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Nails falling off in a 3-year-old
When the nails peel off from the proximal nail folds, the clinical term is onychomadesis and it is important to ask about recent infections or severe metabolic stressors. In children and adults, onychomadesis on multiple fingers may occur after infections and has been associated with hand-foot-mouth disease caused by common viral infections—especially strains of coxsackievirus.1
Because shed nails show evidence of viral infection, one hypothesis for their peeling off is that the tissue of the nail matrix is infected, leading to metabolic changes. As the nail matrix returns to normal function, a new nail is made and ultimately will replace the nail that has come off. In healthy US adults, fingernails grow 3.47 mm per month on average while toenails grow 1.62 mm per month on average.2
Sometimes it’s hard to elicit a history of a very mild viral illness weeks or months after it has resolved. Asking specifically about mouth ulcers may help. If there is a history of a viral illness, no specific work-up or treatment is necessary. Patients may be reassured that nails will improve over several months without lasting effects.
In this case, the patient and her family were given reassurance and the nails returned to normal within a few months.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
1. Kim EJ, Park HS, Yoon HS, et al. Four cases of onychomadesis after hand-foot-mouth disease. Ann Dermatol. 2014;26:777-778. doi: 10.5021/ad.2014.26.6.777
2. Yaemsiri S, Hou N, Slining MM, et al. Growth rate of human fingernails and toenails in healthy American young adults. J Eur Acad Dermatol Venereol. 2010;24:420-423. doi: 10.1111/j.1468-3083.2009.03426.x
When the nails peel off from the proximal nail folds, the clinical term is onychomadesis and it is important to ask about recent infections or severe metabolic stressors. In children and adults, onychomadesis on multiple fingers may occur after infections and has been associated with hand-foot-mouth disease caused by common viral infections—especially strains of coxsackievirus.1
Because shed nails show evidence of viral infection, one hypothesis for their peeling off is that the tissue of the nail matrix is infected, leading to metabolic changes. As the nail matrix returns to normal function, a new nail is made and ultimately will replace the nail that has come off. In healthy US adults, fingernails grow 3.47 mm per month on average while toenails grow 1.62 mm per month on average.2
Sometimes it’s hard to elicit a history of a very mild viral illness weeks or months after it has resolved. Asking specifically about mouth ulcers may help. If there is a history of a viral illness, no specific work-up or treatment is necessary. Patients may be reassured that nails will improve over several months without lasting effects.
In this case, the patient and her family were given reassurance and the nails returned to normal within a few months.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
When the nails peel off from the proximal nail folds, the clinical term is onychomadesis and it is important to ask about recent infections or severe metabolic stressors. In children and adults, onychomadesis on multiple fingers may occur after infections and has been associated with hand-foot-mouth disease caused by common viral infections—especially strains of coxsackievirus.1
Because shed nails show evidence of viral infection, one hypothesis for their peeling off is that the tissue of the nail matrix is infected, leading to metabolic changes. As the nail matrix returns to normal function, a new nail is made and ultimately will replace the nail that has come off. In healthy US adults, fingernails grow 3.47 mm per month on average while toenails grow 1.62 mm per month on average.2
Sometimes it’s hard to elicit a history of a very mild viral illness weeks or months after it has resolved. Asking specifically about mouth ulcers may help. If there is a history of a viral illness, no specific work-up or treatment is necessary. Patients may be reassured that nails will improve over several months without lasting effects.
In this case, the patient and her family were given reassurance and the nails returned to normal within a few months.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.
1. Kim EJ, Park HS, Yoon HS, et al. Four cases of onychomadesis after hand-foot-mouth disease. Ann Dermatol. 2014;26:777-778. doi: 10.5021/ad.2014.26.6.777
2. Yaemsiri S, Hou N, Slining MM, et al. Growth rate of human fingernails and toenails in healthy American young adults. J Eur Acad Dermatol Venereol. 2010;24:420-423. doi: 10.1111/j.1468-3083.2009.03426.x
1. Kim EJ, Park HS, Yoon HS, et al. Four cases of onychomadesis after hand-foot-mouth disease. Ann Dermatol. 2014;26:777-778. doi: 10.5021/ad.2014.26.6.777
2. Yaemsiri S, Hou N, Slining MM, et al. Growth rate of human fingernails and toenails in healthy American young adults. J Eur Acad Dermatol Venereol. 2010;24:420-423. doi: 10.1111/j.1468-3083.2009.03426.x
‘Artificial pancreas’ for all type 1 diabetes pregnancies?
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM ADA 2023
Thoughts on primary care in 2023
As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.
- Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
- Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
- Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.1 The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
- Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.2 Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.
There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.
2. Budd J. J Prim Care Community Health. 2023 Apr 19.
As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.
- Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
- Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
- Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.1 The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
- Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.2 Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.
There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.
2. Budd J. J Prim Care Community Health. 2023 Apr 19.
As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.
- Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
- Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
- Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.1 The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
- Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.2 Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.
There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.
2. Budd J. J Prim Care Community Health. 2023 Apr 19.
Prodrome treatment with ubrogepant prevents migraines
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
AUSTIN, TEX – , according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.
Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.
