Mary Ann Moon

Acetazolamide failed to reduce the duration of invasive mechanical ventilation in chronic obstructive pulmonary disease (COPD) patients who had pure or mixed metabolic alkalosis, according to results from a clinical trial published online Feb. 2 in JAMA.

Acetazolamide is a carbonic anhydrase inhibitor used as a respiratory stimulant in patients who have COPD and metabolic alkalosis. Recent studies suggested that high doses of the drug (1,000 mg/day or more) might shorten the duration of mechanical ventilation in critically ill COPD patients who require invasive mechanical ventilation, by markedly lowering serum bicarbonate and raising minute ventilation, said Dr. Christophe Faisy of the medical intensive care unit, European Georges Pompidou Hospital, Paris, and his associates.

To test this hypothesis, Dr. Faisy and his associates in the DIABOLO trial assessed 380 adults with COPD who were being treated at 15 French ICUs. One patient was receiving ventilation through a tracheotomy tube and the rest through endotracheal intubation. These study participants were randomly assigned in a double-blind fashion to receive either 500 mg acetazolamide twice daily or 1,000 mg acetazolamide twice daily if they were concomitantly receiving loop diuretics (187 patients), or a matching placebo (193 patients), administered as a slow intravenous injection.

Patients in the active-treatment group achieved larger reductions in serum bicarbonate and had fewer days with metabolic alkalosis. Nevertheless, the primary efficacy outcome – the duration of invasive ventilation – did not differ significantly between the two study groups. The median duration of ventilation was 136.5 hours with acetazolamide and 163.0 hours with placebo, which is clinically substantial but did not reach statistical significance, the investigators said (JAMA. 2016 Feb 2. doi: 10.1001/jama.2016.0019).

Acetazolamide didn’t exert a respiratory stimulant effect as measured by changes in respiratory rate, tidal volume, or minute ventilation. And there were no significant differences between the two study groups in secondary outcomes such as time to weaning off ventilation, rate of successful weaning, number of spontaneous breathing trials, use of tracheotomy or noninvasive ventilation after extubation, unplanned extubations, episodes of ventilator-associated pneumonia, laboratory values, length of ICU stay, or in-ICU mortality.

In addition, rates of adjunctive treatment using loop diuretics, glucocorticoids, beta-agonists, or catecholamines were the same between the two study groups, and left ventricular ejection fraction at weaning from ventilation also was the same. The rate of serious adverse events also was comparable.

“Taken together, these findings indicate that the inhibition of the renal carbonic anhydrase enzyme and the resulting serum bicarbonate reduction did not trigger a sufficient respiratory-stimulating effect to affect outcomes of critically ill patients with COPD,” Dr. Faisy and his associates wrote.

However, they noted that in both study groups the median duration of invasive mechanical ventilation was shorter than had been anticipated when the trial was designed, which likely decreased the statistical power of the primary endpoint. “It is possible that the study was underpowered to establish statistical significance,” the researchers said.

It is also possible that higher doses of acetazolamide may have exerted a greater effect on respiratory parameters. However, higher doses also may have increased the workload of the respiratory muscles and induced respiratory muscle fatigue, they added.

Acetazolamide failed to reduce the duration of invasive mechanical ventilation in chronic obstructive pulmonary disease (COPD) patients who had pure or mixed metabolic alkalosis, according to results from a clinical trial published online Feb. 2 in JAMA.

Acetazolamide is a carbonic anhydrase inhibitor used as a respiratory stimulant in patients who have COPD and metabolic alkalosis. Recent studies suggested that high doses of the drug (1,000 mg/day or more) might shorten the duration of mechanical ventilation in critically ill COPD patients who require invasive mechanical ventilation, by markedly lowering serum bicarbonate and raising minute ventilation, said Dr. Christophe Faisy of the medical intensive care unit, European Georges Pompidou Hospital, Paris, and his associates.

To test this hypothesis, Dr. Faisy and his associates in the DIABOLO trial assessed 380 adults with COPD who were being treated at 15 French ICUs. One patient was receiving ventilation through a tracheotomy tube and the rest through endotracheal intubation. These study participants were randomly assigned in a double-blind fashion to receive either 500 mg acetazolamide twice daily or 1,000 mg acetazolamide twice daily if they were concomitantly receiving loop diuretics (187 patients), or a matching placebo (193 patients), administered as a slow intravenous injection.

Patients in the active-treatment group achieved larger reductions in serum bicarbonate and had fewer days with metabolic alkalosis. Nevertheless, the primary efficacy outcome – the duration of invasive ventilation – did not differ significantly between the two study groups. The median duration of ventilation was 136.5 hours with acetazolamide and 163.0 hours with placebo, which is clinically substantial but did not reach statistical significance, the investigators said (JAMA. 2016 Feb 2. doi: 10.1001/jama.2016.0019).

Acetazolamide didn’t exert a respiratory stimulant effect as measured by changes in respiratory rate, tidal volume, or minute ventilation. And there were no significant differences between the two study groups in secondary outcomes such as time to weaning off ventilation, rate of successful weaning, number of spontaneous breathing trials, use of tracheotomy or noninvasive ventilation after extubation, unplanned extubations, episodes of ventilator-associated pneumonia, laboratory values, length of ICU stay, or in-ICU mortality.

In addition, rates of adjunctive treatment using loop diuretics, glucocorticoids, beta-agonists, or catecholamines were the same between the two study groups, and left ventricular ejection fraction at weaning from ventilation also was the same. The rate of serious adverse events also was comparable.

“Taken together, these findings indicate that the inhibition of the renal carbonic anhydrase enzyme and the resulting serum bicarbonate reduction did not trigger a sufficient respiratory-stimulating effect to affect outcomes of critically ill patients with COPD,” Dr. Faisy and his associates wrote.

However, they noted that in both study groups the median duration of invasive mechanical ventilation was shorter than had been anticipated when the trial was designed, which likely decreased the statistical power of the primary endpoint. “It is possible that the study was underpowered to establish statistical significance,” the researchers said.

It is also possible that higher doses of acetazolamide may have exerted a greater effect on respiratory parameters. However, higher doses also may have increased the workload of the respiratory muscles and induced respiratory muscle fatigue, they added.

Acetazolamide failed to reduce the duration of invasive mechanical ventilation in chronic obstructive pulmonary disease (COPD) patients who had pure or mixed metabolic alkalosis, according to results from a clinical trial published online Feb. 2 in JAMA.

Acetazolamide is a carbonic anhydrase inhibitor used as a respiratory stimulant in patients who have COPD and metabolic alkalosis. Recent studies suggested that high doses of the drug (1,000 mg/day or more) might shorten the duration of mechanical ventilation in critically ill COPD patients who require invasive mechanical ventilation, by markedly lowering serum bicarbonate and raising minute ventilation, said Dr. Christophe Faisy of the medical intensive care unit, European Georges Pompidou Hospital, Paris, and his associates.

To test this hypothesis, Dr. Faisy and his associates in the DIABOLO trial assessed 380 adults with COPD who were being treated at 15 French ICUs. One patient was receiving ventilation through a tracheotomy tube and the rest through endotracheal intubation. These study participants were randomly assigned in a double-blind fashion to receive either 500 mg acetazolamide twice daily or 1,000 mg acetazolamide twice daily if they were concomitantly receiving loop diuretics (187 patients), or a matching placebo (193 patients), administered as a slow intravenous injection.

Patients in the active-treatment group achieved larger reductions in serum bicarbonate and had fewer days with metabolic alkalosis. Nevertheless, the primary efficacy outcome – the duration of invasive ventilation – did not differ significantly between the two study groups. The median duration of ventilation was 136.5 hours with acetazolamide and 163.0 hours with placebo, which is clinically substantial but did not reach statistical significance, the investigators said (JAMA. 2016 Feb 2. doi: 10.1001/jama.2016.0019).

Acetazolamide didn’t exert a respiratory stimulant effect as measured by changes in respiratory rate, tidal volume, or minute ventilation. And there were no significant differences between the two study groups in secondary outcomes such as time to weaning off ventilation, rate of successful weaning, number of spontaneous breathing trials, use of tracheotomy or noninvasive ventilation after extubation, unplanned extubations, episodes of ventilator-associated pneumonia, laboratory values, length of ICU stay, or in-ICU mortality.

In addition, rates of adjunctive treatment using loop diuretics, glucocorticoids, beta-agonists, or catecholamines were the same between the two study groups, and left ventricular ejection fraction at weaning from ventilation also was the same. The rate of serious adverse events also was comparable.

“Taken together, these findings indicate that the inhibition of the renal carbonic anhydrase enzyme and the resulting serum bicarbonate reduction did not trigger a sufficient respiratory-stimulating effect to affect outcomes of critically ill patients with COPD,” Dr. Faisy and his associates wrote.

However, they noted that in both study groups the median duration of invasive mechanical ventilation was shorter than had been anticipated when the trial was designed, which likely decreased the statistical power of the primary endpoint. “It is possible that the study was underpowered to establish statistical significance,” the researchers said.

It is also possible that higher doses of acetazolamide may have exerted a greater effect on respiratory parameters. However, higher doses also may have increased the workload of the respiratory muscles and induced respiratory muscle fatigue, they added.

Increasing weight loss between midlife and late life is a marker for mild cognitive impairment, according to a report published online Feb. 1 in JAMA Neurology.

“While weight loss may not be causally related to MCI [mild cognitive impairment], we hypothesize that weight loss may represent a prodromal stage or an early manifestation of MCI,” wrote Dr. Rabe E. Alhurani of the department of neurology, Mayo Clinic, Rochester, Minn. and his associates.

