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Gestational diabetes: Treatment controversy rages on
WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.
If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.
“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.
Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”
ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.
Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”
In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”
ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
Glyburide’s role
Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”
As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.
One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).
A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”
The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).
That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.
Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.
The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
Metformin outcomes
Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).
A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.
Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”
Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.
In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”
The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.
But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
Offspring well-being
Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)
Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.
A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).
A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).
That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).
In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).
WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.
If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.
“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.
Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”
ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.
Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”
In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”
ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
Glyburide’s role
Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”
As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.
One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).
A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”
The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).
That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.
Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.
The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
Metformin outcomes
Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).
A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.
Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”
Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.
In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”
The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.
But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
Offspring well-being
Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)
Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.
A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).
A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).
That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).
In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).
WASHINGTON – Pharmacologic treatment of gestational diabetes remains controversial, with the American College of Obstetricians and Gynecologists and the American Diabetes Association firmly recommending insulin as the preferred first-line pharmacologic therapy, and the Society of Maternal-Fetal Medicine more accepting of metformin as a “reasonable and safe first-line” alternative to insulin and stating that there are no strong data supporting metformin over the sulfonylurea glyburide.
If there’s one main take-away, Mark B. Landon, MD, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America, it was that “the primary concern” about the use of oral agents for treating gestational diabetes mellitus (GDM) is that there is limited long-term follow-up of exposed offspring.
“The claim that long-term safety data are not available for any oral agent is probably the most valid warning [of any of the concerns voiced by professional organizations],” said Dr. Landon, Richard L. Meiling professor and chair of the department of obstetrics and gynecology at The Ohio State University Wexner Medical Center, Columbus.
Otherwise, he said, there are not enough data to firmly prioritize the drugs most commonly used for GDM, and “the superiority of insulin over oral agents simply remains questionable.”
ACOG’s 2017 level A recommendation for insulin as the first-line option when pharmacologic treatment is needed for treating GDM (Obstet Gynecol. 2017;130[1]:e17-37) was followed in 2018 by another updated practice bulletin on GDM (Obstet Gynecol. 2018;131[2]:e49-64) that considered several meta-analyses published in 2017 and reiterated a preference for insulin.
Those recent meta-analyses of pharmacologic treatment of GDM show that the available literature is generally of “poor trial quality,” and that studies are small and not designed to assess equivalence or noninferiority, Mark Turrentine, MD, chair of ACOG’s committee on practice bulletins, said in an interview. “Taking that into account and [considering] that oral antidiabetic medications are not approved by the Food and Drug Administration [for the treatment of GDM], that they cross the placenta, and that we currently lack long-term neonatal safety data ... we felt that insulin is the preferred treatment.”
In its 2017 and 2018 bulletins, ACOG said that metformin is a “reasonable alternative choice” for women who decline insulin therapy or who may be unable to safely administer it (a level B recommendation). The 2018 practice bulletin mentions one additional factor: affordability. “Insurance companies aren’t always covering [insulin],” said Dr. Turrentine, of the department of obstetrics and gynecology, Baylor College of Medicine, Houston. “It’s a challenge – no question.”
ACOG says glyburide should not be recommended as a first-line pharmacologic treatment, “because, in most studies, it does not yield outcomes equivalent to insulin or metformin,” Dr. Turrentine emphasized.
Glyburide’s role
Dr. Landon took issue with ACOG’s stance on the sulfonylurea. “Frankly, I think this [conclusion] is debatable,” he said. The trend in the United States – “at least after the 2017 ACOG document came out”– has been toward use of metformin over glyburide when an oral agent is [used], but “I think glyburide has been unfairly trashed. It probably still has a place.”
As Dr. Landon sees it, research published in 2015 put a damper on the use of glyburide, which “had become the number one agent” after an earlier, seminal trial, led by Oded Langer, MD, had shown equivalent glycemic control in about 400 women with GDM who were randomized to receive either insulin or glyburide (N Engl J Med. 2000;343;1134-8). The trial was not powered to evaluate other outcomes, but there were no significant differences in neonatal complications, Dr. Landon said.
One of the 2015 studies – a large, retrospective, population-based study of more than 9,000 women with GDM treated with glyburide or insulin – showed a higher risk of admission to the neonatal intensive care unit (relative risk, 1.41), hypoglycemia in the newborn (RR, 1.40), and large-for-gestational age (RR, 1.43) with glyburide, compared with insulin (JAMA Pediatr. 2015;169[5]:452-8).
A meta-analysis of glyburide, metformin, and insulin showed significant differences between glyburide and insulin in birth weight, macrosomia (RR, 2.62), and neonatal hypoglycemia (RR, 2.04; BMJ. 2015;350;h102). However, “this was basically a conglomeration of studies with about 50 [individuals] in each arm, and in which entry criteria for the diagnosis of GDM were rather heterogeneous,” said Dr. Landon. “There are real problems with this and other meta-analyses.”
The authors of a 2018 multicenter, noninferiority, randomized, controlled trial of about 900 women concluded that their study failed to show that the use of glyburide, compared with insulin, does not result in a greater frequency of perinatal complications. The authors also wrote, however, that the “increase in perinatal complications [with glyburide] may be no more than 10.5%, compared with insulin” (JAMA. 2018;319[17]:1773-80).
That increase, Dr. Landon said, was “not an absolute 10%, but 10% of the complication rate, which probably translates to about 2%.” The only component of a composite outcome (including macrosomia, hypoglycemia, and hyperbilirubinemia) that was significantly different, he noted, was hypoglycemia, which affected 12.2% of neonates in the glyburide group and 7.2% in the insulin group.
Glyburide’s role may well be substantiated in the future, Dr. Landon said during a discussion period at the meeting, through research underway at the University of Pittsburgh aimed at tailoring treatment to the underlying pathophysiology of a patient’s GDM.
The MATCh-GDM study (Metabolic Analysis for Treatment Choice in GDM) is randomizing women to receive usual, unmatched treatment or treatment matched to GDM mechanism – metformin for predominant insulin resistance, glyburide or insulin for predominant insulin secretion defects, and one of the three for combined mechanisms. The study’s principal investigator, Maisa Feghali, MD, of the department of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, stressed in a presentation on the study that GDM is a heterogeneous condition and that research is needed to understand the impact of GDM subtypes on treatment response.
Metformin outcomes
Concerns about the impact of metformin on short-term perinatal outcomes focus on preterm birth, Dr. Landon said. The only study to date that has shown an increased rate of prematurity, however, is the “seminal” Metformin in Gestational Diabetes (MiG) trial led by Janet A. Rowan, MBChB, that randomized 751 women with GDM in Australia and New Zealand to treatment with metformin or insulin. The researchers found no significant differences between a composite of neonatal complications but did establish that severe hypoglycemia was less common in the metformin group and preterm birth was more common (N Engl J Med. 2008;358:2003-15).
A 2016 systematic review and meta-analysis of short- and long-term outcomes of metformin, compared with insulin, found that metformin did not increase preterm delivery (Diabet Med. 2017;34[1]:27-36). And while the 2015 BMJ meta-analysis found that metformin was associated with higher rates of preterm birth (RR, 1.50), the increased risk “was all driven by the Rowan study,” Dr. Landon said. The 2015 meta-analysis also found that metformin was associated with less maternal weight gain and fewer infants who were large for gestational age.
Metformin is also tainted by high rates of failure in GDM. In the 2008 Rowan study, 46% of patients on metformin failed to achieve glycemic control. “But this is a classic half-full, half-empty [phenomena],” Dr. Landon said. “Some people say this isn’t good, but on the other hand, 54% avoided insulin.”
Indeed, the Society of Maternal-Fetal Medicine (SMFM), in its 2018 statement on the pharmacologic treatment of GDM, said that oral hypoglycemic agents that are used as monotherapy work in “more than half” of GDM pregnancies. The need for adjunctive insulin to achieve glycemic control ranges between 26% and 46% for women using metformin, and 4% and 16% for women using glyburide, it says.
In the society’s view, recent meta-analyses and systemic reviews “support the efficacy and safety of oral agents,” and “although concerns have been raised for more frequent adverse neonatal outcomes with glyburide, including macrosomia and hypoglycemia, the evidence of benefit of one oral agent over the other remains limited.”
The society says that the difference between its statement and the ACOG recommendations is “based on the values placed by different experts and providers on the available evidence,” and it adds that more long-term data are needed.
But as Dr. Landon said, the SMFM is “a little more forgiving” in its interpretation of a limited body of literature. And clinicians, in the meantime, have to navigate the controversy. “The professional organizations don’t make it easy for [us],” he said. At this point, “insulin does not cross the placenta, and the oral agents do cross it. Informed consent is absolutely necessary when choosing oral agents for treating GDM.”
Offspring well-being
Of greater concern than neonatal outcomes are the potential long-term issues for offspring, Dr. Landon said. On the one hand, it is theorized that metformin may protect beta-cell function in offspring and thereby reduce the cross-generational effects of obesity and type 2 diabetes. On the other hand, it is theorized that the drug may cause a decrease in cell-cycle proliferation, which could have “unknown fetal programming effects,” and it may inhibit the mTOR signaling pathway, thus restricting the transport of glucose and amino acids across the placenta, he said. (Findings from in vitro research have suggested that glyburide treatment in GDM might be associated with enhanced transport across the placenta, he noted.)
Long-term follow-up studies of offspring are “clearly needed,” Dr. Landon said. At this point, in regard to long-term safety, he and other experts are concerned primarily about the potential for obesity and metabolic dysfunction in offspring who are exposed to metformin in utero. They are watching follow-up from Dr. Rowan’s MiG trial, as well as elsewhere in the literature, on metformin-exposed offspring from mothers with polycystic ovary syndrome.
A follow-up analysis of offspring from the MiG trial found that children of women with GDM who were exposed to metformin had larger measures of subcutaneous fat at age 2 years, compared with children of mothers treated with insulin alone, but that overall body fat was the same, Dr. Landon noted. The investigators postulated that these children may have less visceral fat and a more favorable pattern of fat distribution (Diab Care. 2011;34:2279-84).
A recently published follow-up analysis of two randomized, controlled trials of women with polycystic ovary syndrome is cause for more concern, he said. That analysis showed that offspring exposed to metformin in utero had a higher body mass index and an increased prevalence of obesity or overweight at age 4 years, compared with placebo groups (J Clin Endocrinol Metab. 2018;103[4]:1612-21).
That analysis of metformin-exposed offspring in the context of polycystic ovary syndrome was published after the SMFM statement, as was another follow-up analysis of MiG trial offspring – this one, at ages 7-9 years – that showed an increase in weight, size, and fat mass in one of two subsets analyzed, despite no difference in large-for-gestational age rates between the metformin- and insulin-exposed offspring (BMJ Open Diabetes Res Care. 2018;6[1]: e000456).
In 2018, a group of 17 prominent diabetes and maternal-fetal medicine researchers cited these findings in a response to the SMFM statement and cautioned against the widespread adoption of metformin use during pregnancy, writing that, based on “both pharmacologic and randomized trial evidence that metformin may create an atypical intrauterine environment ... we believe it is premature to embrace metformin as equivalent to insulin or as superior to glyburide, and that patients should be counseled on the limited long-term safety data and potential for adverse childhood metabolic effects” (Am J Obstet Gynecol. 2018;219[4]:367.e1-7).
EXPERT ANALYSIS FROM DPSG-NA 2019
Docs weigh pulling out of MIPS over paltry payments
If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.
And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.
On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.
Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.
Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.
It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%.
However, it is certainly time to reconsider efforts to participate at the highest level.
Should you or shouldn’t you bother with MIPS?
Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)
The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.
The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.
Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.
These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”
You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.
Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.
The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
Turning frustration into action
Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.
First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.
In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
Smart MIPS hacks that can help you
To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.
The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.
There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.
Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.
The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:
Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.
Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.
Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)
In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.
Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.
But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.
Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.
And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.
On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.
Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.
Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.
It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%.
However, it is certainly time to reconsider efforts to participate at the highest level.
Should you or shouldn’t you bother with MIPS?
Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)
The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.
The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.
Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.
These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”
You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.
Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.
The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
Turning frustration into action
Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.
First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.
In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
Smart MIPS hacks that can help you
To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.
The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.
There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.
Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.
The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:
Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.
Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.
Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)
In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.
Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.
But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.
Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
If you’ve knocked yourself out to earn a Merit-Based Incentive Payment System (MIPS) bonus payment, it’s pretty safe to say that getting a 1.68% payment boost probably didn’t feel like a “win” that was worth the effort.
And although it saved you from having a negative 5% payment adjustment, many physicians don’t feel that it was worth the effort.
On Jan. 6, the Centers for Medicare & Medicaid Services announced the 2020 payouts for MIPS.
Based on 2018 participation, the bonus for those who scored a perfect 100 is only a 1.68% boost in Medicare reimbursement, slightly lower than last year’s 1.88%. This decline comes as no surprise as the agency leader admits: “As the program matures, we expect that the increases in the performance thresholds in future program years will create a smaller distribution of positive payment adjustments.” Overall, more than 97% of participants avoided having a negative 5% payment adjustment.
Indeed, these bonus monies are based on a short-term appropriation of extra funds from Congress. After these temporary funds are no longer available, there will be little, if any, monies to distribute as the program is based on a “losers-feed-the-winners” construct.
It may be very tempting for many physicians to decide to ignore MIPS, with the rationale that 1.68% is not worth the effort. But don’t let your foot off the gas pedal yet, since the penalty for not participating in 2020 is a substantial 9%.
However, it is certainly time to reconsider efforts to participate at the highest level.
Should you or shouldn’t you bother with MIPS?
