Jennie Smith

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.

A clinical algorithm developed in Singapore improved glycemic control fourfold among Muslims with diabetes who fast during Ramadan, according to results from a randomized trial.

Ramadan is a challenge for Muslims with diabetes worldwide. Observing the month-long fast requires a dramatic break from normal eating patterns, which includes abstaining from food and liquids, including medications, from dawn to dusk. Not adjusting medications during fasting may harm glycemic control, and though international guidelines have become available in recent years, a large multinational study showed that fewer than 40% of people with diabetes got help from clinicians on medication management during Ramadan (Diabet Med. 2015;32[6]:819-828).

The Fasting Algorithm for Singaporeans With Type 2 Diabetes (FAST), developed and validated in 2018 by Joyce Lee, PharmD, and her colleagues at the National University of Singapore, is a clinical decision-making tool for both clinicians and patients. It involves clinicians engaging in risk-assessment screening of patients and educating patients on self-monitoring of blood glucose timing and technique, hypoglycemia management, nutrition, and Ramadan-related misconceptions. FAST also provides glucose-lowering medication modification guidance for clinicians along with patient self-dose adjustment guidance based on self-monitoring of blood glucose four times a day. The algorithm specifically requires patients to check their blood glucose levels before their sunset meal, two hours after their sunset meal, before their predawn meal, and a fourth time each day of their choice.

For their new study, published March 9 in Annals of Family Medicine, Dr. Lee and colleagues tested the algorithm in a clinical trial in which patients and clinicians were randomized to follow FAST protocols or receive and provide standard care. All patients (n = 97; mean age 59.5 years; 60% female) had glycated hemoglobin of 9.5% or higher, no history of recurrent hypoglycemia, and an estimated glomerular filtration rate of less than 30 mL/min at baseline (before Ramadan). These patients partook in Ramadan fasting and were willing to self-monitor blood glucose during the study. Pregnant women and people taking corticosteroids were excluded.

The trial took place during two different Ramadan cycles during 2017-2018, and the main endpoint was glycemic control pre- and post-Ramadan. Dr. Lee and her colleagues reported that patients in the algorithm arm (n = 46), showed four times the amount of improvement in HbA1c (–0.4%; –4.4 mmol/mol), compared with subjects receiving standard care (–0.1%; P = .049).

Mean fasting blood glucose decreased in the intervention group (–3.6 mg/dL) and increased in the control group (+20.9 mg/dL) over the study period (P = .034). The control group saw more confirmed incidents of minor hypoglycemia than did the intervention group, but these did not reach statistical significance.

“Before this study, the effect of Ramadan fasting on glycemic control was found to be affected by support from health care clinicians,” Dr. Lee and colleagues wrote in their analysis. “By standardizing diabetes care with the FAST tool, intervention participants showed four times the amount of improvement in glycemic control,” compared with controls. The investigators described the open-label design and the potential for different management practices among the participating clinicians having been used as weaknesses of the study.

In an editorial comment accompanying the article by Dr. Lee and colleagues, Jonathan G. Gabison, MD, of the University of Michigan in Ann Arbor, praised the study as demonstrating “that persons with type 2 diabetes can, with the help of their physicians, engage in safe fasting practices, and they can attain positive health benefits” (Ann Fam Med. 2020;18:98-99). Patients observing the FAST protocol “are less likely to avoid their doctors and have an improved therapeutic relationship with the medical community in their time of spiritual work.” But the study has implications beyond the observant Muslim community, Dr. Gabison argued, as “people with or without diabetes are more frequently engaging in the practice of fasting ... Although a controversial topic in the medical and nutritional community, patients, including those with type 2 diabetes, are increasingly using it as a strategy for weight loss or health benefits.”

While more research is needed, Dr. Gabison wrote, “a protocol to manage diabetes medications safely with intermittent fasting may help keep patients safe while we learn more about the use of these strategies to help combat obesity and diabetes.”

The Singapore Ministry of Education funded Dr. Lee and colleagues’ study. The investigators disclosed no conflicts of interest, and Dr. Gabison also reported no conflicts related to his editorial.

SOURCE: Lee et al. Ann Family Med. 2020;18:139-47.

A clinical algorithm developed in Singapore improved glycemic control fourfold among Muslims with diabetes who fast during Ramadan, according to results from a randomized trial.

Ramadan is a challenge for Muslims with diabetes worldwide. Observing the month-long fast requires a dramatic break from normal eating patterns, which includes abstaining from food and liquids, including medications, from dawn to dusk. Not adjusting medications during fasting may harm glycemic control, and though international guidelines have become available in recent years, a large multinational study showed that fewer than 40% of people with diabetes got help from clinicians on medication management during Ramadan (Diabet Med. 2015;32[6]:819-828).

The Fasting Algorithm for Singaporeans With Type 2 Diabetes (FAST), developed and validated in 2018 by Joyce Lee, PharmD, and her colleagues at the National University of Singapore, is a clinical decision-making tool for both clinicians and patients. It involves clinicians engaging in risk-assessment screening of patients and educating patients on self-monitoring of blood glucose timing and technique, hypoglycemia management, nutrition, and Ramadan-related misconceptions. FAST also provides glucose-lowering medication modification guidance for clinicians along with patient self-dose adjustment guidance based on self-monitoring of blood glucose four times a day. The algorithm specifically requires patients to check their blood glucose levels before their sunset meal, two hours after their sunset meal, before their predawn meal, and a fourth time each day of their choice.

For their new study, published March 9 in Annals of Family Medicine, Dr. Lee and colleagues tested the algorithm in a clinical trial in which patients and clinicians were randomized to follow FAST protocols or receive and provide standard care. All patients (n = 97; mean age 59.5 years; 60% female) had glycated hemoglobin of 9.5% or higher, no history of recurrent hypoglycemia, and an estimated glomerular filtration rate of less than 30 mL/min at baseline (before Ramadan). These patients partook in Ramadan fasting and were willing to self-monitor blood glucose during the study. Pregnant women and people taking corticosteroids were excluded.

The trial took place during two different Ramadan cycles during 2017-2018, and the main endpoint was glycemic control pre- and post-Ramadan. Dr. Lee and her colleagues reported that patients in the algorithm arm (n = 46), showed four times the amount of improvement in HbA1c (–0.4%; –4.4 mmol/mol), compared with subjects receiving standard care (–0.1%; P = .049).

Mean fasting blood glucose decreased in the intervention group (–3.6 mg/dL) and increased in the control group (+20.9 mg/dL) over the study period (P = .034). The control group saw more confirmed incidents of minor hypoglycemia than did the intervention group, but these did not reach statistical significance.

“Before this study, the effect of Ramadan fasting on glycemic control was found to be affected by support from health care clinicians,” Dr. Lee and colleagues wrote in their analysis. “By standardizing diabetes care with the FAST tool, intervention participants showed four times the amount of improvement in glycemic control,” compared with controls. The investigators described the open-label design and the potential for different management practices among the participating clinicians having been used as weaknesses of the study.

In an editorial comment accompanying the article by Dr. Lee and colleagues, Jonathan G. Gabison, MD, of the University of Michigan in Ann Arbor, praised the study as demonstrating “that persons with type 2 diabetes can, with the help of their physicians, engage in safe fasting practices, and they can attain positive health benefits” (Ann Fam Med. 2020;18:98-99). Patients observing the FAST protocol “are less likely to avoid their doctors and have an improved therapeutic relationship with the medical community in their time of spiritual work.” But the study has implications beyond the observant Muslim community, Dr. Gabison argued, as “people with or without diabetes are more frequently engaging in the practice of fasting ... Although a controversial topic in the medical and nutritional community, patients, including those with type 2 diabetes, are increasingly using it as a strategy for weight loss or health benefits.”

While more research is needed, Dr. Gabison wrote, “a protocol to manage diabetes medications safely with intermittent fasting may help keep patients safe while we learn more about the use of these strategies to help combat obesity and diabetes.”

The Singapore Ministry of Education funded Dr. Lee and colleagues’ study. The investigators disclosed no conflicts of interest, and Dr. Gabison also reported no conflicts related to his editorial.

SOURCE: Lee et al. Ann Family Med. 2020;18:139-47.

A clinical algorithm developed in Singapore improved glycemic control fourfold among Muslims with diabetes who fast during Ramadan, according to results from a randomized trial.

Ramadan is a challenge for Muslims with diabetes worldwide. Observing the month-long fast requires a dramatic break from normal eating patterns, which includes abstaining from food and liquids, including medications, from dawn to dusk. Not adjusting medications during fasting may harm glycemic control, and though international guidelines have become available in recent years, a large multinational study showed that fewer than 40% of people with diabetes got help from clinicians on medication management during Ramadan (Diabet Med. 2015;32[6]:819-828).