©Thinkstock

Some recent studies have reported a link between weight loss and dementia, “but overall, the findings of different studies have been inconclusive,” they noted.

To examine any association between weight loss over time and incident MCI, the investigators analyzed information in the population-based Mayo Clinic Study of Aging database, which covered approximately 10,000 residents of Olmsted County, Minn., who were aged 70-89 years at the beginning of the study in 2004. They focused on 1,895 participants who were cognitively normal at entry into the study and whose medical records included data on weight and height from midlife (age 40-65 years) onward. All these study subjects underwent physical examination and extensive neuropsychological evaluation every 15 months for a mean of 4.4 years.

A total of 524 study participants developed MCI during follow-up. The mean weight loss since midlife was significantly greater for people who developed MCI (–2.0 kg) than for those who remained cognitively normal (–1.2 kg). After the data were adjusted to account for patient sex, education level, and apolipoprotein E epsilon-4 allele status, loss of weight after midlife was robustly associated with incident MCI, so that a loss of 5 kg per decade corresponded to a 24% increase in risk of MCI, Dr. Alhurani and his associates reported (JAMA Neurol. 2016 Feb 1. doi: 10.1001/jamaneurol.2015.4756).

These findings remained consistent across all categories of baseline weight, regardless of whether the participants were underweight, normal weight, overweight, or obese at enrollment. The effect sizes of the associations were greater in men than in women but were significant in both sexes.

This study could not establish causality, but the researchers speculated that the association between weight loss and MCI could be due to three possible mechanisms. First, the weight loss could stem from the “anorexia of aging,” meaning that dysfunctional production of certain hormones – such as cholecystokinin, leptin, cytokines, dynorphin, neuropeptide Y, and serotonin – or dysfunctional dietary intakes and energy metabolism could lead patients to eat less, which could in turn raise MCI risk.

Second, “neuropsychiatric symptoms such as depression and apathy, which are prodromal and predictors of MCI and dementia, may contribute to decreased appetite and weight loss prior to the diagnosis of these conditions,” they suggested.

Third, weight loss and MCI could share an etiology. Researchers have reported finding protein deposits, including deposits of Lewy bodies, tau, or amyloid, in the olfactory bulb and central olfactory pathways before the onset of dementia, and olfactory dysfunction is a marker for cognitive impairment and dementia. “Impairment in smell with related changes in taste may contribute to decreased appetite, reduced dietary intake, and the weight loss observed with MCI, Alzheimer dementia, and other neurodegenerative conditions,” Dr. Alhurani and his associates wrote.

This study was supported by the National Institutes of Health, the Mayo Foundation for Medical Education and Research, the Robert H. and Clarice Smith and Abigail van Buren Alzheimer’s Disease Research Program, the National Center for Advancing Translational Sciences, and the Rochester Epidemiology Project. Potential conflicts of interest reported by individual investigators included research support from the NIH, the Alzheimer Drug Discovery Foundation, and the Lewy Body Association; serving on a data safety monitoring board for Janssen, Lundbeck, Pfizer, and the Dominantly Inherited Alzheimer Network study; serving as an investigator for clinical trials sponsored by TauRX, Lilly, and the Alzheimer’s Disease Cooperative Study; serving as a consultant for Roche, Merck, Genentech, Biogen, and Eli Lilly; and receiving publishing royalties for the textbook, “Mild Cognitive Impairment.” 

Increasing weight loss between midlife and late life is a marker for mild cognitive impairment, according to a report published online Feb. 1 in JAMA Neurology.

“While weight loss may not be causally related to MCI [mild cognitive impairment], we hypothesize that weight loss may represent a prodromal stage or an early manifestation of MCI,” wrote Dr. Rabe E. Alhurani of the department of neurology, Mayo Clinic, Rochester, Minn. and his associates.

©Thinkstock

Some recent studies have reported a link between weight loss and dementia, “but overall, the findings of different studies have been inconclusive,” they noted.

To examine any association between weight loss over time and incident MCI, the investigators analyzed information in the population-based Mayo Clinic Study of Aging database, which covered approximately 10,000 residents of Olmsted County, Minn., who were aged 70-89 years at the beginning of the study in 2004. They focused on 1,895 participants who were cognitively normal at entry into the study and whose medical records included data on weight and height from midlife (age 40-65 years) onward. All these study subjects underwent physical examination and extensive neuropsychological evaluation every 15 months for a mean of 4.4 years.

A total of 524 study participants developed MCI during follow-up. The mean weight loss since midlife was significantly greater for people who developed MCI (–2.0 kg) than for those who remained cognitively normal (–1.2 kg). After the data were adjusted to account for patient sex, education level, and apolipoprotein E epsilon-4 allele status, loss of weight after midlife was robustly associated with incident MCI, so that a loss of 5 kg per decade corresponded to a 24% increase in risk of MCI, Dr. Alhurani and his associates reported (JAMA Neurol. 2016 Feb 1. doi: 10.1001/jamaneurol.2015.4756).

These findings remained consistent across all categories of baseline weight, regardless of whether the participants were underweight, normal weight, overweight, or obese at enrollment. The effect sizes of the associations were greater in men than in women but were significant in both sexes.

This study could not establish causality, but the researchers speculated that the association between weight loss and MCI could be due to three possible mechanisms. First, the weight loss could stem from the “anorexia of aging,” meaning that dysfunctional production of certain hormones – such as cholecystokinin, leptin, cytokines, dynorphin, neuropeptide Y, and serotonin – or dysfunctional dietary intakes and energy metabolism could lead patients to eat less, which could in turn raise MCI risk.

Second, “neuropsychiatric symptoms such as depression and apathy, which are prodromal and predictors of MCI and dementia, may contribute to decreased appetite and weight loss prior to the diagnosis of these conditions,” they suggested.

Third, weight loss and MCI could share an etiology. Researchers have reported finding protein deposits, including deposits of Lewy bodies, tau, or amyloid, in the olfactory bulb and central olfactory pathways before the onset of dementia, and olfactory dysfunction is a marker for cognitive impairment and dementia. “Impairment in smell with related changes in taste may contribute to decreased appetite, reduced dietary intake, and the weight loss observed with MCI, Alzheimer dementia, and other neurodegenerative conditions,” Dr. Alhurani and his associates wrote.

This study was supported by the National Institutes of Health, the Mayo Foundation for Medical Education and Research, the Robert H. and Clarice Smith and Abigail van Buren Alzheimer’s Disease Research Program, the National Center for Advancing Translational Sciences, and the Rochester Epidemiology Project. Potential conflicts of interest reported by individual investigators included research support from the NIH, the Alzheimer Drug Discovery Foundation, and the Lewy Body Association; serving on a data safety monitoring board for Janssen, Lundbeck, Pfizer, and the Dominantly Inherited Alzheimer Network study; serving as an investigator for clinical trials sponsored by TauRX, Lilly, and the Alzheimer’s Disease Cooperative Study; serving as a consultant for Roche, Merck, Genentech, Biogen, and Eli Lilly; and receiving publishing royalties for the textbook, “Mild Cognitive Impairment.” 

Increasing weight loss between midlife and late life is a marker for mild cognitive impairment, according to a report published online Feb. 1 in JAMA Neurology.

“While weight loss may not be causally related to MCI [mild cognitive impairment], we hypothesize that weight loss may represent a prodromal stage or an early manifestation of MCI,” wrote Dr. Rabe E. Alhurani of the department of neurology, Mayo Clinic, Rochester, Minn. and his associates.

©Thinkstock

Some recent studies have reported a link between weight loss and dementia, “but overall, the findings of different studies have been inconclusive,” they noted.

To examine any association between weight loss over time and incident MCI, the investigators analyzed information in the population-based Mayo Clinic Study of Aging database, which covered approximately 10,000 residents of Olmsted County, Minn., who were aged 70-89 years at the beginning of the study in 2004. They focused on 1,895 participants who were cognitively normal at entry into the study and whose medical records included data on weight and height from midlife (age 40-65 years) onward. All these study subjects underwent physical examination and extensive neuropsychological evaluation every 15 months for a mean of 4.4 years.

A total of 524 study participants developed MCI during follow-up. The mean weight loss since midlife was significantly greater for people who developed MCI (–2.0 kg) than for those who remained cognitively normal (–1.2 kg). After the data were adjusted to account for patient sex, education level, and apolipoprotein E epsilon-4 allele status, loss of weight after midlife was robustly associated with incident MCI, so that a loss of 5 kg per decade corresponded to a 24% increase in risk of MCI, Dr. Alhurani and his associates reported (JAMA Neurol. 2016 Feb 1. doi: 10.1001/jamaneurol.2015.4756).

These findings remained consistent across all categories of baseline weight, regardless of whether the participants were underweight, normal weight, overweight, or obese at enrollment. The effect sizes of the associations were greater in men than in women but were significant in both sexes.

This study could not establish causality, but the researchers speculated that the association between weight loss and MCI could be due to three possible mechanisms. First, the weight loss could stem from the “anorexia of aging,” meaning that dysfunctional production of certain hormones – such as cholecystokinin, leptin, cytokines, dynorphin, neuropeptide Y, and serotonin – or dysfunctional dietary intakes and energy metabolism could lead patients to eat less, which could in turn raise MCI risk.

Second, “neuropsychiatric symptoms such as depression and apathy, which are prodromal and predictors of MCI and dementia, may contribute to decreased appetite and weight loss prior to the diagnosis of these conditions,” they suggested.

