Hospitalist News (Archived)

It is important to step back occasionally to survey where one has been and to plot a new heading. In an online Aug. 10, 2016, release, the New England Journal of Medicine posted two opinion pieces that provide perspective on hospital medicine. As is often the case when journalism presents two opinions, the viewpoints represent opposite ends of a spectrum and the truth lies somewhere in between.

In one essay, Robert Wachter, MD, and Lee Goldman, MD, highlight the successful growth of hospital medicine (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1607958). In just 2 decades, more than 50,000 physicians have changed their focus to the care of inpatients. The authors state that “many stars had to align” for hospital medicine to grow as rapidly as it has. I would argue instead that many talented leaders of the field have moved heaven and earth to create that alignment and birth this field.

In the other essay, Richard Gunderman, MD, focuses on what he sees as having been lost in this evolution (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1608289). I believe Dr. Gunderman’s viewpoint nostalgically longs for the good old days and a model of an interpersonal doctor-patient relationship that never really existed for a large portion of the population. If you were wealthy, lived most of your life in one location, and had only intermittent or common diseases, then perhaps you had a trusted general internist to provide your medical care and provide the emotional reassurance that nourished both patient and doctor. But in modern medicine, that scenario is uncommon. With large group practices, there is only a small chance that your personal physician will be on call on the night of your admission to a hospital. The next day, as test results and specialty consults trickle in, that personal physician will be trapped in a busy outpatient clinic and not truly available at hospital bedside in “your moment of greatest need,” as Dr. Gunderman phrased it. When your personal physician finally does make rounds, s/he will find the hospital environment inefficient and repeating the same small mistakes that happened to his/her last patient.

I’ve been writing about and teaching professionalism for years. I agree with Dr. Gunderman about the importance of a doctor-patient relationship. I believe reducing physicians to being automatons in a hospital assembly line would be a bad idea. But this essay’s rose-colored and sienna-colored portrait of that relationship is not helpful guidance in the modern world. Surveyors and navigators need sharp, clear vision.

Trade-offs are being made. Many pediatricians in affluent communities do have the opportunity to establish long-term relationships with families, sometimes for multiple generations of children. Those relationships attract medical students into pediatrics and family medicine. I was fortunate enough to establish many of those relationships when I practiced outpatient pediatrics. During my last interstate move, the man packing the picture frames was amused to find amidst my many diplomas a framed crayon drawing. It was a gift to me from a young patient. I told the mover that I would be sadder to have that drawing damaged than if a diploma was damaged in the move. So he wrapped it with extra padding.

Those bonds established with families make up the emotional sustenance throughout a career that justifies the years of sacrifice spent becoming a physician. There is no doubt that it is easier to form those bonds in outpatient pediatrics. At a community hospital, with 7 days on/7 days off scheduling, I usually provide care for the entire hospitalization of a child. That provides emotional satisfaction for both the parents and for me as a physician in ways that 12-hour shifts usually don’t.

The diminishment of those relationships needs to be acknowledged, but not to the exclusion of what a hospitalist can provide. When I practiced general pediatrics and only admitted 1 or 2 children each week, I was often frustrated by inefficiency and errors in the hospital, but I had little recourse for changing it. As a hospitalist admitting 500 patients per year, I can perform problem solving and devote resources to continuously improve the quality and safety of inpatient care. I provide those improvements to all patients admitted to the hospital, whether they have a medical home or not. That fosters social justice. As a function-over-fashion person, that success is emotionally rewarding, too.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

It is important to step back occasionally to survey where one has been and to plot a new heading. In an online Aug. 10, 2016, release, the New England Journal of Medicine posted two opinion pieces that provide perspective on hospital medicine. As is often the case when journalism presents two opinions, the viewpoints represent opposite ends of a spectrum and the truth lies somewhere in between.

In one essay, Robert Wachter, MD, and Lee Goldman, MD, highlight the successful growth of hospital medicine (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1607958). In just 2 decades, more than 50,000 physicians have changed their focus to the care of inpatients. The authors state that “many stars had to align” for hospital medicine to grow as rapidly as it has. I would argue instead that many talented leaders of the field have moved heaven and earth to create that alignment and birth this field.

In the other essay, Richard Gunderman, MD, focuses on what he sees as having been lost in this evolution (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1608289). I believe Dr. Gunderman’s viewpoint nostalgically longs for the good old days and a model of an interpersonal doctor-patient relationship that never really existed for a large portion of the population. If you were wealthy, lived most of your life in one location, and had only intermittent or common diseases, then perhaps you had a trusted general internist to provide your medical care and provide the emotional reassurance that nourished both patient and doctor. But in modern medicine, that scenario is uncommon. With large group practices, there is only a small chance that your personal physician will be on call on the night of your admission to a hospital. The next day, as test results and specialty consults trickle in, that personal physician will be trapped in a busy outpatient clinic and not truly available at hospital bedside in “your moment of greatest need,” as Dr. Gunderman phrased it. When your personal physician finally does make rounds, s/he will find the hospital environment inefficient and repeating the same small mistakes that happened to his/her last patient.

I’ve been writing about and teaching professionalism for years. I agree with Dr. Gunderman about the importance of a doctor-patient relationship. I believe reducing physicians to being automatons in a hospital assembly line would be a bad idea. But this essay’s rose-colored and sienna-colored portrait of that relationship is not helpful guidance in the modern world. Surveyors and navigators need sharp, clear vision.

Trade-offs are being made. Many pediatricians in affluent communities do have the opportunity to establish long-term relationships with families, sometimes for multiple generations of children. Those relationships attract medical students into pediatrics and family medicine. I was fortunate enough to establish many of those relationships when I practiced outpatient pediatrics. During my last interstate move, the man packing the picture frames was amused to find amidst my many diplomas a framed crayon drawing. It was a gift to me from a young patient. I told the mover that I would be sadder to have that drawing damaged than if a diploma was damaged in the move. So he wrapped it with extra padding.

Those bonds established with families make up the emotional sustenance throughout a career that justifies the years of sacrifice spent becoming a physician. There is no doubt that it is easier to form those bonds in outpatient pediatrics. At a community hospital, with 7 days on/7 days off scheduling, I usually provide care for the entire hospitalization of a child. That provides emotional satisfaction for both the parents and for me as a physician in ways that 12-hour shifts usually don’t.

The diminishment of those relationships needs to be acknowledged, but not to the exclusion of what a hospitalist can provide. When I practiced general pediatrics and only admitted 1 or 2 children each week, I was often frustrated by inefficiency and errors in the hospital, but I had little recourse for changing it. As a hospitalist admitting 500 patients per year, I can perform problem solving and devote resources to continuously improve the quality and safety of inpatient care. I provide those improvements to all patients admitted to the hospital, whether they have a medical home or not. That fosters social justice. As a function-over-fashion person, that success is emotionally rewarding, too.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

It is important to step back occasionally to survey where one has been and to plot a new heading. In an online Aug. 10, 2016, release, the New England Journal of Medicine posted two opinion pieces that provide perspective on hospital medicine. As is often the case when journalism presents two opinions, the viewpoints represent opposite ends of a spectrum and the truth lies somewhere in between.

In one essay, Robert Wachter, MD, and Lee Goldman, MD, highlight the successful growth of hospital medicine (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1607958). In just 2 decades, more than 50,000 physicians have changed their focus to the care of inpatients. The authors state that “many stars had to align” for hospital medicine to grow as rapidly as it has. I would argue instead that many talented leaders of the field have moved heaven and earth to create that alignment and birth this field.

In the other essay, Richard Gunderman, MD, focuses on what he sees as having been lost in this evolution (N Eng J Med. 2016, Aug 10. doi: 10.1056/NEJMp1608289). I believe Dr. Gunderman’s viewpoint nostalgically longs for the good old days and a model of an interpersonal doctor-patient relationship that never really existed for a large portion of the population. If you were wealthy, lived most of your life in one location, and had only intermittent or common diseases, then perhaps you had a trusted general internist to provide your medical care and provide the emotional reassurance that nourished both patient and doctor. But in modern medicine, that scenario is uncommon. With large group practices, there is only a small chance that your personal physician will be on call on the night of your admission to a hospital. The next day, as test results and specialty consults trickle in, that personal physician will be trapped in a busy outpatient clinic and not truly available at hospital bedside in “your moment of greatest need,” as Dr. Gunderman phrased it. When your personal physician finally does make rounds, s/he will find the hospital environment inefficient and repeating the same small mistakes that happened to his/her last patient.

I’ve been writing about and teaching professionalism for years. I agree with Dr. Gunderman about the importance of a doctor-patient relationship. I believe reducing physicians to being automatons in a hospital assembly line would be a bad idea. But this essay’s rose-colored and sienna-colored portrait of that relationship is not helpful guidance in the modern world. Surveyors and navigators need sharp, clear vision.

Trade-offs are being made. Many pediatricians in affluent communities do have the opportunity to establish long-term relationships with families, sometimes for multiple generations of children. Those relationships attract medical students into pediatrics and family medicine. I was fortunate enough to establish many of those relationships when I practiced outpatient pediatrics. During my last interstate move, the man packing the picture frames was amused to find amidst my many diplomas a framed crayon drawing. It was a gift to me from a young patient. I told the mover that I would be sadder to have that drawing damaged than if a diploma was damaged in the move. So he wrapped it with extra padding.

Those bonds established with families make up the emotional sustenance throughout a career that justifies the years of sacrifice spent becoming a physician. There is no doubt that it is easier to form those bonds in outpatient pediatrics. At a community hospital, with 7 days on/7 days off scheduling, I usually provide care for the entire hospitalization of a child. That provides emotional satisfaction for both the parents and for me as a physician in ways that 12-hour shifts usually don’t.