The Fasting Algorithm for Singaporeans With Type 2 Diabetes (FAST), developed and validated in 2018 by Joyce Lee, PharmD, and her colleagues at the National University of Singapore, is a clinical decision-making tool for both clinicians and patients. It involves clinicians engaging in risk-assessment screening of patients and educating patients on self-monitoring of blood glucose timing and technique, hypoglycemia management, nutrition, and Ramadan-related misconceptions. FAST also provides glucose-lowering medication modification guidance for clinicians along with patient self-dose adjustment guidance based on self-monitoring of blood glucose four times a day. The algorithm specifically requires patients to check their blood glucose levels before their sunset meal, two hours after their sunset meal, before their predawn meal, and a fourth time each day of their choice.

For their new study, published March 9 in Annals of Family Medicine, Dr. Lee and colleagues tested the algorithm in a clinical trial in which patients and clinicians were randomized to follow FAST protocols or receive and provide standard care. All patients (n = 97; mean age 59.5 years; 60% female) had glycated hemoglobin of 9.5% or higher, no history of recurrent hypoglycemia, and an estimated glomerular filtration rate of less than 30 mL/min at baseline (before Ramadan). These patients partook in Ramadan fasting and were willing to self-monitor blood glucose during the study. Pregnant women and people taking corticosteroids were excluded.

The trial took place during two different Ramadan cycles during 2017-2018, and the main endpoint was glycemic control pre- and post-Ramadan. Dr. Lee and her colleagues reported that patients in the algorithm arm (n = 46), showed four times the amount of improvement in HbA1c (–0.4%; –4.4 mmol/mol), compared with subjects receiving standard care (–0.1%; P = .049).

Mean fasting blood glucose decreased in the intervention group (–3.6 mg/dL) and increased in the control group (+20.9 mg/dL) over the study period (P = .034). The control group saw more confirmed incidents of minor hypoglycemia than did the intervention group, but these did not reach statistical significance.

“Before this study, the effect of Ramadan fasting on glycemic control was found to be affected by support from health care clinicians,” Dr. Lee and colleagues wrote in their analysis. “By standardizing diabetes care with the FAST tool, intervention participants showed four times the amount of improvement in glycemic control,” compared with controls. The investigators described the open-label design and the potential for different management practices among the participating clinicians having been used as weaknesses of the study.

In an editorial comment accompanying the article by Dr. Lee and colleagues, Jonathan G. Gabison, MD, of the University of Michigan in Ann Arbor, praised the study as demonstrating “that persons with type 2 diabetes can, with the help of their physicians, engage in safe fasting practices, and they can attain positive health benefits” (Ann Fam Med. 2020;18:98-99). Patients observing the FAST protocol “are less likely to avoid their doctors and have an improved therapeutic relationship with the medical community in their time of spiritual work.” But the study has implications beyond the observant Muslim community, Dr. Gabison argued, as “people with or without diabetes are more frequently engaging in the practice of fasting ... Although a controversial topic in the medical and nutritional community, patients, including those with type 2 diabetes, are increasingly using it as a strategy for weight loss or health benefits.”

While more research is needed, Dr. Gabison wrote, “a protocol to manage diabetes medications safely with intermittent fasting may help keep patients safe while we learn more about the use of these strategies to help combat obesity and diabetes.”

The Singapore Ministry of Education funded Dr. Lee and colleagues’ study. The investigators disclosed no conflicts of interest, and Dr. Gabison also reported no conflicts related to his editorial.

SOURCE: Lee et al. Ann Family Med. 2020;18:139-47.

While more than half of women aged 75 years and older receive annual mammograms, they do not see a reduced risk of death from breast cancer, compared with women who have stopped regular screening, according to a study published in Annals of Internal Medicine.

copyright/Thinkstock

The lack of benefit is not because older women’s cancer risk is low; a third of breast cancer deaths occur in women diagnosed at or after age 70 years, according to study author Xabier García-Albéniz, MD, PhD, of Harvard University in Boston, and colleagues.

The lack of benefit is not because mammography is less effective in women older than 75 years; indeed, it becomes a better diagnostic tool as women age, said Otis Brawley, MD, of Johns Hopkins University, Baltimore, the author of an editorial related to the study. Rather, the lack of benefit is because breast cancer treatment in older women is less successful, he clarified.
 

Study details

Dr. García-Albéniz and colleagues looked at data from 1,058,013 women enrolled in Medicare across the United States during 2000-2008. All subjects were aged 70-84 years and had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer.

There are little randomized trial data available on mammography and breast cancer deaths for women in their early 70s and none for women older than 75 years. To compensate for this, the researchers aimed to emulate a prospective trial by looking at deaths over an 8-year period for women aged 70 and older who either continued annual screening or stopped it. The investigators conducted separate analyses for women aged 70-74 years and those 75-84 years of age.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but this did not translate to serious reductions in death.

In the continued-screening group, the estimated 8-year risk for breast cancer was 5.5% in women aged 70-74 and 5.8% in women aged 75-84 years. Among women who stopped screening, the estimated 8-year risk for breast cancer was 3.9% in both age groups.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was slightly reduced with continued screening: 2.7 deaths per 1,000 women, compared with 3.7 deaths per 1,000 women for those who stopped screening. The risk difference was –1.0 deaths per 1,000 women, and the hazard ratio was 0.78.

Among women aged 75-84 years, there was no difference in estimated 8-year risk for breast cancer death. Women treated under a continued screening protocol had 3.8 deaths per 1,000, while the stop-screening group had 3.7 deaths per 1,000. The risk difference was 0.07 deaths per 1,000 women, and the hazard ratio was 1.00.

Interpreting the results

In the editorial accompanying this study, Dr. Brawley praised its design as “especially useful in breast cancer screening,” as “prospective randomized studies of mammography are not feasible and are perhaps no longer ethical in older women … because mammography is so widely accepted.”

In an interview, Dr. Brawley stressed that the findings do not argue for denying women aged 75 years and older mammography screening. Decisions about screening require a value judgment tailored to each individual patient’s perceived risks and benefits, he said.

In the absence of randomized trial evidence, “the jury will always be out” on the benefits of regular mammography for women 75 and older, Dr. Brawley said. “A clinical trial or a modeling study always tells you about an average person who doesn’t exist,” he added. “I predict that, in the future, we will have more parameters to tell us, ‘this is a person who’s 80 years old who is likely to benefit from screening; this is a person who is 75 years old who is unlikely to benefit.’ ”

And focusing too much on screening, he said, can divert attention from a key driver of breast cancer mortality in older women: inadequate treatment.

In the United States, Dr. Brawley said, “There’s a lot of emphasis on screening but fewer people writing about the fact that nearly 40% of American women get less than optimal treatment once they’re diagnosed.”

Dr. Brawley cited a 2013 modeling study showing that improvements in delivering current treatments would save more women even if screening rates remained unaltered (Cancer. 2013 Jul 15;119[14]:2541-8).

Among women in their 70s and 80s, Dr. Brawley said, some of the barriers to effective breast cancer care aren’t related to treatment efficacy but to travel and other logistical issues that can become more pronounced with age. “Unfortunately, there’s very little research on why, for women in their 70s and 80s, the treatments don’t work as well as they work in women 20 years younger,” he said.

Dr. García-Albéniz and colleagues’ study was funded by the National Institutes of Health. One coauthor reported financial ties to industry. Dr. Brawley discloses no conflicts of interest related to his editorial.

SOURCE: García-Albéniz X et al. Ann Intern Med 2020. doi: 10.7326/M18-1199.

While more than half of women aged 75 years and older receive annual mammograms, they do not see a reduced risk of death from breast cancer, compared with women who have stopped regular screening, according to a study published in Annals of Internal Medicine.

copyright/Thinkstock

The lack of benefit is not because older women’s cancer risk is low; a third of breast cancer deaths occur in women diagnosed at or after age 70 years, according to study author Xabier García-Albéniz, MD, PhD, of Harvard University in Boston, and colleagues.

The lack of benefit is not because mammography is less effective in women older than 75 years; indeed, it becomes a better diagnostic tool as women age, said Otis Brawley, MD, of Johns Hopkins University, Baltimore, the author of an editorial related to the study. Rather, the lack of benefit is because breast cancer treatment in older women is less successful, he clarified.
 

Study details

Dr. García-Albéniz and colleagues looked at data from 1,058,013 women enrolled in Medicare across the United States during 2000-2008. All subjects were aged 70-84 years and had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer.