Let’s say you have $75,000 in revenue from Medicare Part B per year. Depending on the services you offer in your practice, that equates to 500-750 encounters with Medicare beneficiaries per year. (A reminder that MIPS affects only Part B; Medicare Advantage plans do not partake in the program.)
The recent announcement reveals that perfection would equate to an additional $1,260 per year. That’s only if you received the full 100 points; if you were simply an “exceptional performer,” the government will allot an additional $157. That’s less than you get paid for a single office visit.
The difference between perfection and compliance is approximately $1,000. Failure to participate, however, knocks $6,750 off your bottom line. Clearly, that’s a substantial financial loss that would affect most practices. Obviously, the numbers change if you have higher – or lower – Medicare revenue, but it’s important to do the math.
Why? Physicians are spending a significant amount of money to comply with the program requirements. This includes substantial payments to registries – typically $200 to >$1,000 per year – to report the quality measures for the program; electronic health record (EHR) systems, many of which require additional funding for the “upgrade” to a MIPS-compatible system, are also a sizable investment.
These hard costs pale in comparison with the time spent on understanding the ever-changing requirements of the program and the process by which your practice will implement them. Take, for example, something as innocuous as the required “Support Electronic Referral Loops by Receiving and Incorporating Health Information.”
You first must understand the elements of the measure: What is a “referral loop?” When do we need to generate one? To whom shall it be sent? What needs to be included in “health information?” What is the electronic address to which we should route the information? How do we obtain that address? Then you must determine how your EHR system captures and reports it.
Only then comes the hard part: How are we going to implement this? That’s only one of more than a dozen required elements: six quality measures, two (to four) improvement activities, and four promoting interoperability requirements. Each one of these elements has a host of requirements, all listed on multipage specification sheets.
The government does not seem to be listening. John Cullen, MD, president of the American Academy of Family Physicians, testified at the Senate Finance Committee in May 2019 that MIPS “has created a burdensome and extremely complex program that has increased practice costs ... ” Yet, later that year, CMS issued another hefty ruling that outlines significant changes to the program, despite the fact that it’s in its fourth performance year.
Turning frustration into action
Frustration or even anger may be one reaction, but now is an opportune time to determine your investment in the program. At a minimum, it’s vital to understand and meet the threshold to avoid the penalty. It’s been shifting to date, but it’s now set at 9% for perpetuity.
First, it’s crucial to check on your participation status. CMS revealed that the participation database was recently corrected for so-called inconsistencies, so it pays to double-check. It only takes seconds: Insert your NPI in the QPP Participation Status Tool to determine your eligibility for 2020.
In 2020, the threshold to avoid the penalty is 45 points. To get the 45 points, practices must participate in two improvement activities, which is not difficult as there are 118 options. That will garner 15 points. Then there are 45 points available from the quality category; you need at least 30 to reach the 45-point threshold for penalty avoidance.
Smart MIPS hacks that can help you
To obtain the additional 30 points, turn your attention to the quality category. There are 268 quality measures; choose at least six to measure. If you report directly from your EHR system, you’ll get a bonus point for each reported measure, plus one just for trying. (There are a few other opportunities for bonus points, such as improving your scores over last year.) Those bonus points give you a base with which to work, but getting to 45 will require effort to report successfully on at least a couple of the measures.
The quality category has a total of 100 points available, which are converted to 45 toward your composite score. Since you need 30 to reach that magical 45 (if 15 were attained from improvement activities), that means you must come up with 75 points in the quality category. Between the bonus points and measuring a handful of measures successfully through the year, you’ll achieve this threshold.
There are two other categories in the program: promoting interoperability (PI) and cost. The PI category mirrors the old “meaningful use” program; however, it has become increasingly difficult over the years. If you think that you can meet the required elements, you can pick up 25 more points toward your composite score.
Cost is a bit of an unknown, as the scoring is based on a retrospective review of your claims. You’ll likely pick up a few more points on this 15-point category, but there’s no method to determine performance until after the reporting period. Therefore, be cautious about relying on this category.
The best MIPS hack, however, is if you are a small practice. CMS – remarkably – defines a “small practice” as 15 or fewer eligible professionals. If you qualify under this paradigm, you have multiple options to ease compliance:
Apply for a “hardship exemption” simply on the basis of being small; the exemption relates to the promoting operability category, shifting those points to the quality category.
Gain three points per quality measure, regardless of data completeness; this compares to just one point for other physicians.
Capture all of the points available from the Improvement Activities category by confirming participation with just a single activity. (This also applies to all physicians in rural or Health Professional Shortage Areas.)
In the event that you don’t qualify as a “small practice” or you’re still falling short of the requirements, CMS allows for the ultimate “out”: You can apply for exemption on the basis of an “extreme and uncontrollable circumstance.” The applications for these exceptions open this summer.
Unless you qualify for the program exemption, it’s important to keep pace with the program to ensure that you reach the 45-point threshold. It may not, however, be worthwhile to gear up for all 100 points unless your estimate of the potential return – and what it costs you to get there – reveals otherwise. MIPS is not going anywhere; the program is written into the law.
But that doesn’t mean that CMS can’t make tweaks and updates. Hopefully, the revisions won’t create even more administrative burden as the program is quickly turning into a big stick with only a small carrot at the end.
Elizabeth Woodcock is president of Woodcock & Associates in Atlanta. She has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
CDC: Risk in U.S. from 2019-nCoV remains low
A total of 165 persons in the United States are under investigation for infection with the 2019 Novel Coronavirus (2019-nCoV), with 68 testing negative and only 5 confirming positive, according to data presented Jan. 29 during a Centers for Disease Control and Prevention (CDC) briefing.
The remaining samples are in transit or are being processed at the CDC for testing, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the briefing.
“The genetic sequence for all five viruses detected in the United States to date has been uploaded to the CDC website,” she said. “We are working quickly through the process to get the CDC-developed test into the hands of public health partners in the U.S. and internationally.”
Dr. Messonnier reported that the CDC is expanding screening efforts to U.S. ports of entry that house CDC quarantine stations. Also, in collaboration with U.S. Customs and Border Protection, the agency is expanding distribution of travel health education materials to all travelers from China.
“The good news here is that, despite an aggressive public health investigation to find new cases [of 2019-nCoV], we have not,” she said. “The situation in China is concerning, however, we are looking hard here in the U.S. We will continue to be proactive. I still expect that we will find additional cases.”
In another development, the federal government facilitated the return of a plane full of U.S. citizens living in Wuhan, China, to March Air Reserve Force Base in Riverside County, Calif. “We have taken every precaution to ensure their safety while also continuing to protect the health of our nation and the people around them,” Dr. Messonnier said.
All 195 passengers have been screened, monitored, and evaluated by medical personnel “every step of the way,” including before takeoff, during the flight, during a refueling stop in Alaska, and again upon landing at March Air Reserve Force Base on Jan. 28. “All 195 patients are without the symptoms of the novel coronavirus, and all have been assigned living quarters at the Air Force base,” Dr. Messonnier said.
The CDC has launched a second stage of further screening and information gathering from the passengers, who will be offered testing as part of a thorough risk assessment.
“I understand that many people in the U.S. are worried about this virus and whether it will affect them,” Dr. Messonnier said. “Outbreaks like this are always concerning, particularly when a new virus is emerging. But we are well prepared and working closely with federal, state, and local partners to protect our communities and others nationwide from this public health threat. At this time, we continue to believe that the immediate health risk from this new virus to the general American public is low.”
A total of 165 persons in the United States are under investigation for infection with the 2019 Novel Coronavirus (2019-nCoV), with 68 testing negative and only 5 confirming positive, according to data presented Jan. 29 during a Centers for Disease Control and Prevention (CDC) briefing.
The remaining samples are in transit or are being processed at the CDC for testing, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the briefing.
“The genetic sequence for all five viruses detected in the United States to date has been uploaded to the CDC website,” she said. “We are working quickly through the process to get the CDC-developed test into the hands of public health partners in the U.S. and internationally.”
Dr. Messonnier reported that the CDC is expanding screening efforts to U.S. ports of entry that house CDC quarantine stations. Also, in collaboration with U.S. Customs and Border Protection, the agency is expanding distribution of travel health education materials to all travelers from China.
“The good news here is that, despite an aggressive public health investigation to find new cases [of 2019-nCoV], we have not,” she said. “The situation in China is concerning, however, we are looking hard here in the U.S. We will continue to be proactive. I still expect that we will find additional cases.”
In another development, the federal government facilitated the return of a plane full of U.S. citizens living in Wuhan, China, to March Air Reserve Force Base in Riverside County, Calif. “We have taken every precaution to ensure their safety while also continuing to protect the health of our nation and the people around them,” Dr. Messonnier said.
All 195 passengers have been screened, monitored, and evaluated by medical personnel “every step of the way,” including before takeoff, during the flight, during a refueling stop in Alaska, and again upon landing at March Air Reserve Force Base on Jan. 28. “All 195 patients are without the symptoms of the novel coronavirus, and all have been assigned living quarters at the Air Force base,” Dr. Messonnier said.
The CDC has launched a second stage of further screening and information gathering from the passengers, who will be offered testing as part of a thorough risk assessment.
“I understand that many people in the U.S. are worried about this virus and whether it will affect them,” Dr. Messonnier said. “Outbreaks like this are always concerning, particularly when a new virus is emerging. But we are well prepared and working closely with federal, state, and local partners to protect our communities and others nationwide from this public health threat. At this time, we continue to believe that the immediate health risk from this new virus to the general American public is low.”
A total of 165 persons in the United States are under investigation for infection with the 2019 Novel Coronavirus (2019-nCoV), with 68 testing negative and only 5 confirming positive, according to data presented Jan. 29 during a Centers for Disease Control and Prevention (CDC) briefing.
The remaining samples are in transit or are being processed at the CDC for testing, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the briefing.
“The genetic sequence for all five viruses detected in the United States to date has been uploaded to the CDC website,” she said. “We are working quickly through the process to get the CDC-developed test into the hands of public health partners in the U.S. and internationally.”
Dr. Messonnier reported that the CDC is expanding screening efforts to U.S. ports of entry that house CDC quarantine stations. Also, in collaboration with U.S. Customs and Border Protection, the agency is expanding distribution of travel health education materials to all travelers from China.
“The good news here is that, despite an aggressive public health investigation to find new cases [of 2019-nCoV], we have not,” she said. “The situation in China is concerning, however, we are looking hard here in the U.S. We will continue to be proactive. I still expect that we will find additional cases.”
In another development, the federal government facilitated the return of a plane full of U.S. citizens living in Wuhan, China, to March Air Reserve Force Base in Riverside County, Calif. “We have taken every precaution to ensure their safety while also continuing to protect the health of our nation and the people around them,” Dr. Messonnier said.
All 195 passengers have been screened, monitored, and evaluated by medical personnel “every step of the way,” including before takeoff, during the flight, during a refueling stop in Alaska, and again upon landing at March Air Reserve Force Base on Jan. 28. “All 195 patients are without the symptoms of the novel coronavirus, and all have been assigned living quarters at the Air Force base,” Dr. Messonnier said.
The CDC has launched a second stage of further screening and information gathering from the passengers, who will be offered testing as part of a thorough risk assessment.
“I understand that many people in the U.S. are worried about this virus and whether it will affect them,” Dr. Messonnier said. “Outbreaks like this are always concerning, particularly when a new virus is emerging. But we are well prepared and working closely with federal, state, and local partners to protect our communities and others nationwide from this public health threat. At this time, we continue to believe that the immediate health risk from this new virus to the general American public is low.”
ID Blog: Wuhan coronavirus – just a stop on the zoonotic highway
Emerging viruses that spread to humans from an animal host are commonplace and represent some of the deadliest diseases known. Given the details of the Wuhan coronavirus (2019-nCoV) outbreak, including the genetic profile of the disease agent, the hypothesis of a snake origin was the first raised in the peer-reviewed literature.
It is a highly controversial origin story, however, given that mammals have been the sources of all other such zoonotic coronaviruses, as well as a host of other zoonotic diseases.
An animal source for emerging infections such as the 2019-nCoV is the default hypothesis, because “around 60% of all infectious diseases in humans are zoonotic, as are 75% of all emerging infectious diseases,” according to a United Nations report. The report goes on to say that, “on average, one new infectious disease emerges in humans every 4 months.”
To appreciate the emergence and nature of 2019-nCoV, it is important to examine the history of zoonotic outbreaks of other such diseases, especially with regard to the “mixing-vessel” phenomenon, which has been noted in closely related coronaviruses, including SARS and MERS, as well as the widely disparate HIV, Ebola, and influenza viruses.
Mutants in the mixing vessel
The mixing-vessel phenomenon is conceptually easy but molecularly complex. A single animal is coinfected with two related viruses; the virus genomes recombine together (virus “sex”) in that animal to form a new variant of virus. Such new mutant viruses can be more or less infective, more or less deadly, and more or less able to jump the species or even genus barrier. An emerging viral zoonosis can occur when a human being is exposed to one of these new viruses (either from the origin species or another species intermediate) that is capable of also infecting a human cell. Such exposure can occur from close proximity to animal waste or body fluids, as in the farm environment, or from wildlife pets or the capturing and slaughtering of wildlife for food, as is proposed in the case of the Wuhan seafood market scenario. In fact, the scientists who postulated a snake intermediary as the potential mixing vessel also stated that 2019‐nCoV appears to be a recombinant virus between a bat coronavirus and an origin‐unknown coronavirus.
Coronaviruses in particular have a history of moving from animal to human hosts (and even back again), and their detailed genetic pattern and taxonomy can reveal the animal origin of these diseases.