Third, weight loss and MCI could share an etiology. Researchers have reported finding protein deposits, including deposits of Lewy bodies, tau, or amyloid, in the olfactory bulb and central olfactory pathways before the onset of dementia, and olfactory dysfunction is a marker for cognitive impairment and dementia. “Impairment in smell with related changes in taste may contribute to decreased appetite, reduced dietary intake, and the weight loss observed with MCI, Alzheimer dementia, and other neurodegenerative conditions,” Dr. Alhurani and his associates wrote.

This study was supported by the National Institutes of Health, the Mayo Foundation for Medical Education and Research, the Robert H. and Clarice Smith and Abigail van Buren Alzheimer’s Disease Research Program, the National Center for Advancing Translational Sciences, and the Rochester Epidemiology Project. Potential conflicts of interest reported by individual investigators included research support from the NIH, the Alzheimer Drug Discovery Foundation, and the Lewy Body Association; serving on a data safety monitoring board for Janssen, Lundbeck, Pfizer, and the Dominantly Inherited Alzheimer Network study; serving as an investigator for clinical trials sponsored by TauRX, Lilly, and the Alzheimer’s Disease Cooperative Study; serving as a consultant for Roche, Merck, Genentech, Biogen, and Eli Lilly; and receiving publishing royalties for the textbook, “Mild Cognitive Impairment.” 

Follow-up primary care for adolescents with depression is extremely poor, with 19% overall and 40% of those given antidepressants receiving no follow up at all, according to an analysis of electronic health records for 4,612 patients attending three large and highly regarded primary-care settings, which was published online Feb. 1 in JAMA Pediatrics.

“Current standards of care recommend that adolescents identified with depression symptoms receive further assessment, initiate antidepressant medication and/or psychotherapy treatment, and are monitored for changes in symptoms, especially following an antidepressant prescription. Evidence from this study suggests that quality of care in routine practice diverges from these standards,” said Briannon C. O’Connor, Ph.D., of New York University Child Study Center, and her associates.

Peerayot/©Thinkstock

They analyzed EHR data from two unnamed health maintenance organizations in the western United States and a large network of community health centers in the Northeast. The researchers identified 4,612 adolescents with moderately severe symptoms of depression. At the index visit to their primary care physicians, 47% of these patients were diagnosed as having major depression and 24% as having other/unspecified depression. The most frequently used screen for depression was the Patient Health Questionnaire.

During the 3 months following these index visits, symptom monitoring was documented in 32% (1,486) of the adolescents overall. This means that two-thirds of patients had no symptom monitoring, which is considered basic care even for patients with mild depressive symptoms.

In addition, 19% of adolescents with newly identified depression had no follow-up visits at all with their primary care physicians.

“These findings raise concerns that many adolescents with depression receive an unacceptable level of care, particularly striking because more than half of adolescent suicide completers have chronic, unremitting depression,” the investigators said (JAMA Pediatr. 2016 Feb 1. doi: 10.1001/jamapediatrics.2015.4158).Treatment was initiated in 64% of the adolescents: antidepressants only in 19%, psychotherapy only in 29%, and combined antidepressants and psychotherapy in 16%. Fully 40% of the nearly 900 adolescents who were prescribed antidepressants showed no follow-up visits at all during the 3 months after the index visit. “Current black box warnings highlight the risk for increased suicidality for youth prescribed antidepressants and recommend patients are ‘monitored appropriately and observed closely … especially during the initial few months,’ ” Dr. O’Connor and her associates noted.

These findings are particularly troubling because the participating sites “are often looked to as leaders in cutting-edge care that routinely use quality-improvement initiatives focused on adolescent behavioral health care. Thus, [the study results], as discouraging as they are, may overstate the quality of care in other settings,” the investigators added.

This study was supported by the Agency for Healthcare Research and Quality and the Centers for Medicare & Medicaid Services. Dr. O’Connor and her associates reported having no relevant financial disclosures.

Follow-up primary care for adolescents with depression is extremely poor, with 19% overall and 40% of those given antidepressants receiving no follow up at all, according to an analysis of electronic health records for 4,612 patients attending three large and highly regarded primary-care settings, which was published online Feb. 1 in JAMA Pediatrics.

“Current standards of care recommend that adolescents identified with depression symptoms receive further assessment, initiate antidepressant medication and/or psychotherapy treatment, and are monitored for changes in symptoms, especially following an antidepressant prescription. Evidence from this study suggests that quality of care in routine practice diverges from these standards,” said Briannon C. O’Connor, Ph.D., of New York University Child Study Center, and her associates.

Peerayot/©Thinkstock

They analyzed EHR data from two unnamed health maintenance organizations in the western United States and a large network of community health centers in the Northeast. The researchers identified 4,612 adolescents with moderately severe symptoms of depression. At the index visit to their primary care physicians, 47% of these patients were diagnosed as having major depression and 24% as having other/unspecified depression. The most frequently used screen for depression was the Patient Health Questionnaire.

During the 3 months following these index visits, symptom monitoring was documented in 32% (1,486) of the adolescents overall. This means that two-thirds of patients had no symptom monitoring, which is considered basic care even for patients with mild depressive symptoms.

In addition, 19% of adolescents with newly identified depression had no follow-up visits at all with their primary care physicians.

“These findings raise concerns that many adolescents with depression receive an unacceptable level of care, particularly striking because more than half of adolescent suicide completers have chronic, unremitting depression,” the investigators said (JAMA Pediatr. 2016 Feb 1. doi: 10.1001/jamapediatrics.2015.4158).Treatment was initiated in 64% of the adolescents: antidepressants only in 19%, psychotherapy only in 29%, and combined antidepressants and psychotherapy in 16%. Fully 40% of the nearly 900 adolescents who were prescribed antidepressants showed no follow-up visits at all during the 3 months after the index visit. “Current black box warnings highlight the risk for increased suicidality for youth prescribed antidepressants and recommend patients are ‘monitored appropriately and observed closely … especially during the initial few months,’ ” Dr. O’Connor and her associates noted.

These findings are particularly troubling because the participating sites “are often looked to as leaders in cutting-edge care that routinely use quality-improvement initiatives focused on adolescent behavioral health care. Thus, [the study results], as discouraging as they are, may overstate the quality of care in other settings,” the investigators added.

This study was supported by the Agency for Healthcare Research and Quality and the Centers for Medicare & Medicaid Services. Dr. O’Connor and her associates reported having no relevant financial disclosures.

Follow-up primary care for adolescents with depression is extremely poor, with 19% overall and 40% of those given antidepressants receiving no follow up at all, according to an analysis of electronic health records for 4,612 patients attending three large and highly regarded primary-care settings, which was published online Feb. 1 in JAMA Pediatrics.

“Current standards of care recommend that adolescents identified with depression symptoms receive further assessment, initiate antidepressant medication and/or psychotherapy treatment, and are monitored for changes in symptoms, especially following an antidepressant prescription. Evidence from this study suggests that quality of care in routine practice diverges from these standards,” said Briannon C. O’Connor, Ph.D., of New York University Child Study Center, and her associates.

Peerayot/©Thinkstock

They analyzed EHR data from two unnamed health maintenance organizations in the western United States and a large network of community health centers in the Northeast. The researchers identified 4,612 adolescents with moderately severe symptoms of depression. At the index visit to their primary care physicians, 47% of these patients were diagnosed as having major depression and 24% as having other/unspecified depression. The most frequently used screen for depression was the Patient Health Questionnaire.

During the 3 months following these index visits, symptom monitoring was documented in 32% (1,486) of the adolescents overall. This means that two-thirds of patients had no symptom monitoring, which is considered basic care even for patients with mild depressive symptoms.

In addition, 19% of adolescents with newly identified depression had no follow-up visits at all with their primary care physicians.

“These findings raise concerns that many adolescents with depression receive an unacceptable level of care, particularly striking because more than half of adolescent suicide completers have chronic, unremitting depression,” the investigators said (JAMA Pediatr. 2016 Feb 1. doi: 10.1001/jamapediatrics.2015.4158).Treatment was initiated in 64% of the adolescents: antidepressants only in 19%, psychotherapy only in 29%, and combined antidepressants and psychotherapy in 16%. Fully 40% of the nearly 900 adolescents who were prescribed antidepressants showed no follow-up visits at all during the 3 months after the index visit. “Current black box warnings highlight the risk for increased suicidality for youth prescribed antidepressants and recommend patients are ‘monitored appropriately and observed closely … especially during the initial few months,’ ” Dr. O’Connor and her associates noted.

These findings are particularly troubling because the participating sites “are often looked to as leaders in cutting-edge care that routinely use quality-improvement initiatives focused on adolescent behavioral health care. Thus, [the study results], as discouraging as they are, may overstate the quality of care in other settings,” the investigators added.

This study was supported by the Agency for Healthcare Research and Quality and the Centers for Medicare & Medicaid Services. Dr. O’Connor and her associates reported having no relevant financial disclosures.

Outcomes after contaminated open ventral hernia repair did not differ significantly, whether the incision was closed using sutures, low- or mid-density polypropylene mesh, or non–cross-linked biologic matrix material, in a multicenter study reported online in the Journal of Surgical Research.

In the absence of high-level evidence favoring any of these approaches, surgeons should carefully balance the risks and costs against the benefits when choosing how to close such incisions, said Ioana L. Bondre of the department of surgery, University of Texas Health Science Center, Houston, and her associates.

ollega/©Thinkstock

At present, there is no widely accepted consensus and certainly no clinical guidelines regarding closure of contaminated ventral hernias. It is assumed that synthetic mesh and biologic mesh reduce the rate of hernia recurrence but at the cost of increased wound complications and surgical site infections. To examine this issue, the investigators performed a retrospective analysis of information in a database of all consecutive open ventral hernia repairs performed at seven medical centers during a 2-year period.