There are little randomized trial data available on mammography and breast cancer deaths for women in their early 70s and none for women older than 75 years. To compensate for this, the researchers aimed to emulate a prospective trial by looking at deaths over an 8-year period for women aged 70 and older who either continued annual screening or stopped it. The investigators conducted separate analyses for women aged 70-74 years and those 75-84 years of age.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but this did not translate to serious reductions in death.

In the continued-screening group, the estimated 8-year risk for breast cancer was 5.5% in women aged 70-74 and 5.8% in women aged 75-84 years. Among women who stopped screening, the estimated 8-year risk for breast cancer was 3.9% in both age groups.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was slightly reduced with continued screening: 2.7 deaths per 1,000 women, compared with 3.7 deaths per 1,000 women for those who stopped screening. The risk difference was –1.0 deaths per 1,000 women, and the hazard ratio was 0.78.

Among women aged 75-84 years, there was no difference in estimated 8-year risk for breast cancer death. Women treated under a continued screening protocol had 3.8 deaths per 1,000, while the stop-screening group had 3.7 deaths per 1,000. The risk difference was 0.07 deaths per 1,000 women, and the hazard ratio was 1.00.

Interpreting the results

In the editorial accompanying this study, Dr. Brawley praised its design as “especially useful in breast cancer screening,” as “prospective randomized studies of mammography are not feasible and are perhaps no longer ethical in older women … because mammography is so widely accepted.”

In an interview, Dr. Brawley stressed that the findings do not argue for denying women aged 75 years and older mammography screening. Decisions about screening require a value judgment tailored to each individual patient’s perceived risks and benefits, he said.

In the absence of randomized trial evidence, “the jury will always be out” on the benefits of regular mammography for women 75 and older, Dr. Brawley said. “A clinical trial or a modeling study always tells you about an average person who doesn’t exist,” he added. “I predict that, in the future, we will have more parameters to tell us, ‘this is a person who’s 80 years old who is likely to benefit from screening; this is a person who is 75 years old who is unlikely to benefit.’ ”

And focusing too much on screening, he said, can divert attention from a key driver of breast cancer mortality in older women: inadequate treatment.

In the United States, Dr. Brawley said, “There’s a lot of emphasis on screening but fewer people writing about the fact that nearly 40% of American women get less than optimal treatment once they’re diagnosed.”

Dr. Brawley cited a 2013 modeling study showing that improvements in delivering current treatments would save more women even if screening rates remained unaltered (Cancer. 2013 Jul 15;119[14]:2541-8).

Among women in their 70s and 80s, Dr. Brawley said, some of the barriers to effective breast cancer care aren’t related to treatment efficacy but to travel and other logistical issues that can become more pronounced with age. “Unfortunately, there’s very little research on why, for women in their 70s and 80s, the treatments don’t work as well as they work in women 20 years younger,” he said.

Dr. García-Albéniz and colleagues’ study was funded by the National Institutes of Health. One coauthor reported financial ties to industry. Dr. Brawley discloses no conflicts of interest related to his editorial.

SOURCE: García-Albéniz X et al. Ann Intern Med 2020. doi: 10.7326/M18-1199.

While more than half of women aged 75 years and older receive annual mammograms, they do not see a reduced risk of death from breast cancer, compared with women who have stopped regular screening, according to a study published in Annals of Internal Medicine.

copyright/Thinkstock

The lack of benefit is not because older women’s cancer risk is low; a third of breast cancer deaths occur in women diagnosed at or after age 70 years, according to study author Xabier García-Albéniz, MD, PhD, of Harvard University in Boston, and colleagues.

The lack of benefit is not because mammography is less effective in women older than 75 years; indeed, it becomes a better diagnostic tool as women age, said Otis Brawley, MD, of Johns Hopkins University, Baltimore, the author of an editorial related to the study. Rather, the lack of benefit is because breast cancer treatment in older women is less successful, he clarified.
 

Study details

Dr. García-Albéniz and colleagues looked at data from 1,058,013 women enrolled in Medicare across the United States during 2000-2008. All subjects were aged 70-84 years and had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer.

There are little randomized trial data available on mammography and breast cancer deaths for women in their early 70s and none for women older than 75 years. To compensate for this, the researchers aimed to emulate a prospective trial by looking at deaths over an 8-year period for women aged 70 and older who either continued annual screening or stopped it. The investigators conducted separate analyses for women aged 70-74 years and those 75-84 years of age.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but this did not translate to serious reductions in death.

In the continued-screening group, the estimated 8-year risk for breast cancer was 5.5% in women aged 70-74 and 5.8% in women aged 75-84 years. Among women who stopped screening, the estimated 8-year risk for breast cancer was 3.9% in both age groups.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was slightly reduced with continued screening: 2.7 deaths per 1,000 women, compared with 3.7 deaths per 1,000 women for those who stopped screening. The risk difference was –1.0 deaths per 1,000 women, and the hazard ratio was 0.78.

Among women aged 75-84 years, there was no difference in estimated 8-year risk for breast cancer death. Women treated under a continued screening protocol had 3.8 deaths per 1,000, while the stop-screening group had 3.7 deaths per 1,000. The risk difference was 0.07 deaths per 1,000 women, and the hazard ratio was 1.00.

Interpreting the results

In the editorial accompanying this study, Dr. Brawley praised its design as “especially useful in breast cancer screening,” as “prospective randomized studies of mammography are not feasible and are perhaps no longer ethical in older women … because mammography is so widely accepted.”

In an interview, Dr. Brawley stressed that the findings do not argue for denying women aged 75 years and older mammography screening. Decisions about screening require a value judgment tailored to each individual patient’s perceived risks and benefits, he said.

In the absence of randomized trial evidence, “the jury will always be out” on the benefits of regular mammography for women 75 and older, Dr. Brawley said. “A clinical trial or a modeling study always tells you about an average person who doesn’t exist,” he added. “I predict that, in the future, we will have more parameters to tell us, ‘this is a person who’s 80 years old who is likely to benefit from screening; this is a person who is 75 years old who is unlikely to benefit.’ ”

And focusing too much on screening, he said, can divert attention from a key driver of breast cancer mortality in older women: inadequate treatment.

In the United States, Dr. Brawley said, “There’s a lot of emphasis on screening but fewer people writing about the fact that nearly 40% of American women get less than optimal treatment once they’re diagnosed.”

Dr. Brawley cited a 2013 modeling study showing that improvements in delivering current treatments would save more women even if screening rates remained unaltered (Cancer. 2013 Jul 15;119[14]:2541-8).

Among women in their 70s and 80s, Dr. Brawley said, some of the barriers to effective breast cancer care aren’t related to treatment efficacy but to travel and other logistical issues that can become more pronounced with age. “Unfortunately, there’s very little research on why, for women in their 70s and 80s, the treatments don’t work as well as they work in women 20 years younger,” he said.

Dr. García-Albéniz and colleagues’ study was funded by the National Institutes of Health. One coauthor reported financial ties to industry. Dr. Brawley discloses no conflicts of interest related to his editorial.

SOURCE: García-Albéniz X et al. Ann Intern Med 2020. doi: 10.7326/M18-1199.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

Higher out-of-pocket costs for prescription drugs are associated with poorer adherence across common neurologic conditions, a new study has found, suggesting that physicians should take patient costs into consideration when choosing which drugs to prescribe.

For their study, published online Feb. 19 in Neurology, Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues looked at claims records from a large national private insurer to identify new cases of dementia, Parkinson’s disease, and neuropathy between 2001 and 2016, along with pharmacy records following diagnoses.

The researchers identified more than 52,000 patients with neuropathy on gabapentinoids and another 5,000 treated with serotonin-norepinephrine reuptake inhibitors for the same. They also identified some 20,000 patients with dementia taking cholinesterase inhibitors, and 3,000 with Parkinson’s disease taking dopamine agonists. Dr. Callaghan and colleagues compared patient adherence over 6 months for pairs of drugs in the same class with similar or equal efficacy, but with different costs to the patient.

Such cost differences can be stark: The researchers noted that the average 2016 out-of-pocket cost for 30 days of pregabalin, a drug used in the treatment of peripheral neuropathy, was $65.70, compared with $8.40 for gabapentin. With two common dementia drugs the difference was even more pronounced: $79.30 for rivastigmine compared with $3.10 for donepezil, both cholinesterase inhibitors with similar efficacy and tolerability.