“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
‘Significant’ finding
“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.
Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.
Dr. Rapoport and Dr. Sico were not involved in the study.
Probing the prodrome
The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.
During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).
The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).
Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
A unique result?
One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.
The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.
Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.
Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.
FROM AHS 2023
Family doctors provide most care for several chronic diseases
A population-based retrospective cohort study examined data from nearly 1 million patients with common chronic conditions in Alberta, Canada. Family doctors were the sole providers of care for 85.7% of patients with hypertension and 70.9% of those with diabetes.
The study is part of efforts to encourage more research “by primary care, for primary care,” study author Jessica Kirkwood, MD, family physician and assistant professor of family medicine at the University of Alberta, Edmonton, said in an interview. The prevalence of primary care involvement demonstrates the importance of involving family physicians in creating guidelines for management and developing clinical trials, Dr. Kirkwood said.
The study was published in Canadian Family Physician.
Who provides care?
The study focused on care provided from 2013 to 2017 for seven chronic conditions. The information collected consisted of data from administrative health databases, which track medical services provided by Alberta’s government-funded universal health care system.
Most patients’ care was managed by family physicians alone in four of the conditions studied: hypertension (85.7%), diabetes (70.9%), chronic obstructive pulmonary disease (59.8%), and asthma (65.5%).
Specialists were more involved in the remaining three diseases. They provided the sole management in 49.1% of patients with ischemic heart disease, 42.2% of those with chronic kidney disease, and 35.6% of those with heart failure. For these conditions, family physicians remained involved in the care for a large proportion of patients. Specialist involvement may be more common with these diseases because they sometimes involve interventions that only specialists offer, like angiography and dialysis, said Dr. Kirkwood.
The study also found that nurse practitioners were involved in care for very few patients (less than 1%), in accordance with the small number of nurse practitioners working in primary care settings.
Dr. Kirkwood acknowledged that the data come with certain limitations because they were not intended for research purposes. One limitation is that some conditions may not have been recorded because of “shadow billing.” Salaried physicians and practitioners do not have an incentive to include all diagnostic codes in their records. By comparison, clinicians operating under a fee-for-service model would be likely to indicate all diagnoses.
Developing guidelines
Despite the widespread management of chronic conditions by family physicians, these doctors represented about 17% of the experts who contribute to guidelines and recommendations, according to a 2015 study that the investigators cited.
“Frankly, that’s concerning,” said Dr. Kirkwood, regarding the disconnect between the people creating the recommendations and the people using them. The guidelines should include the perspective of clinicians who regularly work with patients, she said. Providing that perspective would also make the design of clinical trials on interventions more informative, the researchers concluded.
“I know as a family doctor myself that some recommendations are completely overwhelming,” especially given the range of issues that primary care clinicians see, said Dr. Kirkwood. Including primary care representatives who are familiar with the demands of the position “hopefully will make the recommendations much more applicable to the people that they will affect,” she said.
Dr. Kirkwood also noted the need for sufficient support for family doctors to contribute to guideline creation and research, especially for doctors in rural communities who are not already affiliated with a university.
The involvement of primary care providers in research settings is a primary goal of Patients, Experience, Evidence and Research (PEER), a primary care-led group that collaborates with the College of Family Physicians of Canada. The current investigators are members of PEER.
Additional conditions
Commenting on the study, Martin Fortin, MD, clinical teaching professor at the University of Sherbrooke, Quebec, said, “This is a good opportunity to advocate for more studies to be done in the primary care context, where the majority of chronic disease management is done.”
However, Dr. Fortin wishes that more diagnoses had been included in the study, such as mental health and musculoskeletal conditions like back pain and osteoarthritis. These conditions are also commonly seen by primary care clinicians, according to Dr. Fortin.
Because the number of conditions studied is limited, the data may not reflect the true prevalence of multimorbidity, Dr. Fortin added.
Primary care doctors provide a broad perspective on the overall health of patients, compared with specialists who focus on particular conditions. Similarly, during drug trials, pharmaceutical companies aim to reduce complicating factors, even though the medications are prescribed for conditions where multimorbidity is common. “Medication should be tested in the real environment,” said Dr. Fortin.
Ultimately, he added, the study cannot address the complexity of the patients, but it nevertheless sheds light on who is providing care and where the research on these conditions should be done.
The study was conducted without outside funding. Dr. Kirkwood and Dr. Fortin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A population-based retrospective cohort study examined data from nearly 1 million patients with common chronic conditions in Alberta, Canada. Family doctors were the sole providers of care for 85.7% of patients with hypertension and 70.9% of those with diabetes.
The study is part of efforts to encourage more research “by primary care, for primary care,” study author Jessica Kirkwood, MD, family physician and assistant professor of family medicine at the University of Alberta, Edmonton, said in an interview. The prevalence of primary care involvement demonstrates the importance of involving family physicians in creating guidelines for management and developing clinical trials, Dr. Kirkwood said.
The study was published in Canadian Family Physician.
Who provides care?
The study focused on care provided from 2013 to 2017 for seven chronic conditions. The information collected consisted of data from administrative health databases, which track medical services provided by Alberta’s government-funded universal health care system.
