA. Weight loss can significantly improve asthma control, decrease medication use, and improve quality of life.^27,28 Obese patients are less likely to respond to treatment with ICS.² Weight loss also benefits those who suffer from OSA, which may contribute to airway hyperresponsiveness.²⁹

Mental health disorders. Compared with the general population, patients with asthma are more likely to have depression, anxiety, and panic disorders.³⁰ Diagnosis and treatment of these comorbid conditions can lead to better asthma management, increased medication adherence, decreased health care utilization—including fewer ED visits and hospitalizations—and a better quality of life.³⁰

CASE We also addressed our patient’s comorbidities—weight gain, allergic rhinitis, and anxiety. The allergic rhinitis was already well-controlled with a nasal steroid, but we suspected a relationship between Ms. D’s weight gain and increasing anxiety associated with some recent life events. We suggested she see a counselor, and she agreed.

When the patient returned in 12 weeks, she reported that she hardly needed her rescue inhaler anymore and that she was managing her anxiety more effectively. She also told us that she had begun a low-fat dietary regimen, and we confirmed that she had already lost 5 pounds.

CORRESPONDENCE 
Stephen A. Wilson, MD, MPH, FAAFP, UPMC St. Margaret, 815 Freeport Road, Pittsburgh, PA 15215; wilsons2@upmc.edu

CASE Angela D, a 34-year-old patient, has asthma with recurrent exacerbations. She uses a low-dose inhaled corticosteroid (ICS) daily and an albuterol inhaler, as needed, for shortness of breath or wheezing. She also has allergic rhinitis, for which she uses nasal fluticasone. Yet despite this regimen, Ms. D reports she still experiences wheezing, chest tightness, and shortness of breath 3 to 4 times a week and is awak-ened by coughing at least twice a week. In the past 6 months, she has had one emergency department (ED) visit and completed 2 courses of oral steroids.

Ms. D has gained weight since her last visit 3 months ago; her body mass index has gone from 27.5 to 29 kg/m². And, while she has always been somewhat anxious, Ms. D notes that her anxiety has gotten progressively worse, as well.

About 25 million Americans—approximately one in 12—suffer from asthma¹ and, despite improvements in asthma guidelines and treatment in the last 20 years,² many still struggle with uncontrolled symptoms.³ The consequences can be severe.

Suboptimal control of asthma is associated with a significant decrease in quality of life, a greater likelihood of absence from work or school, and an increased risk for life-threatening events, trips to the ED, hospital admissions, and death.¹ A multifaceted approach, including regular assessment, aggressive medication management, and attention to comorbidities, is needed to alleviate the suffering of patients with persistent asthma. This evidence-based review can help you provide such broad-based treatment.

Diagnosis and classification go hand in hand

The cornerstones of asthma management are accurate diagnosis and assessment of disease severity, based on both qualitative and quantitative measures. Start with a patient history, eliciting information about symptoms, triggers, risk factors, and most importantly, how often symptoms occur. Classic high-pitched wheezing sounds during exhalation, a cough that often worsens at night, shortness of breath, and chest tightness should raise suspicion for an asthma diagnosis.² But frequency (and timing) of symptoms and exacerbations, as well as changes in the patient’s ability to function normally, help to determine whether asthma is classified as mild intermittent, mild persistent, moderate persistent, or severe persistent (TABLE).²

TABLE
Classifying asthma severity²

Because asthma treatment should be based on its classification, an accurate assessment of disease severity is especially important for patients like Ms. D, who have been treated for asthma but continue to have unresolved symptoms. Keep in mind that asthma classification should be based on the worst symptom a patient has, not necessarily the symptom that occurs most frequently. Thus, a patient who has daytime symptoms requiring use of a rescue inhaler 2 to 3 times a week but is awakened at night with shortness of breath 2 times a week would receive a diagnosis of moderate persistent asthma on the basis of the night-time symptoms.

In assessing asthma severity, it is also important to ask specifically about recent events, including ED visits, hospitalizations, and intubations. This information, as well as answers to questions about smoking status, mental health problems, quality of life, and treatment compliance—and whether the patient can afford to purchase the asthma medications you’ve prescribed—can be used to assess the likelihood of poor outcomes.²

Factor in spirometry findings
History and physical examination alone cannot adequately diagnose and classify asthma severity.^4,5 Spirometry, a reimbursable office test that can be administered by trained staff members, can be beneficial for any patient older than 5 years for whom a diagnosis of asthma is being considered or disease severity being determined.² Other objective measures, such as the Mini Asthma Quality of Life questionnaire (http://erj.ersjournals.com/content/14/1/32.full.pdf+html) and peak expiratory flow measurement, may be helpful, as well.^2,6

Spirometry measures forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) and calculates the FEV₁/FVC ratio. Reference spirometry values vary according to patient characteristics, such as age, height, sex, and race, as well as the positioning of the patient during the test.⁷ (A seated position is optimal to reduce the risk of falls as a result of the light-headedness some patients may experience.) The American Thoracic Society provides a set of criteria (available at http://www.gp-training.net/protocol/respiratory/copd/spirometry.htm) that should be considered in interpreting test results.⁸

The 3 main spirometry patterns you’ll see are:

• Normal (FEV₁ >80% predicted; FVC >80% predicted; FEV₁/FVC >70%)
• Obstructive (FEV₁ <80% predicted; FVC normal or mildly reduced; FEV₁/FVC <70%)
• Restrictive (FEV₁ normal or mildly reduced; FVC <80% predicted; FEV₁/FVC >70%).

Because asthma is a chronic disease with fluctuating symptomatology and severity, spirometry testing should be repeated and results compared on several occasions as a guide to treatment.⁹ When an obstructive pattern is found, the patient should receive a bronchodilator treatment, then undergo spirometry 15 to 20 minutes later to determine reversibility. A reversible obstructive pattern, defined as an increase in FEV₁ by 12% (≥200 mL), is consistent with an asthma diagnosis. If spirometry results are consistently normal but a high clinical suspicion for obstructive disease remains, the patient should be evaluated with a methacholine or histamine challenge test to definitively rule out asthma.¹⁰

Rule out asthma mimics. Many medical conditions can mimic symptoms of asthma and result in misdiagnosis or incorrect severity classification and unnecessary treatment. Patients should be evaluated for alternate or coexisting pulmonary conditions, including restrictive lung disease, vocal cord dysfunction, cough-variant asthma, malignancy, and allergies. For a patient whose asthma diagnosis is in doubt or who has a restrictive pattern on spirometry, additional evaluation based on signs and symptoms may require comprehensive pulmonary function testing, chest x-ray, bronchoscopy, laryngoscopy, computed tomography, and/or allergy testing.²

Peak expiratory flow (PEF). While measuring PEF should not replace spirometry or formal pulmonary function testing, it can be helpful for evaluating disease severity and monitoring treatment. Patients should use their own peak flow meters, and results compared with their personal best measurements. An improvement of 60 L/min or >20% after treatment with a bronchodilator is suggestive of asthma.⁹ There are a number of free or low-cost apps that patients can use to track their PEF measurements and response to treatment, such as Asthma MD, Huff and Puff (for children), and the Peak Flow Calculator.^11-13

An evidence-based approach to asthma treatment

The first step in treating newly diagnosed asthma is to advise the patient to avoid known triggers, such as allergens, stressors, and particular odors or activities, to the extent possible, and, most importantly, to avoid exposure to smoke. If the patient smokes—cigarettes, marijuana, hookah, or pipe—stress the importance of quitting and living in a home that is smoke free. The link between asthma exacerbations and cockroaches is also well documented, particularly affecting those in urban areas. Avoidance of cockroaches and their droppings is critical, and may require the use of pest control services.^14,15

A general principle of asthma management is to treat it aggressively initially to help the patient achieve quick control, then gradually cut back to the fewest medications and lowest effective doses required to maintain control.² The National Heart, Lung, and Blood Institute (NHLBI)’s 2007 Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma (FIGURE)² call for a stepwise approach.