Dr. Callaghan and colleagues found that such cost differences bore significantly on patient adherence. An increase of $50 in patient costs was seen decreasing adherence by 9% for neuropathy patients on gabapentinoids (adjusted incidence rate ratio [IRR] 0.91, 0.89-0.93) and by 12% for dementia patients on cholinesterase inhibitors (adjusted IRR 0.88, 0.86-0.91, P less than .05 for both). Similar price-linked decreases were seen for neuropathy patients on SNRIs and Parkinson’s patients on dopamine agonists, but the differences did not reach statistical significance.

Black, Asian, and Hispanic patients saw greater drops in adherence than did white patients associated with the same out-of-pocket cost differences, leading the researchers to note that special care should be taken in prescribing decisions for these populations.

“When choosing among medications with differential [out-of-pocket] costs, prescribing the medication with lower [out-of-pocket] expense will likely improve medication adherence while reducing overall costs,” Dr. Callaghan and colleagues wrote in their analysis. “For example, prescribing gabapentin or venlafaxine to patients with newly diagnosed neuropathy is likely to lead to higher adherence compared with pregabalin or duloxetine, and therefore, there is a higher likelihood of relief from neuropathic pain.” The researchers noted that while combination pills and extended-release formulations may be marketed as a way to increase adherence, the higher out-of-pocket costs of such medicines could offset any adherence benefit.

Dr. Callaghan and his colleagues described as strengths of their study its large sample and statistical approach that “allowed us to best estimate the causal relationship between [out-of-pocket] costs and medication adherence by limiting selection bias, residual confounding, and the confounding inherent to medication choice.” Nonadherence – patients who never filled a prescription after diagnosis – was not captured in the study.

The American Academy of Neurology funded the study. Two of its authors reported financial conflicts of interest in the form of compensation from pharmaceutical or device companies. Its lead author, Dr. Callaghan, reported funding for a device maker and performing medical legal consultations.

SOURCE: Reynolds EL et al. Neurology. 2020 Feb 19. doi/10.1212/WNL.0000000000009039.

Cervical cancer is the second most common cancer among women in lower- and middle-income countries, but universal human papillomavirus vaccination for girls would reduce new cervical cancer cases by about 90% over the next century, according to researchers.

Adding twice-lifetime cervical screening with human papillomavirus (HPV) testing would further reduce the incidence of cervical cancer, including in countries with the highest burden, the researchers reported in The Lancet.

Marc Brisson, PhD, of Laval University, Quebec City, and colleagues conducted this study using three models identified by the World Health Organization. The models were used to project reductions in cervical cancer incidence for women in 78 low- and middle-income countries based on the following HPV vaccination and screening scenarios:

• Universal girls-only vaccination at age 9 years, assuming 90% of girls vaccinated and a vaccine that is perfectly effective
• Girls-only vaccination plus cervical screening with HPV testing at age 35 years
• Girls-only vaccination plus screening at ages 35 and 45.

All three scenarios modeled would result in the elimination of cervical cancer, Dr. Brisson and colleagues found. Elimination was defined as four or fewer new cases per 100,000 women-years.

The simplest scenario, universal girls-only vaccination, was predicted to reduce age-standardized cervical cancer incidence from 19.8 cases per 100,000 women-years to 2.1 cases per 100,000 women-years (89.4% reduction) by 2120. That amounts to about 61 million potential cases avoided, with elimination targets reached in 60% of the countries studied.

HPV vaccination plus one-time screening was predicted to reduce the incidence of cervical cancer to 1.0 case per 100,000 women-years (95.0% reduction), and HPV vaccination plus twice-lifetime screening was predicted to reduce the incidence to 0.7 cases per 100,000 women-years (96.7% reduction).

Dr. Brisson and colleagues reported that, for the countries with the highest burden of cervical cancer (more than 25 cases per 100,000 women-years), adding screening would be necessary to achieve elimination.

To meet the same targets across all 78 countries, “our models predict that scale-up of both girls-only HPV vaccination and twice-lifetime screening is necessary, with 90% HPV vaccination coverage, 90% screening uptake, and long-term protection against HPV types 16, 18, 31, 33, 45, 52, and 58,” the researchers wrote.

Dr. Brisson and colleagues claimed that a strength of this study is the modeling approach, which compared three models “that have been extensively peer reviewed and validated with postvaccination surveillance data.”

The researchers acknowledged, however, that their modeling could not account for variations in sexual behavior from country to country, and the study was not designed to anticipate behavioral or technological changes that could affect cervical cancer incidence in the decades to come.

The study was funded by the WHO, the United Nations, and the Canadian and Australian governments. The WHO contributed to the study design, data analysis and interpretation, and writing of the manuscript. Two study authors reported receiving indirect industry funding for a cervical screening trial in Australia.

SOURCE: Brisson M et al. Lancet. 2020 Jan 30. doi: 10.1016/S0140-6736(20)30068-4.

Cervical cancer is the second most common cancer among women in lower- and middle-income countries, but universal human papillomavirus vaccination for girls would reduce new cervical cancer cases by about 90% over the next century, according to researchers.

Adding twice-lifetime cervical screening with human papillomavirus (HPV) testing would further reduce the incidence of cervical cancer, including in countries with the highest burden, the researchers reported in The Lancet.

Marc Brisson, PhD, of Laval University, Quebec City, and colleagues conducted this study using three models identified by the World Health Organization. The models were used to project reductions in cervical cancer incidence for women in 78 low- and middle-income countries based on the following HPV vaccination and screening scenarios:

• Universal girls-only vaccination at age 9 years, assuming 90% of girls vaccinated and a vaccine that is perfectly effective
• Girls-only vaccination plus cervical screening with HPV testing at age 35 years
• Girls-only vaccination plus screening at ages 35 and 45.

All three scenarios modeled would result in the elimination of cervical cancer, Dr. Brisson and colleagues found. Elimination was defined as four or fewer new cases per 100,000 women-years.

The simplest scenario, universal girls-only vaccination, was predicted to reduce age-standardized cervical cancer incidence from 19.8 cases per 100,000 women-years to 2.1 cases per 100,000 women-years (89.4% reduction) by 2120. That amounts to about 61 million potential cases avoided, with elimination targets reached in 60% of the countries studied.

HPV vaccination plus one-time screening was predicted to reduce the incidence of cervical cancer to 1.0 case per 100,000 women-years (95.0% reduction), and HPV vaccination plus twice-lifetime screening was predicted to reduce the incidence to 0.7 cases per 100,000 women-years (96.7% reduction).

Dr. Brisson and colleagues reported that, for the countries with the highest burden of cervical cancer (more than 25 cases per 100,000 women-years), adding screening would be necessary to achieve elimination.

To meet the same targets across all 78 countries, “our models predict that scale-up of both girls-only HPV vaccination and twice-lifetime screening is necessary, with 90% HPV vaccination coverage, 90% screening uptake, and long-term protection against HPV types 16, 18, 31, 33, 45, 52, and 58,” the researchers wrote.

Dr. Brisson and colleagues claimed that a strength of this study is the modeling approach, which compared three models “that have been extensively peer reviewed and validated with postvaccination surveillance data.”

The researchers acknowledged, however, that their modeling could not account for variations in sexual behavior from country to country, and the study was not designed to anticipate behavioral or technological changes that could affect cervical cancer incidence in the decades to come.

The study was funded by the WHO, the United Nations, and the Canadian and Australian governments. The WHO contributed to the study design, data analysis and interpretation, and writing of the manuscript. Two study authors reported receiving indirect industry funding for a cervical screening trial in Australia.

SOURCE: Brisson M et al. Lancet. 2020 Jan 30. doi: 10.1016/S0140-6736(20)30068-4.

Cervical cancer is the second most common cancer among women in lower- and middle-income countries, but universal human papillomavirus vaccination for girls would reduce new cervical cancer cases by about 90% over the next century, according to researchers.

Adding twice-lifetime cervical screening with human papillomavirus (HPV) testing would further reduce the incidence of cervical cancer, including in countries with the highest burden, the researchers reported in The Lancet.

Marc Brisson, PhD, of Laval University, Quebec City, and colleagues conducted this study using three models identified by the World Health Organization. The models were used to project reductions in cervical cancer incidence for women in 78 low- and middle-income countries based on the following HPV vaccination and screening scenarios:

• Universal girls-only vaccination at age 9 years, assuming 90% of girls vaccinated and a vaccine that is perfectly effective
• Girls-only vaccination plus cervical screening with HPV testing at age 35 years
• Girls-only vaccination plus screening at ages 35 and 45.

All three scenarios modeled would result in the elimination of cervical cancer, Dr. Brisson and colleagues found. Elimination was defined as four or fewer new cases per 100,000 women-years.