The diminishment of those relationships needs to be acknowledged, but not to the exclusion of what a hospitalist can provide. When I practiced general pediatrics and only admitted 1 or 2 children each week, I was often frustrated by inefficiency and errors in the hospital, but I had little recourse for changing it. As a hospitalist admitting 500 patients per year, I can perform problem solving and devote resources to continuously improve the quality and safety of inpatient care. I provide those improvements to all patients admitted to the hospital, whether they have a medical home or not. That fosters social justice. As a function-over-fashion person, that success is emotionally rewarding, too.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

A new classification tool helped guide the treatment of bacteremic patients while clinicians awaited antibiotic resistance results, investigators reported.

The clinical decision tree had a positive predictive value of 91% and a negative predictive value of 92% for determining whether certain gram-negative infections produced extended-spectrum beta-lactamase (ESBL), Catherine Goodman, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates wrote online in Clinical Infectious Diseases. “These predictions may assist empiric treatment decisions in order to optimize clinical outcomes while reducing administration of overly broad antibiotic agents that can select for further resistance emergence,” they added.

Bacteria that produce ESBL can hydrolyze all broad-spectrum beta-lactam antibiotics except carbapenems. Rapid tests for beta-lactamase genes can shorten the lag time between gram-stain identification and antimicrobial resistance results, but are cost prohibitive for most clinical laboratories and often do not assess ESBL gene groups, the researchers said. To find a way to predict which infections are characterized by ESBL production, they studied adults hospitalized at Johns Hopkins from October 2008 to March 2015 with bloodstream isolates of Klebsiella pneumoniae (40% of patients), Klebsiella oxytoca (4% of patients), and Escherichia coli (56% of patients). Most bacteremias began as urinary tract infections (34% of cases), followed by intra-abdominal infections (24%), catheter-related infections (16%), and biliary infections (14%) (Clin Infect Dis. 2016 Jul 26. doi:10.1093/cid/ciw425).

A total of 194 patients (15%) had bacteremias that produced ESBL, according to the investigators. Using a technique called binary recursive partitioning, they compared these patients with ESBL-negative patients to create a clinical decision tree based on five yes-or-no questions. The tree first asked if the patient had been colonized or infected with ESBL-producing bacteria within 6 months, and if so, whether the patient currently had an indwelling catheter. Patients meeting both criteria had a 92% chance of being ESBL positive. Patients with a recent history of ESBL but no catheter had an 81% chance of being ESBL positive if they were at least 43 years old, but a 75% chance of being ESBL negative if they were under age 43 years.

Among patients with no recent history of ESBL, the decision tree asked about hospitalization in a country with a high ESBL burden and antibiotic therapy during the past 6 months. Patients responding “yes” to both questions had a 100% chance of being ESBL positive. Patients with only the geographic risk factor had a 63% chance of being ESBL negative, and patients with neither risk factor had a 93% chance of being ESBL negative.

The decision tree detected only half of ESBL cases because there was a subgroup with no recent ESBL history or geographic exposure, the investigators noted. “The poor predictive nature of health care–associated variables within this patient subset may suggest a high proportion of community-acquired ESBL infections. Indeed, although risk factors for ESBLs have traditionally focused on the health care setting, increasing reports describe the community as an important ESBL reservoir,” they added. Nonetheless, of 194 patients with ESBL bacteremia, 35% received empiric carbapenem treatment within 6 hours after identification of the bacterial genus and species, the investigators emphasized. “Utilization of the decision tree would have increased ESBL case detection during the empiric treatment window by approximately 50%.”

The National Institutes of Health funded the study. The researchers reported having no conflicts of interest.

A new classification tool helped guide the treatment of bacteremic patients while clinicians awaited antibiotic resistance results, investigators reported.

The clinical decision tree had a positive predictive value of 91% and a negative predictive value of 92% for determining whether certain gram-negative infections produced extended-spectrum beta-lactamase (ESBL), Catherine Goodman, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates wrote online in Clinical Infectious Diseases. “These predictions may assist empiric treatment decisions in order to optimize clinical outcomes while reducing administration of overly broad antibiotic agents that can select for further resistance emergence,” they added.

Bacteria that produce ESBL can hydrolyze all broad-spectrum beta-lactam antibiotics except carbapenems. Rapid tests for beta-lactamase genes can shorten the lag time between gram-stain identification and antimicrobial resistance results, but are cost prohibitive for most clinical laboratories and often do not assess ESBL gene groups, the researchers said. To find a way to predict which infections are characterized by ESBL production, they studied adults hospitalized at Johns Hopkins from October 2008 to March 2015 with bloodstream isolates of Klebsiella pneumoniae (40% of patients), Klebsiella oxytoca (4% of patients), and Escherichia coli (56% of patients). Most bacteremias began as urinary tract infections (34% of cases), followed by intra-abdominal infections (24%), catheter-related infections (16%), and biliary infections (14%) (Clin Infect Dis. 2016 Jul 26. doi:10.1093/cid/ciw425).

A total of 194 patients (15%) had bacteremias that produced ESBL, according to the investigators. Using a technique called binary recursive partitioning, they compared these patients with ESBL-negative patients to create a clinical decision tree based on five yes-or-no questions. The tree first asked if the patient had been colonized or infected with ESBL-producing bacteria within 6 months, and if so, whether the patient currently had an indwelling catheter. Patients meeting both criteria had a 92% chance of being ESBL positive. Patients with a recent history of ESBL but no catheter had an 81% chance of being ESBL positive if they were at least 43 years old, but a 75% chance of being ESBL negative if they were under age 43 years.

Among patients with no recent history of ESBL, the decision tree asked about hospitalization in a country with a high ESBL burden and antibiotic therapy during the past 6 months. Patients responding “yes” to both questions had a 100% chance of being ESBL positive. Patients with only the geographic risk factor had a 63% chance of being ESBL negative, and patients with neither risk factor had a 93% chance of being ESBL negative.

The decision tree detected only half of ESBL cases because there was a subgroup with no recent ESBL history or geographic exposure, the investigators noted. “The poor predictive nature of health care–associated variables within this patient subset may suggest a high proportion of community-acquired ESBL infections. Indeed, although risk factors for ESBLs have traditionally focused on the health care setting, increasing reports describe the community as an important ESBL reservoir,” they added. Nonetheless, of 194 patients with ESBL bacteremia, 35% received empiric carbapenem treatment within 6 hours after identification of the bacterial genus and species, the investigators emphasized. “Utilization of the decision tree would have increased ESBL case detection during the empiric treatment window by approximately 50%.”

The National Institutes of Health funded the study. The researchers reported having no conflicts of interest.

A new classification tool helped guide the treatment of bacteremic patients while clinicians awaited antibiotic resistance results, investigators reported.

The clinical decision tree had a positive predictive value of 91% and a negative predictive value of 92% for determining whether certain gram-negative infections produced extended-spectrum beta-lactamase (ESBL), Catherine Goodman, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates wrote online in Clinical Infectious Diseases. “These predictions may assist empiric treatment decisions in order to optimize clinical outcomes while reducing administration of overly broad antibiotic agents that can select for further resistance emergence,” they added.

Bacteria that produce ESBL can hydrolyze all broad-spectrum beta-lactam antibiotics except carbapenems. Rapid tests for beta-lactamase genes can shorten the lag time between gram-stain identification and antimicrobial resistance results, but are cost prohibitive for most clinical laboratories and often do not assess ESBL gene groups, the researchers said. To find a way to predict which infections are characterized by ESBL production, they studied adults hospitalized at Johns Hopkins from October 2008 to March 2015 with bloodstream isolates of Klebsiella pneumoniae (40% of patients), Klebsiella oxytoca (4% of patients), and Escherichia coli (56% of patients). Most bacteremias began as urinary tract infections (34% of cases), followed by intra-abdominal infections (24%), catheter-related infections (16%), and biliary infections (14%) (Clin Infect Dis. 2016 Jul 26. doi:10.1093/cid/ciw425).

A total of 194 patients (15%) had bacteremias that produced ESBL, according to the investigators. Using a technique called binary recursive partitioning, they compared these patients with ESBL-negative patients to create a clinical decision tree based on five yes-or-no questions. The tree first asked if the patient had been colonized or infected with ESBL-producing bacteria within 6 months, and if so, whether the patient currently had an indwelling catheter. Patients meeting both criteria had a 92% chance of being ESBL positive. Patients with a recent history of ESBL but no catheter had an 81% chance of being ESBL positive if they were at least 43 years old, but a 75% chance of being ESBL negative if they were under age 43 years.

Among patients with no recent history of ESBL, the decision tree asked about hospitalization in a country with a high ESBL burden and antibiotic therapy during the past 6 months. Patients responding “yes” to both questions had a 100% chance of being ESBL positive. Patients with only the geographic risk factor had a 63% chance of being ESBL negative, and patients with neither risk factor had a 93% chance of being ESBL negative.

The decision tree detected only half of ESBL cases because there was a subgroup with no recent ESBL history or geographic exposure, the investigators noted. “The poor predictive nature of health care–associated variables within this patient subset may suggest a high proportion of community-acquired ESBL infections. Indeed, although risk factors for ESBLs have traditionally focused on the health care setting, increasing reports describe the community as an important ESBL reservoir,” they added. Nonetheless, of 194 patients with ESBL bacteremia, 35% received empiric carbapenem treatment within 6 hours after identification of the bacterial genus and species, the investigators emphasized. “Utilization of the decision tree would have increased ESBL case detection during the empiric treatment window by approximately 50%.”

The National Institutes of Health funded the study. The researchers reported having no conflicts of interest.

The first dose of rotavirus vaccine was again linked to a small, short-term increase in the risk of hospitalization for intussusception, but the benefits of the vaccine exceed this risk, according to a report.

In absolute numbers, there were an estimated 7 to 26 more intussusception cases per year among U.S. children aged 8-11 weeks during the postvaccine era, compared with the prevaccine era, said Jacqueline E. Tate, PhD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, and her associates.