Going batty
Bats, in particular, have been shown to be a reservoir species for both alphacoronaviruses and betacoronaviruses. Given their ecology and behavior, they have been found to play a key role in transmitting coronaviruses between species. A highly pertinent example of this is the SARS coronavirus, which was shown to have likely originated in Chinese horseshoe bats. The SARS virus, which is genetically closely related to the new Wuhan coronavirus, first infected humans in the Guangdong province of southern China in 2002.
Scientists speculate that the virus was then either transmitted directly to humans from bats, or passed through an intermediate host species, with SARS-like viruses isolated from Himalayan palm civets found in a live-animal market in Guangdong. The virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the market.
The MERS coronavirus is a betacoronavirus that was first reported in Saudi Arabia in 2012. It turned out to be far more deadly than either SARS or the Wuhan virus (at least as far as current estimates of the new coronavirus’s behavior). The MERS genotype was found to be closely related to MERS-like viruses in bats in Saudi Arabia, Africa, Europe, and Asia. Studies done on the cell receptor for MERS showed an apparently conserved viral receptor in both bats and humans. And an identical strain of MERS was found in bats in a nearby cave and near the workplace of the first known human patient.
However, in many of the other locations of the outbreak in the Middle East, there appeared to be limited contact between bats and humans, so scientists looked for another vector species, perhaps one that was acting as an intermediate. A high seroprevalence of MERS-CoV or a closely related virus was found in camels across the Arabian Peninsula and parts of eastern and northern Africa, while tests for MERS antibodies were negative in the most-likely other species of livestock or pet animals, including chickens, cows, goats, horses, and sheep.
In addition, the MERS-related CoV carried by camels was genetically highly similar to that detected in humans, as demonstrated in one particular outbreak on a farm in Qatar where the genetic sequences of MERS-CoV in the nasal swabs from 3 of 14 seropositive camels were similar to those of 2 human cases on the same farm. Similar genomic results were found in MERS-CoV from nasal swabs from camels in Saudi Arabia.
Other mixing-vessel zoonoses
HIV, the viral cause of AIDS, provides an almost-textbook origin story of the rise of a zoonotic supervillain. The virus was genetically traced to have a chimpanzee-to-human origin, but it was found to be more complicated than that. The virus first emerged in the 1920s in Africa in what is now the Democratic Republic of the Congo, well before its rise to a global pandemic in the 1980s.
Researchers believe the chimpanzee virus is a hybrid of the simian immunodeficiency viruses (SIVs) naturally infecting two different monkey species: the red-capped mangabey (Cercocebus torquatus) and the greater spot-nosed monkey (Cercopithecus nictitans). Chimpanzees kill and eat monkeys, which is likely how they acquired the monkey viruses. The viruses hybridized in a chimpanzee; the hybrid virus then spread through the chimpanzee population and was later transmitted to humans who captured and slaughtered chimps for meat (becoming exposed to their blood). This was the most likely origin of HIV-1.
HIV-1 also shows one of the major risks of zoonotic infections. They can continue to mutate in its human host, increasing the risk of greater virulence, but also interfering with the production of a universally effective vaccine. Since its transmission to humans, for example, many subtypes of the HIV-1 strain have developed, with genetic differences even in the same subtypes found to be up to 20%.
Ebolavirus, first detected in 1976, is another case of bats being the potential culprit. Genetic analysis has shown that African fruit bats are likely involved in the spread of the virus and may be its reservoir host. Further evidence of this was found in the most recent human-infecting Bombali variant of the virus, which was identified in samples from bats collected from Sierra Leone.
It was also found that pigs can also become infected with Zaire ebolavirus, leading to the fear that pigs could serve as a mixing vessel for it and other filoviruses. Pigs have their own forms of Ebola-like disease viruses, which are not currently transmissible to humans, but could provide a potential mixing-vessel reservoir.
Emergent influenzas
The Western world has been most affected by these highly mutable, multispecies zoonotic viruses. The 1957 and 1968 flu pandemics contained a mixture of gene segments from human and avian influenza viruses. “What is clear from genetic analysis of the viruses that caused these past pandemics is that reassortment (gene swapping) occurred to produce novel influenza viruses that caused the pandemics. In both of these cases, the new viruses that emerged showed major differences from the parent viruses,” according to the Centers for Disease Control and Prevention.
Influenza is, however, a good example that all zoonoses are not the result of a mixing-vessel phenomenon, with evidence showing that the origin of the catastrophic 1918 virus pandemic likely resulted from a bird influenza virus directly infecting humans and pigs at about the same time without reassortment, according to the CDC.
Building a protective infrastructure
The first 2 decades of the 21st century saw a huge increase in efforts to develop an infrastructure to monitor and potentially prevent the spread of new zoonoses. As part of a global effort led by the United Nations, the U.S. Agency for International AID developed the PREDICT program in 2009 “to strengthen global capacity for detection and discovery of zoonotic viruses with pandemic potential. Those include coronaviruses, the family to which SARS and MERS belong; paramyxoviruses, like Nipah virus; influenza viruses; and filoviruses, like the ebolavirus.”
PREDICT funding to the EcoHealth Alliance led to discovery of the likely bat origins of the Zaire ebolavirus during the 2013-2016 outbreak. And throughout the existence of PREDICT, more than 145,000 animals and people were surveyed in areas of likely zoonotic outbreaks, leading to the detection of more than “1,100 unique viruses, including zoonotic diseases of public health concern such as Bombali ebolavirus, Zaire ebolavirus, Marburg virus, and MERS- and SARS-like coronaviruses,” according to PREDICT partner, the University of California, Davis.
PREDICT-2 was launched in 2014 with the continuing goals of “identifying and better characterizing pathogens of known epidemic and unknown pandemic potential; recognizing animal reservoirs and amplification hosts of human-infectious viruses; and efficiently targeting intervention action at human behaviors which amplify disease transmission at critical animal-animal and animal-human interfaces in hotspots of viral evolution, spillover, amplification, and spread.”
However, in October 2019, the Trump administration cut all funding to the PREDICT program, leading to its shutdown. In a New York Times interview, Peter Daszak, president of the EcoHealth Alliance, stated: “PREDICT was an approach to heading off pandemics, instead of sitting there waiting for them to emerge and then mobilizing.”
Ultimately, in addition to its human cost, the current Wuhan coronavirus outbreak can be looked at an object lesson – a test of the pandemic surveillance and control systems currently in place, and a practice run for the next and potentially deadlier zoonotic outbreaks to come. Perhaps it is also a reminder that cutting resources to detect zoonoses at their source in their animal hosts – before they enter the human chain– is perhaps not the most prudent of ideas.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington.
Emerging viruses that spread to humans from an animal host are commonplace and represent some of the deadliest diseases known. Given the details of the Wuhan coronavirus (2019-nCoV) outbreak, including the genetic profile of the disease agent, the hypothesis of a snake origin was the first raised in the peer-reviewed literature.
It is a highly controversial origin story, however, given that mammals have been the sources of all other such zoonotic coronaviruses, as well as a host of other zoonotic diseases.
An animal source for emerging infections such as the 2019-nCoV is the default hypothesis, because “around 60% of all infectious diseases in humans are zoonotic, as are 75% of all emerging infectious diseases,” according to a United Nations report. The report goes on to say that, “on average, one new infectious disease emerges in humans every 4 months.”
To appreciate the emergence and nature of 2019-nCoV, it is important to examine the history of zoonotic outbreaks of other such diseases, especially with regard to the “mixing-vessel” phenomenon, which has been noted in closely related coronaviruses, including SARS and MERS, as well as the widely disparate HIV, Ebola, and influenza viruses.
Mutants in the mixing vessel
The mixing-vessel phenomenon is conceptually easy but molecularly complex. A single animal is coinfected with two related viruses; the virus genomes recombine together (virus “sex”) in that animal to form a new variant of virus. Such new mutant viruses can be more or less infective, more or less deadly, and more or less able to jump the species or even genus barrier. An emerging viral zoonosis can occur when a human being is exposed to one of these new viruses (either from the origin species or another species intermediate) that is capable of also infecting a human cell. Such exposure can occur from close proximity to animal waste or body fluids, as in the farm environment, or from wildlife pets or the capturing and slaughtering of wildlife for food, as is proposed in the case of the Wuhan seafood market scenario. In fact, the scientists who postulated a snake intermediary as the potential mixing vessel also stated that 2019‐nCoV appears to be a recombinant virus between a bat coronavirus and an origin‐unknown coronavirus.
Coronaviruses in particular have a history of moving from animal to human hosts (and even back again), and their detailed genetic pattern and taxonomy can reveal the animal origin of these diseases.
Going batty
Bats, in particular, have been shown to be a reservoir species for both alphacoronaviruses and betacoronaviruses. Given their ecology and behavior, they have been found to play a key role in transmitting coronaviruses between species. A highly pertinent example of this is the SARS coronavirus, which was shown to have likely originated in Chinese horseshoe bats. The SARS virus, which is genetically closely related to the new Wuhan coronavirus, first infected humans in the Guangdong province of southern China in 2002.
Scientists speculate that the virus was then either transmitted directly to humans from bats, or passed through an intermediate host species, with SARS-like viruses isolated from Himalayan palm civets found in a live-animal market in Guangdong. The virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the market.
The MERS coronavirus is a betacoronavirus that was first reported in Saudi Arabia in 2012. It turned out to be far more deadly than either SARS or the Wuhan virus (at least as far as current estimates of the new coronavirus’s behavior). The MERS genotype was found to be closely related to MERS-like viruses in bats in Saudi Arabia, Africa, Europe, and Asia. Studies done on the cell receptor for MERS showed an apparently conserved viral receptor in both bats and humans. And an identical strain of MERS was found in bats in a nearby cave and near the workplace of the first known human patient.
However, in many of the other locations of the outbreak in the Middle East, there appeared to be limited contact between bats and humans, so scientists looked for another vector species, perhaps one that was acting as an intermediate. A high seroprevalence of MERS-CoV or a closely related virus was found in camels across the Arabian Peninsula and parts of eastern and northern Africa, while tests for MERS antibodies were negative in the most-likely other species of livestock or pet animals, including chickens, cows, goats, horses, and sheep.
In addition, the MERS-related CoV carried by camels was genetically highly similar to that detected in humans, as demonstrated in one particular outbreak on a farm in Qatar where the genetic sequences of MERS-CoV in the nasal swabs from 3 of 14 seropositive camels were similar to those of 2 human cases on the same farm. Similar genomic results were found in MERS-CoV from nasal swabs from camels in Saudi Arabia.
Other mixing-vessel zoonoses
HIV, the viral cause of AIDS, provides an almost-textbook origin story of the rise of a zoonotic supervillain. The virus was genetically traced to have a chimpanzee-to-human origin, but it was found to be more complicated than that. The virus first emerged in the 1920s in Africa in what is now the Democratic Republic of the Congo, well before its rise to a global pandemic in the 1980s.
Researchers believe the chimpanzee virus is a hybrid of the simian immunodeficiency viruses (SIVs) naturally infecting two different monkey species: the red-capped mangabey (Cercocebus torquatus) and the greater spot-nosed monkey (Cercopithecus nictitans). Chimpanzees kill and eat monkeys, which is likely how they acquired the monkey viruses. The viruses hybridized in a chimpanzee; the hybrid virus then spread through the chimpanzee population and was later transmitted to humans who captured and slaughtered chimps for meat (becoming exposed to their blood). This was the most likely origin of HIV-1.
HIV-1 also shows one of the major risks of zoonotic infections. They can continue to mutate in its human host, increasing the risk of greater virulence, but also interfering with the production of a universally effective vaccine. Since its transmission to humans, for example, many subtypes of the HIV-1 strain have developed, with genetic differences even in the same subtypes found to be up to 20%.
Ebolavirus, first detected in 1976, is another case of bats being the potential culprit. Genetic analysis has shown that African fruit bats are likely involved in the spread of the virus and may be its reservoir host. Further evidence of this was found in the most recent human-infecting Bombali variant of the virus, which was identified in samples from bats collected from Sierra Leone.
It was also found that pigs can also become infected with Zaire ebolavirus, leading to the fear that pigs could serve as a mixing vessel for it and other filoviruses. Pigs have their own forms of Ebola-like disease viruses, which are not currently transmissible to humans, but could provide a potential mixing-vessel reservoir.
Emergent influenzas
The Western world has been most affected by these highly mutable, multispecies zoonotic viruses. The 1957 and 1968 flu pandemics contained a mixture of gene segments from human and avian influenza viruses. “What is clear from genetic analysis of the viruses that caused these past pandemics is that reassortment (gene swapping) occurred to produce novel influenza viruses that caused the pandemics. In both of these cases, the new viruses that emerged showed major differences from the parent viruses,” according to the Centers for Disease Control and Prevention.
Influenza is, however, a good example that all zoonoses are not the result of a mixing-vessel phenomenon, with evidence showing that the origin of the catastrophic 1918 virus pandemic likely resulted from a bird influenza virus directly infecting humans and pigs at about the same time without reassortment, according to the CDC.
Building a protective infrastructure
The first 2 decades of the 21st century saw a huge increase in efforts to develop an infrastructure to monitor and potentially prevent the spread of new zoonoses. As part of a global effort led by the United Nations, the U.S. Agency for International AID developed the PREDICT program in 2009 “to strengthen global capacity for detection and discovery of zoonotic viruses with pandemic potential. Those include coronaviruses, the family to which SARS and MERS belong; paramyxoviruses, like Nipah virus; influenza viruses; and filoviruses, like the ebolavirus.”
