This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

This month’s journal scan of articles in exocrine pancreatic insufficiency explores the connection between the two functions of the pancreas, both exocrine and endocrine–and demonstrates somewhat differing findings which are worth exploration.

The first paper is from Uysal and Argun out of Istanbul, Turkey which explores the connection between insulin resistance and the development of exocrine pancreatic insufficiency (EPI). Researchers enrolled 65 patients with obesity and ages 16-69. The homeostasis model of assessment (HOMA) was used for the diagnosis of insulin resistance, and EPI was diagnosed with a fecal elastase-1 (FE-1) < 200 µg/g (via enzyme-linked immunosorbent assay). The study looked at both mean FE-1 levels as well as the distribution of EPI amongst patients with and without insulin resistance.

The study reported FE-1 levels (430.27 ± 207.63 vs. 508.64 ± 188.77 µg/g; P = .119) and the rate of EPI (FE-1 < 200 µg/g; 25.7% vs. 10.0%; P = .104) were not significantly different in patients with or without insulin resistance. The authors note that prior studies have suggested a link between EPI and diabetes mellitus (DM); however this study shows the correlation may not be strong in the pre-diabetic insulin resistance, or pre-DM period.

Further along the diabetes spectrum, researchers in China aimed to assess the prevalence of EPI amongst the type 2 DM (T2DM) Chinese population, and to further identify factors associated with the development of EPI. This study was a cross-sectional analysis of 85 adult inpatients with T2DM without known exocrine pancreatic disorders or digestive system diseases. Fecal samples were used to measure FE-1 levels, and blood samples were collected to investigate pancreatic endocrine function and metabolic biomarkers in all participants. Multiple logistic regression analysis was used to evaluate the influencing factors of pancreatic exocrine insufficiency in patients with T2DM.

Ultimately, the prevalence of EPI (FE-1 < 200 µg/g) amongst this patient population was 18.8%. There was a highly significant positive association between FE-1 levels and fasting C-peptide (FCP) levels (correlation coefficient 0.451; P < .001). Logistic regression analysis demonstrated that FCP was independently associated with EPI (odds ratio 0.204; P = .024), and receiver operating characteristic (ROC) analysis demonstrated good predictive value for EPI as well.

In summary, the authors infer a mechanistic conclusion that likely merits further investigation, “the reduced quantity and quality of β-cell lead to insufficient insulin secretion and subsequently results in hyperglycemia and DM. Further, as the trophic function from β-cells on pancreatic acinar cells weaken, the development into exocrine dysfunction in patients with DM is likely.”

Bibliography

1. Uysal BB, Argun D. Assessment of the impact of insulin resistance on pancreatic exocrine functions in obese patients. Med-Science. 2021;10(3):998-1001.
2. Lv Y, Wei Q, Yuan X, et al. Two sides of the pancreas: Exocrine insufficiency is correlated with endocrine dysfunction in type 2 diabetes. Clin Chim Acta. 2021(Sep 14);523:81-86. doi: 10.1016/j.cca.2021.09.008.

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

Contraception prescription patterns vary by specialty and geography

Access to contraceptive services is dependent on both the local availability of healthcare providers as well as the types of contraception services offered by those providers. Little is known about the national US contraception workforce, which includes any type of provider that offers contraceptive care. In this observational study, three national data sources were combined to construct a comprehensive database of the contraception provider workforce to evaluate Medicaid participation and variation in the supply, distribution, and types of contraceptive services offered. The study found that 73.1% of obstetric and gynecologic medical physicians (OBGYN), 72.6% of nurse-midwives, 51.4% of family medicine physicians, 32.4% of pediatricians, 25.2% of advanced practice nurses, 19.8% of internal medicine physicians, and 19.4% of physician assistants prescribed the contraceptive pill, patch, or ring. Approximately half of OBGYNs and family medicine physicians (50.2% and 52.2%, respectively) provided injectable contraception, compared to 34.7% of internal medicine physicians and 34.1% of pediatricians. Intrauterine devices (IUD) were provided by 92.8% of OBGYNs compared with 16.4% of family physicians, 2.6% of internal medicine physicians, and 0.6% of pediatricians. Contraceptive implants were provided by 56.2% of OBGYNs, compared with 13.7% of family medicine physicians, 1.8% of internal medicine physicians, and 4.0% of pediatricians. The contraception workforce also varied by geography, both in the density and types of providers that different communities depend upon. States ranged from provider-to-population ratios of 27.9 to 74.2 providers per 10,000 women of reproductive age. The availability of different specialties and professions also varied between counties, with 675 of the 1,411 counties lacking either OBGYNs or nurse-midwives prescribing contraception. This study also found variation across states and provider types in the proportion of contraceptive providers who accept Medicaid, with rates of Medicaid acceptance highest amongst OBGYNs and lowest amongst internal medicine physicians. This report highlights that the distribution of the contraception workforce and Medicaid acceptance varies widely by location and specialty and documents large gaps in the provision of highly effective contraceptive services including IUDs and implants. Increasing the number and types of providers that can provide family planning is central to providing comprehensive reproductive healthcare and reducing unintended pregnancies.