Short-acting beta-agonists (SABAs) and ICS—first-line asthma therapy—have minimal risks or adverse effects. SABAs help reverse acute shortness of breath and wheezing, and ICS can reduce the frequency of exacerbations.²

FIGURE
Stepwise approach to asthma management for patients ≥12 years

*Consult with an asthma specialist if Step 4 care or higher is required; consider consultation at Step 3.
^†Consider subcutaneous allergen immunotherapy for patients with allergic asthma.
ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LTRA, leukotriene receptor agonist; SABA, short-acting beta-agonist.
Adapted from: National Asthma Education and Prevention Program. J Allergy Clin Immunol. 2007.²

Second-line therapy is less clearcut
There are several options for patients whose symptoms are not well controlled with first-line treatment: (1) Add a long-acting beta-agonist (LABA); (2) add a leukotriene receptor antagonist (LTRA); or (3) increase the ICS dose, the most straightforward approach.

A dose increase avoids both the additional risk of adverse drug reactions and the added cost associated with another medication. But the easiest solution is not necessarily the best. Consider the evidence detailed below, which includes findings from studies published after the NHLBI’s guidelines.

The research on LABAs
LABAs have been widely used as adjunctive therapy for adults with asthma. However, a 2006 study raised safety concerns.¹⁶

The Salmeterol Multicenter Asthma Research Trial (SMART) compared the safety of the LABA salmeterol with a placebo added to usual asthma care over a 28-week treatment period. Overall, the primary composite end point—the number of respiratory-related deaths or life-threatening events—was low, and not statistically significant for salmeterol (50 vs 36; relative risk [RR]=1.40; 95% confidence interval [CI], 0.91-2.14).¹⁶ However, individual outcomes—respiratory-related deaths, asthma-related deaths, and asthma-related deaths or life-threatening episodes—were significantly more likely in the salmeterol group compared with the placebo group. In subgroup analysis, African American patients were found to be at greatest risk.¹⁶

It is hard to draw general conclusions from these data because the study was terminated early and poor outcomes were limited to a particular study year. Nonetheless, many physicians remain wary of LABAs as adjunctive therapy because of these findings and the media publicity they generated.

A 2010 Cochrane review provided additional data on the safety and efficacy of the combination of a LABA and ICS compared with a higher dose of ICS.¹⁷ The review, which included 48 randomized controlled trials, found that combination therapy had a lower risk of exacerbations for which oral corticosteroids were required than a higher dose of ICS (RR=0.88; 95% CI, 0.78-0.98; P=.02). The median number needed to treat (NNT) was 73. No significant difference in the risk of overall adverse events (RR=0.99; 95% CI, 0.95-1.03) was found, but there was an increase in the risk of tremor (RR=1.84; 95% CI, 1.20-2.82) and a decrease in risk for oral thrush (RR=0.58; 95% CI, 0.40-0.86) in the combination therapy group.

While the Cochrane review did not show a combination of LABA and ICS to be less safe overall than higher doses of ICS alone, the findings were less favorable for children and patients with higher baseline lung function, in circumstances in which the combination therapy was taken for a longer duration, and when the LABA being studied was formoterol.¹⁷

Overall, it is when a LABA is delivered via separate inhaler that adverse outcomes have been reported. Findings have been positive when the LABA is combined with ICS, and this combination is recommended as maintenance therapy for moderate to severe asthma.

Two new studies, published in March 2013, reported successful use of a LABA-ICS combination not only for maintenance via scheduled dosing, but also for early phases of exacerbation via extra dosing—an approach called Single inhaler Maintenance and Reliever Therapy (SMART).^18,19 In both studies, SMART resulted in less excessive use of SABAs and less need for oral steroids, fewer hospitalizations for asthma, and fewer cases of progression to a full-blown exacerbation.

The takeaway: LABAs should be reserved for use as an adjunct to ICS in adults with poor baseline pulmonary function tests or severe asthma, and delivered as a combination product with ICS, not as a separate inhaled medication. SMART is a safe and effective means of administering LABA-ICS therapy for some patients at risk for frequent severe exacerbations.

When to consider LTRAs
LTRAs can be valuable medications in asthma management and there are extensive data on their use, particularly in the treatment of children with asthma. A Cochrane review published in 2012, however, supported current guideline recommendations, finding that as monotherapy, ICS are superior to LTRAs.²⁰

When LTRAs as an adjunctive therapy to ICS were compared with ICS monotherapy, researchers found a modest improvement in PEF (weighted mean difference [WMD] =7.7 L/min; 95% CI, 3.6-11.8) in the group receiving combination therapy and a decrease in the need for a SABA as rescue therapy (WMD=1 puff/week; 95% CI, 0.5-2.0).²¹ There was no significant reduction in the risk of exacerbations requiring systemic steroids (RR=0.64; 95% CI, 0.38-1.07).

LABAs and LTRAs go head to head. A 2010 Cochrane review compared the efficacy and safety of a daily LABA vs a LTRA as add-on therapy for patients whose asthma was not well controlled with ICS monotherapy.²² The LABA/ICS combination was significantly better at reducing the risk of exacerbations requiring systemic corticosteroids than monotherapy with either a LTRA or ICS, reducing the risk from 11% to 9% (RR=0.83; 95% CI, 0.71-0.97). The NNT to prevent one exacerbation over 48 weeks was 38 (95% CI, 22-244).²²

The safety of LABAs continues to be a concern, however, as serious adverse events were more common in the LABA group. The number needed to harm (NNH) with LABA therapy vs LTRA over 48 weeks was 78; 95% CI, 33 to infinity.²² (The width of the CI indicates that while harm is possible in as few as 33 patients, it is also possible that an infinite number of patients would need to be treated for one individual to incur harm.) Overall, the evidence suggests that LABAs are superior add-on therapy to ICS for the treatment of uncontrolled asthma compared with LTRAs, but their use nonetheless requires caution and close monitoring in African American and pediatric patients.¹⁷

Is there a role for a long-acting anticholinergic inhaler?

Long-acting anticholinergic medication (LAAM)—tiotropium is the only drug in this class on the market, but there are others in clinical trials—is the mainstay of therapy for chronic obstructive pulmonary disease. This drug class was not widely available or studied as an asthma treatment when the NHLBI guidelines were drafted.

A 2010 study of tiotropium challenged the notion that there is no place for LAAMs in asthma therapy. Using a 3-way crossover design, the study compared the addition of tiotropium to ICS with a double dose of ICS or a LABA/ICS combination.²³

The results suggest that LAAMs could be useful in treating uncontrolled asthma. Compared with the double dose of ICS, the tiotropium/ICS combination increased PEF by a mean difference of 25.8 L/min (P<.001) and resulted in a statistically significant improvement in the proportion of asthma control days, FEV₁, and daily symptom scores.²³ As an adjunctive treatment to ICS, tiotropium was not inferior to a LABA.