Most patients’ care was managed by family physicians alone in four of the conditions studied: hypertension (85.7%), diabetes (70.9%), chronic obstructive pulmonary disease (59.8%), and asthma (65.5%).
Specialists were more involved in the remaining three diseases. They provided the sole management in 49.1% of patients with ischemic heart disease, 42.2% of those with chronic kidney disease, and 35.6% of those with heart failure. For these conditions, family physicians remained involved in the care for a large proportion of patients. Specialist involvement may be more common with these diseases because they sometimes involve interventions that only specialists offer, like angiography and dialysis, said Dr. Kirkwood.
The study also found that nurse practitioners were involved in care for very few patients (less than 1%), in accordance with the small number of nurse practitioners working in primary care settings.
Dr. Kirkwood acknowledged that the data come with certain limitations because they were not intended for research purposes. One limitation is that some conditions may not have been recorded because of “shadow billing.” Salaried physicians and practitioners do not have an incentive to include all diagnostic codes in their records. By comparison, clinicians operating under a fee-for-service model would be likely to indicate all diagnoses.
Developing guidelines
Despite the widespread management of chronic conditions by family physicians, these doctors represented about 17% of the experts who contribute to guidelines and recommendations, according to a 2015 study that the investigators cited.
“Frankly, that’s concerning,” said Dr. Kirkwood, regarding the disconnect between the people creating the recommendations and the people using them. The guidelines should include the perspective of clinicians who regularly work with patients, she said. Providing that perspective would also make the design of clinical trials on interventions more informative, the researchers concluded.
“I know as a family doctor myself that some recommendations are completely overwhelming,” especially given the range of issues that primary care clinicians see, said Dr. Kirkwood. Including primary care representatives who are familiar with the demands of the position “hopefully will make the recommendations much more applicable to the people that they will affect,” she said.
Dr. Kirkwood also noted the need for sufficient support for family doctors to contribute to guideline creation and research, especially for doctors in rural communities who are not already affiliated with a university.
The involvement of primary care providers in research settings is a primary goal of Patients, Experience, Evidence and Research (PEER), a primary care-led group that collaborates with the College of Family Physicians of Canada. The current investigators are members of PEER.
Additional conditions
Commenting on the study, Martin Fortin, MD, clinical teaching professor at the University of Sherbrooke, Quebec, said, “This is a good opportunity to advocate for more studies to be done in the primary care context, where the majority of chronic disease management is done.”
However, Dr. Fortin wishes that more diagnoses had been included in the study, such as mental health and musculoskeletal conditions like back pain and osteoarthritis. These conditions are also commonly seen by primary care clinicians, according to Dr. Fortin.
Because the number of conditions studied is limited, the data may not reflect the true prevalence of multimorbidity, Dr. Fortin added.
Primary care doctors provide a broad perspective on the overall health of patients, compared with specialists who focus on particular conditions. Similarly, during drug trials, pharmaceutical companies aim to reduce complicating factors, even though the medications are prescribed for conditions where multimorbidity is common. “Medication should be tested in the real environment,” said Dr. Fortin.
Ultimately, he added, the study cannot address the complexity of the patients, but it nevertheless sheds light on who is providing care and where the research on these conditions should be done.
The study was conducted without outside funding. Dr. Kirkwood and Dr. Fortin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A population-based retrospective cohort study examined data from nearly 1 million patients with common chronic conditions in Alberta, Canada. Family doctors were the sole providers of care for 85.7% of patients with hypertension and 70.9% of those with diabetes.
The study is part of efforts to encourage more research “by primary care, for primary care,” study author Jessica Kirkwood, MD, family physician and assistant professor of family medicine at the University of Alberta, Edmonton, said in an interview. The prevalence of primary care involvement demonstrates the importance of involving family physicians in creating guidelines for management and developing clinical trials, Dr. Kirkwood said.
The study was published in Canadian Family Physician.
Who provides care?
The study focused on care provided from 2013 to 2017 for seven chronic conditions. The information collected consisted of data from administrative health databases, which track medical services provided by Alberta’s government-funded universal health care system.
Most patients’ care was managed by family physicians alone in four of the conditions studied: hypertension (85.7%), diabetes (70.9%), chronic obstructive pulmonary disease (59.8%), and asthma (65.5%).
Specialists were more involved in the remaining three diseases. They provided the sole management in 49.1% of patients with ischemic heart disease, 42.2% of those with chronic kidney disease, and 35.6% of those with heart failure. For these conditions, family physicians remained involved in the care for a large proportion of patients. Specialist involvement may be more common with these diseases because they sometimes involve interventions that only specialists offer, like angiography and dialysis, said Dr. Kirkwood.
The study also found that nurse practitioners were involved in care for very few patients (less than 1%), in accordance with the small number of nurse practitioners working in primary care settings.
Dr. Kirkwood acknowledged that the data come with certain limitations because they were not intended for research purposes. One limitation is that some conditions may not have been recorded because of “shadow billing.” Salaried physicians and practitioners do not have an incentive to include all diagnostic codes in their records. By comparison, clinicians operating under a fee-for-service model would be likely to indicate all diagnoses.