©jarun011/Thinkstock

The increased risk did not extend to older children, which “is consistent with other U.S. studies,” the investigators said. “[Given] the magnitude of the declines in rotavirus disease compared with the small increased risk of intussusception, the public health benefits of rotavirus vaccination far exceed the increased risk of intussusception.”

Human rotavirus vaccines have been linked to rare events of intussusception since at least 1999, when Rotashield was withdrawn from the market for this reason. The next two rotavirus vaccines to receive Food and Drug Administration approval, RotaTeq and Rotarix, were not linked to intussusception in large trials or early postmarketing studies, but were estimated to cause 1-5 excess cases of intussusception per 100,000 population in more recent studies. Furthermore, a prior analysis of U.S. hospital discharge data found a small increase in the risk of intussusception hospitalization among 8- to 11-week-olds between 2007 to 2009, compared with baseline data from the prevaccine era, the investigators noted (Pediatrics. 2016 Aug 24. doi: 10.1542/peds.2016-1082).

To build on that analysis, they calculated rates of intussusception between 2000 and 2013 overall and among recommended age windows for rotavirus vaccination, which are 6-14 weeks for the first dose, 15-24 weeks for the second dose, and 25-34 weeks for the third dose. For consistency, they also looked at hospitalization rates among children aged 8-11 weeks.

The investigators identified 15,231 intussusception hospitalizations among children under 1 year of age during the study from 2000-2013. There were no overall trends in intussusception hospitalizations for all children under 1 year of age or subgroups of children aged 15-24 weeks or 25-34 weeks. Among children aged 8-11 weeks, intussusception hospitalization rates did rise significantly during the postvaccine era, compared with the prevaccine era for all years except 2011 and 2013. Excluding those two years, annual rates of intussusception hospitalizations among 8- to 11-week-olds were 46%-101% higher (16.7 to 22.9 hospitalizations per 100,000 population) during the postvaccine era than during the prevaccine era (11.4 hospitalizations per 100,000 population).

These results are “consistent with other U.S. studies that have been able to associate an increased risk of intussusception in the first week after the first dose of vaccine,” the researchers concluded. The advent of rotavirus vaccination prevented more than 176,000 hospitalizations, 242,000 emergency department visits, and 1.1 million outpatient visits from 2007 to 2011 (JAMA. 2015;313(22):2282-4), they noted.

The investigators reported no external funding sources and had no disclosures.

The first dose of rotavirus vaccine was again linked to a small, short-term increase in the risk of hospitalization for intussusception, but the benefits of the vaccine exceed this risk, according to a report.

In absolute numbers, there were an estimated 7 to 26 more intussusception cases per year among U.S. children aged 8-11 weeks during the postvaccine era, compared with the prevaccine era, said Jacqueline E. Tate, PhD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, and her associates.

©jarun011/Thinkstock

The increased risk did not extend to older children, which “is consistent with other U.S. studies,” the investigators said. “[Given] the magnitude of the declines in rotavirus disease compared with the small increased risk of intussusception, the public health benefits of rotavirus vaccination far exceed the increased risk of intussusception.”

Human rotavirus vaccines have been linked to rare events of intussusception since at least 1999, when Rotashield was withdrawn from the market for this reason. The next two rotavirus vaccines to receive Food and Drug Administration approval, RotaTeq and Rotarix, were not linked to intussusception in large trials or early postmarketing studies, but were estimated to cause 1-5 excess cases of intussusception per 100,000 population in more recent studies. Furthermore, a prior analysis of U.S. hospital discharge data found a small increase in the risk of intussusception hospitalization among 8- to 11-week-olds between 2007 to 2009, compared with baseline data from the prevaccine era, the investigators noted (Pediatrics. 2016 Aug 24. doi: 10.1542/peds.2016-1082).

To build on that analysis, they calculated rates of intussusception between 2000 and 2013 overall and among recommended age windows for rotavirus vaccination, which are 6-14 weeks for the first dose, 15-24 weeks for the second dose, and 25-34 weeks for the third dose. For consistency, they also looked at hospitalization rates among children aged 8-11 weeks.

The investigators identified 15,231 intussusception hospitalizations among children under 1 year of age during the study from 2000-2013. There were no overall trends in intussusception hospitalizations for all children under 1 year of age or subgroups of children aged 15-24 weeks or 25-34 weeks. Among children aged 8-11 weeks, intussusception hospitalization rates did rise significantly during the postvaccine era, compared with the prevaccine era for all years except 2011 and 2013. Excluding those two years, annual rates of intussusception hospitalizations among 8- to 11-week-olds were 46%-101% higher (16.7 to 22.9 hospitalizations per 100,000 population) during the postvaccine era than during the prevaccine era (11.4 hospitalizations per 100,000 population).

These results are “consistent with other U.S. studies that have been able to associate an increased risk of intussusception in the first week after the first dose of vaccine,” the researchers concluded. The advent of rotavirus vaccination prevented more than 176,000 hospitalizations, 242,000 emergency department visits, and 1.1 million outpatient visits from 2007 to 2011 (JAMA. 2015;313(22):2282-4), they noted.

The investigators reported no external funding sources and had no disclosures.

The first dose of rotavirus vaccine was again linked to a small, short-term increase in the risk of hospitalization for intussusception, but the benefits of the vaccine exceed this risk, according to a report.

In absolute numbers, there were an estimated 7 to 26 more intussusception cases per year among U.S. children aged 8-11 weeks during the postvaccine era, compared with the prevaccine era, said Jacqueline E. Tate, PhD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, and her associates.

©jarun011/Thinkstock

The increased risk did not extend to older children, which “is consistent with other U.S. studies,” the investigators said. “[Given] the magnitude of the declines in rotavirus disease compared with the small increased risk of intussusception, the public health benefits of rotavirus vaccination far exceed the increased risk of intussusception.”

Human rotavirus vaccines have been linked to rare events of intussusception since at least 1999, when Rotashield was withdrawn from the market for this reason. The next two rotavirus vaccines to receive Food and Drug Administration approval, RotaTeq and Rotarix, were not linked to intussusception in large trials or early postmarketing studies, but were estimated to cause 1-5 excess cases of intussusception per 100,000 population in more recent studies. Furthermore, a prior analysis of U.S. hospital discharge data found a small increase in the risk of intussusception hospitalization among 8- to 11-week-olds between 2007 to 2009, compared with baseline data from the prevaccine era, the investigators noted (Pediatrics. 2016 Aug 24. doi: 10.1542/peds.2016-1082).

To build on that analysis, they calculated rates of intussusception between 2000 and 2013 overall and among recommended age windows for rotavirus vaccination, which are 6-14 weeks for the first dose, 15-24 weeks for the second dose, and 25-34 weeks for the third dose. For consistency, they also looked at hospitalization rates among children aged 8-11 weeks.

The investigators identified 15,231 intussusception hospitalizations among children under 1 year of age during the study from 2000-2013. There were no overall trends in intussusception hospitalizations for all children under 1 year of age or subgroups of children aged 15-24 weeks or 25-34 weeks. Among children aged 8-11 weeks, intussusception hospitalization rates did rise significantly during the postvaccine era, compared with the prevaccine era for all years except 2011 and 2013. Excluding those two years, annual rates of intussusception hospitalizations among 8- to 11-week-olds were 46%-101% higher (16.7 to 22.9 hospitalizations per 100,000 population) during the postvaccine era than during the prevaccine era (11.4 hospitalizations per 100,000 population).

These results are “consistent with other U.S. studies that have been able to associate an increased risk of intussusception in the first week after the first dose of vaccine,” the researchers concluded. The advent of rotavirus vaccination prevented more than 176,000 hospitalizations, 242,000 emergency department visits, and 1.1 million outpatient visits from 2007 to 2011 (JAMA. 2015;313(22):2282-4), they noted.

The investigators reported no external funding sources and had no disclosures.

Enforcing more stringent requirements for exclusivity rights, ensuring timely generic drug availability, and providing greater opportunities for meaningful price negotiation by government payers could help combat high medication costs in the United States, according to an analysis published Aug. 23 in JAMA.

Per capita prescription drug spending in the United States exceeds that in all other countries, largely fueled by brand-name drug prices rising at rates far beyond the consumer price index. For example, in 2013, per capita spending on prescription drugs was $858, compared with an average of $400 for 19 other industrialized nations, according to the analysis conducted by Aaron S. Kesselheim, MD, of Brigham & Women’s Hospital, Boston, and colleagues. In addition, between 2008 and 2015, prices for the most commonly used brand-name drugs in the United States rose by 164%, far more than the consumer price index increased (12%), authors reported (JAMA 2016. doi: 10.1001/jama.2016.11237).

“We found that indeed, drug prices in the United States are much high than anywhere else in the world and the main contributors to that are the U.S. drug marketplace which allows drug companies to charge whatever the market will bear and then in many respects, places limitations on the ability of payers to try to negotiate lower drug prices,” Dr. Kesselheim said in a video interview for JAMA.

To reduce high drug prices, authors propose better federal oversight of drug makers who attempt to extend market exclusivity. For example, changing how the U.S. Patent and Trademark Office interprets novelty and non-obviousness when issuing drug patents could help avoid new secondary patents based on clinically irrelevant changes to active drug products. Other strategies outlined include:

• Decrease industry expenses. Reviews have pointed to the increasing expenditures for drug research and development, with the suggestion that steps be taken to make companies’ investments more efficient.

• Pass state laws permitting substitution of clinically similar drugs within the same class in carefully selected circumstances.

• Increase attention to the generic drug marketplace. Proposed federal legislation would forbid brand-name manufacturers from refusing to share samples of products with generic drug manufacturers for necessary bioequivalence studies.

• Authorize Medicare to negotiate prices of drugs paid for by Medicare Part D plans.

Physicians can also play a role in decreasing drug prices by discussing drug prices and choices with patients and limiting practices such as writing “dispense as written” prescriptions to avoid generic medications, Dr. Kesselheim noted. More education about drug costs and value-based prescribing integrated into physicians’ initial and continuing education could also be beneficial.