PREDICT funding to the EcoHealth Alliance led to discovery of the likely bat origins of the Zaire ebolavirus during the 2013-2016 outbreak. And throughout the existence of PREDICT, more than 145,000 animals and people were surveyed in areas of likely zoonotic outbreaks, leading to the detection of more than “1,100 unique viruses, including zoonotic diseases of public health concern such as Bombali ebolavirus, Zaire ebolavirus, Marburg virus, and MERS- and SARS-like coronaviruses,” according to PREDICT partner, the University of California, Davis.
PREDICT-2 was launched in 2014 with the continuing goals of “identifying and better characterizing pathogens of known epidemic and unknown pandemic potential; recognizing animal reservoirs and amplification hosts of human-infectious viruses; and efficiently targeting intervention action at human behaviors which amplify disease transmission at critical animal-animal and animal-human interfaces in hotspots of viral evolution, spillover, amplification, and spread.”
However, in October 2019, the Trump administration cut all funding to the PREDICT program, leading to its shutdown. In a New York Times interview, Peter Daszak, president of the EcoHealth Alliance, stated: “PREDICT was an approach to heading off pandemics, instead of sitting there waiting for them to emerge and then mobilizing.”
Ultimately, in addition to its human cost, the current Wuhan coronavirus outbreak can be looked at an object lesson – a test of the pandemic surveillance and control systems currently in place, and a practice run for the next and potentially deadlier zoonotic outbreaks to come. Perhaps it is also a reminder that cutting resources to detect zoonoses at their source in their animal hosts – before they enter the human chain– is perhaps not the most prudent of ideas.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington.
Emerging viruses that spread to humans from an animal host are commonplace and represent some of the deadliest diseases known. Given the details of the Wuhan coronavirus (2019-nCoV) outbreak, including the genetic profile of the disease agent, the hypothesis of a snake origin was the first raised in the peer-reviewed literature.
It is a highly controversial origin story, however, given that mammals have been the sources of all other such zoonotic coronaviruses, as well as a host of other zoonotic diseases.
An animal source for emerging infections such as the 2019-nCoV is the default hypothesis, because “around 60% of all infectious diseases in humans are zoonotic, as are 75% of all emerging infectious diseases,” according to a United Nations report. The report goes on to say that, “on average, one new infectious disease emerges in humans every 4 months.”
To appreciate the emergence and nature of 2019-nCoV, it is important to examine the history of zoonotic outbreaks of other such diseases, especially with regard to the “mixing-vessel” phenomenon, which has been noted in closely related coronaviruses, including SARS and MERS, as well as the widely disparate HIV, Ebola, and influenza viruses.
Mutants in the mixing vessel
The mixing-vessel phenomenon is conceptually easy but molecularly complex. A single animal is coinfected with two related viruses; the virus genomes recombine together (virus “sex”) in that animal to form a new variant of virus. Such new mutant viruses can be more or less infective, more or less deadly, and more or less able to jump the species or even genus barrier. An emerging viral zoonosis can occur when a human being is exposed to one of these new viruses (either from the origin species or another species intermediate) that is capable of also infecting a human cell. Such exposure can occur from close proximity to animal waste or body fluids, as in the farm environment, or from wildlife pets or the capturing and slaughtering of wildlife for food, as is proposed in the case of the Wuhan seafood market scenario. In fact, the scientists who postulated a snake intermediary as the potential mixing vessel also stated that 2019‐nCoV appears to be a recombinant virus between a bat coronavirus and an origin‐unknown coronavirus.
Coronaviruses in particular have a history of moving from animal to human hosts (and even back again), and their detailed genetic pattern and taxonomy can reveal the animal origin of these diseases.
Going batty
Bats, in particular, have been shown to be a reservoir species for both alphacoronaviruses and betacoronaviruses. Given their ecology and behavior, they have been found to play a key role in transmitting coronaviruses between species. A highly pertinent example of this is the SARS coronavirus, which was shown to have likely originated in Chinese horseshoe bats. The SARS virus, which is genetically closely related to the new Wuhan coronavirus, first infected humans in the Guangdong province of southern China in 2002.
Scientists speculate that the virus was then either transmitted directly to humans from bats, or passed through an intermediate host species, with SARS-like viruses isolated from Himalayan palm civets found in a live-animal market in Guangdong. The virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the market.
The MERS coronavirus is a betacoronavirus that was first reported in Saudi Arabia in 2012. It turned out to be far more deadly than either SARS or the Wuhan virus (at least as far as current estimates of the new coronavirus’s behavior). The MERS genotype was found to be closely related to MERS-like viruses in bats in Saudi Arabia, Africa, Europe, and Asia. Studies done on the cell receptor for MERS showed an apparently conserved viral receptor in both bats and humans. And an identical strain of MERS was found in bats in a nearby cave and near the workplace of the first known human patient.
However, in many of the other locations of the outbreak in the Middle East, there appeared to be limited contact between bats and humans, so scientists looked for another vector species, perhaps one that was acting as an intermediate. A high seroprevalence of MERS-CoV or a closely related virus was found in camels across the Arabian Peninsula and parts of eastern and northern Africa, while tests for MERS antibodies were negative in the most-likely other species of livestock or pet animals, including chickens, cows, goats, horses, and sheep.
In addition, the MERS-related CoV carried by camels was genetically highly similar to that detected in humans, as demonstrated in one particular outbreak on a farm in Qatar where the genetic sequences of MERS-CoV in the nasal swabs from 3 of 14 seropositive camels were similar to those of 2 human cases on the same farm. Similar genomic results were found in MERS-CoV from nasal swabs from camels in Saudi Arabia.
Other mixing-vessel zoonoses
HIV, the viral cause of AIDS, provides an almost-textbook origin story of the rise of a zoonotic supervillain. The virus was genetically traced to have a chimpanzee-to-human origin, but it was found to be more complicated than that. The virus first emerged in the 1920s in Africa in what is now the Democratic Republic of the Congo, well before its rise to a global pandemic in the 1980s.
Researchers believe the chimpanzee virus is a hybrid of the simian immunodeficiency viruses (SIVs) naturally infecting two different monkey species: the red-capped mangabey (Cercocebus torquatus) and the greater spot-nosed monkey (Cercopithecus nictitans). Chimpanzees kill and eat monkeys, which is likely how they acquired the monkey viruses. The viruses hybridized in a chimpanzee; the hybrid virus then spread through the chimpanzee population and was later transmitted to humans who captured and slaughtered chimps for meat (becoming exposed to their blood). This was the most likely origin of HIV-1.
HIV-1 also shows one of the major risks of zoonotic infections. They can continue to mutate in its human host, increasing the risk of greater virulence, but also interfering with the production of a universally effective vaccine. Since its transmission to humans, for example, many subtypes of the HIV-1 strain have developed, with genetic differences even in the same subtypes found to be up to 20%.
Ebolavirus, first detected in 1976, is another case of bats being the potential culprit. Genetic analysis has shown that African fruit bats are likely involved in the spread of the virus and may be its reservoir host. Further evidence of this was found in the most recent human-infecting Bombali variant of the virus, which was identified in samples from bats collected from Sierra Leone.
It was also found that pigs can also become infected with Zaire ebolavirus, leading to the fear that pigs could serve as a mixing vessel for it and other filoviruses. Pigs have their own forms of Ebola-like disease viruses, which are not currently transmissible to humans, but could provide a potential mixing-vessel reservoir.
Emergent influenzas
The Western world has been most affected by these highly mutable, multispecies zoonotic viruses. The 1957 and 1968 flu pandemics contained a mixture of gene segments from human and avian influenza viruses. “What is clear from genetic analysis of the viruses that caused these past pandemics is that reassortment (gene swapping) occurred to produce novel influenza viruses that caused the pandemics. In both of these cases, the new viruses that emerged showed major differences from the parent viruses,” according to the Centers for Disease Control and Prevention.
Influenza is, however, a good example that all zoonoses are not the result of a mixing-vessel phenomenon, with evidence showing that the origin of the catastrophic 1918 virus pandemic likely resulted from a bird influenza virus directly infecting humans and pigs at about the same time without reassortment, according to the CDC.
Building a protective infrastructure
The first 2 decades of the 21st century saw a huge increase in efforts to develop an infrastructure to monitor and potentially prevent the spread of new zoonoses. As part of a global effort led by the United Nations, the U.S. Agency for International AID developed the PREDICT program in 2009 “to strengthen global capacity for detection and discovery of zoonotic viruses with pandemic potential. Those include coronaviruses, the family to which SARS and MERS belong; paramyxoviruses, like Nipah virus; influenza viruses; and filoviruses, like the ebolavirus.”
PREDICT funding to the EcoHealth Alliance led to discovery of the likely bat origins of the Zaire ebolavirus during the 2013-2016 outbreak. And throughout the existence of PREDICT, more than 145,000 animals and people were surveyed in areas of likely zoonotic outbreaks, leading to the detection of more than “1,100 unique viruses, including zoonotic diseases of public health concern such as Bombali ebolavirus, Zaire ebolavirus, Marburg virus, and MERS- and SARS-like coronaviruses,” according to PREDICT partner, the University of California, Davis.
PREDICT-2 was launched in 2014 with the continuing goals of “identifying and better characterizing pathogens of known epidemic and unknown pandemic potential; recognizing animal reservoirs and amplification hosts of human-infectious viruses; and efficiently targeting intervention action at human behaviors which amplify disease transmission at critical animal-animal and animal-human interfaces in hotspots of viral evolution, spillover, amplification, and spread.”
However, in October 2019, the Trump administration cut all funding to the PREDICT program, leading to its shutdown. In a New York Times interview, Peter Daszak, president of the EcoHealth Alliance, stated: “PREDICT was an approach to heading off pandemics, instead of sitting there waiting for them to emerge and then mobilizing.”
Ultimately, in addition to its human cost, the current Wuhan coronavirus outbreak can be looked at an object lesson – a test of the pandemic surveillance and control systems currently in place, and a practice run for the next and potentially deadlier zoonotic outbreaks to come. Perhaps it is also a reminder that cutting resources to detect zoonoses at their source in their animal hosts – before they enter the human chain– is perhaps not the most prudent of ideas.
Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor of the department of biochemistry and molecular & celluar biology at Georgetown University, Washington.
Journal editors seek more complete disclosure from authors
A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.
The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).
“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).
The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.
It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.
Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.
An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.
The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).
Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.
The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.
“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”
Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.
The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.
Broader national efforts
Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.
Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.
More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.
In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.
Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.
Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?
Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.
The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.
A push for registries
The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.
The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.
The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.
Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.
A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.
The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).
“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).
The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.
It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.
Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.
An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.
The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).
Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.
The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.
“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”
Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.
The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.
Broader national efforts
Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.
Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.
More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.
In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.
Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.
Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?
Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.
The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.
A push for registries
The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.
The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.
The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.
Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.
A group of leading medical journal editors is seeking to improve the completeness and transparency of financial disclosure reporting with a proposed new disclosure form that puts more onus on readers to decide whether relationships and activities should influence how they view published papers.
The proposed changes are described in an editorial published simultaneously today in the Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, The Lancet, New England Journal of Medicine, and several other journals whose editors are members of the International Committee of Medical Journal Editors (ICMJE).
“While no approach to disclosure will be perfect or foolproof, we hope the changes we propose will help promote transparency and trust,” the editorial stated (Ann Intern Med. 2020 Jan 27. doi: 10.7326/M19-3933).
The ICMJE adopted its currently used electronic form – the “ICMJE Form for the Disclosure of Potential Conflicts of Interest” – 10 years ago in an effort to create some uniformity amidst a patchwork of differing disclosure requirements for authors.
It’s not known how many journals outside of the ICMJE’s member journals routinely use the disclosure form, but the organization’s website houses an extensive list of journals whose editors or publishers have requested to be listed as following the ICMJE’s recommendations for editing, reporting, and publishing, including those concerning disclosures. The ICMJE does not “certify” journals. The full set of recommendations was updated in December 2019.
Most authors are committed to transparent reporting, but “opinions differ over which relationships or activities to report,” the editorial stated.
An author might choose to omit an item that others deem important because of a difference in opinion regarding “relevance,” confusion over definitions, or a simple oversight. Some authors may be “concerned that readers will interpret the listing of any item as a ‘potential conflict of interest’ as indicative of problematic influence and wrongdoing,” the editorial stated.
The revised form, like the current one, asks authors to disclose relationships and activities that are directly related to the reported work, as well as those that are topically related (within the broadly defined field addressed in the work). But unlike the current form, the new version provides a checklist of relationships and activities and asks authors to check ‘yes’ or ‘no’ for each one (and to name them when the answer is ‘yes’).
Items in the checklist include grants, payments/honoraria for lectures, patents issued or planned, stock/stock options, and leadership or fiduciary roles in committees, boards, or societies.
The proposed new form makes no mention of “potential conflicts of interest” or “relevancy,” per say. Authors aren’t asked to determine what might be interpreted as a potential conflict of interest, but instead are asked for a “complete listing” of what readers may find “pertinent” to their work.
“We’re trying to move away from calling everything a [potential] ‘conflict,’ ” Darren B. Taichman, MD, PhD, secretary of ICMJE and executive editor of the Annals of Internal Medicine, said in an interview. “We want to remove for authors the concern or stigma, if you will, that anything listed on a form implies that there is something wrong, because that’s just not true. … We want readers to decide what relationships are important as they interpret the work.”
Dr. Taichman said in the interview that the ICMJE’s updating of the form was more a function of “good housekeeping” and continuous appreciation of disclosure as an important issue, rather than any one specific issue, such as concern over a “relevancy” approach to disclosures.
The ICMJE is seeking feedback about its proposed form, which is available with a link for providing comments, at www.icmje.org.