CASE After a detailed history, physical exam, and diagnostic testing, Ms. D was given a diagnosis of moderate persistent asthma. We recognized the need to step up her treatment. Prior to making any changes in her medication regimen, however, our team, which included a clinical pharmacist, observed her use of inhaled medications and verified that she was using the inhaler properly. We then initiated combination therapy, pairing a LABA and ICS.

Comorbidities complicate asthma management

Asthma management is often complicated by other uncontrolled coexisting medical problems. Common comorbidities that can affect asthma severity include allergic rhinitis, chronic sinusitis, gastroesophageal reflux disease (GERD), obesity, obstructive sleep apnea (OSA), mental health disorders, tobacco use, and hormonal disturbances.²

Allergic rhinitis. Allergic rhinitis has been associated with worse asthma control and a negative impact on quality of life, and the upper airway inflammation associated with it should be treated.²⁴

Antihistamines and nasal steroids are the most effective medical management. Some patients with allergic rhinitis benefit from blood or skin allergy testing for confirmation or to aid in avoidance. Referral to an allergist may be necessary if symptoms are recalcitrant, a food allergy is in question, or the diagnosis is unclear.

GERD. Compared with the general population, patients with asthma have a much higher risk of GERD, although it is not always symptomatic. While results are inconsistent and difficult to predict, treating symptomatic GERD with acid-blocking medications can result in better asthma control for some patients. However, proton pump inhibitors should not be used to treat asthma symptoms in patients with asymptomatic GERD.^25,26

Obesity and OSA. Weight loss can significantly improve asthma control, decrease medication use, and improve quality of life.^27,28 Obese patients are less likely to respond to treatment with ICS.² Weight loss also benefits those who suffer from OSA, which may contribute to airway hyperresponsiveness.²⁹

Mental health disorders. Compared with the general population, patients with asthma are more likely to have depression, anxiety, and panic disorders.³⁰ Diagnosis and treatment of these comorbid conditions can lead to better asthma management, increased medication adherence, decreased health care utilization—including fewer ED visits and hospitalizations—and a better quality of life.³⁰

CASE We also addressed our patient’s comorbidities—weight gain, allergic rhinitis, and anxiety. The allergic rhinitis was already well-controlled with a nasal steroid, but we suspected a relationship between Ms. D’s weight gain and increasing anxiety associated with some recent life events. We suggested she see a counselor, and she agreed.

When the patient returned in 12 weeks, she reported that she hardly needed her rescue inhaler anymore and that she was managing her anxiety more effectively. She also told us that she had begun a low-fat dietary regimen, and we confirmed that she had already lost 5 pounds.

CORRESPONDENCE 
Stephen A. Wilson, MD, MPH, FAAFP, UPMC St. Margaret, 815 Freeport Road, Pittsburgh, PA 15215; wilsons2@upmc.edu

Baseball players and other athletes who spend much of their time throwing a ball risk a variety of shoulder injuries because the repetitive motion causes repeated microtraumatic stress in the area. Injuries result from overuse of the muscles involved, improper technique—or both.

The review that follows will help you zero in on the correct diagnosis and identify the treatment that’s best for your patient.

First step: Cover these points in the history

In order to gather a detailed history of a patient with shoulder pain, you’ll want to do the following:

Ask about the location of the pain. Anterior shoulder pain is associated with subluxation, multidirectional instability, subacromial bursitis, and injury to the biceps, supraspinatus or subscapularis.¹ Posterior shoulder pain has been linked to infraspinatus injuries.

Assess the severity of the pain. Ask patients: “On a scale of one to 10, where 10 is the worst pain you have ever felt, how would you rate the pain you are feeling?”

Pinpoint the timing of the pain. Determine the phase of the throwing process that reproduces the primary symptoms. The 6 phases are wind up, early cocking, late cocking, acceleration, deceleration, and follow-through (FIGURE 1). So if, for instance, the patient tells you that his arm “went dead” during the late cocking, or early acceleration phase, it should prompt you to suspect subluxation.²

Videos

See how the Neer’s and Hawkin’s tests are done

Christopher Faubel, MD, Thepainsource.com

 

 

 Neer’s Impingement test

 

 

Hawkins test

FIGURE 1
The 6 phases of throwing

Ascertain the nature of the patient’s pain after activity. Does the patient experience the pain at night? If he answers Yes, you’ll want to consider the possibility of a rotator cuff tear.

Ask these targeted questions:

• When you raise your arm, do you feel a pinching pain in your shoulder? This may suggest the presence of impingement.
• Is your shoulder “catching” or “locking up”? If so, consider a labral tear or loose body, eg, a piece of cartilage or bone floating around in the joint.
• Does your shoulder feel like it is coming out of its socket—either partially or completely? This suggests shoulder instability.
• Is it difficult for you to reach behind your back, or do you have shoulder pain when you try to do this? This may indicate glenohumeral internal rotation deficit.
• Do you feel like you are throwing the ball slower, or with less accuracy? This may be an indication that there is something wrong with the rotator cuff muscles, the innervation around the shoulders, or the labrum that partly holds the shoulder together. Sometimes, a tear of the labrum presents simply as a “loss of power” in throwing, as defined by the athlete who is used to throwing the ball faster or farther.

Diagnoses to consider

Based on the patient’s history and responses to your questions, you’ll likely consider one of the following diagnoses as part of the differential.

External or internal impingement syndromes
What you’ll see. External or “subacromial” impingement syndrome results from compression of the rotator cuff between the coracoacromial arch and the humeral head. A sloping or hooked acromion or osteophyte may contribute to the syndrome.³ Neer’s and Hawkin’s tests are often positive, and there may be pain with the arc of motion. (For more on these and the other tests mentioned here, see “Athlete has shoulder problems? Consider these tests”.)

Internal impingement results from pinching of the rotator cuff between the posterosuperior labrum and the greater tuberosity. The pain usually occurs with repetitive maximal shoulder internal rotation and abduction, which leads to cumulative microtrauma and eventual articular-sided rotator cuff pathology.⁴ The patient will complain of pain with shoulder internal rotation and abduction. Neer’s and Hawkin’s tests are helpful in detecting internal impingement.

Shoulder girdle fatigue from lack of conditioning and overthrowing—or the tight posterior capsule often seen in throwing athletes—may also contribute to the disorder.⁴

Treatment. Proper management involves relative rest from overhead activities, and an individualized rehabilitation program that includes dynamic stretching/strengthening through the rotator cuff, posterior capsule, and scapular stabilizers. Injecting a corticosteroid-analgesic solution into the subacromial space may help you arrive at a diagnosis and also offers symptomatic relief.^1,3 Consider bursectomy, arthroscopic acromioplasty, capsulotomy and/or debridement for recalcitrant cases.^4,5

Shoulder labrum pathology
What you’ll see. Overhead-throwing athletes are at risk of labral tears. The externally rotated, abducted arm of a thrower causes posterior rotation of the biceps anchor, peeling the biceps from its superior labrum attachment,⁶ a superior labrum anterior and posterior (SLAP) tear, or a type II tear from anterior to posterior. SLAP tears may lead to shoulder catching and locking. The patient may complain of vague shoulder pain,⁷ which is worse in the late cocking phase. O’Brien’s test will be positive.