Developing guidelines
Despite the widespread management of chronic conditions by family physicians, these doctors represented about 17% of the experts who contribute to guidelines and recommendations, according to a 2015 study that the investigators cited.
“Frankly, that’s concerning,” said Dr. Kirkwood, regarding the disconnect between the people creating the recommendations and the people using them. The guidelines should include the perspective of clinicians who regularly work with patients, she said. Providing that perspective would also make the design of clinical trials on interventions more informative, the researchers concluded.
“I know as a family doctor myself that some recommendations are completely overwhelming,” especially given the range of issues that primary care clinicians see, said Dr. Kirkwood. Including primary care representatives who are familiar with the demands of the position “hopefully will make the recommendations much more applicable to the people that they will affect,” she said.
Dr. Kirkwood also noted the need for sufficient support for family doctors to contribute to guideline creation and research, especially for doctors in rural communities who are not already affiliated with a university.
The involvement of primary care providers in research settings is a primary goal of Patients, Experience, Evidence and Research (PEER), a primary care-led group that collaborates with the College of Family Physicians of Canada. The current investigators are members of PEER.
Additional conditions
Commenting on the study, Martin Fortin, MD, clinical teaching professor at the University of Sherbrooke, Quebec, said, “This is a good opportunity to advocate for more studies to be done in the primary care context, where the majority of chronic disease management is done.”
However, Dr. Fortin wishes that more diagnoses had been included in the study, such as mental health and musculoskeletal conditions like back pain and osteoarthritis. These conditions are also commonly seen by primary care clinicians, according to Dr. Fortin.
Because the number of conditions studied is limited, the data may not reflect the true prevalence of multimorbidity, Dr. Fortin added.
Primary care doctors provide a broad perspective on the overall health of patients, compared with specialists who focus on particular conditions. Similarly, during drug trials, pharmaceutical companies aim to reduce complicating factors, even though the medications are prescribed for conditions where multimorbidity is common. “Medication should be tested in the real environment,” said Dr. Fortin.
Ultimately, he added, the study cannot address the complexity of the patients, but it nevertheless sheds light on who is providing care and where the research on these conditions should be done.
The study was conducted without outside funding. Dr. Kirkwood and Dr. Fortin reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CANADIAN FAMILY PHYSICIAN
CV benefit from vitamin D caps hinted in huge D-Health trial
in an analysis from a large prospective randomized trial.
Risk reductions on vitamin D in the mixed primary- and secondary-prevention population were slight in absolute terms but reached a significant 19% in the case of myocardial infarction (MI).
Over 5 years, 6.6% of those in placebo group experienced major CV events, the primary endpoint, compared with 6% in the vitamin D group. The difference, which corresponded to 5.8 fewer events per 1,000 participants, was short of significance in adjusted analysis.
Still, vitamin-D supplementation was associated with the potential MI benefit and an 11% drop in risk for coronary revascularization.
Also, a subgroup analysis hinted at a potentially reduced CV-event risk from vitamin-D supplementation among individuals who entered the trial on statins or other CV medications generally.
“Most other studies have not found benefit for vitamin D for major CV events,” senior investigator Rachel E. Neale, PhD, said in an interview. Although there was a significant effect for MI, the difference in the composite primary endpoint fell short of significance “in keeping with the other studies.”
“However, the effects for myocardial infarction in people taking statins or cardiovascular disease drugs at baseline are suggestive of benefit,” said Dr. Neale, of QIMR Berghofer Medical Research Institute, Queensland, Australia. Still, “it is important to keep in mind that these may be chance findings.”
The analysis based on the D-Health study was published online in The BMJ.
Benefits minimal
The 21,302 patients in the D-Health trial, conducted in Australia from 2014 to 2020, were randomly assigned double-blind to receive either placebo or vitamin D3 supplements for a planned 5 years. They were instructed to take one placebo or vitamin D capsule per month, each active capsule containing 60,000 IU of the vitamin.
People with self-reported hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis, and those taking greater than 500 IU/day vitamin D supplements were excluded from enrollment. Participants ranged in age from 60 to 84 at randomization and 46% were women.
With 80% of the 10,658 participants assigned to vitamin D and 78% of the 10,644 control subjects completing the 5-year intervention, 6% and 6.6%, respectively, met the primary endpoint of a major CV event, defined as MI, stroke, or coronary revascularization.
The hazard ratio for a vitamin-D effect on the primary endpoint was 0.91 (95% confidence interval, 0.81-1.01). The number needed to treat to avoid one major CV event was 172.
The HR for MI was 0.81 (95% CI, 0.67-0.98), for coronary intervention was 0.89 (0.78-1.01), and for stroke was 0.99 (0.80-1.23).
Adverse event rates were similar at about 16% in both groups and included hypercalcemia, kidney stones, gastrointestinal issues, and skin rash.
Vitamin D at moderate dosages has low toxicity, Dr. Neale said, “so I think it would be reasonable for clinicians to consider supplementing elderly people who do not have contraindications, particularly those who have underlying risk factors for CV disease,” Dr. Neale said. But patients should be told that the evidence for such a recommendation is not strong, so they can make an informed decision, she added.