The simplest scenario, universal girls-only vaccination, was predicted to reduce age-standardized cervical cancer incidence from 19.8 cases per 100,000 women-years to 2.1 cases per 100,000 women-years (89.4% reduction) by 2120. That amounts to about 61 million potential cases avoided, with elimination targets reached in 60% of the countries studied.

HPV vaccination plus one-time screening was predicted to reduce the incidence of cervical cancer to 1.0 case per 100,000 women-years (95.0% reduction), and HPV vaccination plus twice-lifetime screening was predicted to reduce the incidence to 0.7 cases per 100,000 women-years (96.7% reduction).

Dr. Brisson and colleagues reported that, for the countries with the highest burden of cervical cancer (more than 25 cases per 100,000 women-years), adding screening would be necessary to achieve elimination.

To meet the same targets across all 78 countries, “our models predict that scale-up of both girls-only HPV vaccination and twice-lifetime screening is necessary, with 90% HPV vaccination coverage, 90% screening uptake, and long-term protection against HPV types 16, 18, 31, 33, 45, 52, and 58,” the researchers wrote.

Dr. Brisson and colleagues claimed that a strength of this study is the modeling approach, which compared three models “that have been extensively peer reviewed and validated with postvaccination surveillance data.”

The researchers acknowledged, however, that their modeling could not account for variations in sexual behavior from country to country, and the study was not designed to anticipate behavioral or technological changes that could affect cervical cancer incidence in the decades to come.

The study was funded by the WHO, the United Nations, and the Canadian and Australian governments. The WHO contributed to the study design, data analysis and interpretation, and writing of the manuscript. Two study authors reported receiving indirect industry funding for a cervical screening trial in Australia.

SOURCE: Brisson M et al. Lancet. 2020 Jan 30. doi: 10.1016/S0140-6736(20)30068-4.

Young people treated with bariatric surgery for severe obesity did not experience better mental health in the 5 years following their procedures, Swedish researchers said, and indeed fared worse than their nontreated peers on certain measures.

The results of this study do not necessarily argue “that metabolic and bariatric surgery during adolescence causes mental health problems,” the investigators wrote in the Lancet Child and Adolescent Health, but “it is reasonable to conclude that metabolic and bariatric surgery does not result in a substantial alleviation of mental health problems in adolescents with severe obesity,” and that “long-term mental health support should be required in programs providing adolescent metabolic and bariatric surgery.”

Kajsa Järvholm, PhD, of Skåne University Hospital, in Malmö, Sweden, and colleagues reported results from a prospective nonrandomized study that recruited 81 adolescents in Sweden aged 13-18 years (mean age, 16.5) who had a body mass index of 40 or higher, or BMI of 35 with obesity-related comorbidities and who underwent Roux-en-Y gastric bypass for weight loss. Subjects were matched by age, sex, and BMI to 80 controls (mean age, 15.8 years) who were assigned to conventional nonsurgical treatment. All patients were assessed at 1, 2, and 5 years.

Although mental health treatment, including use of psychiatric drugs, did not differ between the groups at baseline, during the follow-up period the subjects who underwent surgery saw 15% more impatient and outpatient mental health treatment, compared with controls, a significant difference. About a quarter of patients in the surgically treated group required specialized mental health treatment for the first time after their surgeries.

Though the surgical group lost much more weight – mean BMI was 32.3 at 5 years, compared with 41.7 for controls – none of the mental health changes from baseline were significantly associated with percentage change of BMI at 5 years.

The findings from the study are consistent with results from studies in adults in which bariatric surgery improves many health outcomes but does not alter the need for mental health treatment. Although 5 years is a longer follow-up than in previous studies in young patients – a key strength of the study – Dr. Järvholm and colleagues acknowledged some weaknesses, including a nonrandomized design, lack of a comparison group of nonobese youths for mental health measures, a small sample size, and a surgical procedure that is now out of favor in adolescents.

The study was funded by Swedish government and health foundations. Dr. Järvholm disclosed pharmaceutical industry funding not related to the study, and three coauthors also disclosed industry relationships.

SOURCE: Järvholm K et al. Lancet Child Adolesc Health. 2020. doi: 10.1016/s2352-4642(20)30024-9.

Young people treated with bariatric surgery for severe obesity did not experience better mental health in the 5 years following their procedures, Swedish researchers said, and indeed fared worse than their nontreated peers on certain measures.

The results of this study do not necessarily argue “that metabolic and bariatric surgery during adolescence causes mental health problems,” the investigators wrote in the Lancet Child and Adolescent Health, but “it is reasonable to conclude that metabolic and bariatric surgery does not result in a substantial alleviation of mental health problems in adolescents with severe obesity,” and that “long-term mental health support should be required in programs providing adolescent metabolic and bariatric surgery.”

Kajsa Järvholm, PhD, of Skåne University Hospital, in Malmö, Sweden, and colleagues reported results from a prospective nonrandomized study that recruited 81 adolescents in Sweden aged 13-18 years (mean age, 16.5) who had a body mass index of 40 or higher, or BMI of 35 with obesity-related comorbidities and who underwent Roux-en-Y gastric bypass for weight loss. Subjects were matched by age, sex, and BMI to 80 controls (mean age, 15.8 years) who were assigned to conventional nonsurgical treatment. All patients were assessed at 1, 2, and 5 years.

Although mental health treatment, including use of psychiatric drugs, did not differ between the groups at baseline, during the follow-up period the subjects who underwent surgery saw 15% more impatient and outpatient mental health treatment, compared with controls, a significant difference. About a quarter of patients in the surgically treated group required specialized mental health treatment for the first time after their surgeries.

Though the surgical group lost much more weight – mean BMI was 32.3 at 5 years, compared with 41.7 for controls – none of the mental health changes from baseline were significantly associated with percentage change of BMI at 5 years.

The findings from the study are consistent with results from studies in adults in which bariatric surgery improves many health outcomes but does not alter the need for mental health treatment. Although 5 years is a longer follow-up than in previous studies in young patients – a key strength of the study – Dr. Järvholm and colleagues acknowledged some weaknesses, including a nonrandomized design, lack of a comparison group of nonobese youths for mental health measures, a small sample size, and a surgical procedure that is now out of favor in adolescents.

The study was funded by Swedish government and health foundations. Dr. Järvholm disclosed pharmaceutical industry funding not related to the study, and three coauthors also disclosed industry relationships.

SOURCE: Järvholm K et al. Lancet Child Adolesc Health. 2020. doi: 10.1016/s2352-4642(20)30024-9.

Young people treated with bariatric surgery for severe obesity did not experience better mental health in the 5 years following their procedures, Swedish researchers said, and indeed fared worse than their nontreated peers on certain measures.

The results of this study do not necessarily argue “that metabolic and bariatric surgery during adolescence causes mental health problems,” the investigators wrote in the Lancet Child and Adolescent Health, but “it is reasonable to conclude that metabolic and bariatric surgery does not result in a substantial alleviation of mental health problems in adolescents with severe obesity,” and that “long-term mental health support should be required in programs providing adolescent metabolic and bariatric surgery.”

Kajsa Järvholm, PhD, of Skåne University Hospital, in Malmö, Sweden, and colleagues reported results from a prospective nonrandomized study that recruited 81 adolescents in Sweden aged 13-18 years (mean age, 16.5) who had a body mass index of 40 or higher, or BMI of 35 with obesity-related comorbidities and who underwent Roux-en-Y gastric bypass for weight loss. Subjects were matched by age, sex, and BMI to 80 controls (mean age, 15.8 years) who were assigned to conventional nonsurgical treatment. All patients were assessed at 1, 2, and 5 years.

Although mental health treatment, including use of psychiatric drugs, did not differ between the groups at baseline, during the follow-up period the subjects who underwent surgery saw 15% more impatient and outpatient mental health treatment, compared with controls, a significant difference. About a quarter of patients in the surgically treated group required specialized mental health treatment for the first time after their surgeries.

Though the surgical group lost much more weight – mean BMI was 32.3 at 5 years, compared with 41.7 for controls – none of the mental health changes from baseline were significantly associated with percentage change of BMI at 5 years.

The findings from the study are consistent with results from studies in adults in which bariatric surgery improves many health outcomes but does not alter the need for mental health treatment. Although 5 years is a longer follow-up than in previous studies in young patients – a key strength of the study – Dr. Järvholm and colleagues acknowledged some weaknesses, including a nonrandomized design, lack of a comparison group of nonobese youths for mental health measures, a small sample size, and a surgical procedure that is now out of favor in adolescents.