Broader national efforts
Editors and others have been increasingly moving, however, toward asking for more complete disclosures where authors aren’t asked to judge “relevancy” and where readers can make decisions on their own. The American Society of Clinical Oncology, which produces the Journal of Clinical Oncology (JCO) as well as practice guidelines and continuing medical education programs, moved about 5 years ago to a system of general disclosure that asks physicians and others to disclose all financial interests and industry relationships, with no qualifiers.
Earlier in January 2020, the Accreditation Council for Continuing Medical Education issued proposed revisions to its Standards for Integrity and Independence in Accredited Continuing Education. These revisions, which are open for comment, require CME providers to collect disclosure information about all financial relationships of speakers and presenters. It’s up to the CME provider to then determine which relationships are relevant, according to the proposed document.
More change is on the way, as disclosure issues are being deliberated nationally in the wake of a highly publicized disclosure failure at Memorial Sloan Kettering Cancer Center in 2018. Chief medical officer José Baselga, MD, PhD, failed to report millions of dollars of industry payments and ownership interests in journal articles he wrote or cowrote over several years.
In February 2019, leaders from journals, academia, medical societies, and other institutions gathered in Washington for a closed-door meeting to hash out various disclosure related issues.
Hosted by the Association of American Medical Colleges and cosponsored by Memorial Sloan Kettering Cancer Center, ASCO, JAMA, and the Council of Medical Specialty Societies, the meeting led to a series of working groups that are creating additional recommendations “due out soon in 2020,” Heather Pierce, senior director of science policy and regulatory counsel for the AAMC, said in an interview.
Among the questions being discussed: What disclosures should be verified and who should do so? How can disclosures be made more complete and easier for researchers? And, “most importantly,” said Ms. Pierce, how can policy requirements across each of these sectors be aligned so that there’s more coordination and oversight – and with it, public trust?
Some critics of current disclosure policies have called for more reporting of compensation amounts, and Ms. Pierce said that this has been part of cross-sector discussions.
The ICMJE’s proposed form invites, but does not require, authors to indicate what payments were made to them or their institutions. “Part of this is due to the fact that it’s hard to define, let alone agree on, what’s an important amount,” Dr. Taichman said.
A push for registries
The ICMJE is also aiming to make the disclosure process more efficient for authors – and to eliminate inconsistent and incomplete disclosures – by accepting disclosures from web-based repositories, according to the editorial. Repositories allow authors to maintain an inventory of their relationships and activities and then create electronic disclosures that are tailored to the requirements of the ICMJE, medical societies, and other entities.
The AAMC-run repository, called Convey, is consistent with ICMJE reporting requirements and other criteria (e.g., there are no fees for individuals to enter, store, or export their data), but the development of other repositories may be helpful “for meeting regional, linguistic, and regulatory needs” of authors across the world, the editorial stated.
The Annals of Internal Medicine and the New England Journal of Medicine are both currently collecting disclosures through Convey. The platform was born from discussions that followed a 2009 Institute of Medicine report on conflicts of interest.
Signers of the ICMJE editorial include representatives of the National Library of Medicine and the World Association of Medical Editors, in addition to editors in chief and other leaders of the ICMJE member journals.
FROM ANNALS OF INTERNAL MEDICINE
Wuhan coronavirus cluster suggests human-to-human spread
A Chinese man became ill from a novel coronavirus (2019-nCoV) 4 days after arriving in Vietnam to visit his 27-year-old son. Three days later the healthy young man was also stricken, according to a report published online Jan. 28 in the New England Journal of Medicine.
“This family cluster of 2019-nCoV infection that occurred outside China arouses concern regarding human-to-human transmission,” the authors wrote.
The father, age 65 years and with multiple comorbidities including hypertension, type 2 diabetes, coronary heart disease with stent placement, and lung cancer, flew to Hanoi with his wife on January 13; they traveled from the Wuchang district in Wuhan, China, where outbreaks of 2019-nCoV have been occurring.
On Jan. 17, the older man and his wife met their adult son in Ho Chi Minh City, Vietnam, and shared a hotel room with him for 3 days. The father developed a fever that same day and the son developed a dry cough, fever, diarrhea, and vomiting on Jan. 20. Both men went to a hospital ED on Jan. 22.
The authors say the timing of the son’s symptoms suggests the incubation period may have been 3 days or fewer.
Upon admission to the hospital, the father reported that he had not visited a “wet market” where live and dead animals are sold while he was in Wuhan. Throat swabs were positive for 2019-nCoV on real-time reverse-transcription–polymerase-chain-reaction assays.
The man was placed in isolation and “treated empirically with antiviral agents, broad-spectrum antibiotics, and supportive therapies,” wrote Lan T. Phan, PhD, from the Pasteur Institute Ho Chi Minh City and coauthors.
On admission, chest radiographs revealed an infiltrate in the upper lobe of his left lung; he developed worsening dyspnea with hypoxemia on Jan. 25 and required supplemental oxygen at 5 L/min by nasal cannula. Chest radiographs showed a progressive infiltrate and consolidation. His fever resolved on that day and he has progressively improved.
The man’s son had a fever of 39° C (102.2° F) when the two men arrived at the hospital on Jan. 22; hospital staff isolated the son, and chest radiographs and other laboratory tests were normal with the exception of an increased C-reactive protein level.
The son’s throat swab was positive for 2019-nCoV and he is believed to have been exposed from his father; however, the strains have not been ascertained.
“This family had traveled to four cities across Vietnam using various forms of transportation, including planes, trains, and taxis,” the authors wrote. A total of 28 close contacts were identified, none of whom have developed respiratory symptoms. The older man’s wife has been healthy as well.
The authors have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
A Chinese man became ill from a novel coronavirus (2019-nCoV) 4 days after arriving in Vietnam to visit his 27-year-old son. Three days later the healthy young man was also stricken, according to a report published online Jan. 28 in the New England Journal of Medicine.
“This family cluster of 2019-nCoV infection that occurred outside China arouses concern regarding human-to-human transmission,” the authors wrote.
The father, age 65 years and with multiple comorbidities including hypertension, type 2 diabetes, coronary heart disease with stent placement, and lung cancer, flew to Hanoi with his wife on January 13; they traveled from the Wuchang district in Wuhan, China, where outbreaks of 2019-nCoV have been occurring.
On Jan. 17, the older man and his wife met their adult son in Ho Chi Minh City, Vietnam, and shared a hotel room with him for 3 days. The father developed a fever that same day and the son developed a dry cough, fever, diarrhea, and vomiting on Jan. 20. Both men went to a hospital ED on Jan. 22.
The authors say the timing of the son’s symptoms suggests the incubation period may have been 3 days or fewer.
Upon admission to the hospital, the father reported that he had not visited a “wet market” where live and dead animals are sold while he was in Wuhan. Throat swabs were positive for 2019-nCoV on real-time reverse-transcription–polymerase-chain-reaction assays.
The man was placed in isolation and “treated empirically with antiviral agents, broad-spectrum antibiotics, and supportive therapies,” wrote Lan T. Phan, PhD, from the Pasteur Institute Ho Chi Minh City and coauthors.
On admission, chest radiographs revealed an infiltrate in the upper lobe of his left lung; he developed worsening dyspnea with hypoxemia on Jan. 25 and required supplemental oxygen at 5 L/min by nasal cannula. Chest radiographs showed a progressive infiltrate and consolidation. His fever resolved on that day and he has progressively improved.
The man’s son had a fever of 39° C (102.2° F) when the two men arrived at the hospital on Jan. 22; hospital staff isolated the son, and chest radiographs and other laboratory tests were normal with the exception of an increased C-reactive protein level.
The son’s throat swab was positive for 2019-nCoV and he is believed to have been exposed from his father; however, the strains have not been ascertained.
“This family had traveled to four cities across Vietnam using various forms of transportation, including planes, trains, and taxis,” the authors wrote. A total of 28 close contacts were identified, none of whom have developed respiratory symptoms. The older man’s wife has been healthy as well.
The authors have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
A Chinese man became ill from a novel coronavirus (2019-nCoV) 4 days after arriving in Vietnam to visit his 27-year-old son. Three days later the healthy young man was also stricken, according to a report published online Jan. 28 in the New England Journal of Medicine.
“This family cluster of 2019-nCoV infection that occurred outside China arouses concern regarding human-to-human transmission,” the authors wrote.
The father, age 65 years and with multiple comorbidities including hypertension, type 2 diabetes, coronary heart disease with stent placement, and lung cancer, flew to Hanoi with his wife on January 13; they traveled from the Wuchang district in Wuhan, China, where outbreaks of 2019-nCoV have been occurring.
On Jan. 17, the older man and his wife met their adult son in Ho Chi Minh City, Vietnam, and shared a hotel room with him for 3 days. The father developed a fever that same day and the son developed a dry cough, fever, diarrhea, and vomiting on Jan. 20. Both men went to a hospital ED on Jan. 22.
The authors say the timing of the son’s symptoms suggests the incubation period may have been 3 days or fewer.
Upon admission to the hospital, the father reported that he had not visited a “wet market” where live and dead animals are sold while he was in Wuhan. Throat swabs were positive for 2019-nCoV on real-time reverse-transcription–polymerase-chain-reaction assays.
The man was placed in isolation and “treated empirically with antiviral agents, broad-spectrum antibiotics, and supportive therapies,” wrote Lan T. Phan, PhD, from the Pasteur Institute Ho Chi Minh City and coauthors.
On admission, chest radiographs revealed an infiltrate in the upper lobe of his left lung; he developed worsening dyspnea with hypoxemia on Jan. 25 and required supplemental oxygen at 5 L/min by nasal cannula. Chest radiographs showed a progressive infiltrate and consolidation. His fever resolved on that day and he has progressively improved.
The man’s son had a fever of 39° C (102.2° F) when the two men arrived at the hospital on Jan. 22; hospital staff isolated the son, and chest radiographs and other laboratory tests were normal with the exception of an increased C-reactive protein level.
The son’s throat swab was positive for 2019-nCoV and he is believed to have been exposed from his father; however, the strains have not been ascertained.
“This family had traveled to four cities across Vietnam using various forms of transportation, including planes, trains, and taxis,” the authors wrote. A total of 28 close contacts were identified, none of whom have developed respiratory symptoms. The older man’s wife has been healthy as well.
The authors have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
HHS: Coronavirus risk low in U.S., vaccine development underway
U.S. public health officials attempted to stymie concerns about the coronavirus during a press conference on Tuesday,
“Right now, there is no spread of this virus in our communities here at home,” Centers for Disease Control and Prevention director Robert Redfield, MD, said during the Jan. 28 press conference. “This is why our current assessment is that the immediate health risk of this new virus to the general public is low in our nation. The coming days and weeks are likely to bring more confirmed cases here and around the world, including the possibility of some person-to-person spreading, but our goal of the ongoing U.S. public health response is to contain this outbreak and prevent sustained spread of the virus in our country.”
During the press conference, Department Health & Human Services Secretary Alex M. Azar II, reiterated there have been only five confirmed U.S. cases of the coronavirus thus far and all were associated with travel to Wuhan, China, where the virus first appeared. The number of confirmed cases in China, meanwhile, has risen to more than 4,500 with about 100 associated deaths.
U.S. health providers should be on the lookout for any patient who has traveled to China recently, particularly to Hubei province, and they should pay close attention to any relevant symptoms, Secretary Azar said during the press conference.
He defended the decision not to declare a public health emergency at this time, stressing that such a move is based on standards and requirements not yet met by the coronavirus.
“It’s important to remember where we are right now; we have five cases in the United States, each of those individuals with direct contact to Wuhan and no person-to-person transmission in the United States,” Secretary Azar said. “I won’t hesitate at all to invoke any authorities that I need to ensure that we’re taking all the steps to protect the American people, but I’ll do it when it’s appropriate under the standards that we have and the authorities that I need.”
In the meantime, a number of efforts are underway by U.S. agencies to assess the nation’s emergency preparedness stockpile, to assist American families in China with evacuation, and to pursue research into diagnostics and a potential vaccine for the virus, Secretary Azar said.
With regard to countermeasures, the CDC has rapidly developed a diagnostic based on the published sequence of the virus, said Anthony Fauci, MD, director for the National Institute of Allergy and Infectious Diseases (NIAID). The National Institutes of Health and the CDC are now working on the development of next-generation diagnostics to better identify the virus in the United States and throughout the world, Dr. Fauci said during the press conference.
Currently, there are no proven therapeutics for the coronavirus infection, Dr. Fauci said. Based on experiences with SARS and MERS, however, researchers are studying certain antiviral drugs that could potentially treat the virus, he said. This includes the antiviral drug remdesivir, which was developed for the treatment of the Ebola virus, and lopinavir/ritonavir (Kaletra), a combination therapy commonly used to treat HIV. In addition, monoclonal antibodies developed during the SARS outbreak are also being studied.
“Given the somewhat close homology between SARS and the new novel coronavirus, there could be some cross reactivity there that could be utilized,” he said.
Most importantly, he said, vaccine development is underway. Since China isolated the virus and published its sequence, U.S. researchers have already analyzed the components and determined an immunogen to be used in a vaccine, Dr. Fauci said. He anticipates moving to a Phase 1 trial within the next 3 months. The trial would then move to Phase 2 after another few more months for safety data.
“What we do from that point will be determined by what has happened with the outbreak over those months,” he said. “We are proceeding as if we will have to deploy a vaccine. In other words, we’re looking at the worst scenario that this becomes a bigger outbreak.”
Federal health officials, however, stressed that more data about infected patients in China is needed for research. HHS has repeatedly offered to send a CDC team to China to help with public health efforts, research, and response, but China has so far declined the offer, Secretary Azar added.