Magnetic resonance imaging (MRI) with arthrogram can reveal a labral tear. Consider ordering an MRI when the athlete’s pain is accompanied by mechanical symptoms, such as locking, catching, or instability, or if the shoulder signs and symptoms do not appear to be responding to appropriate physical therapy interventions after a period of time—usually 4 to 6 weeks.

Treatment. For small tears, conservative management includes relative rest and physical therapy.³ Depending on the tear morphology, consider arthroscopic labral debridement or repair if conservative measures fail. The literature offers mixed conclusions on the benefits of surgery, with varying rates of full return to play.^8-10

Shoulder instability
What you’ll see. Instability in throwing athletes is multifactorial, and rarely due to an isolated shoulder structure injury.¹¹ Patients will complain that their shoulder feels as if it is going to come out of its socket, even when they are not throwing. To help detect instability, look for the sulcus sign, and do a load and shift test and an apprehension-relocation test.

Two categories of injury. Instability injuries fall into 2 primary categories: TUBS (Traumatic, Unilateral, associated with Bankart lesion, treated with Surgery) and AMBRI (Atraumatic, Multidirectional, Bilateral, treated with Rehabilitation, Inferior capsular shift).

As its name makes clear, TUBS is associated with a Bankart lesion (an avulsion of the anteroinferior glenoid labrum to its attachment to the humerus). Shoulder x-rays, including outlet, axillary lateral, and anteroposterior views,³ may reveal a bony Bankart lesion. You may also see a Hill-Sachs lesion here, which is noted on the humeral posterolateral head as a depression in the bony cortex.

AMBRI is more common than TUBS in throwers. Athletes often gain a competitive edge by increasing external rotation. However, when overdone, this results in the excessive laxity seen in AMBRI. While rare, acute traumatic dislocation can occur in those with AMBRI-type instability.

Treatment. Scapular stabilization exercises, dynamic rotator cuff strengthening, relative rest, and a short course (7-10 days) of nonsteroidal anti-inflammatory drugs are the mainstays of shoulder instability treatment in the throwing athlete.^1,3 A throwing program may be started when the athlete is asymptomatic and has rested. You may also need to prescribe a longer rest period of 4 to 6 weeks if the symptoms return after commencing activity. For recalcitrant cases, consider surgery (via open or arthroscopic approaches⁶) to treat the associated underlying pathology.

Glenohumeral internal rotation deficit
What you’ll see. Posterior capsular contracture, common in the throwing athlete’s shoulder, causes decreased internal rotation and posterior shift of the total arc of glenohumeral motion.³ The patient may complain of decreased ability to reach backwards or pain when attempting to do so.

The anterior aspect of the shoulder’s capsule also lengthens, allowing anterior capsular laxity that causes additional problems, including internal impingement, SLAP tears, articular-sided, partial-thickness rotator cuff tears, and posterosuperior rotator cuff impingement. The risk for this cascade of complications increases in patients with throwing-shoulder internal rotation deficits ≥25° compared with the nonthrowing side, and a total arc of motion <180°.¹²

Treatment. Stretching the tight posterior capsule using the sleeper stretch (FIGURE 2) or the cross-body stretch (FIGURE 3) has proven very successful, with 90% of athletes seeing their symptoms resolve within 2 weeks.^13,14 If conservative treatment is ineffective, consider selective arthroscopic capsular release of the posterior inferior glenohumeral ligament.

FIGURE 2
The sleeper stretch

FIGURE 3
The cross-body stretch

Rotator cuff tears
What you’ll see. Partial-thickness, articular-sided tears of the supraspinatus, infraspinatus, or both—found posterosuperiorly at the posterior rotator interval—are common in throwing athletes. The patient may complain of weakness when trying to do overhead tasks or movements requiring shoulder abduction. The supraspinatus is usually the muscle affected, and so testing of this muscle with the “empty can test” will show pain with weakness if there is a tear. However, full-thickness rotator cuff tears are rare;³ consider a diagnosis of instability or a partial tear in such cases. An MRI can reveal a rotator cuff tear. In fact, the imaging may be necessary for any suspicion of a tear in an athlete.

Treatment. Recommend strengthening exercises to patients before considering surgery. Nonoperative treatment is preferred, and should be given a fair trial before surgery; studies have not consistently supported the operative approach to rotator cuff tears.^5,15 However, if conservative management fails, arthroscopic debridement of torn tissues is recommended over open procedures.³

Scapular dyskinesis and “SICK syndrome”
What you’ll see. Poor development of, or fatigue in, the scapular stabilizers leads to scapular dyskinesis (poor scapular control and motion). Scapulothoracic dyskinesis can progress to an overuse muscular fatigue syndrome called the “SICK syndrome” (Scapular malposition, Inferior medial border prominence, Coracoid pain and malposition, and dysKinesis of scapular movement).¹⁶ The most common symptoms include anterior shoulder pain, posterior/superior scapular pain with or without radiation,¹⁶ and a “dead arm” sensation. If not treated, this can result in rotator cuff lesions, impingement, and labral pathology.

Treatment. Both treatment and prevention are dependent on the proper biomechanics to retract and rotate the scapula correctly during throwing.¹ Strengthening the scapular stabilizers and stretching tight posterior structures help to promote proper biomechanics, and enable a successful return to throwing.¹⁴

Help patients prevent injuries in the first place

To reduce the risk of shoulder injuries, athletes need to maintain an appropriate “thrower’s motion” at the glenohumeral joint.¹⁷ Overhead throwing athletes often exhibit excessive external rotation in their dominant shoulders,¹⁸ while internal rotation is reduced.¹⁹

Frequent gentle stretching may help maintain equal total motion in both the throwing shoulder and the nondominant shoulder. However, warn patients to avoid overaggressive stretching to gain mobility; the goal should be to maintain mobility.¹⁷

Strengthening of the entire upper extremity (shoulder, scapula, elbow, and wrist) is essential. While the individual needs of each athlete must be addressed, electromyographic studies of the throwing motion suggest that stretching, strengthening, and retraining of the muscles that allow the shoulders to rotate upwards and backwards help the shoulder blade keep close to the rib cage at the back. These are the most important initial steps in rehabilitating shoulder injuries in a throwing athlete.

Prevention and treatment programs for the throwing athlete should always incorporate dynamic stabilization and neuromuscular control.¹⁷ Additionally, the transfer of kinetic energy, as well as proximal stability with distal mobility of the upper extremity, are enhanced by core stabilization drills, including planks and side planks, as well as lower body training. As such, core strengthening is a very important component of injury prevention exercise regimens for throwing athletes.

Lastly, throwing programs incorporating maximum pitch counts per day, rest days, and gentle throwing are key to injury prevention. Direct young throwing athletes and their parents to resources such as http://pediatrics.aappublications.org/content/129/3/e842.full.pdf+html. (Tell them to see the recommendations at the end of the document.) Keep in mind, however, that there are no clear recommendations for college and professional pitching.

Young athletes. It is important to note that athletes with immature skeletons are at particular risk of injury due to the relative weakness of the open growth plate and the development of muscle imbalance. It is essential to appropriately apply the principles discussed here to young athletes to prevent injury.

CORRESPONDENCE 
George Guntur A. Pujalte, MD, Penn State Milton S. Hershey Medical Center, 500 Hershey Center Drive, Hershey, PA 17033; gpujalte@hmc.psu.edu

Baseball players and other athletes who spend much of their time throwing a ball risk a variety of shoulder injuries because the repetitive motion causes repeated microtraumatic stress in the area. Injuries result from overuse of the muscles involved, improper technique—or both.