Also, in general “we would be cautious about extrapolating to formulations other than those used in the study,” Dr. Neale said. “However, in this case, I think it would be reasonable to extrapolate to the use of 2,000 IU per day taken orally, provided that the same adherence can be maintained for a lengthy period.”
Chance findings?
Based on the current study and in light of prior research, “it is premature to recommend vitamin D supplementation for cardiovascular disease prevention specifically,” Nour Makarem, PhD, of the Mailman School of Public Health, Columbia University, New York, said in an interview.
“Prior clinical trials did not show an association between vitamin D supplementation and cardiovascular events,” observed Dr. Makarem, who is not affiliated with the current study. Also, she agreed, it looked at “multiple outcomes, which increases the likelihood that findings may be due to chance.”
She added that the study’s authors observed a possible vitamin-D protective effect “among people who were vitamin D sufficient at baseline but not among those who were insufficient. It is important to interpret this finding with caution because they used predicted, not measured, vitamin D status for these analyses.”
There’s a need for studies in other populations, including younger persons and “particularly populations with higher rates of vitamin D deficiency,” Dr. Makarem observed. Also, further research should aim to “understand the interactions between vitamin D supplementation and cardiovascular medications, including statins.”
The D-Health Trial is funded by National Health and Medical Research Council project grants. Dr. Neale was supported by fellowships from the NHMRC. Neither she nor Dr. Makarem reported any relevant financial relationships.
A version of this article first appeared on Medscape.com.
in an analysis from a large prospective randomized trial.
Risk reductions on vitamin D in the mixed primary- and secondary-prevention population were slight in absolute terms but reached a significant 19% in the case of myocardial infarction (MI).
Over 5 years, 6.6% of those in placebo group experienced major CV events, the primary endpoint, compared with 6% in the vitamin D group. The difference, which corresponded to 5.8 fewer events per 1,000 participants, was short of significance in adjusted analysis.
Still, vitamin-D supplementation was associated with the potential MI benefit and an 11% drop in risk for coronary revascularization.
Also, a subgroup analysis hinted at a potentially reduced CV-event risk from vitamin-D supplementation among individuals who entered the trial on statins or other CV medications generally.
“Most other studies have not found benefit for vitamin D for major CV events,” senior investigator Rachel E. Neale, PhD, said in an interview. Although there was a significant effect for MI, the difference in the composite primary endpoint fell short of significance “in keeping with the other studies.”
“However, the effects for myocardial infarction in people taking statins or cardiovascular disease drugs at baseline are suggestive of benefit,” said Dr. Neale, of QIMR Berghofer Medical Research Institute, Queensland, Australia. Still, “it is important to keep in mind that these may be chance findings.”
The analysis based on the D-Health study was published online in The BMJ.
Benefits minimal
The 21,302 patients in the D-Health trial, conducted in Australia from 2014 to 2020, were randomly assigned double-blind to receive either placebo or vitamin D3 supplements for a planned 5 years. They were instructed to take one placebo or vitamin D capsule per month, each active capsule containing 60,000 IU of the vitamin.
People with self-reported hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis, and those taking greater than 500 IU/day vitamin D supplements were excluded from enrollment. Participants ranged in age from 60 to 84 at randomization and 46% were women.
With 80% of the 10,658 participants assigned to vitamin D and 78% of the 10,644 control subjects completing the 5-year intervention, 6% and 6.6%, respectively, met the primary endpoint of a major CV event, defined as MI, stroke, or coronary revascularization.
The hazard ratio for a vitamin-D effect on the primary endpoint was 0.91 (95% confidence interval, 0.81-1.01). The number needed to treat to avoid one major CV event was 172.
The HR for MI was 0.81 (95% CI, 0.67-0.98), for coronary intervention was 0.89 (0.78-1.01), and for stroke was 0.99 (0.80-1.23).
Adverse event rates were similar at about 16% in both groups and included hypercalcemia, kidney stones, gastrointestinal issues, and skin rash.
Vitamin D at moderate dosages has low toxicity, Dr. Neale said, “so I think it would be reasonable for clinicians to consider supplementing elderly people who do not have contraindications, particularly those who have underlying risk factors for CV disease,” Dr. Neale said. But patients should be told that the evidence for such a recommendation is not strong, so they can make an informed decision, she added.
Also, in general “we would be cautious about extrapolating to formulations other than those used in the study,” Dr. Neale said. “However, in this case, I think it would be reasonable to extrapolate to the use of 2,000 IU per day taken orally, provided that the same adherence can be maintained for a lengthy period.”
Chance findings?
Based on the current study and in light of prior research, “it is premature to recommend vitamin D supplementation for cardiovascular disease prevention specifically,” Nour Makarem, PhD, of the Mailman School of Public Health, Columbia University, New York, said in an interview.
“Prior clinical trials did not show an association between vitamin D supplementation and cardiovascular events,” observed Dr. Makarem, who is not affiliated with the current study. Also, she agreed, it looked at “multiple outcomes, which increases the likelihood that findings may be due to chance.”