In addition, the CDC has updated its travel advisory in response to the illness. The latest travel guidance recommends that travelers avoid all nonessential travel to all parts of China.
U.S. public health officials attempted to stymie concerns about the coronavirus during a press conference on Tuesday,
“Right now, there is no spread of this virus in our communities here at home,” Centers for Disease Control and Prevention director Robert Redfield, MD, said during the Jan. 28 press conference. “This is why our current assessment is that the immediate health risk of this new virus to the general public is low in our nation. The coming days and weeks are likely to bring more confirmed cases here and around the world, including the possibility of some person-to-person spreading, but our goal of the ongoing U.S. public health response is to contain this outbreak and prevent sustained spread of the virus in our country.”
During the press conference, Department Health & Human Services Secretary Alex M. Azar II, reiterated there have been only five confirmed U.S. cases of the coronavirus thus far and all were associated with travel to Wuhan, China, where the virus first appeared. The number of confirmed cases in China, meanwhile, has risen to more than 4,500 with about 100 associated deaths.
U.S. health providers should be on the lookout for any patient who has traveled to China recently, particularly to Hubei province, and they should pay close attention to any relevant symptoms, Secretary Azar said during the press conference.
He defended the decision not to declare a public health emergency at this time, stressing that such a move is based on standards and requirements not yet met by the coronavirus.
“It’s important to remember where we are right now; we have five cases in the United States, each of those individuals with direct contact to Wuhan and no person-to-person transmission in the United States,” Secretary Azar said. “I won’t hesitate at all to invoke any authorities that I need to ensure that we’re taking all the steps to protect the American people, but I’ll do it when it’s appropriate under the standards that we have and the authorities that I need.”
In the meantime, a number of efforts are underway by U.S. agencies to assess the nation’s emergency preparedness stockpile, to assist American families in China with evacuation, and to pursue research into diagnostics and a potential vaccine for the virus, Secretary Azar said.
With regard to countermeasures, the CDC has rapidly developed a diagnostic based on the published sequence of the virus, said Anthony Fauci, MD, director for the National Institute of Allergy and Infectious Diseases (NIAID). The National Institutes of Health and the CDC are now working on the development of next-generation diagnostics to better identify the virus in the United States and throughout the world, Dr. Fauci said during the press conference.
Currently, there are no proven therapeutics for the coronavirus infection, Dr. Fauci said. Based on experiences with SARS and MERS, however, researchers are studying certain antiviral drugs that could potentially treat the virus, he said. This includes the antiviral drug remdesivir, which was developed for the treatment of the Ebola virus, and lopinavir/ritonavir (Kaletra), a combination therapy commonly used to treat HIV. In addition, monoclonal antibodies developed during the SARS outbreak are also being studied.
“Given the somewhat close homology between SARS and the new novel coronavirus, there could be some cross reactivity there that could be utilized,” he said.
Most importantly, he said, vaccine development is underway. Since China isolated the virus and published its sequence, U.S. researchers have already analyzed the components and determined an immunogen to be used in a vaccine, Dr. Fauci said. He anticipates moving to a Phase 1 trial within the next 3 months. The trial would then move to Phase 2 after another few more months for safety data.
“What we do from that point will be determined by what has happened with the outbreak over those months,” he said. “We are proceeding as if we will have to deploy a vaccine. In other words, we’re looking at the worst scenario that this becomes a bigger outbreak.”
Federal health officials, however, stressed that more data about infected patients in China is needed for research. HHS has repeatedly offered to send a CDC team to China to help with public health efforts, research, and response, but China has so far declined the offer, Secretary Azar added.
In addition, the CDC has updated its travel advisory in response to the illness. The latest travel guidance recommends that travelers avoid all nonessential travel to all parts of China.
U.S. public health officials attempted to stymie concerns about the coronavirus during a press conference on Tuesday,
“Right now, there is no spread of this virus in our communities here at home,” Centers for Disease Control and Prevention director Robert Redfield, MD, said during the Jan. 28 press conference. “This is why our current assessment is that the immediate health risk of this new virus to the general public is low in our nation. The coming days and weeks are likely to bring more confirmed cases here and around the world, including the possibility of some person-to-person spreading, but our goal of the ongoing U.S. public health response is to contain this outbreak and prevent sustained spread of the virus in our country.”
During the press conference, Department Health & Human Services Secretary Alex M. Azar II, reiterated there have been only five confirmed U.S. cases of the coronavirus thus far and all were associated with travel to Wuhan, China, where the virus first appeared. The number of confirmed cases in China, meanwhile, has risen to more than 4,500 with about 100 associated deaths.
U.S. health providers should be on the lookout for any patient who has traveled to China recently, particularly to Hubei province, and they should pay close attention to any relevant symptoms, Secretary Azar said during the press conference.
He defended the decision not to declare a public health emergency at this time, stressing that such a move is based on standards and requirements not yet met by the coronavirus.
“It’s important to remember where we are right now; we have five cases in the United States, each of those individuals with direct contact to Wuhan and no person-to-person transmission in the United States,” Secretary Azar said. “I won’t hesitate at all to invoke any authorities that I need to ensure that we’re taking all the steps to protect the American people, but I’ll do it when it’s appropriate under the standards that we have and the authorities that I need.”
In the meantime, a number of efforts are underway by U.S. agencies to assess the nation’s emergency preparedness stockpile, to assist American families in China with evacuation, and to pursue research into diagnostics and a potential vaccine for the virus, Secretary Azar said.
With regard to countermeasures, the CDC has rapidly developed a diagnostic based on the published sequence of the virus, said Anthony Fauci, MD, director for the National Institute of Allergy and Infectious Diseases (NIAID). The National Institutes of Health and the CDC are now working on the development of next-generation diagnostics to better identify the virus in the United States and throughout the world, Dr. Fauci said during the press conference.
Currently, there are no proven therapeutics for the coronavirus infection, Dr. Fauci said. Based on experiences with SARS and MERS, however, researchers are studying certain antiviral drugs that could potentially treat the virus, he said. This includes the antiviral drug remdesivir, which was developed for the treatment of the Ebola virus, and lopinavir/ritonavir (Kaletra), a combination therapy commonly used to treat HIV. In addition, monoclonal antibodies developed during the SARS outbreak are also being studied.
“Given the somewhat close homology between SARS and the new novel coronavirus, there could be some cross reactivity there that could be utilized,” he said.
Most importantly, he said, vaccine development is underway. Since China isolated the virus and published its sequence, U.S. researchers have already analyzed the components and determined an immunogen to be used in a vaccine, Dr. Fauci said. He anticipates moving to a Phase 1 trial within the next 3 months. The trial would then move to Phase 2 after another few more months for safety data.
“What we do from that point will be determined by what has happened with the outbreak over those months,” he said. “We are proceeding as if we will have to deploy a vaccine. In other words, we’re looking at the worst scenario that this becomes a bigger outbreak.”
Federal health officials, however, stressed that more data about infected patients in China is needed for research. HHS has repeatedly offered to send a CDC team to China to help with public health efforts, research, and response, but China has so far declined the offer, Secretary Azar added.
In addition, the CDC has updated its travel advisory in response to the illness. The latest travel guidance recommends that travelers avoid all nonessential travel to all parts of China.
Echoes of SARS mark 2019 novel coronavirus outbreak
The current outbreak of severe respiratory infections caused by the 2019 novel coronarvirus (2019-nCoV) has a clinical presentation resembling the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreak that began in 2002, Chinese investigators caution.
By Jan. 2, 2020, 41 patients with confirmed 2019-nCoV had been admitted to a designated hospital in the city of Wuhan, Hubei Province, in central China. Thirteen required ICU admission and six died, reported Chaolin Huang, MD, from Jin Yin-tan Hospital in Wuhan, and colleagues.
“2019-nCoV still needs to be studied deeply in case it becomes a global health threat. Reliable quick pathogen tests and feasible differential diagnosis based on clinical description are crucial for clinicians in their first contact with suspected patients. Because of the pandemic potential of 2019-nCoV, careful surveillance is essential to monitor its future host adaption, viral evolution, infectivity, transmissibility, and pathogenicity,” they wrote in a review published online by The Lancet.
According to the U.S. Centers for Disease Control and Prevention, as of Jan. 28, 2020, the total number of 2019-nCoV cases reported in the United States stood at five, but further cases of the infection – which Chinese health officials have confirmed can be transmitted person-to-person – are expected.
Dr. Huang and colleagues note that although most human coronavirus infections are mild, SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV) were responsible for more than 10,000 infections, with mortality rates ranging from 10% with SARS to 37% with MERS. To date, 2019-nCoV has “caused clusters of fatal pneumonia greatly resembling SARS-CoV,” they write.
The authors studied the epidemiological, clinical, laboratory, and radiological characteristics as well as treatments and clinical outcomes of 41 patients admitted or transferred to the Jin Yin-tan Hospital with laboratory-confirmed 2019-nCoV infections.
The median patient age was 49 years. Thirty of the 41 patients (73%) were male. Comorbid conditions included diabetes in 13 of the 41 patients (32%), hypertension in 6 (15%), and cardiovascular disease in 6.
In all 27 of the 41 patients had been exposed to the Huanan seafood market in Wuhan, the suspected epicenter of the outbreak that was shut down by health authorities on Jan. 1 of this year.
The most common symptoms at the onset of the illness were fever in all but one of the 41 patients, cough in 31, and myalgia or fatigue in 18. Other, less frequent symptoms included sputum production in 11, headache in three, hemoptysis in two, and diarrhea in one.
“In this cohort, most patients presented with fever, dry cough, dyspnoea, and bilateral ground-glass opacities on chest CT scans. These features of 2019-nCoV infection bear some resemblance to SARS-CoV and MERS-CoV infections. However, few patients with 2019-nCoV infection had prominent upper respiratory tract signs and symptoms (e.g., rhinorrhoea, sneezing, or sore throat), indicating that the target cells might be located in the lower airway. Furthermore, 2019-nCoV patients rarely developed intestinal signs and symptoms (e.g., diarrhoea), whereas about 20%-25% of patients with MERS-CoV or SARS-CoV infection had diarrhoea.”
In all, 22 patients developed dyspnea, with a median time from illness onset to dyspnea of 8 days. The median time from illness onset to admission was 7 days, median time to shortness of breath was 8 days, median time to acute respiratory distress syndrome (ARDS) was 9 days, and median time to both mechanical ventilation and ICU admission was 10.5 days.
All of the patients developed pneumonia with abnormal findings on chest CT scan. In addition, 12 patients developed ARDS, six had RNAaemia, five developed acute cardiac injury, and four developed a secondary infection. As noted before, 13 of the 14 patients were admitted to an ICU, and six died. RNAaemia is a positive result for real-time polymerase chain reaction in plasma samples. Patients admitted to the ICU had higher initial concentrations of multiple inflammatory cytokines than patients who did not need ICU care, “suggesting that the cytokine storm was associated with disease severity.”
All of the patients received empirical antibiotics, 38 were treated with oseltamivir (Tamiflu), and 9 received systemic corticosteroids.
The investigators have initiated a randomized controlled trial of the antiviral agents lopinavir and ritonavir for patients hospitalized with 2019-nCoV infection.
The study was funded by the Chinese Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission. All authors declared having no competing interests.
SOURCE: Huang C et al. Lancet. 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.
The current outbreak of severe respiratory infections caused by the 2019 novel coronarvirus (2019-nCoV) has a clinical presentation resembling the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreak that began in 2002, Chinese investigators caution.
By Jan. 2, 2020, 41 patients with confirmed 2019-nCoV had been admitted to a designated hospital in the city of Wuhan, Hubei Province, in central China. Thirteen required ICU admission and six died, reported Chaolin Huang, MD, from Jin Yin-tan Hospital in Wuhan, and colleagues.
“2019-nCoV still needs to be studied deeply in case it becomes a global health threat. Reliable quick pathogen tests and feasible differential diagnosis based on clinical description are crucial for clinicians in their first contact with suspected patients. Because of the pandemic potential of 2019-nCoV, careful surveillance is essential to monitor its future host adaption, viral evolution, infectivity, transmissibility, and pathogenicity,” they wrote in a review published online by The Lancet.
According to the U.S. Centers for Disease Control and Prevention, as of Jan. 28, 2020, the total number of 2019-nCoV cases reported in the United States stood at five, but further cases of the infection – which Chinese health officials have confirmed can be transmitted person-to-person – are expected.
Dr. Huang and colleagues note that although most human coronavirus infections are mild, SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV) were responsible for more than 10,000 infections, with mortality rates ranging from 10% with SARS to 37% with MERS. To date, 2019-nCoV has “caused clusters of fatal pneumonia greatly resembling SARS-CoV,” they write.
The authors studied the epidemiological, clinical, laboratory, and radiological characteristics as well as treatments and clinical outcomes of 41 patients admitted or transferred to the Jin Yin-tan Hospital with laboratory-confirmed 2019-nCoV infections.
The median patient age was 49 years. Thirty of the 41 patients (73%) were male. Comorbid conditions included diabetes in 13 of the 41 patients (32%), hypertension in 6 (15%), and cardiovascular disease in 6.
In all 27 of the 41 patients had been exposed to the Huanan seafood market in Wuhan, the suspected epicenter of the outbreak that was shut down by health authorities on Jan. 1 of this year.
The most common symptoms at the onset of the illness were fever in all but one of the 41 patients, cough in 31, and myalgia or fatigue in 18. Other, less frequent symptoms included sputum production in 11, headache in three, hemoptysis in two, and diarrhea in one.