The review that follows will help you zero in on the correct diagnosis and identify the treatment that’s best for your patient.

First step: Cover these points in the history

In order to gather a detailed history of a patient with shoulder pain, you’ll want to do the following:

Ask about the location of the pain. Anterior shoulder pain is associated with subluxation, multidirectional instability, subacromial bursitis, and injury to the biceps, supraspinatus or subscapularis.¹ Posterior shoulder pain has been linked to infraspinatus injuries.

Assess the severity of the pain. Ask patients: “On a scale of one to 10, where 10 is the worst pain you have ever felt, how would you rate the pain you are feeling?”

Pinpoint the timing of the pain. Determine the phase of the throwing process that reproduces the primary symptoms. The 6 phases are wind up, early cocking, late cocking, acceleration, deceleration, and follow-through (FIGURE 1). So if, for instance, the patient tells you that his arm “went dead” during the late cocking, or early acceleration phase, it should prompt you to suspect subluxation.²

Videos

See how the Neer’s and Hawkin’s tests are done

Christopher Faubel, MD, Thepainsource.com

 

 

 Neer’s Impingement test

 

 

Hawkins test

FIGURE 1
The 6 phases of throwing

Ascertain the nature of the patient’s pain after activity. Does the patient experience the pain at night? If he answers Yes, you’ll want to consider the possibility of a rotator cuff tear.

Ask these targeted questions:

• When you raise your arm, do you feel a pinching pain in your shoulder? This may suggest the presence of impingement.
• Is your shoulder “catching” or “locking up”? If so, consider a labral tear or loose body, eg, a piece of cartilage or bone floating around in the joint.
• Does your shoulder feel like it is coming out of its socket—either partially or completely? This suggests shoulder instability.
• Is it difficult for you to reach behind your back, or do you have shoulder pain when you try to do this? This may indicate glenohumeral internal rotation deficit.
• Do you feel like you are throwing the ball slower, or with less accuracy? This may be an indication that there is something wrong with the rotator cuff muscles, the innervation around the shoulders, or the labrum that partly holds the shoulder together. Sometimes, a tear of the labrum presents simply as a “loss of power” in throwing, as defined by the athlete who is used to throwing the ball faster or farther.

Diagnoses to consider

Based on the patient’s history and responses to your questions, you’ll likely consider one of the following diagnoses as part of the differential.

External or internal impingement syndromes
What you’ll see. External or “subacromial” impingement syndrome results from compression of the rotator cuff between the coracoacromial arch and the humeral head. A sloping or hooked acromion or osteophyte may contribute to the syndrome.³ Neer’s and Hawkin’s tests are often positive, and there may be pain with the arc of motion. (For more on these and the other tests mentioned here, see “Athlete has shoulder problems? Consider these tests”.)

Internal impingement results from pinching of the rotator cuff between the posterosuperior labrum and the greater tuberosity. The pain usually occurs with repetitive maximal shoulder internal rotation and abduction, which leads to cumulative microtrauma and eventual articular-sided rotator cuff pathology.⁴ The patient will complain of pain with shoulder internal rotation and abduction. Neer’s and Hawkin’s tests are helpful in detecting internal impingement.

Shoulder girdle fatigue from lack of conditioning and overthrowing—or the tight posterior capsule often seen in throwing athletes—may also contribute to the disorder.⁴

Treatment. Proper management involves relative rest from overhead activities, and an individualized rehabilitation program that includes dynamic stretching/strengthening through the rotator cuff, posterior capsule, and scapular stabilizers. Injecting a corticosteroid-analgesic solution into the subacromial space may help you arrive at a diagnosis and also offers symptomatic relief.^1,3 Consider bursectomy, arthroscopic acromioplasty, capsulotomy and/or debridement for recalcitrant cases.^4,5

Shoulder labrum pathology
What you’ll see. Overhead-throwing athletes are at risk of labral tears. The externally rotated, abducted arm of a thrower causes posterior rotation of the biceps anchor, peeling the biceps from its superior labrum attachment,⁶ a superior labrum anterior and posterior (SLAP) tear, or a type II tear from anterior to posterior. SLAP tears may lead to shoulder catching and locking. The patient may complain of vague shoulder pain,⁷ which is worse in the late cocking phase. O’Brien’s test will be positive.

Magnetic resonance imaging (MRI) with arthrogram can reveal a labral tear. Consider ordering an MRI when the athlete’s pain is accompanied by mechanical symptoms, such as locking, catching, or instability, or if the shoulder signs and symptoms do not appear to be responding to appropriate physical therapy interventions after a period of time—usually 4 to 6 weeks.

Treatment. For small tears, conservative management includes relative rest and physical therapy.³ Depending on the tear morphology, consider arthroscopic labral debridement or repair if conservative measures fail. The literature offers mixed conclusions on the benefits of surgery, with varying rates of full return to play.^8-10

Shoulder instability
What you’ll see. Instability in throwing athletes is multifactorial, and rarely due to an isolated shoulder structure injury.¹¹ Patients will complain that their shoulder feels as if it is going to come out of its socket, even when they are not throwing. To help detect instability, look for the sulcus sign, and do a load and shift test and an apprehension-relocation test.

Two categories of injury. Instability injuries fall into 2 primary categories: TUBS (Traumatic, Unilateral, associated with Bankart lesion, treated with Surgery) and AMBRI (Atraumatic, Multidirectional, Bilateral, treated with Rehabilitation, Inferior capsular shift).

As its name makes clear, TUBS is associated with a Bankart lesion (an avulsion of the anteroinferior glenoid labrum to its attachment to the humerus). Shoulder x-rays, including outlet, axillary lateral, and anteroposterior views,³ may reveal a bony Bankart lesion. You may also see a Hill-Sachs lesion here, which is noted on the humeral posterolateral head as a depression in the bony cortex.

AMBRI is more common than TUBS in throwers. Athletes often gain a competitive edge by increasing external rotation. However, when overdone, this results in the excessive laxity seen in AMBRI. While rare, acute traumatic dislocation can occur in those with AMBRI-type instability.

Treatment. Scapular stabilization exercises, dynamic rotator cuff strengthening, relative rest, and a short course (7-10 days) of nonsteroidal anti-inflammatory drugs are the mainstays of shoulder instability treatment in the throwing athlete.^1,3 A throwing program may be started when the athlete is asymptomatic and has rested. You may also need to prescribe a longer rest period of 4 to 6 weeks if the symptoms return after commencing activity. For recalcitrant cases, consider surgery (via open or arthroscopic approaches⁶) to treat the associated underlying pathology.

Glenohumeral internal rotation deficit
What you’ll see. Posterior capsular contracture, common in the throwing athlete’s shoulder, causes decreased internal rotation and posterior shift of the total arc of glenohumeral motion.³ The patient may complain of decreased ability to reach backwards or pain when attempting to do so.

The anterior aspect of the shoulder’s capsule also lengthens, allowing anterior capsular laxity that causes additional problems, including internal impingement, SLAP tears, articular-sided, partial-thickness rotator cuff tears, and posterosuperior rotator cuff impingement. The risk for this cascade of complications increases in patients with throwing-shoulder internal rotation deficits ≥25° compared with the nonthrowing side, and a total arc of motion <180°.¹²

Treatment. Stretching the tight posterior capsule using the sleeper stretch (FIGURE 2) or the cross-body stretch (FIGURE 3) has proven very successful, with 90% of athletes seeing their symptoms resolve within 2 weeks.^13,14 If conservative treatment is ineffective, consider selective arthroscopic capsular release of the posterior inferior glenohumeral ligament.