The study was funded by Swedish government and health foundations. Dr. Järvholm disclosed pharmaceutical industry funding not related to the study, and three coauthors also disclosed industry relationships.

SOURCE: Järvholm K et al. Lancet Child Adolesc Health. 2020. doi: 10.1016/s2352-4642(20)30024-9.

A 4-month intensive program of family-focused therapy worked better than a less-intensive program in delaying new mood episodes among young people at risk of developing bipolar disorder, new research shows.

“This study extends the results of other randomized clinical trials indicating effects of family psychoeducation and skill training on the long-term trajectory of depressive symptoms in pediatric mood disorders,” wrote David J. Miklowitz, PhD, of the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, and colleagues. The study was published in JAMA Psychiatry.

For their research, the investigators recruited 127 subjects aged 9-17 years (mean age, 13 years) deemed at high risk for later bipolar I or II disorder for having depression or subthreshold mania along with active mood symptoms and a family history of bipolar disorder. Some 85% of subjects had depression symptoms at enrollment.

Subjects were randomized to 12 sessions over 4 months of family-focused therapy – a psychoeducation, communication, and problem-solving training program incorporating caretakers and also siblings if possible (n = 61) – or to 3 sessions of family-focused therapy and an additional 3 of individual therapy in the same 4-month time frame (n = 66). Medication was allowed for all subjects, and patients were followed for a median 2 years after the intervention. Baseline characteristics, medication use, and dropout rates were similar between the groups.

Both groups saw similarly high rates of new episodes of major depression, mania, or hypomania during follow-up; however, those in the intensive family-focused therapy group saw longer intervals of wellness, with a median 81 weeks (95% confidence interval, 56-123 weeks) from randomization until the first observed mood episode, compared with 63 weeks (95% CI, 44-78 weeks) to an episode for the less-intensive group (P = .03). Dr. Miklowitz and colleagues did not find differences in the severity of mood episodes following either treatment mode or in later conversion to bipolar I or II.

The researchers described as limitations of their study its inability to measure the “temporal relationship between changes in family communication and symptom changes in patients,” which would help answer whether improvements in communication patterns aid symptom regulation, or whether more stable patients are better able to manage difficult family interactions.

Family-focused therapy “may have uniquely enduring effects that extend into the maintenance phase of treatment,” Dr. Miklowitz and colleagues wrote.

The study was funded by the National Institute of Mental Health. Several coauthors, including the lead author, reported receiving research grants from NIMH and other foundations. Two additional coauthors reported receiving pharmaceutical industry funding, including advisory board and consulting fees.

SOURCE: Miklowitz DJ et al. JAMA Psychiatry. 2020 Jan 15. doi: 10.1001/jamapsychiatry.2019.4520.

A 4-month intensive program of family-focused therapy worked better than a less-intensive program in delaying new mood episodes among young people at risk of developing bipolar disorder, new research shows.

“This study extends the results of other randomized clinical trials indicating effects of family psychoeducation and skill training on the long-term trajectory of depressive symptoms in pediatric mood disorders,” wrote David J. Miklowitz, PhD, of the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, and colleagues. The study was published in JAMA Psychiatry.

For their research, the investigators recruited 127 subjects aged 9-17 years (mean age, 13 years) deemed at high risk for later bipolar I or II disorder for having depression or subthreshold mania along with active mood symptoms and a family history of bipolar disorder. Some 85% of subjects had depression symptoms at enrollment.

Subjects were randomized to 12 sessions over 4 months of family-focused therapy – a psychoeducation, communication, and problem-solving training program incorporating caretakers and also siblings if possible (n = 61) – or to 3 sessions of family-focused therapy and an additional 3 of individual therapy in the same 4-month time frame (n = 66). Medication was allowed for all subjects, and patients were followed for a median 2 years after the intervention. Baseline characteristics, medication use, and dropout rates were similar between the groups.

Both groups saw similarly high rates of new episodes of major depression, mania, or hypomania during follow-up; however, those in the intensive family-focused therapy group saw longer intervals of wellness, with a median 81 weeks (95% confidence interval, 56-123 weeks) from randomization until the first observed mood episode, compared with 63 weeks (95% CI, 44-78 weeks) to an episode for the less-intensive group (P = .03). Dr. Miklowitz and colleagues did not find differences in the severity of mood episodes following either treatment mode or in later conversion to bipolar I or II.

The researchers described as limitations of their study its inability to measure the “temporal relationship between changes in family communication and symptom changes in patients,” which would help answer whether improvements in communication patterns aid symptom regulation, or whether more stable patients are better able to manage difficult family interactions.

Family-focused therapy “may have uniquely enduring effects that extend into the maintenance phase of treatment,” Dr. Miklowitz and colleagues wrote.

The study was funded by the National Institute of Mental Health. Several coauthors, including the lead author, reported receiving research grants from NIMH and other foundations. Two additional coauthors reported receiving pharmaceutical industry funding, including advisory board and consulting fees.

SOURCE: Miklowitz DJ et al. JAMA Psychiatry. 2020 Jan 15. doi: 10.1001/jamapsychiatry.2019.4520.

A 4-month intensive program of family-focused therapy worked better than a less-intensive program in delaying new mood episodes among young people at risk of developing bipolar disorder, new research shows.

“This study extends the results of other randomized clinical trials indicating effects of family psychoeducation and skill training on the long-term trajectory of depressive symptoms in pediatric mood disorders,” wrote David J. Miklowitz, PhD, of the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, and colleagues. The study was published in JAMA Psychiatry.

For their research, the investigators recruited 127 subjects aged 9-17 years (mean age, 13 years) deemed at high risk for later bipolar I or II disorder for having depression or subthreshold mania along with active mood symptoms and a family history of bipolar disorder. Some 85% of subjects had depression symptoms at enrollment.

Subjects were randomized to 12 sessions over 4 months of family-focused therapy – a psychoeducation, communication, and problem-solving training program incorporating caretakers and also siblings if possible (n = 61) – or to 3 sessions of family-focused therapy and an additional 3 of individual therapy in the same 4-month time frame (n = 66). Medication was allowed for all subjects, and patients were followed for a median 2 years after the intervention. Baseline characteristics, medication use, and dropout rates were similar between the groups.

Both groups saw similarly high rates of new episodes of major depression, mania, or hypomania during follow-up; however, those in the intensive family-focused therapy group saw longer intervals of wellness, with a median 81 weeks (95% confidence interval, 56-123 weeks) from randomization until the first observed mood episode, compared with 63 weeks (95% CI, 44-78 weeks) to an episode for the less-intensive group (P = .03). Dr. Miklowitz and colleagues did not find differences in the severity of mood episodes following either treatment mode or in later conversion to bipolar I or II.

The researchers described as limitations of their study its inability to measure the “temporal relationship between changes in family communication and symptom changes in patients,” which would help answer whether improvements in communication patterns aid symptom regulation, or whether more stable patients are better able to manage difficult family interactions.

Family-focused therapy “may have uniquely enduring effects that extend into the maintenance phase of treatment,” Dr. Miklowitz and colleagues wrote.

The study was funded by the National Institute of Mental Health. Several coauthors, including the lead author, reported receiving research grants from NIMH and other foundations. Two additional coauthors reported receiving pharmaceutical industry funding, including advisory board and consulting fees.

SOURCE: Miklowitz DJ et al. JAMA Psychiatry. 2020 Jan 15. doi: 10.1001/jamapsychiatry.2019.4520.

Risk for preterm birth in women with prepregancy obesity differs significantly by the mother’s age and race/ethnicity, according to new findings from an analysis that used a large, ethnically diverse population sample.

Previous study findings have demonstrated that pregnant women with obesity have a higher risk of giving birth to preterm babies, but the effect of age and race on that risk was not clear until now.

In this latest study, Wei Bao, MD, and colleagues at the University of Iowa, Iowa City, looked at records from 7.14 million live births registered in the U.S. National Vital Statistics System for 2016 and 2017, of which about 7.4% were preterm. The researchers excluded from their sample women with preexisting diabetes or hypertension.

For the cohort overall, there was a significant association between prepregnancy body mass index and preterm birth, with mothers who were overweight (adjusted odds ratio, 1.02; 95% confidence interval, 1.01–1.03) or obese (aOR, 1.18; 95%CI, 1.18–1.19), having a significantly higher risk of preterm birth, compared with healthy weight mothers. Underweight women also had a greater risk of preterm birth, compared with the healthy weight references (aOR, 1.33; 95% CI, 1.31–1.35), the researchers reported, adding that the association between maternal underweight and preterm birth was consistent across the maternal age and race/ethnicity groups.