They focused on 761 patients in whom the repair was closed using sutures (38%), synthetic mesh (40%), or biologic matrix (22%). Thirty-day rates of surgical site infection (15.1%, 17.8%, and 21.0%, respectively), hernia recurrence (17.8%, 13.5%, and 21.5%, respectively), and reoperation (31.7%, 10.9%, and 15.6%, respectively) did not differ significantly among these three groups, Ms. Bondre and her associates said (J Surg Res. 2016 Feb;200[2]:488-94).

“Based on the available evidence, we currently recommend decisions to be based on the primary purpose of the procedure. If the primary purpose is not to perform a hernia repair (e.g., laparoscopic appendectomy for appendicitis), then a suture repair should be performed (e.g., umbilical hernia repair with sutures). However, if the primary purpose of the procedure includes hernia repair (e.g., colostomy reversal and parastomal hernia repair), mesh reinforcement should be used. Given the current evidence and practice patterns, we use mid-density synthetic mesh in wound class I procedures and biologic mesh in wound class II-IV repairs,” they noted.

This study was limited in that many patients were followed for only 1 month, which may not be sufficient time to capture long-term outcomes. Moreover, the database didn’t include information regarding outcomes that are most important to patients, such as chronic pain, chronic infections, and nonhealing surgical wounds, Ms. Bondre and her associates added.

This study was supported by the Center for Clinical and Translational Sciences. The authors’ financial disclosures were not reported.

Outcomes after contaminated open ventral hernia repair did not differ significantly, whether the incision was closed using sutures, low- or mid-density polypropylene mesh, or non–cross-linked biologic matrix material, in a multicenter study reported online in the Journal of Surgical Research.

In the absence of high-level evidence favoring any of these approaches, surgeons should carefully balance the risks and costs against the benefits when choosing how to close such incisions, said Ioana L. Bondre of the department of surgery, University of Texas Health Science Center, Houston, and her associates.

ollega/©Thinkstock

At present, there is no widely accepted consensus and certainly no clinical guidelines regarding closure of contaminated ventral hernias. It is assumed that synthetic mesh and biologic mesh reduce the rate of hernia recurrence but at the cost of increased wound complications and surgical site infections. To examine this issue, the investigators performed a retrospective analysis of information in a database of all consecutive open ventral hernia repairs performed at seven medical centers during a 2-year period.

They focused on 761 patients in whom the repair was closed using sutures (38%), synthetic mesh (40%), or biologic matrix (22%). Thirty-day rates of surgical site infection (15.1%, 17.8%, and 21.0%, respectively), hernia recurrence (17.8%, 13.5%, and 21.5%, respectively), and reoperation (31.7%, 10.9%, and 15.6%, respectively) did not differ significantly among these three groups, Ms. Bondre and her associates said (J Surg Res. 2016 Feb;200[2]:488-94).

“Based on the available evidence, we currently recommend decisions to be based on the primary purpose of the procedure. If the primary purpose is not to perform a hernia repair (e.g., laparoscopic appendectomy for appendicitis), then a suture repair should be performed (e.g., umbilical hernia repair with sutures). However, if the primary purpose of the procedure includes hernia repair (e.g., colostomy reversal and parastomal hernia repair), mesh reinforcement should be used. Given the current evidence and practice patterns, we use mid-density synthetic mesh in wound class I procedures and biologic mesh in wound class II-IV repairs,” they noted.

This study was limited in that many patients were followed for only 1 month, which may not be sufficient time to capture long-term outcomes. Moreover, the database didn’t include information regarding outcomes that are most important to patients, such as chronic pain, chronic infections, and nonhealing surgical wounds, Ms. Bondre and her associates added.

This study was supported by the Center for Clinical and Translational Sciences. The authors’ financial disclosures were not reported.

Outcomes after contaminated open ventral hernia repair did not differ significantly, whether the incision was closed using sutures, low- or mid-density polypropylene mesh, or non–cross-linked biologic matrix material, in a multicenter study reported online in the Journal of Surgical Research.

In the absence of high-level evidence favoring any of these approaches, surgeons should carefully balance the risks and costs against the benefits when choosing how to close such incisions, said Ioana L. Bondre of the department of surgery, University of Texas Health Science Center, Houston, and her associates.

ollega/©Thinkstock

At present, there is no widely accepted consensus and certainly no clinical guidelines regarding closure of contaminated ventral hernias. It is assumed that synthetic mesh and biologic mesh reduce the rate of hernia recurrence but at the cost of increased wound complications and surgical site infections. To examine this issue, the investigators performed a retrospective analysis of information in a database of all consecutive open ventral hernia repairs performed at seven medical centers during a 2-year period.

They focused on 761 patients in whom the repair was closed using sutures (38%), synthetic mesh (40%), or biologic matrix (22%). Thirty-day rates of surgical site infection (15.1%, 17.8%, and 21.0%, respectively), hernia recurrence (17.8%, 13.5%, and 21.5%, respectively), and reoperation (31.7%, 10.9%, and 15.6%, respectively) did not differ significantly among these three groups, Ms. Bondre and her associates said (J Surg Res. 2016 Feb;200[2]:488-94).

“Based on the available evidence, we currently recommend decisions to be based on the primary purpose of the procedure. If the primary purpose is not to perform a hernia repair (e.g., laparoscopic appendectomy for appendicitis), then a suture repair should be performed (e.g., umbilical hernia repair with sutures). However, if the primary purpose of the procedure includes hernia repair (e.g., colostomy reversal and parastomal hernia repair), mesh reinforcement should be used. Given the current evidence and practice patterns, we use mid-density synthetic mesh in wound class I procedures and biologic mesh in wound class II-IV repairs,” they noted.

This study was limited in that many patients were followed for only 1 month, which may not be sufficient time to capture long-term outcomes. Moreover, the database didn’t include information regarding outcomes that are most important to patients, such as chronic pain, chronic infections, and nonhealing surgical wounds, Ms. Bondre and her associates added.

This study was supported by the Center for Clinical and Translational Sciences. The authors’ financial disclosures were not reported.

Enzalutamide cut the rate of disease progression or death by 76% and extended progression-free survival by more than 1 year in castration-resistant prostate cancer, compared with standard bicalutamide, in a phase II trial published in the Journal of Clinical Oncology.

Currently there is no approved therapy for men with nonmetastatic castration-resistant prostate cancer. For men with metastatic disease, “bicalutamide 50 mg per day is commonly used for patients for whom androgen deprivation therapy has failed, despite the lack of randomized clinical trials showing a durable or widely experienced clinical benefit in the setting of castration resistance,” said Dr. David F. Penson of Vanderbilt University Medical Center and the Tennessee Valley Veterans Administration Medical Center, both in Nashville, and his associates.

Enzalutamide is an androgen receptor inhibitor that binds to the androgen receptor as bicalutamide does, but with a tenfold greater affinity. It has improved overall survival compared with placebo in two large preliminary studies, both in the prechemotherapy and postchemotherapy settings, they noted.

The investigators compared the two agents head to head in their randomized double-blind trial at 62 sites across the United States. The study was supported by Medivation and Astellas Pharma, codevelopers of enzalutamide. A total of 198 men received enzalutamide and 198 received bicalutamide.

Enzalutamide reduced the primary endpoint, risk of disease progression or death, by 76%, compared with bicalutamide. Median progression-free survival was 19.4 months, compared with 5.7 months. The median progression-free survival was not reached among men with nonmetastatic disease taking enzalutamide, while it was 8.6 months with bicalutamide (HR, 0.24). The median progression-free survival was 16.5 months among men with metastatic disease taking enzalutamide, while it was 5.5 months with bicalutamide (HR, 0.24), Dr. Penson and his associates noted (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.64.9285).

This survival benefit occurred across all subgroups of patients. All secondary endpoints also strongly favored enzalutamide. For example, it reduced the risk of radiographic disease progression or death by 68% in metastatic disease and by 76% in nonmetastatic disease. Among men who had measurable soft-tissue metastases at baseline, 60% in the enzalutamide group showed clinically meaningful tumor shrinkage, compared with only 14% of those in the bicalutamide group.

Enzalutamide also reduced the risk of prostate-specific antigen (PSA) progression by 81%. And 81% of men taking enzalutamide achieved a PSA response of 50% or greater, compared with 31% of men taking bicalutamide.

Adverse events and serious adverse events occurred at similar rates in the two study groups. The most common adverse events for both agents were fatigue and hot flashes, but these did not affect quality of life as assessed by the FACT-P questionnaire.

“These data suggest that enzalutamide should replace bicalutamide in the treatment of men with castration-resistant prostate cancer,” Dr. Penson and his associates said.

Enzalutamide cut the rate of disease progression or death by 76% and extended progression-free survival by more than 1 year in castration-resistant prostate cancer, compared with standard bicalutamide, in a phase II trial published in the Journal of Clinical Oncology.

Currently there is no approved therapy for men with nonmetastatic castration-resistant prostate cancer. For men with metastatic disease, “bicalutamide 50 mg per day is commonly used for patients for whom androgen deprivation therapy has failed, despite the lack of randomized clinical trials showing a durable or widely experienced clinical benefit in the setting of castration resistance,” said Dr. David F. Penson of Vanderbilt University Medical Center and the Tennessee Valley Veterans Administration Medical Center, both in Nashville, and his associates.