She added that the study’s authors observed a possible vitamin-D protective effect “among people who were vitamin D sufficient at baseline but not among those who were insufficient. It is important to interpret this finding with caution because they used predicted, not measured, vitamin D status for these analyses.”
There’s a need for studies in other populations, including younger persons and “particularly populations with higher rates of vitamin D deficiency,” Dr. Makarem observed. Also, further research should aim to “understand the interactions between vitamin D supplementation and cardiovascular medications, including statins.”
The D-Health Trial is funded by National Health and Medical Research Council project grants. Dr. Neale was supported by fellowships from the NHMRC. Neither she nor Dr. Makarem reported any relevant financial relationships.
A version of this article first appeared on Medscape.com.
in an analysis from a large prospective randomized trial.
Risk reductions on vitamin D in the mixed primary- and secondary-prevention population were slight in absolute terms but reached a significant 19% in the case of myocardial infarction (MI).
Over 5 years, 6.6% of those in placebo group experienced major CV events, the primary endpoint, compared with 6% in the vitamin D group. The difference, which corresponded to 5.8 fewer events per 1,000 participants, was short of significance in adjusted analysis.
Still, vitamin-D supplementation was associated with the potential MI benefit and an 11% drop in risk for coronary revascularization.
Also, a subgroup analysis hinted at a potentially reduced CV-event risk from vitamin-D supplementation among individuals who entered the trial on statins or other CV medications generally.
“Most other studies have not found benefit for vitamin D for major CV events,” senior investigator Rachel E. Neale, PhD, said in an interview. Although there was a significant effect for MI, the difference in the composite primary endpoint fell short of significance “in keeping with the other studies.”
“However, the effects for myocardial infarction in people taking statins or cardiovascular disease drugs at baseline are suggestive of benefit,” said Dr. Neale, of QIMR Berghofer Medical Research Institute, Queensland, Australia. Still, “it is important to keep in mind that these may be chance findings.”
The analysis based on the D-Health study was published online in The BMJ.
Benefits minimal
The 21,302 patients in the D-Health trial, conducted in Australia from 2014 to 2020, were randomly assigned double-blind to receive either placebo or vitamin D3 supplements for a planned 5 years. They were instructed to take one placebo or vitamin D capsule per month, each active capsule containing 60,000 IU of the vitamin.
People with self-reported hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis, and those taking greater than 500 IU/day vitamin D supplements were excluded from enrollment. Participants ranged in age from 60 to 84 at randomization and 46% were women.
With 80% of the 10,658 participants assigned to vitamin D and 78% of the 10,644 control subjects completing the 5-year intervention, 6% and 6.6%, respectively, met the primary endpoint of a major CV event, defined as MI, stroke, or coronary revascularization.
The hazard ratio for a vitamin-D effect on the primary endpoint was 0.91 (95% confidence interval, 0.81-1.01). The number needed to treat to avoid one major CV event was 172.
The HR for MI was 0.81 (95% CI, 0.67-0.98), for coronary intervention was 0.89 (0.78-1.01), and for stroke was 0.99 (0.80-1.23).
Adverse event rates were similar at about 16% in both groups and included hypercalcemia, kidney stones, gastrointestinal issues, and skin rash.
Vitamin D at moderate dosages has low toxicity, Dr. Neale said, “so I think it would be reasonable for clinicians to consider supplementing elderly people who do not have contraindications, particularly those who have underlying risk factors for CV disease,” Dr. Neale said. But patients should be told that the evidence for such a recommendation is not strong, so they can make an informed decision, she added.
Also, in general “we would be cautious about extrapolating to formulations other than those used in the study,” Dr. Neale said. “However, in this case, I think it would be reasonable to extrapolate to the use of 2,000 IU per day taken orally, provided that the same adherence can be maintained for a lengthy period.”
Chance findings?
Based on the current study and in light of prior research, “it is premature to recommend vitamin D supplementation for cardiovascular disease prevention specifically,” Nour Makarem, PhD, of the Mailman School of Public Health, Columbia University, New York, said in an interview.
“Prior clinical trials did not show an association between vitamin D supplementation and cardiovascular events,” observed Dr. Makarem, who is not affiliated with the current study. Also, she agreed, it looked at “multiple outcomes, which increases the likelihood that findings may be due to chance.”
She added that the study’s authors observed a possible vitamin-D protective effect “among people who were vitamin D sufficient at baseline but not among those who were insufficient. It is important to interpret this finding with caution because they used predicted, not measured, vitamin D status for these analyses.”
There’s a need for studies in other populations, including younger persons and “particularly populations with higher rates of vitamin D deficiency,” Dr. Makarem observed. Also, further research should aim to “understand the interactions between vitamin D supplementation and cardiovascular medications, including statins.”
The D-Health Trial is funded by National Health and Medical Research Council project grants. Dr. Neale was supported by fellowships from the NHMRC. Neither she nor Dr. Makarem reported any relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE BMJ
Survodutide impresses in phase 2 weight loss trial
SAN DIEGO – but without type 2 diabetes.
Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.
Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.
Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.
The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.
Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”
“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.
Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.
“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
Close to 400 patients, five doses, 46-week endpoint
The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m2 (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.