“There needs to be more education of patients and physicians about the implications of high drug prices and ways they can ensure that the prescribing they are doing is of highest value,” Dr. Kesselheim said in the video interview.

[email protected]

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Enforcing more stringent requirements for exclusivity rights, ensuring timely generic drug availability, and providing greater opportunities for meaningful price negotiation by government payers could help combat high medication costs in the United States, according to an analysis published Aug. 23 in JAMA.

Per capita prescription drug spending in the United States exceeds that in all other countries, largely fueled by brand-name drug prices rising at rates far beyond the consumer price index. For example, in 2013, per capita spending on prescription drugs was $858, compared with an average of $400 for 19 other industrialized nations, according to the analysis conducted by Aaron S. Kesselheim, MD, of Brigham & Women’s Hospital, Boston, and colleagues. In addition, between 2008 and 2015, prices for the most commonly used brand-name drugs in the United States rose by 164%, far more than the consumer price index increased (12%), authors reported (JAMA 2016. doi: 10.1001/jama.2016.11237).

“We found that indeed, drug prices in the United States are much high than anywhere else in the world and the main contributors to that are the U.S. drug marketplace which allows drug companies to charge whatever the market will bear and then in many respects, places limitations on the ability of payers to try to negotiate lower drug prices,” Dr. Kesselheim said in a video interview for JAMA.

To reduce high drug prices, authors propose better federal oversight of drug makers who attempt to extend market exclusivity. For example, changing how the U.S. Patent and Trademark Office interprets novelty and non-obviousness when issuing drug patents could help avoid new secondary patents based on clinically irrelevant changes to active drug products. Other strategies outlined include:

• Decrease industry expenses. Reviews have pointed to the increasing expenditures for drug research and development, with the suggestion that steps be taken to make companies’ investments more efficient.

• Pass state laws permitting substitution of clinically similar drugs within the same class in carefully selected circumstances.

• Increase attention to the generic drug marketplace. Proposed federal legislation would forbid brand-name manufacturers from refusing to share samples of products with generic drug manufacturers for necessary bioequivalence studies.

• Authorize Medicare to negotiate prices of drugs paid for by Medicare Part D plans.

Physicians can also play a role in decreasing drug prices by discussing drug prices and choices with patients and limiting practices such as writing “dispense as written” prescriptions to avoid generic medications, Dr. Kesselheim noted. More education about drug costs and value-based prescribing integrated into physicians’ initial and continuing education could also be beneficial.

“There needs to be more education of patients and physicians about the implications of high drug prices and ways they can ensure that the prescribing they are doing is of highest value,” Dr. Kesselheim said in the video interview.

[email protected]

On Twitter @legal_med

Enforcing more stringent requirements for exclusivity rights, ensuring timely generic drug availability, and providing greater opportunities for meaningful price negotiation by government payers could help combat high medication costs in the United States, according to an analysis published Aug. 23 in JAMA.

Per capita prescription drug spending in the United States exceeds that in all other countries, largely fueled by brand-name drug prices rising at rates far beyond the consumer price index. For example, in 2013, per capita spending on prescription drugs was $858, compared with an average of $400 for 19 other industrialized nations, according to the analysis conducted by Aaron S. Kesselheim, MD, of Brigham & Women’s Hospital, Boston, and colleagues. In addition, between 2008 and 2015, prices for the most commonly used brand-name drugs in the United States rose by 164%, far more than the consumer price index increased (12%), authors reported (JAMA 2016. doi: 10.1001/jama.2016.11237).

“We found that indeed, drug prices in the United States are much high than anywhere else in the world and the main contributors to that are the U.S. drug marketplace which allows drug companies to charge whatever the market will bear and then in many respects, places limitations on the ability of payers to try to negotiate lower drug prices,” Dr. Kesselheim said in a video interview for JAMA.

To reduce high drug prices, authors propose better federal oversight of drug makers who attempt to extend market exclusivity. For example, changing how the U.S. Patent and Trademark Office interprets novelty and non-obviousness when issuing drug patents could help avoid new secondary patents based on clinically irrelevant changes to active drug products. Other strategies outlined include:

• Decrease industry expenses. Reviews have pointed to the increasing expenditures for drug research and development, with the suggestion that steps be taken to make companies’ investments more efficient.

• Pass state laws permitting substitution of clinically similar drugs within the same class in carefully selected circumstances.

• Increase attention to the generic drug marketplace. Proposed federal legislation would forbid brand-name manufacturers from refusing to share samples of products with generic drug manufacturers for necessary bioequivalence studies.

• Authorize Medicare to negotiate prices of drugs paid for by Medicare Part D plans.

Physicians can also play a role in decreasing drug prices by discussing drug prices and choices with patients and limiting practices such as writing “dispense as written” prescriptions to avoid generic medications, Dr. Kesselheim noted. More education about drug costs and value-based prescribing integrated into physicians’ initial and continuing education could also be beneficial.

“There needs to be more education of patients and physicians about the implications of high drug prices and ways they can ensure that the prescribing they are doing is of highest value,” Dr. Kesselheim said in the video interview.

[email protected]

On Twitter @legal_med

Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.

Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).

“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”

Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”

In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”

The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”

Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”

Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”

[email protected]

Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.

Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).

“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”

Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”

In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”

The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”

Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”

Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”

[email protected]

Sepsis is a medical emergency that begins outside of the hospital in 79% of cases. In addition, 72% of patients with sepsis had recently used healthcare services or had chronic diseases that required frequent medical care.

Those are key findings from a special report in Morbidity and Mortality Weekly Report published by the U.S. Centers for Disease Control and Prevention (Morb Mortal Wkly Rep. 2016 Aug 23. doi: 10.15585/mmwr.mm6533e1).

“The treatment of sepsis is a race against time,” CDC Director Tom Frieden, MD, said during a media teleconference about the report. “We can protect more people from sepsis by informing patients and their families, treating infections promptly, and acting fast when sepsis does occur.”

Each year, between 1 and 3 million people in the United States are diagnosed with sepsis, a syndrome marked by the body’s overwhelming and life-threatening response to an infection, Dr. Frieden said. Of these, 15%-30% will die from the condition, for which there is no blood test. “Health care providers are on the front lines of both sepsis prevention and early recognition,” he emphasized. “Prevention really is possible.” For example, he continued, if a patient with diabetes visits their regular doctor and is found to have increased blood sugar and a small wound on their foot, “this is a prime opportunity to think about infection and reduce the risk of sepsis. In addition to treating the infection, the clinician can inform the patient and family members about how to care for the wound, how to recognize the signs that the infection may be getting worse, and when to seek additional medical care. If the infection gets worse the patient could be at risk for sepsis. Taking the opportunity to both treat and inform patients could save their life, and helping patients know to ask, ‘Could this be sepsis?’ empowers patients and families and could save lives.”

In an effort to describe the characteristics of patients with sepsis, researchers from the CDC and from New York State conducted a retrospective review of medical records from 246 adults and 79 children with sepsis who were treated at four New York hospitals. They found that sepsis most often occurs in patients older than age 65 years and in infants younger than 1 year of age, and the median hospital length of stay is 10 days. Six key signs and symptoms of sepsis were shivering or feeling cold; pain or discomfort; clammy or sweaty skin; being confused or disoriented; shortness of breath, and having a rapid heartbeat. “People with chronic diseases such as diabetes or weakened immune systems from things like tobacco use are at higher risk of sepsis,” Dr. Frieden said. “But even healthy people can develop sepsis from an infection, especially if it’s not treated properly and promptly.”

The four types of infections most commonly associated with sepsis include those involving the lungs, urinary tract, skin, and intestines, while the most common germs that can cause sepsis are Staphylococcus aureus, Escherichia coli (E. coli), and some types of Streptococcus. Infection prevention strategies such as increasing vaccination rates for pneumococcal disease and for influenza are likely to reduce the incidence of sepsis, according to the report. “We could also improve infections by improving handwashing at health care facilities as well as in the community,” Dr. Frieden added. “We can [also] improve recognition of sepsis both in the community and in health care facilities and act fast if sepsis is suspected in a patient. We’ve been able to reduce the rates of some infections that cause sepsis in health care facilities by half, but preventing more infections and stopping the spread of antibiotic resistant infections will protect even more patients from sepsis.”

Mitchell Levy, MD, founding member of the Surviving Sepsis Campaign, said during the teleconference that clinicians have made “tremendous progress in sepsis,” despite current challenges. “First, we now understand the importance of early identification and treatment of sepsis,” he said. “Second, we have seen improved survival through routine screening and treatment that is integrated into the work flow of hospitals. And third, frontline health care providers really do make a difference. What’s clear is that we need to expand these successes to other parts of hospitals and to other care locations.”

Forthcoming free CDC webinars related to sepsis for health care providers include one on Sept. 13 at 3 p.m., ET, entitled “Advances in Sepsis: Protecting Patients Throughout the Lifespan.” Another webinar will be offered on Sept. 22 at 2 p.m., ET, entitled “Empowering Nurses for Early Sepsis Recognition.”

[email protected]

The scientific evidence does not support tight glycemic control as a means to prevent the complications of type 2 diabetes, even though most clinical practice guidelines, quality-of-care measures, quality improvement interventions, and academic and clinical statements unequivocally endorse tight glycemic control for that purpose, according to a report published online Aug. 23 in Circulation: Cardiovascular Quality and Outcomes.

There is an enormous disconnect between the widespread consensus that tight glycemic control is essential on the one hand, and the overwhelming data demonstrating that it doesn’t prevent 10 of the 11 micro- and macrovascular complications that matter most to patients on the other hand. “This consensus and its downstream consequences to practice, policy, and research” must be recalibrated, said Rene Rodriguez-Gutierrez, MD, and Victor M. Montori, MD, both of the Knowledge and Evaluation Research Unit, Division of Endocrinology, Mayo Clinic, Rochester, Minn.