“In this cohort, most patients presented with fever, dry cough, dyspnoea, and bilateral ground-glass opacities on chest CT scans. These features of 2019-nCoV infection bear some resemblance to SARS-CoV and MERS-CoV infections. However, few patients with 2019-nCoV infection had prominent upper respiratory tract signs and symptoms (e.g., rhinorrhoea, sneezing, or sore throat), indicating that the target cells might be located in the lower airway. Furthermore, 2019-nCoV patients rarely developed intestinal signs and symptoms (e.g., diarrhoea), whereas about 20%-25% of patients with MERS-CoV or SARS-CoV infection had diarrhoea.”
In all, 22 patients developed dyspnea, with a median time from illness onset to dyspnea of 8 days. The median time from illness onset to admission was 7 days, median time to shortness of breath was 8 days, median time to acute respiratory distress syndrome (ARDS) was 9 days, and median time to both mechanical ventilation and ICU admission was 10.5 days.
All of the patients developed pneumonia with abnormal findings on chest CT scan. In addition, 12 patients developed ARDS, six had RNAaemia, five developed acute cardiac injury, and four developed a secondary infection. As noted before, 13 of the 14 patients were admitted to an ICU, and six died. RNAaemia is a positive result for real-time polymerase chain reaction in plasma samples. Patients admitted to the ICU had higher initial concentrations of multiple inflammatory cytokines than patients who did not need ICU care, “suggesting that the cytokine storm was associated with disease severity.”
All of the patients received empirical antibiotics, 38 were treated with oseltamivir (Tamiflu), and 9 received systemic corticosteroids.
The investigators have initiated a randomized controlled trial of the antiviral agents lopinavir and ritonavir for patients hospitalized with 2019-nCoV infection.
The study was funded by the Chinese Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission. All authors declared having no competing interests.
SOURCE: Huang C et al. Lancet. 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.
The current outbreak of severe respiratory infections caused by the 2019 novel coronarvirus (2019-nCoV) has a clinical presentation resembling the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreak that began in 2002, Chinese investigators caution.
By Jan. 2, 2020, 41 patients with confirmed 2019-nCoV had been admitted to a designated hospital in the city of Wuhan, Hubei Province, in central China. Thirteen required ICU admission and six died, reported Chaolin Huang, MD, from Jin Yin-tan Hospital in Wuhan, and colleagues.
“2019-nCoV still needs to be studied deeply in case it becomes a global health threat. Reliable quick pathogen tests and feasible differential diagnosis based on clinical description are crucial for clinicians in their first contact with suspected patients. Because of the pandemic potential of 2019-nCoV, careful surveillance is essential to monitor its future host adaption, viral evolution, infectivity, transmissibility, and pathogenicity,” they wrote in a review published online by The Lancet.
According to the U.S. Centers for Disease Control and Prevention, as of Jan. 28, 2020, the total number of 2019-nCoV cases reported in the United States stood at five, but further cases of the infection – which Chinese health officials have confirmed can be transmitted person-to-person – are expected.
Dr. Huang and colleagues note that although most human coronavirus infections are mild, SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV) were responsible for more than 10,000 infections, with mortality rates ranging from 10% with SARS to 37% with MERS. To date, 2019-nCoV has “caused clusters of fatal pneumonia greatly resembling SARS-CoV,” they write.
The authors studied the epidemiological, clinical, laboratory, and radiological characteristics as well as treatments and clinical outcomes of 41 patients admitted or transferred to the Jin Yin-tan Hospital with laboratory-confirmed 2019-nCoV infections.
The median patient age was 49 years. Thirty of the 41 patients (73%) were male. Comorbid conditions included diabetes in 13 of the 41 patients (32%), hypertension in 6 (15%), and cardiovascular disease in 6.
In all 27 of the 41 patients had been exposed to the Huanan seafood market in Wuhan, the suspected epicenter of the outbreak that was shut down by health authorities on Jan. 1 of this year.
The most common symptoms at the onset of the illness were fever in all but one of the 41 patients, cough in 31, and myalgia or fatigue in 18. Other, less frequent symptoms included sputum production in 11, headache in three, hemoptysis in two, and diarrhea in one.
“In this cohort, most patients presented with fever, dry cough, dyspnoea, and bilateral ground-glass opacities on chest CT scans. These features of 2019-nCoV infection bear some resemblance to SARS-CoV and MERS-CoV infections. However, few patients with 2019-nCoV infection had prominent upper respiratory tract signs and symptoms (e.g., rhinorrhoea, sneezing, or sore throat), indicating that the target cells might be located in the lower airway. Furthermore, 2019-nCoV patients rarely developed intestinal signs and symptoms (e.g., diarrhoea), whereas about 20%-25% of patients with MERS-CoV or SARS-CoV infection had diarrhoea.”
In all, 22 patients developed dyspnea, with a median time from illness onset to dyspnea of 8 days. The median time from illness onset to admission was 7 days, median time to shortness of breath was 8 days, median time to acute respiratory distress syndrome (ARDS) was 9 days, and median time to both mechanical ventilation and ICU admission was 10.5 days.
All of the patients developed pneumonia with abnormal findings on chest CT scan. In addition, 12 patients developed ARDS, six had RNAaemia, five developed acute cardiac injury, and four developed a secondary infection. As noted before, 13 of the 14 patients were admitted to an ICU, and six died. RNAaemia is a positive result for real-time polymerase chain reaction in plasma samples. Patients admitted to the ICU had higher initial concentrations of multiple inflammatory cytokines than patients who did not need ICU care, “suggesting that the cytokine storm was associated with disease severity.”
All of the patients received empirical antibiotics, 38 were treated with oseltamivir (Tamiflu), and 9 received systemic corticosteroids.
The investigators have initiated a randomized controlled trial of the antiviral agents lopinavir and ritonavir for patients hospitalized with 2019-nCoV infection.
The study was funded by the Chinese Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission. All authors declared having no competing interests.
SOURCE: Huang C et al. Lancet. 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.
FROM THE LANCET
Cannabis use in pregnancy and lactation: A changing landscape
National survey data from 2007-2012 of more than 93,000 pregnant women suggest that around 7% of pregnant respondents reported any cannabis use in the last 2-12 months; of those, 16% reported daily or almost daily use. Among pregnant past-year users in the same survey, 70% perceived slight or no risk of harm from cannabis use 1-2 times a week in pregnancy.1
Data from the Kaiser Northern California health plan involving more than 279,000 pregnancies followed during 2009-2016 suggest that there has been a significant upward trend in use of cannabis during pregnancy, from 4% to 7%, as reported by the mother and/or identified by routine urine screening. The highest prevalence in that study was seen among 18- to 24-year-old pregnant women, increasing from 13% to 22% over the 7-year study period. Importantly, more than 50% of cannabis users in the sample were identified by toxicology screening alone.2,3 Common reasons given for use of cannabis in pregnancy include anxiety, pain, and nausea and vomiting of pregnancy.4
With respect to adverse perinatal outcomes, several case-control studies have examined risks for major birth defects with maternal self-report of cannabis use. Some have noted very modest increased risks for selected major birth defects (odds ratios less than 2); however, data still are very limited.5,6
A number of prospective studies have addressed risks of preterm birth and growth restriction, accounting for mother’s concomitant tobacco use.7-11 Some of these studies have suggested about a twofold to threefold increased risk for preterm delivery and an increased risk for reduced birth weight – particularly with heavier or regular cannabis use – but study findings have not been entirely consistent.
Given its psychoactive properties, there has been high interest in understanding whether there are any short- or long-term neurodevelopmental effects on children prenatally exposed to cannabis. These outcomes have been studied in two small older cohorts in the United States and Canada and one more recent cohort in the Netherlands.12-15 Deficits in several measures of cognition and behavior were noted in follow-up of those children from birth to adulthood. However, it is unclear to what extent these findings may have been influenced by heredity, environment, or other factors.
There have been limitations in almost all studies published to date, including small sample sizes, no biomarker validation of maternal report of dose and gestational timing of cannabis use, and lack of detailed data on common coexposures, such as alcohol, tobacco, and other drugs. In addition, newer studies of pregnancy outcomes in women who use currently available cannabis products are needed, given the substantial increase in the potency of cannabis used today, compared with that of 20 years ago. For example, the tetrahydrocannabinol (THC) concentration in commonly cultivated marijuana plants has increased threefold from 4% to 12% between 1995 and 2014.16
There are very limited data on the presence of cannabis in breast milk and the potential effects of exposure to THC and other metabolites for breastfed infants. However, two recent studies have demonstrated there are low but measurable levels of some cannabis metabolites in breast milk.17-18 Further work is needed to determine if these metabolites accumulate in milk and if at a given dose and age of the breastfed infant, there are any growth, neurodevelopmental, or other clinically important adverse effects.
Related questions, such as potential differences in the effects of exposure during pregnancy or lactation based on the route of administration (edible vs. inhaled) and the use of cannabidiol (CBD) products, have not been studied.
At the present time, the American College of Obstetricians and Gynecologists recommends that women who are pregnant or contemplating pregnancy be encouraged to discontinue marijuana use. With respect to lactation and breastfeeding, ACOG concludes there are insufficient data to evaluate the effects on infants, and in the absence of such data, marijuana use is discouraged. Similarly, the American Academy of Pediatrics recommends women of childbearing age abstain from marijuana use while pregnant or breastfeeding because of potential adverse consequences to the fetus, infant, or child.
In August 2019, the U.S. Surgeon General issued an advisory regarding potential harm to developing brains from the use of marijuana during pregnancy and lactation. The Food and Drug Administration issued a similar statement in October 2019 strongly advising against the use of CBD, THC, and marijuana in any form during pregnancy or while breastfeeding.
Dr. Chambers is professor of pediatrics and director of clinical research at Rady Children’s Hospital and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is also director of MotherToBaby California, president of the Organization of Teratology Information Specialists, and past president of the Teratology Society.
References
1. Am J Obstet Gynecol. 2015 Aug;213(2):201.e1-10.
2. JAMA. 2017 Dec 26;318(24):2490-1.
3. JAMA. 2017 Jan 10;317(2):207-9.
4. Complement Ther Clin Pract. 2009 Nov;15(4)242-6.
5. Paediatr Perinat Epidemiol. 2014 Sep; 28(5): 424-33.
6. J Toxicol Environ Health A. 2007 Jan;70(1):7-18.
7. Am J Obstet Gynecol. 1983 Aug 15;146(8):992-4.
8. Clin Perinatol. 1991 Mar;18(1):77-91.
9. Am J Epidemiol. 1986 Dec;124(6):986-93.
10. Pediatr Res. 2012 Feb;71(2):215-9.
11. Reprod Toxicol. 2016;62:77-86.
12. Neurotoxicol Teratol. 1987 Jan-Feb;9(1):1-7.
13. Neurotoxicol Teratol. 1994 Mar-Apr;16(2):169-75.
14. Biol Psychiatry. 2016 Jun 15;79(12):971-9.
15. Pharmacol Ther. 2018 Feb;182:133-51.
16. Biol Psychiatry. 2016 Apr 1;79(7):613-9.
17. Obstet Gynecol. 2018 May;131(5):783-8.
18. Pediatrics. 2018 Sep;142(3):e20181076.
National survey data from 2007-2012 of more than 93,000 pregnant women suggest that around 7% of pregnant respondents reported any cannabis use in the last 2-12 months; of those, 16% reported daily or almost daily use. Among pregnant past-year users in the same survey, 70% perceived slight or no risk of harm from cannabis use 1-2 times a week in pregnancy.1
Data from the Kaiser Northern California health plan involving more than 279,000 pregnancies followed during 2009-2016 suggest that there has been a significant upward trend in use of cannabis during pregnancy, from 4% to 7%, as reported by the mother and/or identified by routine urine screening. The highest prevalence in that study was seen among 18- to 24-year-old pregnant women, increasing from 13% to 22% over the 7-year study period. Importantly, more than 50% of cannabis users in the sample were identified by toxicology screening alone.2,3 Common reasons given for use of cannabis in pregnancy include anxiety, pain, and nausea and vomiting of pregnancy.4
With respect to adverse perinatal outcomes, several case-control studies have examined risks for major birth defects with maternal self-report of cannabis use. Some have noted very modest increased risks for selected major birth defects (odds ratios less than 2); however, data still are very limited.5,6
A number of prospective studies have addressed risks of preterm birth and growth restriction, accounting for mother’s concomitant tobacco use.7-11 Some of these studies have suggested about a twofold to threefold increased risk for preterm delivery and an increased risk for reduced birth weight – particularly with heavier or regular cannabis use – but study findings have not been entirely consistent.
Given its psychoactive properties, there has been high interest in understanding whether there are any short- or long-term neurodevelopmental effects on children prenatally exposed to cannabis. These outcomes have been studied in two small older cohorts in the United States and Canada and one more recent cohort in the Netherlands.12-15 Deficits in several measures of cognition and behavior were noted in follow-up of those children from birth to adulthood. However, it is unclear to what extent these findings may have been influenced by heredity, environment, or other factors.
There have been limitations in almost all studies published to date, including small sample sizes, no biomarker validation of maternal report of dose and gestational timing of cannabis use, and lack of detailed data on common coexposures, such as alcohol, tobacco, and other drugs. In addition, newer studies of pregnancy outcomes in women who use currently available cannabis products are needed, given the substantial increase in the potency of cannabis used today, compared with that of 20 years ago. For example, the tetrahydrocannabinol (THC) concentration in commonly cultivated marijuana plants has increased threefold from 4% to 12% between 1995 and 2014.16
There are very limited data on the presence of cannabis in breast milk and the potential effects of exposure to THC and other metabolites for breastfed infants. However, two recent studies have demonstrated there are low but measurable levels of some cannabis metabolites in breast milk.17-18 Further work is needed to determine if these metabolites accumulate in milk and if at a given dose and age of the breastfed infant, there are any growth, neurodevelopmental, or other clinically important adverse effects.