On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m2, and 68% were women.
They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).
The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.
Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.
In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.
Primary outcome was the percentage change in body weight from baseline to week 46.
Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.
Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.
Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.
That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.
In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.
In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.
Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.
Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.
There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.
These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
Survodutide has FDA fast track designation for NASH
Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.
The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.
A version of this article first appeared on Medscape.com.
SAN DIEGO – but without type 2 diabetes.
Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.
Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.
Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.
The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.
Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”
“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.
Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.
“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
Close to 400 patients, five doses, 46-week endpoint
The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m2 (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.
On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m2, and 68% were women.
They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).
The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.
Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.
In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.
Primary outcome was the percentage change in body weight from baseline to week 46.
Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.
Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.
Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.
That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.
In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.
In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.
Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.
Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.
There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.
These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
Survodutide has FDA fast track designation for NASH
Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.
The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.
A version of this article first appeared on Medscape.com.
SAN DIEGO – but without type 2 diabetes.
Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.
Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.
Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.
The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.
Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”
“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.
Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.
“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
Close to 400 patients, five doses, 46-week endpoint
The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m2 (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.
On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m2, and 68% were women.
They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).
The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.
Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.
In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.
Primary outcome was the percentage change in body weight from baseline to week 46.
Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.
Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.
Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.
That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.
In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.
In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.
Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.
Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.
There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.
These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
Survodutide has FDA fast track designation for NASH
Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.
The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Medical cannabis does not reduce use of prescription meds
TOPLINE:
, according to a new study published in Annals of Internal Medicine.
METHODOLOGY:
- Cannabis advocates suggest that legal medical cannabis can be a partial solution to the opioid overdose crisis in the United States, which claimed more than 80,000 lives in 2021.
- Current research on how legalized cannabis reduces dependence on prescription pain medication is inconclusive.
- Researchers examined insurance data for the period 2010-2022 from 583,820 adults with chronic noncancer pain.
- They drew from 12 states in which medical cannabis is legal and from 17 in which it is not legal to create a hypothetical randomized trial. The control group simulated prescription rates where medical cannabis was not available.
- Authors evaluated prescription rates for opioids, nonopioid painkillers, and pain interventions, such as physical therapy.
TAKEAWAY:
In a given month during the first 3 years after legalization, for states with medical cannabis, the investigators found the following:
- There was an average decrease of 1.07 percentage points in the proportion of patients who received any opioid prescription, compared to a 1.12 percentage point decrease in the control group.
- There was an average increase of 1.14 percentage points in the proportion of patients who received any nonopioid prescription painkiller, compared to a 1.19 percentage point increase in the control group.
- There was a 0.17 percentage point decrease in the proportion of patients who received any pain procedure, compared to a 0.001 percentage point decrease in the control group.
IN PRACTICE:
“This study did not identify important effects of medical cannabis laws on receipt of opioid or nonopioid pain treatment among patients with chronic noncancer pain,” according to the researchers.
SOURCE:
The study was led by Emma E. McGinty, PhD, of Weill Cornell Medicine, New York, and was funded by the National Institute on Drug Abuse.
LIMITATIONS:
The investigators used a simulated, hypothetical control group that was based on untestable assumptions. They also drew data solely from insured individuals, so the study does not necessarily represent uninsured populations.
DISCLOSURES:
Dr. McGinty reports receiving a grant from NIDA. Her coauthors reported receiving support from NIDA and the National Institutes of Health.
A version of this article first appeared on Medscape.com.
TOPLINE:
, according to a new study published in Annals of Internal Medicine.
METHODOLOGY:
- Cannabis advocates suggest that legal medical cannabis can be a partial solution to the opioid overdose crisis in the United States, which claimed more than 80,000 lives in 2021.
- Current research on how legalized cannabis reduces dependence on prescription pain medication is inconclusive.
- Researchers examined insurance data for the period 2010-2022 from 583,820 adults with chronic noncancer pain.
- They drew from 12 states in which medical cannabis is legal and from 17 in which it is not legal to create a hypothetical randomized trial. The control group simulated prescription rates where medical cannabis was not available.
- Authors evaluated prescription rates for opioids, nonopioid painkillers, and pain interventions, such as physical therapy.
TAKEAWAY:
In a given month during the first 3 years after legalization, for states with medical cannabis, the investigators found the following:
- There was an average decrease of 1.07 percentage points in the proportion of patients who received any opioid prescription, compared to a 1.12 percentage point decrease in the control group.
- There was an average increase of 1.14 percentage points in the proportion of patients who received any nonopioid prescription painkiller, compared to a 1.19 percentage point increase in the control group.
- There was a 0.17 percentage point decrease in the proportion of patients who received any pain procedure, compared to a 0.001 percentage point decrease in the control group.
IN PRACTICE:
“This study did not identify important effects of medical cannabis laws on receipt of opioid or nonopioid pain treatment among patients with chronic noncancer pain,” according to the researchers.
SOURCE:
The study was led by Emma E. McGinty, PhD, of Weill Cornell Medicine, New York, and was funded by the National Institute on Drug Abuse.