FIGURE 2
The sleeper stretch

FIGURE 3
The cross-body stretch

Rotator cuff tears
What you’ll see. Partial-thickness, articular-sided tears of the supraspinatus, infraspinatus, or both—found posterosuperiorly at the posterior rotator interval—are common in throwing athletes. The patient may complain of weakness when trying to do overhead tasks or movements requiring shoulder abduction. The supraspinatus is usually the muscle affected, and so testing of this muscle with the “empty can test” will show pain with weakness if there is a tear. However, full-thickness rotator cuff tears are rare;³ consider a diagnosis of instability or a partial tear in such cases. An MRI can reveal a rotator cuff tear. In fact, the imaging may be necessary for any suspicion of a tear in an athlete.

Treatment. Recommend strengthening exercises to patients before considering surgery. Nonoperative treatment is preferred, and should be given a fair trial before surgery; studies have not consistently supported the operative approach to rotator cuff tears.^5,15 However, if conservative management fails, arthroscopic debridement of torn tissues is recommended over open procedures.³

Scapular dyskinesis and “SICK syndrome”
What you’ll see. Poor development of, or fatigue in, the scapular stabilizers leads to scapular dyskinesis (poor scapular control and motion). Scapulothoracic dyskinesis can progress to an overuse muscular fatigue syndrome called the “SICK syndrome” (Scapular malposition, Inferior medial border prominence, Coracoid pain and malposition, and dysKinesis of scapular movement).¹⁶ The most common symptoms include anterior shoulder pain, posterior/superior scapular pain with or without radiation,¹⁶ and a “dead arm” sensation. If not treated, this can result in rotator cuff lesions, impingement, and labral pathology.

Treatment. Both treatment and prevention are dependent on the proper biomechanics to retract and rotate the scapula correctly during throwing.¹ Strengthening the scapular stabilizers and stretching tight posterior structures help to promote proper biomechanics, and enable a successful return to throwing.¹⁴

Help patients prevent injuries in the first place

To reduce the risk of shoulder injuries, athletes need to maintain an appropriate “thrower’s motion” at the glenohumeral joint.¹⁷ Overhead throwing athletes often exhibit excessive external rotation in their dominant shoulders,¹⁸ while internal rotation is reduced.¹⁹

Frequent gentle stretching may help maintain equal total motion in both the throwing shoulder and the nondominant shoulder. However, warn patients to avoid overaggressive stretching to gain mobility; the goal should be to maintain mobility.¹⁷

Strengthening of the entire upper extremity (shoulder, scapula, elbow, and wrist) is essential. While the individual needs of each athlete must be addressed, electromyographic studies of the throwing motion suggest that stretching, strengthening, and retraining of the muscles that allow the shoulders to rotate upwards and backwards help the shoulder blade keep close to the rib cage at the back. These are the most important initial steps in rehabilitating shoulder injuries in a throwing athlete.

Prevention and treatment programs for the throwing athlete should always incorporate dynamic stabilization and neuromuscular control.¹⁷ Additionally, the transfer of kinetic energy, as well as proximal stability with distal mobility of the upper extremity, are enhanced by core stabilization drills, including planks and side planks, as well as lower body training. As such, core strengthening is a very important component of injury prevention exercise regimens for throwing athletes.

Lastly, throwing programs incorporating maximum pitch counts per day, rest days, and gentle throwing are key to injury prevention. Direct young throwing athletes and their parents to resources such as http://pediatrics.aappublications.org/content/129/3/e842.full.pdf+html. (Tell them to see the recommendations at the end of the document.) Keep in mind, however, that there are no clear recommendations for college and professional pitching.

Young athletes. It is important to note that athletes with immature skeletons are at particular risk of injury due to the relative weakness of the open growth plate and the development of muscle imbalance. It is essential to appropriately apply the principles discussed here to young athletes to prevent injury.

CORRESPONDENCE 
George Guntur A. Pujalte, MD, Penn State Milton S. Hershey Medical Center, 500 Hershey Center Drive, Hershey, PA 17033; gpujalte@hmc.psu.edu

Baseball players and other athletes who spend much of their time throwing a ball risk a variety of shoulder injuries because the repetitive motion causes repeated microtraumatic stress in the area. Injuries result from overuse of the muscles involved, improper technique—or both.

The review that follows will help you zero in on the correct diagnosis and identify the treatment that’s best for your patient.

First step: Cover these points in the history

In order to gather a detailed history of a patient with shoulder pain, you’ll want to do the following:

Ask about the location of the pain. Anterior shoulder pain is associated with subluxation, multidirectional instability, subacromial bursitis, and injury to the biceps, supraspinatus or subscapularis.¹ Posterior shoulder pain has been linked to infraspinatus injuries.

Assess the severity of the pain. Ask patients: “On a scale of one to 10, where 10 is the worst pain you have ever felt, how would you rate the pain you are feeling?”

Pinpoint the timing of the pain. Determine the phase of the throwing process that reproduces the primary symptoms. The 6 phases are wind up, early cocking, late cocking, acceleration, deceleration, and follow-through (FIGURE 1). So if, for instance, the patient tells you that his arm “went dead” during the late cocking, or early acceleration phase, it should prompt you to suspect subluxation.²

Videos

See how the Neer’s and Hawkin’s tests are done

Christopher Faubel, MD, Thepainsource.com

 

 

 Neer’s Impingement test

 

 

Hawkins test

FIGURE 1
The 6 phases of throwing

Ascertain the nature of the patient’s pain after activity. Does the patient experience the pain at night? If he answers Yes, you’ll want to consider the possibility of a rotator cuff tear.

Ask these targeted questions:

• When you raise your arm, do you feel a pinching pain in your shoulder? This may suggest the presence of impingement.
• Is your shoulder “catching” or “locking up”? If so, consider a labral tear or loose body, eg, a piece of cartilage or bone floating around in the joint.
• Does your shoulder feel like it is coming out of its socket—either partially or completely? This suggests shoulder instability.
• Is it difficult for you to reach behind your back, or do you have shoulder pain when you try to do this? This may indicate glenohumeral internal rotation deficit.
• Do you feel like you are throwing the ball slower, or with less accuracy? This may be an indication that there is something wrong with the rotator cuff muscles, the innervation around the shoulders, or the labrum that partly holds the shoulder together. Sometimes, a tear of the labrum presents simply as a “loss of power” in throwing, as defined by the athlete who is used to throwing the ball faster or farther.

Diagnoses to consider

Based on the patient’s history and responses to your questions, you’ll likely consider one of the following diagnoses as part of the differential.

External or internal impingement syndromes
What you’ll see. External or “subacromial” impingement syndrome results from compression of the rotator cuff between the coracoacromial arch and the humeral head. A sloping or hooked acromion or osteophyte may contribute to the syndrome.³ Neer’s and Hawkin’s tests are often positive, and there may be pain with the arc of motion. (For more on these and the other tests mentioned here, see “Athlete has shoulder problems? Consider these tests”.)

Internal impingement results from pinching of the rotator cuff between the posterosuperior labrum and the greater tuberosity. The pain usually occurs with repetitive maximal shoulder internal rotation and abduction, which leads to cumulative microtrauma and eventual articular-sided rotator cuff pathology.⁴ The patient will complain of pain with shoulder internal rotation and abduction. Neer’s and Hawkin’s tests are helpful in detecting internal impingement.