Enzalutamide is an androgen receptor inhibitor that binds to the androgen receptor as bicalutamide does, but with a tenfold greater affinity. It has improved overall survival compared with placebo in two large preliminary studies, both in the prechemotherapy and postchemotherapy settings, they noted.

The investigators compared the two agents head to head in their randomized double-blind trial at 62 sites across the United States. The study was supported by Medivation and Astellas Pharma, codevelopers of enzalutamide. A total of 198 men received enzalutamide and 198 received bicalutamide.

Enzalutamide reduced the primary endpoint, risk of disease progression or death, by 76%, compared with bicalutamide. Median progression-free survival was 19.4 months, compared with 5.7 months. The median progression-free survival was not reached among men with nonmetastatic disease taking enzalutamide, while it was 8.6 months with bicalutamide (HR, 0.24). The median progression-free survival was 16.5 months among men with metastatic disease taking enzalutamide, while it was 5.5 months with bicalutamide (HR, 0.24), Dr. Penson and his associates noted (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.64.9285).

This survival benefit occurred across all subgroups of patients. All secondary endpoints also strongly favored enzalutamide. For example, it reduced the risk of radiographic disease progression or death by 68% in metastatic disease and by 76% in nonmetastatic disease. Among men who had measurable soft-tissue metastases at baseline, 60% in the enzalutamide group showed clinically meaningful tumor shrinkage, compared with only 14% of those in the bicalutamide group.

Enzalutamide also reduced the risk of prostate-specific antigen (PSA) progression by 81%. And 81% of men taking enzalutamide achieved a PSA response of 50% or greater, compared with 31% of men taking bicalutamide.

Adverse events and serious adverse events occurred at similar rates in the two study groups. The most common adverse events for both agents were fatigue and hot flashes, but these did not affect quality of life as assessed by the FACT-P questionnaire.

“These data suggest that enzalutamide should replace bicalutamide in the treatment of men with castration-resistant prostate cancer,” Dr. Penson and his associates said.

Enzalutamide cut the rate of disease progression or death by 76% and extended progression-free survival by more than 1 year in castration-resistant prostate cancer, compared with standard bicalutamide, in a phase II trial published in the Journal of Clinical Oncology.

Currently there is no approved therapy for men with nonmetastatic castration-resistant prostate cancer. For men with metastatic disease, “bicalutamide 50 mg per day is commonly used for patients for whom androgen deprivation therapy has failed, despite the lack of randomized clinical trials showing a durable or widely experienced clinical benefit in the setting of castration resistance,” said Dr. David F. Penson of Vanderbilt University Medical Center and the Tennessee Valley Veterans Administration Medical Center, both in Nashville, and his associates.

Enzalutamide is an androgen receptor inhibitor that binds to the androgen receptor as bicalutamide does, but with a tenfold greater affinity. It has improved overall survival compared with placebo in two large preliminary studies, both in the prechemotherapy and postchemotherapy settings, they noted.

The investigators compared the two agents head to head in their randomized double-blind trial at 62 sites across the United States. The study was supported by Medivation and Astellas Pharma, codevelopers of enzalutamide. A total of 198 men received enzalutamide and 198 received bicalutamide.

Enzalutamide reduced the primary endpoint, risk of disease progression or death, by 76%, compared with bicalutamide. Median progression-free survival was 19.4 months, compared with 5.7 months. The median progression-free survival was not reached among men with nonmetastatic disease taking enzalutamide, while it was 8.6 months with bicalutamide (HR, 0.24). The median progression-free survival was 16.5 months among men with metastatic disease taking enzalutamide, while it was 5.5 months with bicalutamide (HR, 0.24), Dr. Penson and his associates noted (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.64.9285).

This survival benefit occurred across all subgroups of patients. All secondary endpoints also strongly favored enzalutamide. For example, it reduced the risk of radiographic disease progression or death by 68% in metastatic disease and by 76% in nonmetastatic disease. Among men who had measurable soft-tissue metastases at baseline, 60% in the enzalutamide group showed clinically meaningful tumor shrinkage, compared with only 14% of those in the bicalutamide group.

Enzalutamide also reduced the risk of prostate-specific antigen (PSA) progression by 81%. And 81% of men taking enzalutamide achieved a PSA response of 50% or greater, compared with 31% of men taking bicalutamide.

Adverse events and serious adverse events occurred at similar rates in the two study groups. The most common adverse events for both agents were fatigue and hot flashes, but these did not affect quality of life as assessed by the FACT-P questionnaire.

“These data suggest that enzalutamide should replace bicalutamide in the treatment of men with castration-resistant prostate cancer,” Dr. Penson and his associates said.

Among pregnant women at high risk for having a child with asthma, high doses of vitamin D administered during the third trimester failed to prevent persistent wheezing illness in their children at age 3, according to two separate reports published online Jan. 26 in JAMA.

Both studies were conducted because vitamin D insufficiency during pregnancy is commonplace and is thought to affect fetal immune programming and to contribute to asthma pathogenesis. In addition, observational studies have found an association between low levels of vitamin D in cord blood and later asthma in the child.

© © ©istock/Thinkstock.com

The two randomized, double-blind placebo-controlled clinical trials found that neither 2,800 IU/day nor 4,400 IU/day of vitamin D significantly reduced the risk of persistent wheeze in the offspring through 3 years of age. However, both research groups noted that their studies may have been underpowered to detect a clinically important protective effect, and both recommended longer-term observation of their study participants, as well as further studies using larger sample sizes, higher doses of vitamin D, administration earlier in pregnancy, and postnatal supplementation to establish a definitive result.

In the first study – conducted as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort – 623 Danish women already taking the standard 400 IU of vitamin D₃ during pregnancy were randomly assigned to receive an additional 2,400 IU (315 women) or a matching placebo (308 women) from 22 to 26 weeks’ gestation until delivery. After exclusions, researchers analyzed data on 581 children.

Maternal serum vitamin D levels increased markedly in the active-treatment group. “Correspondingly, the percentage of women with sufficient levels of vitamin D (greater than 30 ng/mL) after the intervention was 81% in the vitamin D group, compared with 44% in the control group,” wrote Dr. Bo L. Chawes of Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, and his associates.

Persistent wheeze developed in 104 (18%) of the 581 children: 47 (16%) in the vitamin D group and 57 (20%) in the control group, a nonsignificant difference. Similarly, asthma was diagnosed in 79 children: 32 (12%) in the vitamin D group and 47 (14%) in the control group, another nonsignificant difference.

Vitamin D supplementation also made no difference in infants’ levels of C-reactive protein, interleukin-6, tumor necrosis factor–alpha, or CXCL8, nor in the number of upper respiratory tract infections (5.2 per year vs 5.3 per year), the number of lower respiratory tract infections (32% vs 33%), the risk of allergic sensitization as measured by skin prick test or specific IgE level, or the development of eczema (23% vs 25%).

However, the risk of persistent wheeze was higher in children whose mothers’ vitamin D levels were lowest, compared with those whose mothers’ vitamin D levels were in the middle and upper tertiles. And high-dose vitamin D was protective with regard to some secondary endpoints, such as preventing more episodes of “troublesome lung symptoms” (5.9 vs. 7.2).

This finding, together with the study’s somewhat reduced statistical power, mean that a clinically important protective effect cannot be ruled out. In addition, the supplementation dose may have been too low or may have been given too late in the course of pregnancy to produce a significant effect, Dr. Chawes and his associates wrote (JAMA. 2016;315[4]:353-61. doi: 10.1001/jama.2015.18318).In the second study – the Vitamin D Antenatal Asthma Reduction Trial – 876 pregnant women in Boston, St. Louis, and San Diego who were already taking the standard 400 IU of vitamin D were randomly assigned to receive either an additional 4,000 IU/day (440 participants) or a matching placebo (436 participants). Maternal levels of vitamin D rose markedly in the active-treatment group (mean, 39.2 ng/mL), compared with the control group (mean, 26.8 ng/mL), and the proportion of women who achieved higher than “inadequate” levels was much greater (74.9% vs 34.0%), reported Dr. Augusto A. Litonjua of Brigham and Women’s Hospital, Boston, and his associates.

A total of 24.3% of the vitamin D group and 30.4% of the control group developed asthma or recurrent wheeze by age 3 years, a nonsignificant difference. However, the incidence of asthma was so much lower than anticipated in both study groups that the study may have lost statistical power to detect a clinically meaningful difference, according to the investigators (JAMA. 2016;315[4]:362-70. doi: 10.1001/jama.2015.18589).

It remains unclear whether vitamin D supplementation during pregnancy will reduce asthma and persistent wheezing in the offspring. “Larger studies and longer follow-up of the children in this study will be needed to answer the question,” the investigators wrote. “If additional studies identify a significant effect, given the high prevalence of low vitamin D levels in pregnant women, the effect of this inexpensive intervention on child health could be substantial.”

The first study was supported by the Copenhagen Prospective Study on Asthma in Childhood, which is funded by private and public research groups. One of the coauthors reported receiving consulting fees from Chiesi. The Vitamin D Antenatal Asthma Reduction Trial was supported by the U.S. National Heart, Lung, and Blood Institute and the National Centers for Advancing Translational Sciences. The lead author, Dr. Litonjua, reported receiving personal fees from UpToDate and Springer Humana Press; his associates reported ties to numerous industry sources.

Among pregnant women at high risk for having a child with asthma, high doses of vitamin D administered during the third trimester failed to prevent persistent wheezing illness in their children at age 3, according to two separate reports published online Jan. 26 in JAMA.

Both studies were conducted because vitamin D insufficiency during pregnancy is commonplace and is thought to affect fetal immune programming and to contribute to asthma pathogenesis. In addition, observational studies have found an association between low levels of vitamin D in cord blood and later asthma in the child.