Dr. Bao and colleagues found that, among non-Hispanic white women (who made up about half the cohort), maternal obesity was inversely associated with preterm birth when mothers were younger than 20 years (aOR, 0.92; 95% CI, 0.88-0.97), but there was a crossover effect at age 20, when maternal obesity became positively associated with preterm birth until age 39 (aOR, 1.04 at ages 20-24, to 1.40 at ages 35-39). A similar pattern was seen in Hispanic women, for whom maternal obesity was not associated with preterm birth when they were younger than 20 (aOR, 0.98; 95% CI, 0.93-1.04), but was positively associated with preterm birth after age 20 until age 39 (aOR, 1.06 at ages 20-24, to 1.38 at ages 35-39).

However, the crossover effect occurred considerably later in black women with obesity, for whom maternal obesity remained inversely associated with preterm birth until age 30 (aOR, 0.76 before age 20; 0.83 at ages 20-24; 0.98 at ages 25-29), at which point the crossover effect kicked in, and maternal obesity became positively associated with preterm birth, increasing steadily with advancing age (aOR, 1.15 at ages 30-34; 1.26 at ages 35-39; 1.29 from age 40). “Our results, which are based on a large and diverse U.S. population, provide, for the first time, a comprehensive review of the association between maternal obesity and preterm birth for women [at a] range of ages,” Dr. Bao and colleagues wrote in their analysis, which was published in Lancet Diabetes & Endocrinology.

The researchers hypothesized that the inverse association between prepregnancy obesity and preterm birth in teenagers and younger women could be explained by the fact that “[healthy weight] teenagers, who are still growing and developing, might compete with the fetus for nutrients, which could subsequently affect physiological and metabolic systems involved with parturition,” whereas pregnant teenagers with obesity “might not need to compete (or compete to a lesser extent) for nutrients with their babies for their own growth.” The researchers stressed that more research was needed to understand the underlying mechanisms of the associations. The findings of a protective effect until age 30 in black women also require further study, Dr. Bao and colleagues said.

They stressed that the findings do not argue for weight gain as a preventive measure against preterm birth for normal weight young women, as “younger women, whether obese or not, have a higher risk of preterm birth than women aged 25-29 years do in Hispanic and in non-Hispanic white populations. Additionally, the adverse effects that maternal obesity has on other perinatal and neonatal outcomes should not be overlooked.”

The National Institutes of Health funded the study. The authors declared no conflicts of interest.

SOURCE: Bao et al. Lancet Diabetes Endocrinol. 2019;7:707-14.

Risk for preterm birth in women with prepregancy obesity differs significantly by the mother’s age and race/ethnicity, according to new findings from an analysis that used a large, ethnically diverse population sample.

Previous study findings have demonstrated that pregnant women with obesity have a higher risk of giving birth to preterm babies, but the effect of age and race on that risk was not clear until now.

In this latest study, Wei Bao, MD, and colleagues at the University of Iowa, Iowa City, looked at records from 7.14 million live births registered in the U.S. National Vital Statistics System for 2016 and 2017, of which about 7.4% were preterm. The researchers excluded from their sample women with preexisting diabetes or hypertension.

For the cohort overall, there was a significant association between prepregnancy body mass index and preterm birth, with mothers who were overweight (adjusted odds ratio, 1.02; 95% confidence interval, 1.01–1.03) or obese (aOR, 1.18; 95%CI, 1.18–1.19), having a significantly higher risk of preterm birth, compared with healthy weight mothers. Underweight women also had a greater risk of preterm birth, compared with the healthy weight references (aOR, 1.33; 95% CI, 1.31–1.35), the researchers reported, adding that the association between maternal underweight and preterm birth was consistent across the maternal age and race/ethnicity groups.

Dr. Bao and colleagues found that, among non-Hispanic white women (who made up about half the cohort), maternal obesity was inversely associated with preterm birth when mothers were younger than 20 years (aOR, 0.92; 95% CI, 0.88-0.97), but there was a crossover effect at age 20, when maternal obesity became positively associated with preterm birth until age 39 (aOR, 1.04 at ages 20-24, to 1.40 at ages 35-39). A similar pattern was seen in Hispanic women, for whom maternal obesity was not associated with preterm birth when they were younger than 20 (aOR, 0.98; 95% CI, 0.93-1.04), but was positively associated with preterm birth after age 20 until age 39 (aOR, 1.06 at ages 20-24, to 1.38 at ages 35-39).

However, the crossover effect occurred considerably later in black women with obesity, for whom maternal obesity remained inversely associated with preterm birth until age 30 (aOR, 0.76 before age 20; 0.83 at ages 20-24; 0.98 at ages 25-29), at which point the crossover effect kicked in, and maternal obesity became positively associated with preterm birth, increasing steadily with advancing age (aOR, 1.15 at ages 30-34; 1.26 at ages 35-39; 1.29 from age 40). “Our results, which are based on a large and diverse U.S. population, provide, for the first time, a comprehensive review of the association between maternal obesity and preterm birth for women [at a] range of ages,” Dr. Bao and colleagues wrote in their analysis, which was published in Lancet Diabetes & Endocrinology.

The researchers hypothesized that the inverse association between prepregnancy obesity and preterm birth in teenagers and younger women could be explained by the fact that “[healthy weight] teenagers, who are still growing and developing, might compete with the fetus for nutrients, which could subsequently affect physiological and metabolic systems involved with parturition,” whereas pregnant teenagers with obesity “might not need to compete (or compete to a lesser extent) for nutrients with their babies for their own growth.” The researchers stressed that more research was needed to understand the underlying mechanisms of the associations. The findings of a protective effect until age 30 in black women also require further study, Dr. Bao and colleagues said.

They stressed that the findings do not argue for weight gain as a preventive measure against preterm birth for normal weight young women, as “younger women, whether obese or not, have a higher risk of preterm birth than women aged 25-29 years do in Hispanic and in non-Hispanic white populations. Additionally, the adverse effects that maternal obesity has on other perinatal and neonatal outcomes should not be overlooked.”

The National Institutes of Health funded the study. The authors declared no conflicts of interest.

SOURCE: Bao et al. Lancet Diabetes Endocrinol. 2019;7:707-14.

Risk for preterm birth in women with prepregancy obesity differs significantly by the mother’s age and race/ethnicity, according to new findings from an analysis that used a large, ethnically diverse population sample.

Previous study findings have demonstrated that pregnant women with obesity have a higher risk of giving birth to preterm babies, but the effect of age and race on that risk was not clear until now.

In this latest study, Wei Bao, MD, and colleagues at the University of Iowa, Iowa City, looked at records from 7.14 million live births registered in the U.S. National Vital Statistics System for 2016 and 2017, of which about 7.4% were preterm. The researchers excluded from their sample women with preexisting diabetes or hypertension.

For the cohort overall, there was a significant association between prepregnancy body mass index and preterm birth, with mothers who were overweight (adjusted odds ratio, 1.02; 95% confidence interval, 1.01–1.03) or obese (aOR, 1.18; 95%CI, 1.18–1.19), having a significantly higher risk of preterm birth, compared with healthy weight mothers. Underweight women also had a greater risk of preterm birth, compared with the healthy weight references (aOR, 1.33; 95% CI, 1.31–1.35), the researchers reported, adding that the association between maternal underweight and preterm birth was consistent across the maternal age and race/ethnicity groups.

Dr. Bao and colleagues found that, among non-Hispanic white women (who made up about half the cohort), maternal obesity was inversely associated with preterm birth when mothers were younger than 20 years (aOR, 0.92; 95% CI, 0.88-0.97), but there was a crossover effect at age 20, when maternal obesity became positively associated with preterm birth until age 39 (aOR, 1.04 at ages 20-24, to 1.40 at ages 35-39). A similar pattern was seen in Hispanic women, for whom maternal obesity was not associated with preterm birth when they were younger than 20 (aOR, 0.98; 95% CI, 0.93-1.04), but was positively associated with preterm birth after age 20 until age 39 (aOR, 1.06 at ages 20-24, to 1.38 at ages 35-39).

However, the crossover effect occurred considerably later in black women with obesity, for whom maternal obesity remained inversely associated with preterm birth until age 30 (aOR, 0.76 before age 20; 0.83 at ages 20-24; 0.98 at ages 25-29), at which point the crossover effect kicked in, and maternal obesity became positively associated with preterm birth, increasing steadily with advancing age (aOR, 1.15 at ages 30-34; 1.26 at ages 35-39; 1.29 from age 40). “Our results, which are based on a large and diverse U.S. population, provide, for the first time, a comprehensive review of the association between maternal obesity and preterm birth for women [at a] range of ages,” Dr. Bao and colleagues wrote in their analysis, which was published in Lancet Diabetes & Endocrinology.