Shoulder girdle fatigue from lack of conditioning and overthrowing—or the tight posterior capsule often seen in throwing athletes—may also contribute to the disorder.⁴

Treatment. Proper management involves relative rest from overhead activities, and an individualized rehabilitation program that includes dynamic stretching/strengthening through the rotator cuff, posterior capsule, and scapular stabilizers. Injecting a corticosteroid-analgesic solution into the subacromial space may help you arrive at a diagnosis and also offers symptomatic relief.^1,3 Consider bursectomy, arthroscopic acromioplasty, capsulotomy and/or debridement for recalcitrant cases.^4,5

Shoulder labrum pathology
What you’ll see. Overhead-throwing athletes are at risk of labral tears. The externally rotated, abducted arm of a thrower causes posterior rotation of the biceps anchor, peeling the biceps from its superior labrum attachment,⁶ a superior labrum anterior and posterior (SLAP) tear, or a type II tear from anterior to posterior. SLAP tears may lead to shoulder catching and locking. The patient may complain of vague shoulder pain,⁷ which is worse in the late cocking phase. O’Brien’s test will be positive.

Magnetic resonance imaging (MRI) with arthrogram can reveal a labral tear. Consider ordering an MRI when the athlete’s pain is accompanied by mechanical symptoms, such as locking, catching, or instability, or if the shoulder signs and symptoms do not appear to be responding to appropriate physical therapy interventions after a period of time—usually 4 to 6 weeks.

Treatment. For small tears, conservative management includes relative rest and physical therapy.³ Depending on the tear morphology, consider arthroscopic labral debridement or repair if conservative measures fail. The literature offers mixed conclusions on the benefits of surgery, with varying rates of full return to play.^8-10

Shoulder instability
What you’ll see. Instability in throwing athletes is multifactorial, and rarely due to an isolated shoulder structure injury.¹¹ Patients will complain that their shoulder feels as if it is going to come out of its socket, even when they are not throwing. To help detect instability, look for the sulcus sign, and do a load and shift test and an apprehension-relocation test.

Two categories of injury. Instability injuries fall into 2 primary categories: TUBS (Traumatic, Unilateral, associated with Bankart lesion, treated with Surgery) and AMBRI (Atraumatic, Multidirectional, Bilateral, treated with Rehabilitation, Inferior capsular shift).

As its name makes clear, TUBS is associated with a Bankart lesion (an avulsion of the anteroinferior glenoid labrum to its attachment to the humerus). Shoulder x-rays, including outlet, axillary lateral, and anteroposterior views,³ may reveal a bony Bankart lesion. You may also see a Hill-Sachs lesion here, which is noted on the humeral posterolateral head as a depression in the bony cortex.

AMBRI is more common than TUBS in throwers. Athletes often gain a competitive edge by increasing external rotation. However, when overdone, this results in the excessive laxity seen in AMBRI. While rare, acute traumatic dislocation can occur in those with AMBRI-type instability.

Treatment. Scapular stabilization exercises, dynamic rotator cuff strengthening, relative rest, and a short course (7-10 days) of nonsteroidal anti-inflammatory drugs are the mainstays of shoulder instability treatment in the throwing athlete.^1,3 A throwing program may be started when the athlete is asymptomatic and has rested. You may also need to prescribe a longer rest period of 4 to 6 weeks if the symptoms return after commencing activity. For recalcitrant cases, consider surgery (via open or arthroscopic approaches⁶) to treat the associated underlying pathology.

Glenohumeral internal rotation deficit
What you’ll see. Posterior capsular contracture, common in the throwing athlete’s shoulder, causes decreased internal rotation and posterior shift of the total arc of glenohumeral motion.³ The patient may complain of decreased ability to reach backwards or pain when attempting to do so.

The anterior aspect of the shoulder’s capsule also lengthens, allowing anterior capsular laxity that causes additional problems, including internal impingement, SLAP tears, articular-sided, partial-thickness rotator cuff tears, and posterosuperior rotator cuff impingement. The risk for this cascade of complications increases in patients with throwing-shoulder internal rotation deficits ≥25° compared with the nonthrowing side, and a total arc of motion <180°.¹²

Treatment. Stretching the tight posterior capsule using the sleeper stretch (FIGURE 2) or the cross-body stretch (FIGURE 3) has proven very successful, with 90% of athletes seeing their symptoms resolve within 2 weeks.^13,14 If conservative treatment is ineffective, consider selective arthroscopic capsular release of the posterior inferior glenohumeral ligament.

FIGURE 2
The sleeper stretch

FIGURE 3
The cross-body stretch

Rotator cuff tears
What you’ll see. Partial-thickness, articular-sided tears of the supraspinatus, infraspinatus, or both—found posterosuperiorly at the posterior rotator interval—are common in throwing athletes. The patient may complain of weakness when trying to do overhead tasks or movements requiring shoulder abduction. The supraspinatus is usually the muscle affected, and so testing of this muscle with the “empty can test” will show pain with weakness if there is a tear. However, full-thickness rotator cuff tears are rare;³ consider a diagnosis of instability or a partial tear in such cases. An MRI can reveal a rotator cuff tear. In fact, the imaging may be necessary for any suspicion of a tear in an athlete.

Treatment. Recommend strengthening exercises to patients before considering surgery. Nonoperative treatment is preferred, and should be given a fair trial before surgery; studies have not consistently supported the operative approach to rotator cuff tears.^5,15 However, if conservative management fails, arthroscopic debridement of torn tissues is recommended over open procedures.³

Scapular dyskinesis and “SICK syndrome”
What you’ll see. Poor development of, or fatigue in, the scapular stabilizers leads to scapular dyskinesis (poor scapular control and motion). Scapulothoracic dyskinesis can progress to an overuse muscular fatigue syndrome called the “SICK syndrome” (Scapular malposition, Inferior medial border prominence, Coracoid pain and malposition, and dysKinesis of scapular movement).¹⁶ The most common symptoms include anterior shoulder pain, posterior/superior scapular pain with or without radiation,¹⁶ and a “dead arm” sensation. If not treated, this can result in rotator cuff lesions, impingement, and labral pathology.

Treatment. Both treatment and prevention are dependent on the proper biomechanics to retract and rotate the scapula correctly during throwing.¹ Strengthening the scapular stabilizers and stretching tight posterior structures help to promote proper biomechanics, and enable a successful return to throwing.¹⁴

Help patients prevent injuries in the first place

To reduce the risk of shoulder injuries, athletes need to maintain an appropriate “thrower’s motion” at the glenohumeral joint.¹⁷ Overhead throwing athletes often exhibit excessive external rotation in their dominant shoulders,¹⁸ while internal rotation is reduced.¹⁹

Frequent gentle stretching may help maintain equal total motion in both the throwing shoulder and the nondominant shoulder. However, warn patients to avoid overaggressive stretching to gain mobility; the goal should be to maintain mobility.¹⁷

Strengthening of the entire upper extremity (shoulder, scapula, elbow, and wrist) is essential. While the individual needs of each athlete must be addressed, electromyographic studies of the throwing motion suggest that stretching, strengthening, and retraining of the muscles that allow the shoulders to rotate upwards and backwards help the shoulder blade keep close to the rib cage at the back. These are the most important initial steps in rehabilitating shoulder injuries in a throwing athlete.