LIMITATIONS:
The investigators used a simulated, hypothetical control group that was based on untestable assumptions. They also drew data solely from insured individuals, so the study does not necessarily represent uninsured populations.
DISCLOSURES:
Dr. McGinty reports receiving a grant from NIDA. Her coauthors reported receiving support from NIDA and the National Institutes of Health.
A version of this article first appeared on Medscape.com.
TOPLINE:
, according to a new study published in Annals of Internal Medicine.
METHODOLOGY:
- Cannabis advocates suggest that legal medical cannabis can be a partial solution to the opioid overdose crisis in the United States, which claimed more than 80,000 lives in 2021.
- Current research on how legalized cannabis reduces dependence on prescription pain medication is inconclusive.
- Researchers examined insurance data for the period 2010-2022 from 583,820 adults with chronic noncancer pain.
- They drew from 12 states in which medical cannabis is legal and from 17 in which it is not legal to create a hypothetical randomized trial. The control group simulated prescription rates where medical cannabis was not available.
- Authors evaluated prescription rates for opioids, nonopioid painkillers, and pain interventions, such as physical therapy.
TAKEAWAY:
In a given month during the first 3 years after legalization, for states with medical cannabis, the investigators found the following:
- There was an average decrease of 1.07 percentage points in the proportion of patients who received any opioid prescription, compared to a 1.12 percentage point decrease in the control group.
- There was an average increase of 1.14 percentage points in the proportion of patients who received any nonopioid prescription painkiller, compared to a 1.19 percentage point increase in the control group.
- There was a 0.17 percentage point decrease in the proportion of patients who received any pain procedure, compared to a 0.001 percentage point decrease in the control group.
IN PRACTICE:
“This study did not identify important effects of medical cannabis laws on receipt of opioid or nonopioid pain treatment among patients with chronic noncancer pain,” according to the researchers.
SOURCE:
The study was led by Emma E. McGinty, PhD, of Weill Cornell Medicine, New York, and was funded by the National Institute on Drug Abuse.
LIMITATIONS:
The investigators used a simulated, hypothetical control group that was based on untestable assumptions. They also drew data solely from insured individuals, so the study does not necessarily represent uninsured populations.
DISCLOSURES:
Dr. McGinty reports receiving a grant from NIDA. Her coauthors reported receiving support from NIDA and the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Lean muscle mass protective against Alzheimer’s?
Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.
They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.
On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.
“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.
Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.
The study was published online in BMJ Medicine.
Naturally randomized research
Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.
“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”
Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.
In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.
MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.”
The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
Genetic proxy
As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.
Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.
This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.
The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.
In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.
The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.
Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).
The findings remained “consistent” in sensitivity analyses.
A modifiable risk factor?
Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).
“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.
They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.
The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.
Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
Novel strategies
In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”
The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”
In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.
More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”
Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.
They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.
On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.
“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.
Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.
The study was published online in BMJ Medicine.
Naturally randomized research
Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.
“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”
Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.
In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.
MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.”
The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
Genetic proxy
As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.
Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.
This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.
The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.
In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.
The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.
Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).
The findings remained “consistent” in sensitivity analyses.
A modifiable risk factor?
Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).
“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.
They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.
The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.
Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
Novel strategies
In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”
The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”
In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.
More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”
Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.
They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.
On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.
“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.
Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.
The study was published online in BMJ Medicine.
Naturally randomized research
Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.
“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”
Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.
In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.
MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.”
The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
Genetic proxy
As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.
Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.
This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.
The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.
In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.
The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.
Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).
The findings remained “consistent” in sensitivity analyses.
A modifiable risk factor?
Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).
“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.
They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.
The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.
Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
Novel strategies
In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”
The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”
In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.
More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”
Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BMJ MEDICINE
Do oral contraceptives increase depression risk?
In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.
The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.
Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.
This effect remained, even after analysis of potential familial confounding.
“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.
The study was published online in Epidemiology and Psychiatric Sciences.
Inconsistent findings
Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.
The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.
They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.
Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.
The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.
They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.
Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.
They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
Adolescents at highest risk
Of the participants, 80.6% had used OCs at some point.
The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).
Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).
Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).
Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.
OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).
Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).
In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.
The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
Flawed study
In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”
She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”
The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.
Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.
And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.
“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.
The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.
The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.
Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.
This effect remained, even after analysis of potential familial confounding.
“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.
The study was published online in Epidemiology and Psychiatric Sciences.
Inconsistent findings
Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.
The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.
They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.
Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.
The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.
They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.
Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.
They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
Adolescents at highest risk
Of the participants, 80.6% had used OCs at some point.
The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).
Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).
Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).
Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.
OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).
Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).
In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.
The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
Flawed study
In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”
She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”
The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.
Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.
And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.
“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.
The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.
The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.
Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.
This effect remained, even after analysis of potential familial confounding.
“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.
The study was published online in Epidemiology and Psychiatric Sciences.
Inconsistent findings
Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.
The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.
They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.
Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.
The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.
They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.
Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.
They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
Adolescents at highest risk
Of the participants, 80.6% had used OCs at some point.
The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).
Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).
Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).
Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.
OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).
Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).
In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.
The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
Flawed study
In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”
She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”
The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.
Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.
And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.
“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.
The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EPIDEMIOLOGY AND PSYCHIATRIC SCIENCES