© © ©istock/Thinkstock.com

The two randomized, double-blind placebo-controlled clinical trials found that neither 2,800 IU/day nor 4,400 IU/day of vitamin D significantly reduced the risk of persistent wheeze in the offspring through 3 years of age. However, both research groups noted that their studies may have been underpowered to detect a clinically important protective effect, and both recommended longer-term observation of their study participants, as well as further studies using larger sample sizes, higher doses of vitamin D, administration earlier in pregnancy, and postnatal supplementation to establish a definitive result.

In the first study – conducted as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort – 623 Danish women already taking the standard 400 IU of vitamin D₃ during pregnancy were randomly assigned to receive an additional 2,400 IU (315 women) or a matching placebo (308 women) from 22 to 26 weeks’ gestation until delivery. After exclusions, researchers analyzed data on 581 children.

Maternal serum vitamin D levels increased markedly in the active-treatment group. “Correspondingly, the percentage of women with sufficient levels of vitamin D (greater than 30 ng/mL) after the intervention was 81% in the vitamin D group, compared with 44% in the control group,” wrote Dr. Bo L. Chawes of Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, and his associates.

Persistent wheeze developed in 104 (18%) of the 581 children: 47 (16%) in the vitamin D group and 57 (20%) in the control group, a nonsignificant difference. Similarly, asthma was diagnosed in 79 children: 32 (12%) in the vitamin D group and 47 (14%) in the control group, another nonsignificant difference.

Vitamin D supplementation also made no difference in infants’ levels of C-reactive protein, interleukin-6, tumor necrosis factor–alpha, or CXCL8, nor in the number of upper respiratory tract infections (5.2 per year vs 5.3 per year), the number of lower respiratory tract infections (32% vs 33%), the risk of allergic sensitization as measured by skin prick test or specific IgE level, or the development of eczema (23% vs 25%).

However, the risk of persistent wheeze was higher in children whose mothers’ vitamin D levels were lowest, compared with those whose mothers’ vitamin D levels were in the middle and upper tertiles. And high-dose vitamin D was protective with regard to some secondary endpoints, such as preventing more episodes of “troublesome lung symptoms” (5.9 vs. 7.2).

This finding, together with the study’s somewhat reduced statistical power, mean that a clinically important protective effect cannot be ruled out. In addition, the supplementation dose may have been too low or may have been given too late in the course of pregnancy to produce a significant effect, Dr. Chawes and his associates wrote (JAMA. 2016;315[4]:353-61. doi: 10.1001/jama.2015.18318).In the second study – the Vitamin D Antenatal Asthma Reduction Trial – 876 pregnant women in Boston, St. Louis, and San Diego who were already taking the standard 400 IU of vitamin D were randomly assigned to receive either an additional 4,000 IU/day (440 participants) or a matching placebo (436 participants). Maternal levels of vitamin D rose markedly in the active-treatment group (mean, 39.2 ng/mL), compared with the control group (mean, 26.8 ng/mL), and the proportion of women who achieved higher than “inadequate” levels was much greater (74.9% vs 34.0%), reported Dr. Augusto A. Litonjua of Brigham and Women’s Hospital, Boston, and his associates.

A total of 24.3% of the vitamin D group and 30.4% of the control group developed asthma or recurrent wheeze by age 3 years, a nonsignificant difference. However, the incidence of asthma was so much lower than anticipated in both study groups that the study may have lost statistical power to detect a clinically meaningful difference, according to the investigators (JAMA. 2016;315[4]:362-70. doi: 10.1001/jama.2015.18589).

It remains unclear whether vitamin D supplementation during pregnancy will reduce asthma and persistent wheezing in the offspring. “Larger studies and longer follow-up of the children in this study will be needed to answer the question,” the investigators wrote. “If additional studies identify a significant effect, given the high prevalence of low vitamin D levels in pregnant women, the effect of this inexpensive intervention on child health could be substantial.”

The first study was supported by the Copenhagen Prospective Study on Asthma in Childhood, which is funded by private and public research groups. One of the coauthors reported receiving consulting fees from Chiesi. The Vitamin D Antenatal Asthma Reduction Trial was supported by the U.S. National Heart, Lung, and Blood Institute and the National Centers for Advancing Translational Sciences. The lead author, Dr. Litonjua, reported receiving personal fees from UpToDate and Springer Humana Press; his associates reported ties to numerous industry sources.

Among pregnant women at high risk for having a child with asthma, high doses of vitamin D administered during the third trimester failed to prevent persistent wheezing illness in their children at age 3, according to two separate reports published online Jan. 26 in JAMA.

Both studies were conducted because vitamin D insufficiency during pregnancy is commonplace and is thought to affect fetal immune programming and to contribute to asthma pathogenesis. In addition, observational studies have found an association between low levels of vitamin D in cord blood and later asthma in the child.

© © ©istock/Thinkstock.com

The two randomized, double-blind placebo-controlled clinical trials found that neither 2,800 IU/day nor 4,400 IU/day of vitamin D significantly reduced the risk of persistent wheeze in the offspring through 3 years of age. However, both research groups noted that their studies may have been underpowered to detect a clinically important protective effect, and both recommended longer-term observation of their study participants, as well as further studies using larger sample sizes, higher doses of vitamin D, administration earlier in pregnancy, and postnatal supplementation to establish a definitive result.

In the first study – conducted as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort – 623 Danish women already taking the standard 400 IU of vitamin D₃ during pregnancy were randomly assigned to receive an additional 2,400 IU (315 women) or a matching placebo (308 women) from 22 to 26 weeks’ gestation until delivery. After exclusions, researchers analyzed data on 581 children.

Maternal serum vitamin D levels increased markedly in the active-treatment group. “Correspondingly, the percentage of women with sufficient levels of vitamin D (greater than 30 ng/mL) after the intervention was 81% in the vitamin D group, compared with 44% in the control group,” wrote Dr. Bo L. Chawes of Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, and his associates.

Persistent wheeze developed in 104 (18%) of the 581 children: 47 (16%) in the vitamin D group and 57 (20%) in the control group, a nonsignificant difference. Similarly, asthma was diagnosed in 79 children: 32 (12%) in the vitamin D group and 47 (14%) in the control group, another nonsignificant difference.

Vitamin D supplementation also made no difference in infants’ levels of C-reactive protein, interleukin-6, tumor necrosis factor–alpha, or CXCL8, nor in the number of upper respiratory tract infections (5.2 per year vs 5.3 per year), the number of lower respiratory tract infections (32% vs 33%), the risk of allergic sensitization as measured by skin prick test or specific IgE level, or the development of eczema (23% vs 25%).

However, the risk of persistent wheeze was higher in children whose mothers’ vitamin D levels were lowest, compared with those whose mothers’ vitamin D levels were in the middle and upper tertiles. And high-dose vitamin D was protective with regard to some secondary endpoints, such as preventing more episodes of “troublesome lung symptoms” (5.9 vs. 7.2).

This finding, together with the study’s somewhat reduced statistical power, mean that a clinically important protective effect cannot be ruled out. In addition, the supplementation dose may have been too low or may have been given too late in the course of pregnancy to produce a significant effect, Dr. Chawes and his associates wrote (JAMA. 2016;315[4]:353-61. doi: 10.1001/jama.2015.18318).In the second study – the Vitamin D Antenatal Asthma Reduction Trial – 876 pregnant women in Boston, St. Louis, and San Diego who were already taking the standard 400 IU of vitamin D were randomly assigned to receive either an additional 4,000 IU/day (440 participants) or a matching placebo (436 participants). Maternal levels of vitamin D rose markedly in the active-treatment group (mean, 39.2 ng/mL), compared with the control group (mean, 26.8 ng/mL), and the proportion of women who achieved higher than “inadequate” levels was much greater (74.9% vs 34.0%), reported Dr. Augusto A. Litonjua of Brigham and Women’s Hospital, Boston, and his associates.

A total of 24.3% of the vitamin D group and 30.4% of the control group developed asthma or recurrent wheeze by age 3 years, a nonsignificant difference. However, the incidence of asthma was so much lower than anticipated in both study groups that the study may have lost statistical power to detect a clinically meaningful difference, according to the investigators (JAMA. 2016;315[4]:362-70. doi: 10.1001/jama.2015.18589).

It remains unclear whether vitamin D supplementation during pregnancy will reduce asthma and persistent wheezing in the offspring. “Larger studies and longer follow-up of the children in this study will be needed to answer the question,” the investigators wrote. “If additional studies identify a significant effect, given the high prevalence of low vitamin D levels in pregnant women, the effect of this inexpensive intervention on child health could be substantial.”

The first study was supported by the Copenhagen Prospective Study on Asthma in Childhood, which is funded by private and public research groups. One of the coauthors reported receiving consulting fees from Chiesi. The Vitamin D Antenatal Asthma Reduction Trial was supported by the U.S. National Heart, Lung, and Blood Institute and the National Centers for Advancing Translational Sciences. The lead author, Dr. Litonjua, reported receiving personal fees from UpToDate and Springer Humana Press; his associates reported ties to numerous industry sources.

Prescriptions for hydrocodone analgesics abruptly and markedly declined after the U.S. Drug Enforcement Administration reclassified them from schedule III to the more restrictive schedule II of the Controlled Substances Act, according to a research letter to the editor published online in JAMA Internal Medicine Jan. 25.