Prevention and treatment programs for the throwing athlete should always incorporate dynamic stabilization and neuromuscular control.¹⁷ Additionally, the transfer of kinetic energy, as well as proximal stability with distal mobility of the upper extremity, are enhanced by core stabilization drills, including planks and side planks, as well as lower body training. As such, core strengthening is a very important component of injury prevention exercise regimens for throwing athletes.

Lastly, throwing programs incorporating maximum pitch counts per day, rest days, and gentle throwing are key to injury prevention. Direct young throwing athletes and their parents to resources such as http://pediatrics.aappublications.org/content/129/3/e842.full.pdf+html. (Tell them to see the recommendations at the end of the document.) Keep in mind, however, that there are no clear recommendations for college and professional pitching.

Young athletes. It is important to note that athletes with immature skeletons are at particular risk of injury due to the relative weakness of the open growth plate and the development of muscle imbalance. It is essential to appropriately apply the principles discussed here to young athletes to prevent injury.

CORRESPONDENCE 
George Guntur A. Pujalte, MD, Penn State Milton S. Hershey Medical Center, 500 Hershey Center Drive, Hershey, PA 17033; gpujalte@hmc.psu.edu

A survey from the National Institute of Child Health and Human Development estimated that 20% of 6th through 10th graders admitted to bullying their classmates.¹ In addition to an increased risk for personal injury, bullied children are more likely to report low self-esteem and emotional problems² and often experience loneliness.¹ In contrast, children who bully suffer in their school performance¹ and are more likely to engage in drug use³ and violence⁴ later in life. Child psychiatrists often see both bullies and their victims.

Evidence-based recommendations are available to help educators improve the school climate⁵ and identify children who are at an increased risk for bullying,⁶ but research supporting specific clinical strategies for managing a child who bullies is limited. Establishing rapport and engaging a bully often is challenging; these difficulties further complicate assessment and successful management of such children.

We present the mnemonic MEAN to help clinicians assess and understand children who bully.

Model. Discuss, demonstrate, and practice models of alternative social skills and behaviors, including active listening, being open to others’ views, accepting failure, controlling impulses, developing problem-solving techniques, and treating others with respect.

Empathize. Encourage children who bully to explore their feelings about themselves—which may uncover poor self-esteem, anger, or guilt—and acknowledge the hurt they cause others by bullying. Focusing on the pain they inflict on others in the context of personal experiences of pain that likely is driving their aggression may enable bullies to empathize with their victims.

Assess. Help the bully assess the costs and benefits of his or her behavior. Point out what the bully stands to gain from ending his or her aggressive behavior, which likely already has resulted in lost recesses, after school detentions, missed sports practices, and the loss of privileges at home. Most importantly, assess and treat any underlying psychopathology, including mood and anxiety disorders.

Nurture. Aid the bully in identifying his or her prosocial strengths to build self-esteem and thereby reduce the need to commit aggressive acts as a means of gaining a sense of control or personal security. Disarm the child with your genuine concern for his or her well-being.

Using these psychotherapeutic techniques may enhance establishing rapport with a child who bullies and may improve outcomes.

Disclosures

Dr. Kepple reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Madaan receives grant or research support from Eli Lilly and Company, Forest Pharmaceuticals, Merck, Otsuka, Pfizer Inc., and Shire.

A survey from the National Institute of Child Health and Human Development estimated that 20% of 6th through 10th graders admitted to bullying their classmates.¹ In addition to an increased risk for personal injury, bullied children are more likely to report low self-esteem and emotional problems² and often experience loneliness.¹ In contrast, children who bully suffer in their school performance¹ and are more likely to engage in drug use³ and violence⁴ later in life. Child psychiatrists often see both bullies and their victims.

Evidence-based recommendations are available to help educators improve the school climate⁵ and identify children who are at an increased risk for bullying,⁶ but research supporting specific clinical strategies for managing a child who bullies is limited. Establishing rapport and engaging a bully often is challenging; these difficulties further complicate assessment and successful management of such children.

We present the mnemonic MEAN to help clinicians assess and understand children who bully.

Model. Discuss, demonstrate, and practice models of alternative social skills and behaviors, including active listening, being open to others’ views, accepting failure, controlling impulses, developing problem-solving techniques, and treating others with respect.

Empathize. Encourage children who bully to explore their feelings about themselves—which may uncover poor self-esteem, anger, or guilt—and acknowledge the hurt they cause others by bullying. Focusing on the pain they inflict on others in the context of personal experiences of pain that likely is driving their aggression may enable bullies to empathize with their victims.

Assess. Help the bully assess the costs and benefits of his or her behavior. Point out what the bully stands to gain from ending his or her aggressive behavior, which likely already has resulted in lost recesses, after school detentions, missed sports practices, and the loss of privileges at home. Most importantly, assess and treat any underlying psychopathology, including mood and anxiety disorders.

Nurture. Aid the bully in identifying his or her prosocial strengths to build self-esteem and thereby reduce the need to commit aggressive acts as a means of gaining a sense of control or personal security. Disarm the child with your genuine concern for his or her well-being.

Using these psychotherapeutic techniques may enhance establishing rapport with a child who bullies and may improve outcomes.

Disclosures

Dr. Kepple reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Madaan receives grant or research support from Eli Lilly and Company, Forest Pharmaceuticals, Merck, Otsuka, Pfizer Inc., and Shire.

A survey from the National Institute of Child Health and Human Development estimated that 20% of 6th through 10th graders admitted to bullying their classmates.¹ In addition to an increased risk for personal injury, bullied children are more likely to report low self-esteem and emotional problems² and often experience loneliness.¹ In contrast, children who bully suffer in their school performance¹ and are more likely to engage in drug use³ and violence⁴ later in life. Child psychiatrists often see both bullies and their victims.

Evidence-based recommendations are available to help educators improve the school climate⁵ and identify children who are at an increased risk for bullying,⁶ but research supporting specific clinical strategies for managing a child who bullies is limited. Establishing rapport and engaging a bully often is challenging; these difficulties further complicate assessment and successful management of such children.

We present the mnemonic MEAN to help clinicians assess and understand children who bully.

Model. Discuss, demonstrate, and practice models of alternative social skills and behaviors, including active listening, being open to others’ views, accepting failure, controlling impulses, developing problem-solving techniques, and treating others with respect.

Empathize. Encourage children who bully to explore their feelings about themselves—which may uncover poor self-esteem, anger, or guilt—and acknowledge the hurt they cause others by bullying. Focusing on the pain they inflict on others in the context of personal experiences of pain that likely is driving their aggression may enable bullies to empathize with their victims.

Assess. Help the bully assess the costs and benefits of his or her behavior. Point out what the bully stands to gain from ending his or her aggressive behavior, which likely already has resulted in lost recesses, after school detentions, missed sports practices, and the loss of privileges at home. Most importantly, assess and treat any underlying psychopathology, including mood and anxiety disorders.

Nurture. Aid the bully in identifying his or her prosocial strengths to build self-esteem and thereby reduce the need to commit aggressive acts as a means of gaining a sense of control or personal security. Disarm the child with your genuine concern for his or her well-being.

Using these psychotherapeutic techniques may enhance establishing rapport with a child who bullies and may improve outcomes.

Disclosures

Dr. Kepple reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Madaan receives grant or research support from Eli Lilly and Company, Forest Pharmaceuticals, Merck, Otsuka, Pfizer Inc., and Shire.