The researchers hypothesized that the inverse association between prepregnancy obesity and preterm birth in teenagers and younger women could be explained by the fact that “[healthy weight] teenagers, who are still growing and developing, might compete with the fetus for nutrients, which could subsequently affect physiological and metabolic systems involved with parturition,” whereas pregnant teenagers with obesity “might not need to compete (or compete to a lesser extent) for nutrients with their babies for their own growth.” The researchers stressed that more research was needed to understand the underlying mechanisms of the associations. The findings of a protective effect until age 30 in black women also require further study, Dr. Bao and colleagues said.

They stressed that the findings do not argue for weight gain as a preventive measure against preterm birth for normal weight young women, as “younger women, whether obese or not, have a higher risk of preterm birth than women aged 25-29 years do in Hispanic and in non-Hispanic white populations. Additionally, the adverse effects that maternal obesity has on other perinatal and neonatal outcomes should not be overlooked.”

The National Institutes of Health funded the study. The authors declared no conflicts of interest.

SOURCE: Bao et al. Lancet Diabetes Endocrinol. 2019;7:707-14.

Physicians treating transgender patients – in particular, transgender men who were born female – are faced with a confusing process when prescribing isotretinoin for severe acne.

A research letter published in the Journal of the American Academy of Dermatology reports that half of dermatologists surveyed reported having encountered difficulties classifying a transgender patient in iPLEDGE, the risk-management registry established to prevent female patients from starting isotretinoin therapy while pregnant or from becoming pregnant while exposed to the teratogenic medication.

Nearly 90% of respondents favored changing the current gender-specific categories in iPLEDGE to gender-neutral ones, classifying patients only by whether or not they have the ability to become pregnant.

For their research, Courtney Ensslin, MD, of the department of dermatology at Johns Hopkins University, Baltimore, and colleagues, distributed an 18-point questionnaire to 385 members of the Association of Professors of Dermatology that included questions assessing clinicians’ knowledge about the reproductive potential of transgender men and women. The recipients were asked to distribute it to faculty members and residents. The survey also described three clinical scenarios in which the physician needed to decide how to register a patient in iPLEDGE. The clinicians largely opted to class transgender men as women with childbearing potential, even if the category conflicted with the patient’s self-identified and legally recognized male gender.

Of the 136 clinicians who responded, 60% were women, almost half were aged 25-34 years. About 12% of respondents said the complexities of prescribing isotretinoin to a transgender patient led them to choose alternative therapies. And the survey revealed some gaps on providers’ general literacy on transgender patients and their reproductive potential. For example, fewer than a third of respondents answered correctly as to whether testosterone treatment decreases the quality and development of an immature ovum.

The researchers wrote that the survey results, while limited by a small sample of respondents that skewed toward younger women providers, suggest that “continued education on fertility in transgender patients is needed because prescribers must fully understand each patient’s reproductive potential to safely prescribe teratogenic medications.” Additionally, they pointed out, the results support ongoing efforts to reform iPLEDGE, as the current categories “do not offer an inclusive approach to care for transgender patients.”

Earlier this year the American Academy of Dermatology issued a position statement that described a number of ongoing initiatives aimed at improving treatment for patients who are members of gender and sexual minorities. These included the “revision of the AAD position statement on isotretinoin to support a gender-neutral categorization model for [iPLEDGE] … based on child-bearing potential rather than on gender identity,” the statement said.

Dr. Ensslin and colleagues reported conflicts of interest related to their research. The study was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health.

SOURCE: Ensslin C et al. J Am Acad Dermatol. 2019 Dec;81(6):1426-9.

Physicians treating transgender patients – in particular, transgender men who were born female – are faced with a confusing process when prescribing isotretinoin for severe acne.

A research letter published in the Journal of the American Academy of Dermatology reports that half of dermatologists surveyed reported having encountered difficulties classifying a transgender patient in iPLEDGE, the risk-management registry established to prevent female patients from starting isotretinoin therapy while pregnant or from becoming pregnant while exposed to the teratogenic medication.

Nearly 90% of respondents favored changing the current gender-specific categories in iPLEDGE to gender-neutral ones, classifying patients only by whether or not they have the ability to become pregnant.

For their research, Courtney Ensslin, MD, of the department of dermatology at Johns Hopkins University, Baltimore, and colleagues, distributed an 18-point questionnaire to 385 members of the Association of Professors of Dermatology that included questions assessing clinicians’ knowledge about the reproductive potential of transgender men and women. The recipients were asked to distribute it to faculty members and residents. The survey also described three clinical scenarios in which the physician needed to decide how to register a patient in iPLEDGE. The clinicians largely opted to class transgender men as women with childbearing potential, even if the category conflicted with the patient’s self-identified and legally recognized male gender.

Of the 136 clinicians who responded, 60% were women, almost half were aged 25-34 years. About 12% of respondents said the complexities of prescribing isotretinoin to a transgender patient led them to choose alternative therapies. And the survey revealed some gaps on providers’ general literacy on transgender patients and their reproductive potential. For example, fewer than a third of respondents answered correctly as to whether testosterone treatment decreases the quality and development of an immature ovum.

The researchers wrote that the survey results, while limited by a small sample of respondents that skewed toward younger women providers, suggest that “continued education on fertility in transgender patients is needed because prescribers must fully understand each patient’s reproductive potential to safely prescribe teratogenic medications.” Additionally, they pointed out, the results support ongoing efforts to reform iPLEDGE, as the current categories “do not offer an inclusive approach to care for transgender patients.”

Earlier this year the American Academy of Dermatology issued a position statement that described a number of ongoing initiatives aimed at improving treatment for patients who are members of gender and sexual minorities. These included the “revision of the AAD position statement on isotretinoin to support a gender-neutral categorization model for [iPLEDGE] … based on child-bearing potential rather than on gender identity,” the statement said.

Dr. Ensslin and colleagues reported conflicts of interest related to their research. The study was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health.

SOURCE: Ensslin C et al. J Am Acad Dermatol. 2019 Dec;81(6):1426-9.

Physicians treating transgender patients – in particular, transgender men who were born female – are faced with a confusing process when prescribing isotretinoin for severe acne.

A research letter published in the Journal of the American Academy of Dermatology reports that half of dermatologists surveyed reported having encountered difficulties classifying a transgender patient in iPLEDGE, the risk-management registry established to prevent female patients from starting isotretinoin therapy while pregnant or from becoming pregnant while exposed to the teratogenic medication.

Nearly 90% of respondents favored changing the current gender-specific categories in iPLEDGE to gender-neutral ones, classifying patients only by whether or not they have the ability to become pregnant.

For their research, Courtney Ensslin, MD, of the department of dermatology at Johns Hopkins University, Baltimore, and colleagues, distributed an 18-point questionnaire to 385 members of the Association of Professors of Dermatology that included questions assessing clinicians’ knowledge about the reproductive potential of transgender men and women. The recipients were asked to distribute it to faculty members and residents. The survey also described three clinical scenarios in which the physician needed to decide how to register a patient in iPLEDGE. The clinicians largely opted to class transgender men as women with childbearing potential, even if the category conflicted with the patient’s self-identified and legally recognized male gender.

Of the 136 clinicians who responded, 60% were women, almost half were aged 25-34 years. About 12% of respondents said the complexities of prescribing isotretinoin to a transgender patient led them to choose alternative therapies. And the survey revealed some gaps on providers’ general literacy on transgender patients and their reproductive potential. For example, fewer than a third of respondents answered correctly as to whether testosterone treatment decreases the quality and development of an immature ovum.

The researchers wrote that the survey results, while limited by a small sample of respondents that skewed toward younger women providers, suggest that “continued education on fertility in transgender patients is needed because prescribers must fully understand each patient’s reproductive potential to safely prescribe teratogenic medications.” Additionally, they pointed out, the results support ongoing efforts to reform iPLEDGE, as the current categories “do not offer an inclusive approach to care for transgender patients.”

Earlier this year the American Academy of Dermatology issued a position statement that described a number of ongoing initiatives aimed at improving treatment for patients who are members of gender and sexual minorities. These included the “revision of the AAD position statement on isotretinoin to support a gender-neutral categorization model for [iPLEDGE] … based on child-bearing potential rather than on gender identity,” the statement said.

Dr. Ensslin and colleagues reported conflicts of interest related to their research. The study was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health.

SOURCE: Ensslin C et al. J Am Acad Dermatol. 2019 Dec;81(6):1426-9.