©CDC

They systematically reviewed the current evidence regarding tight glycemic control (achieving hemoglobin A_1c under 7%) published in the five “most impactful” general medical journals (the New England Journal of Medicine, the Lancet, JAMA, the British Medical Journal, and Annals of Internal Medicine) and the two most impactful specialty journals (Diabetes Care and the Journal of the American College of Cardiology) between 2006 and 2015. This included 328 research articles, 16 sets of treatment guidelines, 11 meta-analyses, and five large, randomized clinical trials and their extension studies, as well as relevant letters, commentaries, and editorials. They also reviewed national guidelines and standards of care published in all languages during the study period.

The investigators focused on the effect of tight glycemic control, as opposed to looser control, on 11 outcomes most important to patients: end-stage renal disease or the need for dialysis, renal death, blindness, clinical neuropathy, microalbuminuria, retinal photocoagulation, all-cause mortality, cardiovascular mortality, nonfatal MI, fatal and nonfatal stroke, and peripheral vascular events or amputations.

Regarding the microvascular complications, good evidence shows that tight glycemic control has no significant impact on the risk of end-stage renal disease, renal death, blindness, or clinical neuropathy, and that there is no threshold HbA1_c effect on risk. Moreover, the incidence of such complications is very low (less than 6%). Nevertheless, “practice guidelines and published statements offer a consistent and confident consensus, with 100% of the guidelines and 77%-100% of academic and clinical statements in favor of tight glycemic control to prevent microvascular complications,” according to Dr. Rodriguez-Gutierrez and Dr. Montori (Circ Cardiovasc Qual Outcomes. 2016 Aug 23;9:00-00. doi: 10.1161/CIRCOUTCOMES.116.002901).

Regarding the macrovascular complications, the evidence consistently shows that tight glycemic control exerts no significant effect on all-cause or cardiovascular mortality or on fatal or nonfatal stroke. The putative protective effect reported on amputations is “imprecise,” as it is based on very few such events. The only protective effect of tight glycemic control in this category of complications is that it reduces the risk of nonfatal MI by 15%.

Since the publication of the ACCORD trial, which clearly questioned the ability of tight glycemic control to prevent macrovascular complications, the consensus on this point has “withered.” At present, 64%-79% of published statements now express “uncertainty and skepticism” that tight glycemic control is essential. Yet two sets of guidelines – the American Diabetes Association standards published in 2003 and 2004 – did so.

The study findings indicate that despite good evidence to the contrary, the unsupported “consensus” on tight glycemic control drives most guidelines and quality-of-care interventions. It also underlies “the Food and Drug Administration policy to approve diabetes mellitus drugs only on the basis of their antihyperglycemic effect, without requiring evidence of reduction in the risk of complications,” the investigators said.

“This consensus is also driving studies such as the National Institutes of Health–funded GRADE trial comparing antihyperglycemic drugs on their ability to reduce HbA_1c, rather than to reduce the risk of diabetes complications,” they added.

The narrow focus on tight glycemic control has undercut research on other possible interventions to prevent these complications. There are zero trials currently under way assessing treatment possibilities other than drugs that reduce hyperglycemia, and there are zero evidence-based therapies either mentioned in guidelines or routinely prescribed to patients for preventing these complications, Dr. Rodriguez-Gutierrez and Dr. Montori wrote.

“A careful and thoughtful recalibration” is needed. “Today, patients with type 2 diabetes, at least in some parts of the world, seem to live longer lives with fewer complications. The evidence summarized here requires us to explore factors other than tight glycemic control to explain this improvement and better address the diabetes epidemic,” they noted.

This study was supported by the National Center for Advancing Translational Sciences, a component of the National Institutes of Health. Dr. Rodriguez-Gutierrez and Dr. Montori reported having no relevant financial disclosures.

The scientific evidence does not support tight glycemic control as a means to prevent the complications of type 2 diabetes, even though most clinical practice guidelines, quality-of-care measures, quality improvement interventions, and academic and clinical statements unequivocally endorse tight glycemic control for that purpose, according to a report published online Aug. 23 in Circulation: Cardiovascular Quality and Outcomes.

There is an enormous disconnect between the widespread consensus that tight glycemic control is essential on the one hand, and the overwhelming data demonstrating that it doesn’t prevent 10 of the 11 micro- and macrovascular complications that matter most to patients on the other hand. “This consensus and its downstream consequences to practice, policy, and research” must be recalibrated, said Rene Rodriguez-Gutierrez, MD, and Victor M. Montori, MD, both of the Knowledge and Evaluation Research Unit, Division of Endocrinology, Mayo Clinic, Rochester, Minn.

©CDC

They systematically reviewed the current evidence regarding tight glycemic control (achieving hemoglobin A_1c under 7%) published in the five “most impactful” general medical journals (the New England Journal of Medicine, the Lancet, JAMA, the British Medical Journal, and Annals of Internal Medicine) and the two most impactful specialty journals (Diabetes Care and the Journal of the American College of Cardiology) between 2006 and 2015. This included 328 research articles, 16 sets of treatment guidelines, 11 meta-analyses, and five large, randomized clinical trials and their extension studies, as well as relevant letters, commentaries, and editorials. They also reviewed national guidelines and standards of care published in all languages during the study period.

The investigators focused on the effect of tight glycemic control, as opposed to looser control, on 11 outcomes most important to patients: end-stage renal disease or the need for dialysis, renal death, blindness, clinical neuropathy, microalbuminuria, retinal photocoagulation, all-cause mortality, cardiovascular mortality, nonfatal MI, fatal and nonfatal stroke, and peripheral vascular events or amputations.

Regarding the microvascular complications, good evidence shows that tight glycemic control has no significant impact on the risk of end-stage renal disease, renal death, blindness, or clinical neuropathy, and that there is no threshold HbA1_c effect on risk. Moreover, the incidence of such complications is very low (less than 6%). Nevertheless, “practice guidelines and published statements offer a consistent and confident consensus, with 100% of the guidelines and 77%-100% of academic and clinical statements in favor of tight glycemic control to prevent microvascular complications,” according to Dr. Rodriguez-Gutierrez and Dr. Montori (Circ Cardiovasc Qual Outcomes. 2016 Aug 23;9:00-00. doi: 10.1161/CIRCOUTCOMES.116.002901).

Regarding the macrovascular complications, the evidence consistently shows that tight glycemic control exerts no significant effect on all-cause or cardiovascular mortality or on fatal or nonfatal stroke. The putative protective effect reported on amputations is “imprecise,” as it is based on very few such events. The only protective effect of tight glycemic control in this category of complications is that it reduces the risk of nonfatal MI by 15%.

Since the publication of the ACCORD trial, which clearly questioned the ability of tight glycemic control to prevent macrovascular complications, the consensus on this point has “withered.” At present, 64%-79% of published statements now express “uncertainty and skepticism” that tight glycemic control is essential. Yet two sets of guidelines – the American Diabetes Association standards published in 2003 and 2004 – did so.

The study findings indicate that despite good evidence to the contrary, the unsupported “consensus” on tight glycemic control drives most guidelines and quality-of-care interventions. It also underlies “the Food and Drug Administration policy to approve diabetes mellitus drugs only on the basis of their antihyperglycemic effect, without requiring evidence of reduction in the risk of complications,” the investigators said.

“This consensus is also driving studies such as the National Institutes of Health–funded GRADE trial comparing antihyperglycemic drugs on their ability to reduce HbA_1c, rather than to reduce the risk of diabetes complications,” they added.

The narrow focus on tight glycemic control has undercut research on other possible interventions to prevent these complications. There are zero trials currently under way assessing treatment possibilities other than drugs that reduce hyperglycemia, and there are zero evidence-based therapies either mentioned in guidelines or routinely prescribed to patients for preventing these complications, Dr. Rodriguez-Gutierrez and Dr. Montori wrote.

“A careful and thoughtful recalibration” is needed. “Today, patients with type 2 diabetes, at least in some parts of the world, seem to live longer lives with fewer complications. The evidence summarized here requires us to explore factors other than tight glycemic control to explain this improvement and better address the diabetes epidemic,” they noted.

This study was supported by the National Center for Advancing Translational Sciences, a component of the National Institutes of Health. Dr. Rodriguez-Gutierrez and Dr. Montori reported having no relevant financial disclosures.

The scientific evidence does not support tight glycemic control as a means to prevent the complications of type 2 diabetes, even though most clinical practice guidelines, quality-of-care measures, quality improvement interventions, and academic and clinical statements unequivocally endorse tight glycemic control for that purpose, according to a report published online Aug. 23 in Circulation: Cardiovascular Quality and Outcomes.

There is an enormous disconnect between the widespread consensus that tight glycemic control is essential on the one hand, and the overwhelming data demonstrating that it doesn’t prevent 10 of the 11 micro- and macrovascular complications that matter most to patients on the other hand. “This consensus and its downstream consequences to practice, policy, and research” must be recalibrated, said Rene Rodriguez-Gutierrez, MD, and Victor M. Montori, MD, both of the Knowledge and Evaluation Research Unit, Division of Endocrinology, Mayo Clinic, Rochester, Minn.

©CDC

They systematically reviewed the current evidence regarding tight glycemic control (achieving hemoglobin A_1c under 7%) published in the five “most impactful” general medical journals (the New England Journal of Medicine, the Lancet, JAMA, the British Medical Journal, and Annals of Internal Medicine) and the two most impactful specialty journals (Diabetes Care and the Journal of the American College of Cardiology) between 2006 and 2015. This included 328 research articles, 16 sets of treatment guidelines, 11 meta-analyses, and five large, randomized clinical trials and their extension studies, as well as relevant letters, commentaries, and editorials. They also reviewed national guidelines and standards of care published in all languages during the study period.