Hydrocodone, usually formulated in combination with nonopioid analgesics, is one of the most frequently abused opioids, accounting for nearly 100,000 abuse-related emergency department visits during one recent year. In October 2014, the DEA rescheduled these agents to subject them to more rigorous control, said Christopher M. Jones, Pharm.D., MPH, of the Department of Health and Human Services, Washington, and his associates.

David Tulk/Thinkstock

To assess any effect this rescheduling had on prescribing patterns, the investigators analyzed information in the IMS Health National Prescription Audit, a database that captures nearly 80% of all prescriptions dispensed from U.S. pharmacies, focusing on the 3 years before and the 1 year after rescheduling. They also analyzed information in an American Medical Association database to assess prescribing of hydrocodone combination agents across medical specialties during the year after rescheduling.

Prescriptions for hydrocodone combination agents decreased by 22% after rescheduling, and those for hydrocodone combination tablets decreased by 16%. There were 26.3 million fewer prescriptions for hydrocodone combination products, and 1.1 billion fewer hydrocodone combination tablets in the year after rescheduling.

Most of this decline (74%) was attributable to a profound reduction in refills, which is “consistent with the prohibition on prescription refills for schedule II medications,” Dr. Jones and his associates said (JAMA Intern Med. 2016 Jan 25. doi: 10.1001/jamainternmed.2015.7799).

In contrast, prescriptions for nonhydrocodone combination opioid analgesics increased by 5%, and those for nonhydrocodone tablets by 1%, during the year after rescheduling.

The reductions in prescribing occurred across most medical specialties. Surgeons and primary care physicians accounted for the largest decreases in both hydrocodone-containing prescriptions (-38.4% and -22.9%, respectively) and tablets (-30.8% and -17.1%, respectively). Oncologists, emergency medicine specialists, and nurse practitioners and physician assistants also contributed heavily to the declines. Dentists and physical/rehabilitation/occupational medicine specialists accounted for smaller reductions.

In contrast, pain medicine specialists showed modest increases in prescriptions for hydrocodone combination products and tablets.

“Future research should examine whether these changes are sustained, have had an effect on access for patients, and are associated with the desired goals of reduced abuse, addiction, and overdose,” Dr. Jones and his associates noted.

This study was funded by the U.S. Food and Drug Administration. Dr. Jones and his associates reported having no relevant financial disclosures.

Prescriptions for hydrocodone analgesics abruptly and markedly declined after the U.S. Drug Enforcement Administration reclassified them from schedule III to the more restrictive schedule II of the Controlled Substances Act, according to a research letter to the editor published online in JAMA Internal Medicine Jan. 25.

Hydrocodone, usually formulated in combination with nonopioid analgesics, is one of the most frequently abused opioids, accounting for nearly 100,000 abuse-related emergency department visits during one recent year. In October 2014, the DEA rescheduled these agents to subject them to more rigorous control, said Christopher M. Jones, Pharm.D., MPH, of the Department of Health and Human Services, Washington, and his associates.

David Tulk/Thinkstock

To assess any effect this rescheduling had on prescribing patterns, the investigators analyzed information in the IMS Health National Prescription Audit, a database that captures nearly 80% of all prescriptions dispensed from U.S. pharmacies, focusing on the 3 years before and the 1 year after rescheduling. They also analyzed information in an American Medical Association database to assess prescribing of hydrocodone combination agents across medical specialties during the year after rescheduling.

Prescriptions for hydrocodone combination agents decreased by 22% after rescheduling, and those for hydrocodone combination tablets decreased by 16%. There were 26.3 million fewer prescriptions for hydrocodone combination products, and 1.1 billion fewer hydrocodone combination tablets in the year after rescheduling.

Most of this decline (74%) was attributable to a profound reduction in refills, which is “consistent with the prohibition on prescription refills for schedule II medications,” Dr. Jones and his associates said (JAMA Intern Med. 2016 Jan 25. doi: 10.1001/jamainternmed.2015.7799).

In contrast, prescriptions for nonhydrocodone combination opioid analgesics increased by 5%, and those for nonhydrocodone tablets by 1%, during the year after rescheduling.

The reductions in prescribing occurred across most medical specialties. Surgeons and primary care physicians accounted for the largest decreases in both hydrocodone-containing prescriptions (-38.4% and -22.9%, respectively) and tablets (-30.8% and -17.1%, respectively). Oncologists, emergency medicine specialists, and nurse practitioners and physician assistants also contributed heavily to the declines. Dentists and physical/rehabilitation/occupational medicine specialists accounted for smaller reductions.

In contrast, pain medicine specialists showed modest increases in prescriptions for hydrocodone combination products and tablets.

“Future research should examine whether these changes are sustained, have had an effect on access for patients, and are associated with the desired goals of reduced abuse, addiction, and overdose,” Dr. Jones and his associates noted.

This study was funded by the U.S. Food and Drug Administration. Dr. Jones and his associates reported having no relevant financial disclosures.

Prescriptions for hydrocodone analgesics abruptly and markedly declined after the U.S. Drug Enforcement Administration reclassified them from schedule III to the more restrictive schedule II of the Controlled Substances Act, according to a research letter to the editor published online in JAMA Internal Medicine Jan. 25.

Hydrocodone, usually formulated in combination with nonopioid analgesics, is one of the most frequently abused opioids, accounting for nearly 100,000 abuse-related emergency department visits during one recent year. In October 2014, the DEA rescheduled these agents to subject them to more rigorous control, said Christopher M. Jones, Pharm.D., MPH, of the Department of Health and Human Services, Washington, and his associates.

David Tulk/Thinkstock

To assess any effect this rescheduling had on prescribing patterns, the investigators analyzed information in the IMS Health National Prescription Audit, a database that captures nearly 80% of all prescriptions dispensed from U.S. pharmacies, focusing on the 3 years before and the 1 year after rescheduling. They also analyzed information in an American Medical Association database to assess prescribing of hydrocodone combination agents across medical specialties during the year after rescheduling.

Prescriptions for hydrocodone combination agents decreased by 22% after rescheduling, and those for hydrocodone combination tablets decreased by 16%. There were 26.3 million fewer prescriptions for hydrocodone combination products, and 1.1 billion fewer hydrocodone combination tablets in the year after rescheduling.

Most of this decline (74%) was attributable to a profound reduction in refills, which is “consistent with the prohibition on prescription refills for schedule II medications,” Dr. Jones and his associates said (JAMA Intern Med. 2016 Jan 25. doi: 10.1001/jamainternmed.2015.7799).

In contrast, prescriptions for nonhydrocodone combination opioid analgesics increased by 5%, and those for nonhydrocodone tablets by 1%, during the year after rescheduling.

The reductions in prescribing occurred across most medical specialties. Surgeons and primary care physicians accounted for the largest decreases in both hydrocodone-containing prescriptions (-38.4% and -22.9%, respectively) and tablets (-30.8% and -17.1%, respectively). Oncologists, emergency medicine specialists, and nurse practitioners and physician assistants also contributed heavily to the declines. Dentists and physical/rehabilitation/occupational medicine specialists accounted for smaller reductions.

In contrast, pain medicine specialists showed modest increases in prescriptions for hydrocodone combination products and tablets.

“Future research should examine whether these changes are sustained, have had an effect on access for patients, and are associated with the desired goals of reduced abuse, addiction, and overdose,” Dr. Jones and his associates noted.

This study was funded by the U.S. Food and Drug Administration. Dr. Jones and his associates reported having no relevant financial disclosures.

The American Society of Addiction Medicine has released a practice guideline to help clinicians evaluate and treat opioid use disorder, with the ultimate goal of getting more physicians to provide effective treatment.

Effective treatment of opioid use disorder “requires skill and time that are not generally available to primary care doctors in most practice models,” so much of the treatment provided in primary care has been “suboptimal.” This has probably worsened what the Centers for Disease Control and Prevention has described as an epidemic of opioid misuse and related deaths, said Dr. Kyle Kampman and Dr. Margaret Jarvis, cochairs of the ASAM’s guideline committee.

“At the same time, access to competent treatment is profoundly restricted because few physicians are willing and able to provide it,” they noted.

This guideline “is primarily intended for clinicians involved in evaluating patients and providing authorization for pharmacologic treatments at any level,” said Dr. Kampman of the University of Pennsylvania, Philadelphia, and Dr. Jarvis, of the Marworth Alcohol & Chemical Dependency Center, an entity of the Geisinger Health System, Waverly, Pa.

To develop the guideline, the committee – experts and researchers in internal medicine, family medicine, addiction medicine, addiction psychiatry, general psychiatry, obstetrics, pharmacology, and neurobiology, including some with allopathic or osteopathic training – first reviewed 34 existing clinical guidelines and 27 recent studies in the literature assessing medications used with psychosocial interventions. None of the existing guidelines included all the medications currently in use, and few addressed critical special populations such as pregnant women, patients with comorbid psychiatric disorders, and patients with chronic pain.

The ASAM guideline specifically addresses these and other special populations (for example, adolescents, patients in the criminal justice system). It includes detailed sections on treating opioid withdrawal and opioid overdose, as well as comprehensive discussions of methadone, buprenorphine, naltrexone, and psychosocial therapies.

The guideline offers numerous clinical recommendations regarding patient assessment and diagnosis (J Addict Med. 2015;9:358:67).

First, “addiction should be considered a bio-psycho-social-spiritual illness, for which the use of medication(s) is but only one component of overall treatment.” In addition to a thorough history and physical exam (including specific laboratory tests needed for this patient population), patients should undergo a mental health assessment with particular attention to possible psychiatric comorbidities. And since opioid use often co-occurs with other substance-related disorders, “the totality of substances that surround the addiction” should be assessed before treatment is considered.