Related questions, such as potential differences in the effects of exposure during pregnancy or lactation based on the route of administration (edible vs. inhaled) and the use of cannabidiol (CBD) products, have not been studied.
At the present time, the American College of Obstetricians and Gynecologists recommends that women who are pregnant or contemplating pregnancy be encouraged to discontinue marijuana use. With respect to lactation and breastfeeding, ACOG concludes there are insufficient data to evaluate the effects on infants, and in the absence of such data, marijuana use is discouraged. Similarly, the American Academy of Pediatrics recommends women of childbearing age abstain from marijuana use while pregnant or breastfeeding because of potential adverse consequences to the fetus, infant, or child.
In August 2019, the U.S. Surgeon General issued an advisory regarding potential harm to developing brains from the use of marijuana during pregnancy and lactation. The Food and Drug Administration issued a similar statement in October 2019 strongly advising against the use of CBD, THC, and marijuana in any form during pregnancy or while breastfeeding.
Dr. Chambers is professor of pediatrics and director of clinical research at Rady Children’s Hospital and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is also director of MotherToBaby California, president of the Organization of Teratology Information Specialists, and past president of the Teratology Society.
References
1. Am J Obstet Gynecol. 2015 Aug;213(2):201.e1-10.
2. JAMA. 2017 Dec 26;318(24):2490-1.
3. JAMA. 2017 Jan 10;317(2):207-9.
4. Complement Ther Clin Pract. 2009 Nov;15(4)242-6.
5. Paediatr Perinat Epidemiol. 2014 Sep; 28(5): 424-33.
6. J Toxicol Environ Health A. 2007 Jan;70(1):7-18.
7. Am J Obstet Gynecol. 1983 Aug 15;146(8):992-4.
8. Clin Perinatol. 1991 Mar;18(1):77-91.
9. Am J Epidemiol. 1986 Dec;124(6):986-93.
10. Pediatr Res. 2012 Feb;71(2):215-9.
11. Reprod Toxicol. 2016;62:77-86.
12. Neurotoxicol Teratol. 1987 Jan-Feb;9(1):1-7.
13. Neurotoxicol Teratol. 1994 Mar-Apr;16(2):169-75.
14. Biol Psychiatry. 2016 Jun 15;79(12):971-9.
15. Pharmacol Ther. 2018 Feb;182:133-51.
16. Biol Psychiatry. 2016 Apr 1;79(7):613-9.
17. Obstet Gynecol. 2018 May;131(5):783-8.
18. Pediatrics. 2018 Sep;142(3):e20181076.
National survey data from 2007-2012 of more than 93,000 pregnant women suggest that around 7% of pregnant respondents reported any cannabis use in the last 2-12 months; of those, 16% reported daily or almost daily use. Among pregnant past-year users in the same survey, 70% perceived slight or no risk of harm from cannabis use 1-2 times a week in pregnancy.1
Data from the Kaiser Northern California health plan involving more than 279,000 pregnancies followed during 2009-2016 suggest that there has been a significant upward trend in use of cannabis during pregnancy, from 4% to 7%, as reported by the mother and/or identified by routine urine screening. The highest prevalence in that study was seen among 18- to 24-year-old pregnant women, increasing from 13% to 22% over the 7-year study period. Importantly, more than 50% of cannabis users in the sample were identified by toxicology screening alone.2,3 Common reasons given for use of cannabis in pregnancy include anxiety, pain, and nausea and vomiting of pregnancy.4
With respect to adverse perinatal outcomes, several case-control studies have examined risks for major birth defects with maternal self-report of cannabis use. Some have noted very modest increased risks for selected major birth defects (odds ratios less than 2); however, data still are very limited.5,6
A number of prospective studies have addressed risks of preterm birth and growth restriction, accounting for mother’s concomitant tobacco use.7-11 Some of these studies have suggested about a twofold to threefold increased risk for preterm delivery and an increased risk for reduced birth weight – particularly with heavier or regular cannabis use – but study findings have not been entirely consistent.
Given its psychoactive properties, there has been high interest in understanding whether there are any short- or long-term neurodevelopmental effects on children prenatally exposed to cannabis. These outcomes have been studied in two small older cohorts in the United States and Canada and one more recent cohort in the Netherlands.12-15 Deficits in several measures of cognition and behavior were noted in follow-up of those children from birth to adulthood. However, it is unclear to what extent these findings may have been influenced by heredity, environment, or other factors.
There have been limitations in almost all studies published to date, including small sample sizes, no biomarker validation of maternal report of dose and gestational timing of cannabis use, and lack of detailed data on common coexposures, such as alcohol, tobacco, and other drugs. In addition, newer studies of pregnancy outcomes in women who use currently available cannabis products are needed, given the substantial increase in the potency of cannabis used today, compared with that of 20 years ago. For example, the tetrahydrocannabinol (THC) concentration in commonly cultivated marijuana plants has increased threefold from 4% to 12% between 1995 and 2014.16
There are very limited data on the presence of cannabis in breast milk and the potential effects of exposure to THC and other metabolites for breastfed infants. However, two recent studies have demonstrated there are low but measurable levels of some cannabis metabolites in breast milk.17-18 Further work is needed to determine if these metabolites accumulate in milk and if at a given dose and age of the breastfed infant, there are any growth, neurodevelopmental, or other clinically important adverse effects.
Related questions, such as potential differences in the effects of exposure during pregnancy or lactation based on the route of administration (edible vs. inhaled) and the use of cannabidiol (CBD) products, have not been studied.
At the present time, the American College of Obstetricians and Gynecologists recommends that women who are pregnant or contemplating pregnancy be encouraged to discontinue marijuana use. With respect to lactation and breastfeeding, ACOG concludes there are insufficient data to evaluate the effects on infants, and in the absence of such data, marijuana use is discouraged. Similarly, the American Academy of Pediatrics recommends women of childbearing age abstain from marijuana use while pregnant or breastfeeding because of potential adverse consequences to the fetus, infant, or child.
In August 2019, the U.S. Surgeon General issued an advisory regarding potential harm to developing brains from the use of marijuana during pregnancy and lactation. The Food and Drug Administration issued a similar statement in October 2019 strongly advising against the use of CBD, THC, and marijuana in any form during pregnancy or while breastfeeding.
Dr. Chambers is professor of pediatrics and director of clinical research at Rady Children’s Hospital and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is also director of MotherToBaby California, president of the Organization of Teratology Information Specialists, and past president of the Teratology Society.
References
1. Am J Obstet Gynecol. 2015 Aug;213(2):201.e1-10.
2. JAMA. 2017 Dec 26;318(24):2490-1.
3. JAMA. 2017 Jan 10;317(2):207-9.
4. Complement Ther Clin Pract. 2009 Nov;15(4)242-6.
5. Paediatr Perinat Epidemiol. 2014 Sep; 28(5): 424-33.
6. J Toxicol Environ Health A. 2007 Jan;70(1):7-18.
7. Am J Obstet Gynecol. 1983 Aug 15;146(8):992-4.
8. Clin Perinatol. 1991 Mar;18(1):77-91.
9. Am J Epidemiol. 1986 Dec;124(6):986-93.
10. Pediatr Res. 2012 Feb;71(2):215-9.
11. Reprod Toxicol. 2016;62:77-86.
12. Neurotoxicol Teratol. 1987 Jan-Feb;9(1):1-7.
13. Neurotoxicol Teratol. 1994 Mar-Apr;16(2):169-75.
14. Biol Psychiatry. 2016 Jun 15;79(12):971-9.
15. Pharmacol Ther. 2018 Feb;182:133-51.
16. Biol Psychiatry. 2016 Apr 1;79(7):613-9.
17. Obstet Gynecol. 2018 May;131(5):783-8.
18. Pediatrics. 2018 Sep;142(3):e20181076.
CDC: Five confirmed 2019-nCoV cases in the U.S.
Five cases of the new infectious coronavirus, 2019-nCoV, have been confirmed in the United States, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during a Jan. 27 press briefing.
A total of 110 individuals are under investigation in 26 states, she said. While five cases have been confirmed positive for the virus, 32 cases were confirmed negative. There have been no new cases overnight.
Last week, CDC scientists developed a real-time polymerase chain reaction (PCR) test that can diagnose the virus in respiratory and serum samples from clinical specimens. On Jan. 24, the protocol for this test was publicly posted. “This is essentially a blueprint to make the test,” Dr. Messonnier explained. “Currently, we are refining the use of the test so that it can provide optimal guidance to states and labs on how to use it. We are working on a plan so that priority states get these test kits as soon as possible. In the coming weeks, we will share these tests with domestic and international partners so they can test for this virus themselves.”
The CDC uploaded the entire genome of the virus from the first two cases in the United States to GenBank. It was similar to the one that China had previously posted. “Right now, based on CDC’s analysis of the available data, it doesn’t look like the virus has mutated,” she said. “And we are growing the virus in cell culture, which is necessary for further studies, including the additional genetic characterization.”
As of today, 16 international locations, including the United States, have identified cases of the virus. CDC officials are continuing to screen passengers from Wuhan, China, at five designated airports. “This serves two purposes: first to detect the illness and rapidly respond to [affected] people entering the country,” Dr. Messonnier said. “The second purpose is to educate travelers about the symptoms of this new virus, and what to do if they develop symptoms. I expect that in the coming days, our travel recommendations will change. Risk depends on exposure. Right now, we have an handful of new patients with this new virus here in the U.S. However, at this time in the U.S., this virus is not spreading in the community. For that reason, we believe that the immediate health risk of the new virus to the general American public is low.”
The CDC is asking its clinical lab partners to send virus samples to the CDC to ensure that results are analyzed as accurately as possible.
Five cases of the new infectious coronavirus, 2019-nCoV, have been confirmed in the United States, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during a Jan. 27 press briefing.
A total of 110 individuals are under investigation in 26 states, she said. While five cases have been confirmed positive for the virus, 32 cases were confirmed negative. There have been no new cases overnight.
Last week, CDC scientists developed a real-time polymerase chain reaction (PCR) test that can diagnose the virus in respiratory and serum samples from clinical specimens. On Jan. 24, the protocol for this test was publicly posted. “This is essentially a blueprint to make the test,” Dr. Messonnier explained. “Currently, we are refining the use of the test so that it can provide optimal guidance to states and labs on how to use it. We are working on a plan so that priority states get these test kits as soon as possible. In the coming weeks, we will share these tests with domestic and international partners so they can test for this virus themselves.”
The CDC uploaded the entire genome of the virus from the first two cases in the United States to GenBank. It was similar to the one that China had previously posted. “Right now, based on CDC’s analysis of the available data, it doesn’t look like the virus has mutated,” she said. “And we are growing the virus in cell culture, which is necessary for further studies, including the additional genetic characterization.”
As of today, 16 international locations, including the United States, have identified cases of the virus. CDC officials are continuing to screen passengers from Wuhan, China, at five designated airports. “This serves two purposes: first to detect the illness and rapidly respond to [affected] people entering the country,” Dr. Messonnier said. “The second purpose is to educate travelers about the symptoms of this new virus, and what to do if they develop symptoms. I expect that in the coming days, our travel recommendations will change. Risk depends on exposure. Right now, we have an handful of new patients with this new virus here in the U.S. However, at this time in the U.S., this virus is not spreading in the community. For that reason, we believe that the immediate health risk of the new virus to the general American public is low.”
The CDC is asking its clinical lab partners to send virus samples to the CDC to ensure that results are analyzed as accurately as possible.
Five cases of the new infectious coronavirus, 2019-nCoV, have been confirmed in the United States, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during a Jan. 27 press briefing.
A total of 110 individuals are under investigation in 26 states, she said. While five cases have been confirmed positive for the virus, 32 cases were confirmed negative. There have been no new cases overnight.
Last week, CDC scientists developed a real-time polymerase chain reaction (PCR) test that can diagnose the virus in respiratory and serum samples from clinical specimens. On Jan. 24, the protocol for this test was publicly posted. “This is essentially a blueprint to make the test,” Dr. Messonnier explained. “Currently, we are refining the use of the test so that it can provide optimal guidance to states and labs on how to use it. We are working on a plan so that priority states get these test kits as soon as possible. In the coming weeks, we will share these tests with domestic and international partners so they can test for this virus themselves.”
The CDC uploaded the entire genome of the virus from the first two cases in the United States to GenBank. It was similar to the one that China had previously posted. “Right now, based on CDC’s analysis of the available data, it doesn’t look like the virus has mutated,” she said. “And we are growing the virus in cell culture, which is necessary for further studies, including the additional genetic characterization.”
As of today, 16 international locations, including the United States, have identified cases of the virus. CDC officials are continuing to screen passengers from Wuhan, China, at five designated airports. “This serves two purposes: first to detect the illness and rapidly respond to [affected] people entering the country,” Dr. Messonnier said. “The second purpose is to educate travelers about the symptoms of this new virus, and what to do if they develop symptoms. I expect that in the coming days, our travel recommendations will change. Risk depends on exposure. Right now, we have an handful of new patients with this new virus here in the U.S. However, at this time in the U.S., this virus is not spreading in the community. For that reason, we believe that the immediate health risk of the new virus to the general American public is low.”
The CDC is asking its clinical lab partners to send virus samples to the CDC to ensure that results are analyzed as accurately as possible.