The investigators focused on the effect of tight glycemic control, as opposed to looser control, on 11 outcomes most important to patients: end-stage renal disease or the need for dialysis, renal death, blindness, clinical neuropathy, microalbuminuria, retinal photocoagulation, all-cause mortality, cardiovascular mortality, nonfatal MI, fatal and nonfatal stroke, and peripheral vascular events or amputations.

Regarding the microvascular complications, good evidence shows that tight glycemic control has no significant impact on the risk of end-stage renal disease, renal death, blindness, or clinical neuropathy, and that there is no threshold HbA1_c effect on risk. Moreover, the incidence of such complications is very low (less than 6%). Nevertheless, “practice guidelines and published statements offer a consistent and confident consensus, with 100% of the guidelines and 77%-100% of academic and clinical statements in favor of tight glycemic control to prevent microvascular complications,” according to Dr. Rodriguez-Gutierrez and Dr. Montori (Circ Cardiovasc Qual Outcomes. 2016 Aug 23;9:00-00. doi: 10.1161/CIRCOUTCOMES.116.002901).

Regarding the macrovascular complications, the evidence consistently shows that tight glycemic control exerts no significant effect on all-cause or cardiovascular mortality or on fatal or nonfatal stroke. The putative protective effect reported on amputations is “imprecise,” as it is based on very few such events. The only protective effect of tight glycemic control in this category of complications is that it reduces the risk of nonfatal MI by 15%.

Since the publication of the ACCORD trial, which clearly questioned the ability of tight glycemic control to prevent macrovascular complications, the consensus on this point has “withered.” At present, 64%-79% of published statements now express “uncertainty and skepticism” that tight glycemic control is essential. Yet two sets of guidelines – the American Diabetes Association standards published in 2003 and 2004 – did so.

The study findings indicate that despite good evidence to the contrary, the unsupported “consensus” on tight glycemic control drives most guidelines and quality-of-care interventions. It also underlies “the Food and Drug Administration policy to approve diabetes mellitus drugs only on the basis of their antihyperglycemic effect, without requiring evidence of reduction in the risk of complications,” the investigators said.

“This consensus is also driving studies such as the National Institutes of Health–funded GRADE trial comparing antihyperglycemic drugs on their ability to reduce HbA_1c, rather than to reduce the risk of diabetes complications,” they added.

The narrow focus on tight glycemic control has undercut research on other possible interventions to prevent these complications. There are zero trials currently under way assessing treatment possibilities other than drugs that reduce hyperglycemia, and there are zero evidence-based therapies either mentioned in guidelines or routinely prescribed to patients for preventing these complications, Dr. Rodriguez-Gutierrez and Dr. Montori wrote.

“A careful and thoughtful recalibration” is needed. “Today, patients with type 2 diabetes, at least in some parts of the world, seem to live longer lives with fewer complications. The evidence summarized here requires us to explore factors other than tight glycemic control to explain this improvement and better address the diabetes epidemic,” they noted.

This study was supported by the National Center for Advancing Translational Sciences, a component of the National Institutes of Health. Dr. Rodriguez-Gutierrez and Dr. Montori reported having no relevant financial disclosures.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

The genetic tests used for more than a decade to identify patients or family members who carry genetic mutations linked to hypertrophic cardiomyopathy are seriously flawed.

The tests have been erroneously flagging people as genetically positive for hypertrophic cardiomyopathy (HC) when they actually carried benign genetic variants, according to a new reassessment of the genetic linkages by researchers using a more genetically diverse database. Five genetic variants now reclassified as benign were collectively responsible for flagging 74% of people flagged at genetic risk for HC in the more than 8,500 cases examined.

The results call into question any genetic diagnosis of HC made since genetic testing entered the mainstream in 2003, especially among African Americans who seem to have been disproportionately affected by these mislabeled genetic markers because of inadequate population diversity when the markers were first established.

In addition, the results more broadly cast a shadow over the full spectrum of genetic tests for disease-linked variants now in routine medical practice because of the possibility that other linkage determinations derived from an inadequately-representative reference population, reported Arjun K. Manrai, PhD, and his associates (N Engl J Med. 2016 Aug 18;375[7]:655-65). The researchers call the HC experience they document a “cautionary tale of broad relevance to genetic diagnosis.”

The findings “powerfully illustrate the importance of racial and genetic diversity” when running linkage studies aimed at validating genetic markers for widespread clinical use, Isaac S. Kohane, MD, senior author of the study, said in a written statement. “Racial and ethnic inclusiveness improves the validity and accuracy” of genetic tests, said Dr. Kohane, professor of biomedical informatics and pediatrics at Harvard Medical School in Boston.

Jim Harrison

“We believe that what we’re seeing in the case of hypertrophic cardiomyopathy may be the tip of the iceberg of a larger problem that transcends a single genetic disease,” Dr. Manrai, a biomedical informatics researcher at Harvard, said in the same statement. “Much genetic assessment today relies on historical links between a disorder and variant, sometimes decades old. We believe our findings illustrate the critical need to systematically reevaluate prior assertions about genetic variants,” Dr. Manrai added in an interview.

The two researchers and their associates reexamined the link between genetic variants and HC in three genetic databases that involved a total of more than 8,500 people. One database included 4,300 white Americans and 2,203 black Americans. A second database included genetic data from 1,092 people from 14 worldwide populations, and the third had genetic data from 938 people from 51 worldwide populations.

The analysis showed that although 94 distinct genetic variants that had previously been reported as associated with HC were confirmed as linked, just 5 met the study’s definition of a “high-frequency” variant with an allele frequent of more than 1%. These five variants together accounted for 74% of the overall total of linkages seen in these 8,533 people. Further analysis classified all five of these high-frequency genetic variants as benign with no discernible link to HC.

These five high-frequency variants occurred disproportionately higher among black Americans, and the consequences of this showed up in the patient records the researchers reviewed from one large U.S. genetic testing laboratory. They examined in detail HC genetic test results during 2004-2013 from 2,912 unrelated people. The records showed seven people had been labeled as carrying either a pathogenic or “presumed pathogenic” variant when in fact they had one of the five high-frequency variants now declared benign. Five of the seven mislabeled people were of African ancestry; the other two had unknown ancestry.

The researchers called for reevaluating known variants for all genetic diseases in more diverse populations and to immediately release the results of updated linkage assessments. This has the potential to meaningfully rewrite current gospel for many genetic variants and linkages.

“Our findings point to the value of patients staying in contact with their genetic counselors and physicians, even years after genetic testing,” Dr. Manrai said. Reassessments using more diverse populations will take time, he acknowledged, but tools are available to allow clinical geneticists to update old variants and apply new ones in real time, as soon as a new assessment completes.

Dr. Manrai and Dr. Kohane had no disclosures.

[email protected]

On Twitter @mitchelzoler

The genetic tests used for more than a decade to identify patients or family members who carry genetic mutations linked to hypertrophic cardiomyopathy are seriously flawed.

The tests have been erroneously flagging people as genetically positive for hypertrophic cardiomyopathy (HC) when they actually carried benign genetic variants, according to a new reassessment of the genetic linkages by researchers using a more genetically diverse database. Five genetic variants now reclassified as benign were collectively responsible for flagging 74% of people flagged at genetic risk for HC in the more than 8,500 cases examined.

The results call into question any genetic diagnosis of HC made since genetic testing entered the mainstream in 2003, especially among African Americans who seem to have been disproportionately affected by these mislabeled genetic markers because of inadequate population diversity when the markers were first established.

In addition, the results more broadly cast a shadow over the full spectrum of genetic tests for disease-linked variants now in routine medical practice because of the possibility that other linkage determinations derived from an inadequately-representative reference population, reported Arjun K. Manrai, PhD, and his associates (N Engl J Med. 2016 Aug 18;375[7]:655-65). The researchers call the HC experience they document a “cautionary tale of broad relevance to genetic diagnosis.”

The findings “powerfully illustrate the importance of racial and genetic diversity” when running linkage studies aimed at validating genetic markers for widespread clinical use, Isaac S. Kohane, MD, senior author of the study, said in a written statement. “Racial and ethnic inclusiveness improves the validity and accuracy” of genetic tests, said Dr. Kohane, professor of biomedical informatics and pediatrics at Harvard Medical School in Boston.

Jim Harrison

“We believe that what we’re seeing in the case of hypertrophic cardiomyopathy may be the tip of the iceberg of a larger problem that transcends a single genetic disease,” Dr. Manrai, a biomedical informatics researcher at Harvard, said in the same statement. “Much genetic assessment today relies on historical links between a disorder and variant, sometimes decades old. We believe our findings illustrate the critical need to systematically reevaluate prior assertions about genetic variants,” Dr. Manrai added in an interview.

The two researchers and their associates reexamined the link between genetic variants and HC in three genetic databases that involved a total of more than 8,500 people. One database included 4,300 white Americans and 2,203 black Americans. A second database included genetic data from 1,092 people from 14 worldwide populations, and the third had genetic data from 938 people from 51 worldwide populations.

The analysis showed that although 94 distinct genetic variants that had previously been reported as associated with HC were confirmed as linked, just 5 met the study’s definition of a “high-frequency” variant with an allele frequent of more than 1%. These five variants together accounted for 74% of the overall total of linkages seen in these 8,533 people. Further analysis classified all five of these high-frequency genetic variants as benign with no discernible link to HC.

These five high-frequency variants occurred disproportionately higher among black Americans, and the consequences of this showed up in the patient records the researchers reviewed from one large U.S. genetic testing laboratory. They examined in detail HC genetic test results during 2004-2013 from 2,912 unrelated people. The records showed seven people had been labeled as carrying either a pathogenic or “presumed pathogenic” variant when in fact they had one of the five high-frequency variants now declared benign. Five of the seven mislabeled people were of African ancestry; the other two had unknown ancestry.

The researchers called for reevaluating known variants for all genetic diseases in more diverse populations and to immediately release the results of updated linkage assessments. This has the potential to meaningfully rewrite current gospel for many genetic variants and linkages.