Notably, the concomitant use of alcohol, sedatives, hypnotics, or anxiolytics with opioids can cause respiratory depression. Patients who use these agents may automatically require a higher level of care than that offered in typical primary care practices.

As well, social and environmental factors should be assessed, to identify both barriers to and facilitators for addiction treatment in general and pharmacotherapy in particular. “At a minimum, psychosocial treatment should include the following: psychosocial needs assessment, supportive counseling, links to existing family supports, and referrals to community services.” Physicians should be prepared to collaborate with qualified behavioral health care providers, the guideline states.

Urinary drug testing is recommended, both during the assessment process and frequently throughout treatment.

Regarding treatment, the guideline recommends considering the patient’s preferences, past treatment history, and the treatment setting when deciding whether to prescribe methadone, bupenorphrine, or naltrexone. The treatment venue is as important as the specific medication selected. Office-based treatment, which provides medication prescribed either weekly or monthly, is limited to buprenorphine only. It might not be suitable for patients who regularly use alcohol or other substances.

In contrast, treatment programs provide daily supervised dosing of methadone and, increasingly, buprenorphine. Methadone is recommended for patients who fail on buprenorphine or who would benefit from daily dosing and supervision.

Naltrexone can be prescribed in any setting by any clinician, but prescribers must be aware that adherence to oral naltrexone is generally poor, which often leads to treatment failure. Extended-release injectable naltrexone reduces but doesn’t eliminate adherence issues. Clinicians should reserve naltrexone “for patients who would be able to comply with special techniques to enhance their adherence, such as observed dosing.”

Dr. Kampton disclosed research ties with Braeburn Pharmaceuticals; Dr. Jarvis disclosed business ties with U.S. Preventive Medicine.

The American Society of Addiction Medicine has released a practice guideline to help clinicians evaluate and treat opioid use disorder, with the ultimate goal of getting more physicians to provide effective treatment.

Effective treatment of opioid use disorder “requires skill and time that are not generally available to primary care doctors in most practice models,” so much of the treatment provided in primary care has been “suboptimal.” This has probably worsened what the Centers for Disease Control and Prevention has described as an epidemic of opioid misuse and related deaths, said Dr. Kyle Kampman and Dr. Margaret Jarvis, cochairs of the ASAM’s guideline committee.

“At the same time, access to competent treatment is profoundly restricted because few physicians are willing and able to provide it,” they noted.

This guideline “is primarily intended for clinicians involved in evaluating patients and providing authorization for pharmacologic treatments at any level,” said Dr. Kampman of the University of Pennsylvania, Philadelphia, and Dr. Jarvis, of the Marworth Alcohol & Chemical Dependency Center, an entity of the Geisinger Health System, Waverly, Pa.

To develop the guideline, the committee – experts and researchers in internal medicine, family medicine, addiction medicine, addiction psychiatry, general psychiatry, obstetrics, pharmacology, and neurobiology, including some with allopathic or osteopathic training – first reviewed 34 existing clinical guidelines and 27 recent studies in the literature assessing medications used with psychosocial interventions. None of the existing guidelines included all the medications currently in use, and few addressed critical special populations such as pregnant women, patients with comorbid psychiatric disorders, and patients with chronic pain.

The ASAM guideline specifically addresses these and other special populations (for example, adolescents, patients in the criminal justice system). It includes detailed sections on treating opioid withdrawal and opioid overdose, as well as comprehensive discussions of methadone, buprenorphine, naltrexone, and psychosocial therapies.

The guideline offers numerous clinical recommendations regarding patient assessment and diagnosis (J Addict Med. 2015;9:358:67).

First, “addiction should be considered a bio-psycho-social-spiritual illness, for which the use of medication(s) is but only one component of overall treatment.” In addition to a thorough history and physical exam (including specific laboratory tests needed for this patient population), patients should undergo a mental health assessment with particular attention to possible psychiatric comorbidities. And since opioid use often co-occurs with other substance-related disorders, “the totality of substances that surround the addiction” should be assessed before treatment is considered.

Notably, the concomitant use of alcohol, sedatives, hypnotics, or anxiolytics with opioids can cause respiratory depression. Patients who use these agents may automatically require a higher level of care than that offered in typical primary care practices.

As well, social and environmental factors should be assessed, to identify both barriers to and facilitators for addiction treatment in general and pharmacotherapy in particular. “At a minimum, psychosocial treatment should include the following: psychosocial needs assessment, supportive counseling, links to existing family supports, and referrals to community services.” Physicians should be prepared to collaborate with qualified behavioral health care providers, the guideline states.

Urinary drug testing is recommended, both during the assessment process and frequently throughout treatment.

Regarding treatment, the guideline recommends considering the patient’s preferences, past treatment history, and the treatment setting when deciding whether to prescribe methadone, bupenorphrine, or naltrexone. The treatment venue is as important as the specific medication selected. Office-based treatment, which provides medication prescribed either weekly or monthly, is limited to buprenorphine only. It might not be suitable for patients who regularly use alcohol or other substances.

In contrast, treatment programs provide daily supervised dosing of methadone and, increasingly, buprenorphine. Methadone is recommended for patients who fail on buprenorphine or who would benefit from daily dosing and supervision.

Naltrexone can be prescribed in any setting by any clinician, but prescribers must be aware that adherence to oral naltrexone is generally poor, which often leads to treatment failure. Extended-release injectable naltrexone reduces but doesn’t eliminate adherence issues. Clinicians should reserve naltrexone “for patients who would be able to comply with special techniques to enhance their adherence, such as observed dosing.”

Dr. Kampton disclosed research ties with Braeburn Pharmaceuticals; Dr. Jarvis disclosed business ties with U.S. Preventive Medicine.

The American Society of Addiction Medicine has released a practice guideline to help clinicians evaluate and treat opioid use disorder, with the ultimate goal of getting more physicians to provide effective treatment.

Effective treatment of opioid use disorder “requires skill and time that are not generally available to primary care doctors in most practice models,” so much of the treatment provided in primary care has been “suboptimal.” This has probably worsened what the Centers for Disease Control and Prevention has described as an epidemic of opioid misuse and related deaths, said Dr. Kyle Kampman and Dr. Margaret Jarvis, cochairs of the ASAM’s guideline committee.

“At the same time, access to competent treatment is profoundly restricted because few physicians are willing and able to provide it,” they noted.

This guideline “is primarily intended for clinicians involved in evaluating patients and providing authorization for pharmacologic treatments at any level,” said Dr. Kampman of the University of Pennsylvania, Philadelphia, and Dr. Jarvis, of the Marworth Alcohol & Chemical Dependency Center, an entity of the Geisinger Health System, Waverly, Pa.

To develop the guideline, the committee – experts and researchers in internal medicine, family medicine, addiction medicine, addiction psychiatry, general psychiatry, obstetrics, pharmacology, and neurobiology, including some with allopathic or osteopathic training – first reviewed 34 existing clinical guidelines and 27 recent studies in the literature assessing medications used with psychosocial interventions. None of the existing guidelines included all the medications currently in use, and few addressed critical special populations such as pregnant women, patients with comorbid psychiatric disorders, and patients with chronic pain.

The ASAM guideline specifically addresses these and other special populations (for example, adolescents, patients in the criminal justice system). It includes detailed sections on treating opioid withdrawal and opioid overdose, as well as comprehensive discussions of methadone, buprenorphine, naltrexone, and psychosocial therapies.

The guideline offers numerous clinical recommendations regarding patient assessment and diagnosis (J Addict Med. 2015;9:358:67).

First, “addiction should be considered a bio-psycho-social-spiritual illness, for which the use of medication(s) is but only one component of overall treatment.” In addition to a thorough history and physical exam (including specific laboratory tests needed for this patient population), patients should undergo a mental health assessment with particular attention to possible psychiatric comorbidities. And since opioid use often co-occurs with other substance-related disorders, “the totality of substances that surround the addiction” should be assessed before treatment is considered.

Notably, the concomitant use of alcohol, sedatives, hypnotics, or anxiolytics with opioids can cause respiratory depression. Patients who use these agents may automatically require a higher level of care than that offered in typical primary care practices.

As well, social and environmental factors should be assessed, to identify both barriers to and facilitators for addiction treatment in general and pharmacotherapy in particular. “At a minimum, psychosocial treatment should include the following: psychosocial needs assessment, supportive counseling, links to existing family supports, and referrals to community services.” Physicians should be prepared to collaborate with qualified behavioral health care providers, the guideline states.

Urinary drug testing is recommended, both during the assessment process and frequently throughout treatment.

Regarding treatment, the guideline recommends considering the patient’s preferences, past treatment history, and the treatment setting when deciding whether to prescribe methadone, bupenorphrine, or naltrexone. The treatment venue is as important as the specific medication selected. Office-based treatment, which provides medication prescribed either weekly or monthly, is limited to buprenorphine only. It might not be suitable for patients who regularly use alcohol or other substances.

In contrast, treatment programs provide daily supervised dosing of methadone and, increasingly, buprenorphine. Methadone is recommended for patients who fail on buprenorphine or who would benefit from daily dosing and supervision.

Naltrexone can be prescribed in any setting by any clinician, but prescribers must be aware that adherence to oral naltrexone is generally poor, which often leads to treatment failure. Extended-release injectable naltrexone reduces but doesn’t eliminate adherence issues. Clinicians should reserve naltrexone “for patients who would be able to comply with special techniques to enhance their adherence, such as observed dosing.”

Dr. Kampton disclosed research ties with Braeburn Pharmaceuticals; Dr. Jarvis disclosed business ties with U.S. Preventive Medicine.