“Our findings point to the value of patients staying in contact with their genetic counselors and physicians, even years after genetic testing,” Dr. Manrai said. Reassessments using more diverse populations will take time, he acknowledged, but tools are available to allow clinical geneticists to update old variants and apply new ones in real time, as soon as a new assessment completes.

Dr. Manrai and Dr. Kohane had no disclosures.

[email protected]

On Twitter @mitchelzoler

The genetic tests used for more than a decade to identify patients or family members who carry genetic mutations linked to hypertrophic cardiomyopathy are seriously flawed.

The tests have been erroneously flagging people as genetically positive for hypertrophic cardiomyopathy (HC) when they actually carried benign genetic variants, according to a new reassessment of the genetic linkages by researchers using a more genetically diverse database. Five genetic variants now reclassified as benign were collectively responsible for flagging 74% of people flagged at genetic risk for HC in the more than 8,500 cases examined.

The results call into question any genetic diagnosis of HC made since genetic testing entered the mainstream in 2003, especially among African Americans who seem to have been disproportionately affected by these mislabeled genetic markers because of inadequate population diversity when the markers were first established.

In addition, the results more broadly cast a shadow over the full spectrum of genetic tests for disease-linked variants now in routine medical practice because of the possibility that other linkage determinations derived from an inadequately-representative reference population, reported Arjun K. Manrai, PhD, and his associates (N Engl J Med. 2016 Aug 18;375[7]:655-65). The researchers call the HC experience they document a “cautionary tale of broad relevance to genetic diagnosis.”

The findings “powerfully illustrate the importance of racial and genetic diversity” when running linkage studies aimed at validating genetic markers for widespread clinical use, Isaac S. Kohane, MD, senior author of the study, said in a written statement. “Racial and ethnic inclusiveness improves the validity and accuracy” of genetic tests, said Dr. Kohane, professor of biomedical informatics and pediatrics at Harvard Medical School in Boston.

Jim Harrison

“We believe that what we’re seeing in the case of hypertrophic cardiomyopathy may be the tip of the iceberg of a larger problem that transcends a single genetic disease,” Dr. Manrai, a biomedical informatics researcher at Harvard, said in the same statement. “Much genetic assessment today relies on historical links between a disorder and variant, sometimes decades old. We believe our findings illustrate the critical need to systematically reevaluate prior assertions about genetic variants,” Dr. Manrai added in an interview.

The two researchers and their associates reexamined the link between genetic variants and HC in three genetic databases that involved a total of more than 8,500 people. One database included 4,300 white Americans and 2,203 black Americans. A second database included genetic data from 1,092 people from 14 worldwide populations, and the third had genetic data from 938 people from 51 worldwide populations.

The analysis showed that although 94 distinct genetic variants that had previously been reported as associated with HC were confirmed as linked, just 5 met the study’s definition of a “high-frequency” variant with an allele frequent of more than 1%. These five variants together accounted for 74% of the overall total of linkages seen in these 8,533 people. Further analysis classified all five of these high-frequency genetic variants as benign with no discernible link to HC.

These five high-frequency variants occurred disproportionately higher among black Americans, and the consequences of this showed up in the patient records the researchers reviewed from one large U.S. genetic testing laboratory. They examined in detail HC genetic test results during 2004-2013 from 2,912 unrelated people. The records showed seven people had been labeled as carrying either a pathogenic or “presumed pathogenic” variant when in fact they had one of the five high-frequency variants now declared benign. Five of the seven mislabeled people were of African ancestry; the other two had unknown ancestry.

The researchers called for reevaluating known variants for all genetic diseases in more diverse populations and to immediately release the results of updated linkage assessments. This has the potential to meaningfully rewrite current gospel for many genetic variants and linkages.

“Our findings point to the value of patients staying in contact with their genetic counselors and physicians, even years after genetic testing,” Dr. Manrai said. Reassessments using more diverse populations will take time, he acknowledged, but tools are available to allow clinical geneticists to update old variants and apply new ones in real time, as soon as a new assessment completes.

Dr. Manrai and Dr. Kohane had no disclosures.

[email protected]

On Twitter @mitchelzoler

A new appellate ruling protects doctors from federal prosecution when they recommend medical marijuana in accordance with state law.

In an Aug. 16 opinion, the 9th U.S. Circuit Court of Appeals ruled that the U.S. Department of Justice cannot spend funding to prosecute physicians and patients who allegedly violate federal drug laws if their actions comply with state medical cannabis statutes.

Smithore

The decision supports the longstanding policies of several medical specialty societies.

“The conflict between state and federal law regarding medical marijuana can be concerning for patients and physicians who may consider using or recommending marijuana as a treatment option,” Hilary Daniel, senior health policy analyst for the American College of Physicians, said in an interview. “We are encouraged that the decision by the 9th U.S. Circuit Court of Appeals may help to address some of these conflicts and remain cognizant of the potential challenges faced by physicians and patients outside the jurisdiction of the 9th Circuit.”

The ruling stems from a 2014 federal appropriations law that banned the Justice Department from interfering with state implementation of marijuana laws. Short-term measures since then have extended the prohibition, which now continues through Sept. 30, 2016. Defendants in 10 criminal cases sued the federal government, requesting their prosecutions be dismissed on the grounds that the Justice Department is prevented from spending funds to prosecute them. The parties were accused of various federal marijuana offenses, including conspiracy to manufacture and possession with intent to distribute. The Justice Department argued it is not preventing states from operating their medical marijuana laws by prosecuting private individuals. Three district courts declined to halt the prosecutions from proceeding.

But the appeals court ruled that the Justice Department is prohibited from spending funds from relevant federal appropriation to prosecute the defendants if their conduct was permitted by state medical marijuana laws. Judges remanded the cases to the district courts with instructions that if the Justice Department wishes to continue the cases, the appellants are entitled to hearings to determine whether their actions were authorized by state laws.

The decision is significant because it establishes an appellate level precedent regarding enforcement of the Congressional budget requirements, said Joshua Prober, general counsel and senior vice president for the American Osteopathic Association. However, the decision does not overturn federal criminal laws regarding marijuana use and is limited to the impact of Congress’ specific budgetary authorization measure, he said.

“As noted in the court’s opinion, it is quite possible that a future Congress will not put the same restrictions in place on federal prosecutorial activity,” Mr. Prober said in an interview. “And obviously there are the procedural limitations, i.e., the decision is only the view of one appellate circuit. It is possible that a different appellate court might find the Department of Justice’s arguments to be more persuasive.”

The appeals ruling comes less than a week after the U.S. Drug Enforcement Agency refused to reclassify marijuana under the Controlled Substances Act. Marijuana remains a schedule I controlled substance, noting in its decision that marijuana does not meet the criteria for currently accepted medical use in the United States, that there is a lack of accepted safety for its use under medical supervision, and that it has a high potential for abuse.

“The DEA and FDA continue to believe that scientifically valid and well-controlled clinical trials conducted under investigational new drug applications are the proper way to research all potential new medicines, including marijuana,” DEA Acting Administrator Chuck Rosenberg wrote in a letter to state governors. “Furthermore, we believe that the drug approval process is the proper way to assess whether a product derived from marijuana or its constituent parts is safe and effective for medical use.”

While tension between state and federal law regarding marijuana lingers, more states continue to approve marijuana for recreational and medical use, noted John A. DiNome, a health law attorney based in Philadelphia. So far, Oregon, Colorado, Washington, and Alaska allow recreational marijuana use, while 25 states have approved marijuana for medical use. At least 9 more states will consider recreational marijuana use in November.

“For the time being, the problem still exists,” Mr. DiNome said in an interview. “This temporarily keeps doctors off the hook from prosecution, but it doesn’t solve the underlying problem, which is: Is federal law going to change?”

[email protected]

On Twitter @legal_med

A new appellate ruling protects doctors from federal prosecution when they recommend medical marijuana in accordance with state law.

In an Aug. 16 opinion, the 9th U.S. Circuit Court of Appeals ruled that the U.S. Department of Justice cannot spend funding to prosecute physicians and patients who allegedly violate federal drug laws if their actions comply with state medical cannabis statutes.

Smithore

The decision supports the longstanding policies of several medical specialty societies.

“The conflict between state and federal law regarding medical marijuana can be concerning for patients and physicians who may consider using or recommending marijuana as a treatment option,” Hilary Daniel, senior health policy analyst for the American College of Physicians, said in an interview. “We are encouraged that the decision by the 9th U.S. Circuit Court of Appeals may help to address some of these conflicts and remain cognizant of the potential challenges faced by physicians and patients outside the jurisdiction of the 9th Circuit.”

The ruling stems from a 2014 federal appropriations law that banned the Justice Department from interfering with state implementation of marijuana laws. Short-term measures since then have extended the prohibition, which now continues through Sept. 30, 2016. Defendants in 10 criminal cases sued the federal government, requesting their prosecutions be dismissed on the grounds that the Justice Department is prevented from spending funds to prosecute them. The parties were accused of various federal marijuana offenses, including conspiracy to manufacture and possession with intent to distribute. The Justice Department argued it is not preventing states from operating their medical marijuana laws by prosecuting private individuals. Three district courts declined to halt the prosecutions from proceeding.

But the appeals court ruled that the Justice Department is prohibited from spending funds from relevant federal appropriation to prosecute the defendants if their conduct was permitted by state medical marijuana laws. Judges remanded the cases to the district courts with instructions that if the Justice Department wishes to continue the cases, the appellants are entitled to hearings to determine whether their actions were authorized by state laws.

The decision is significant because it establishes an appellate level precedent regarding enforcement of the Congressional budget requirements, said Joshua Prober, general counsel and senior vice president for the American Osteopathic Association. However, the decision does not overturn federal criminal laws regarding marijuana use and is limited to the impact of Congress’ specific budgetary authorization measure, he said.

“As noted in the court’s opinion, it is quite possible that a future Congress will not put the same restrictions in place on federal prosecutorial activity,” Mr. Prober said in an interview. “And obviously there are the procedural limitations, i.e., the decision is only the view of one appellate circuit. It is possible that a different appellate court might find the Department of Justice’s arguments to be more persuasive.”

The appeals ruling comes less than a week after the U.S. Drug Enforcement Agency refused to reclassify marijuana under the Controlled Substances Act. Marijuana remains a schedule I controlled substance, noting in its decision that marijuana does not meet the criteria for currently accepted medical use in the United States, that there is a lack of accepted safety for its use under medical supervision, and that it has a high potential for abuse.

“The DEA and FDA continue to believe that scientifically valid and well-controlled clinical trials conducted under investigational new drug applications are the proper way to research all potential new medicines, including marijuana,” DEA Acting Administrator Chuck Rosenberg wrote in a letter to state governors. “Furthermore, we believe that the drug approval process is the proper way to assess whether a product derived from marijuana or its constituent parts is safe and effective for medical use.”

While tension between state and federal law regarding marijuana lingers, more states continue to approve marijuana for recreational and medical use, noted John A. DiNome, a health law attorney based in Philadelphia. So far, Oregon, Colorado, Washington, and Alaska allow recreational marijuana use, while 25 states have approved marijuana for medical use. At least 9 more states will consider recreational marijuana use in November.

“For the time being, the problem still exists,” Mr. DiNome said in an interview. “This temporarily keeps doctors off the hook from prosecution, but it doesn’t solve the underlying problem, which is: Is federal law going to change?”

[email protected]

On Twitter @legal_med

A new appellate ruling protects doctors from federal prosecution when they recommend medical marijuana in accordance with state law.

In an Aug. 16 opinion, the 9th U.S. Circuit Court of Appeals ruled that the U.S. Department of Justice cannot spend funding to prosecute physicians and patients who allegedly violate federal drug laws if their actions comply with state medical cannabis statutes.

Smithore

The decision supports the longstanding policies of several medical specialty societies.

“The conflict between state and federal law regarding medical marijuana can be concerning for patients and physicians who may consider using or recommending marijuana as a treatment option,” Hilary Daniel, senior health policy analyst for the American College of Physicians, said in an interview. “We are encouraged that the decision by the 9th U.S. Circuit Court of Appeals may help to address some of these conflicts and remain cognizant of the potential challenges faced by physicians and patients outside the jurisdiction of the 9th Circuit.”

The ruling stems from a 2014 federal appropriations law that banned the Justice Department from interfering with state implementation of marijuana laws. Short-term measures since then have extended the prohibition, which now continues through Sept. 30, 2016. Defendants in 10 criminal cases sued the federal government, requesting their prosecutions be dismissed on the grounds that the Justice Department is prevented from spending funds to prosecute them. The parties were accused of various federal marijuana offenses, including conspiracy to manufacture and possession with intent to distribute. The Justice Department argued it is not preventing states from operating their medical marijuana laws by prosecuting private individuals. Three district courts declined to halt the prosecutions from proceeding.

But the appeals court ruled that the Justice Department is prohibited from spending funds from relevant federal appropriation to prosecute the defendants if their conduct was permitted by state medical marijuana laws. Judges remanded the cases to the district courts with instructions that if the Justice Department wishes to continue the cases, the appellants are entitled to hearings to determine whether their actions were authorized by state laws.

The decision is significant because it establishes an appellate level precedent regarding enforcement of the Congressional budget requirements, said Joshua Prober, general counsel and senior vice president for the American Osteopathic Association. However, the decision does not overturn federal criminal laws regarding marijuana use and is limited to the impact of Congress’ specific budgetary authorization measure, he said.

“As noted in the court’s opinion, it is quite possible that a future Congress will not put the same restrictions in place on federal prosecutorial activity,” Mr. Prober said in an interview. “And obviously there are the procedural limitations, i.e., the decision is only the view of one appellate circuit. It is possible that a different appellate court might find the Department of Justice’s arguments to be more persuasive.”

The appeals ruling comes less than a week after the U.S. Drug Enforcement Agency refused to reclassify marijuana under the Controlled Substances Act. Marijuana remains a schedule I controlled substance, noting in its decision that marijuana does not meet the criteria for currently accepted medical use in the United States, that there is a lack of accepted safety for its use under medical supervision, and that it has a high potential for abuse.

“The DEA and FDA continue to believe that scientifically valid and well-controlled clinical trials conducted under investigational new drug applications are the proper way to research all potential new medicines, including marijuana,” DEA Acting Administrator Chuck Rosenberg wrote in a letter to state governors. “Furthermore, we believe that the drug approval process is the proper way to assess whether a product derived from marijuana or its constituent parts is safe and effective for medical use.”

While tension between state and federal law regarding marijuana lingers, more states continue to approve marijuana for recreational and medical use, noted John A. DiNome, a health law attorney based in Philadelphia. So far, Oregon, Colorado, Washington, and Alaska allow recreational marijuana use, while 25 states have approved marijuana for medical use. At least 9 more states will consider recreational marijuana use in November.

“For the time being, the problem still exists,” Mr. DiNome said in an interview. “This temporarily keeps doctors off the hook from prosecution, but it doesn’t solve the underlying problem, which is: Is federal law going to change?”

[email protected]

On Twitter @legal_med

A majority of pertussis cases in the United States may go undetected in people under the age of 50, particularly in adults, results of a retrospective database cohort study suggest.

“The incidence of pertussis in adolescents and adults is very difficult to quantify,” wrote Chi-Chang Chen, MD, of IMS Health, Plymouth Meeting, Pa., and associates. Symptoms may be misdiagnosed as other respiratory illnesses, infected individuals may not seek treatment, and pertussis may not be considered as a possible diagnosis in adults, they noted.

©Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

To project the possible range of pertussis incidence in this population, the investigator used three different models to analyze information from private insurance and laboratory databases as well as data from the Centers for Disease Control and Prevention for a 6-year period. The first method, which used medical claims for ICD-9 diagnosed pertussis, found an annual incidence rate of 9/100,000 population. The second used a proxy pertussis model that was based on symptoms that could indicate undiagnosed pertussis, showing an incidence rate of 21/100,000. The third method used pathogen data to estimate the fraction of cough illness statistically attributable to pertussis, resulting in an incidence rate of 649/100,000 population, which is 58-93 times higher than the ICD-9 estimated incidence.

These estimates “highlight the need for improved preventive measures – such as increased vaccination – against pertussis,” the investigators said, noting that immunization recommendations for additional age groups and research involving strategies to reduce waning immunity after vaccination should be considered.

The study was funded by GlaxoSmithKline Vaccines.

Read the full study in Human Vaccines & Immunotherapeutics (2016 May. doi: 10.1080/21645515.2016.1186313).

[email protected]

A majority of pertussis cases in the United States may go undetected in people under the age of 50, particularly in adults, results of a retrospective database cohort study suggest.

“The incidence of pertussis in adolescents and adults is very difficult to quantify,” wrote Chi-Chang Chen, MD, of IMS Health, Plymouth Meeting, Pa., and associates. Symptoms may be misdiagnosed as other respiratory illnesses, infected individuals may not seek treatment, and pertussis may not be considered as a possible diagnosis in adults, they noted.

©Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

To project the possible range of pertussis incidence in this population, the investigator used three different models to analyze information from private insurance and laboratory databases as well as data from the Centers for Disease Control and Prevention for a 6-year period. The first method, which used medical claims for ICD-9 diagnosed pertussis, found an annual incidence rate of 9/100,000 population. The second used a proxy pertussis model that was based on symptoms that could indicate undiagnosed pertussis, showing an incidence rate of 21/100,000. The third method used pathogen data to estimate the fraction of cough illness statistically attributable to pertussis, resulting in an incidence rate of 649/100,000 population, which is 58-93 times higher than the ICD-9 estimated incidence.

These estimates “highlight the need for improved preventive measures – such as increased vaccination – against pertussis,” the investigators said, noting that immunization recommendations for additional age groups and research involving strategies to reduce waning immunity after vaccination should be considered.

The study was funded by GlaxoSmithKline Vaccines.

Read the full study in Human Vaccines & Immunotherapeutics (2016 May. doi: 10.1080/21645515.2016.1186313).

[email protected]

A majority of pertussis cases in the United States may go undetected in people under the age of 50, particularly in adults, results of a retrospective database cohort study suggest.

“The incidence of pertussis in adolescents and adults is very difficult to quantify,” wrote Chi-Chang Chen, MD, of IMS Health, Plymouth Meeting, Pa., and associates. Symptoms may be misdiagnosed as other respiratory illnesses, infected individuals may not seek treatment, and pertussis may not be considered as a possible diagnosis in adults, they noted.

©Jacopo Werther/Wikimedia Commons/Creative Commons Attribution 2.0

To project the possible range of pertussis incidence in this population, the investigator used three different models to analyze information from private insurance and laboratory databases as well as data from the Centers for Disease Control and Prevention for a 6-year period. The first method, which used medical claims for ICD-9 diagnosed pertussis, found an annual incidence rate of 9/100,000 population. The second used a proxy pertussis model that was based on symptoms that could indicate undiagnosed pertussis, showing an incidence rate of 21/100,000. The third method used pathogen data to estimate the fraction of cough illness statistically attributable to pertussis, resulting in an incidence rate of 649/100,000 population, which is 58-93 times higher than the ICD-9 estimated incidence.

These estimates “highlight the need for improved preventive measures – such as increased vaccination – against pertussis,” the investigators said, noting that immunization recommendations for additional age groups and research involving strategies to reduce waning immunity after vaccination should be considered.

The study was funded by GlaxoSmithKline Vaccines.

Read the full study in Human Vaccines & Immunotherapeutics (2016 May. doi: 10.1080/21645515.2016.1186313).

[email protected]