US Healthcare provider practices related to Emergency Contraception

Emergency contraception (EC) can prevent pregnancy after sexual encounters in which contraception was not used or used incorrectly. The US Selected Practice Recommendations for Contraceptive Use (US SPR) was initially released in 2013 and includes recommendations for healthcare providers on the initiation of EC, increasing access to EC through advance provision of EC pills, and initiation of regular contraception in conjunction with provision of EC pills. The objective of this study was to assess the percentage of healthcare providers reporting frequent provision of select EC practices around the time of and after the release of the US SPR. Two cross-sectional mailed surveys were conducted using different nationwide samples of office-based physicians and public-sector providers around the time of (2013-2014) and after (2019) the initial US SPR release. Providers were asked to indicate how often in the past year they had: 1) provided an advance prescription of EC pills to a woman not specifically seeking EC; 2) provided an advanced supply of EC pills to a woman not specifically seeking EC; 3) provided or prescribed a contraceptive at the same time as EC pills were provided; and 4) provided a copper IUD as EC. Data was pooled from both surveys, resulting in an overall sample size of 3,480 providers (n = 2,060 for the 2013-2014 survey and n = 1,420 for the 2019 survey). In the 2019 nationwide sample, 16% of respondents frequently provided an advance prescription of EC pills, 7% provided an advanced supply of EC pills, 8% provided the copper IUD as EC, and 41% cfrequently provided regular contraception at the time of EC pills. Overall, there were no significant changes in prevalence of frequently providing or prescribing an advance supply of EC pills between 2013-2014 and 2019, which may reflect changes in provider practices based on availability of over-the-counter levonogestrel EC pills in 2013. An increase in the proportion of providers who frequently provided regular contraception at the same time as EC pills and who provided a copper IUD for EC between 2013-2014 and 2019 was observed. In 2019, providers who reported using the US SPR were more likely to provide contraception at the same time as EC pills and provide the copper IUD for EC compared with those who did not use the US SPR. Wider implementation of the US SPR recommendations and an improved understanding of the barriers faced by providers in implementing these practices may improve access to EC. A recent report found that the levonorgestrel 52 IUD provides EC with efficacy similar to that of the copper IUD and may lead to more widespread placement of IUDs for EC (Turok).  


Progestogen-only pill shows promise as a potential non-prescription contraception option for both breastfeeding and non-breastfeeding women

An initiative is currently underway to apply for US Food and Drug Administration (FDA) approval for over-the-counter sales of a progestogen-only contraceptive pill (POP) containing 75 mg/day norgestrel. Although 75 mg/day norgestrel is approved by the FDA for prescription use, this formulation is not currently available in the US as marketing of this product was discontinued in 2005 for reasons not related to safety or effectiveness. The failure rate of the POP is presently reported to be the same as that of combined oral contraceptive pills (COC): 9% typical use and 0.3% perfect use unintended pregnancy rate. The objective of this review is to summarize and present the published data regarding the contraceptive effectiveness of 75 mg/day norgestrel amongst breastfeeding and non-breastfeeding women. A literature search was conducted in 2019 and identified 13 articles that specifically assessed the contraceptive efficacy of 75 mg/day norgestrel. Seven of the 13 studies included a total of 5,258 women who were breastfeeding and six of the 13 studies included a total 3,144 non-breastfeeding women. Taken together, the six studies of 3,144 non-breastfeeding women provide data on 35,319 months of use with a range of overall 12-month failure rates from 0-2.4/hundred woman-years from 75 mg/day norgestrel during typical use with a calculated aggregate Pearl Index of 2.2. Among breastfeeding women, the 12-month life table cumulative pregnancy rates for 75 mg/day norgestrel ranged from 0-3.4. This review concluded that the data support that 75 mg/day norgestrel is highly effective in clinical use, with similar estimates of failure in breastfeeding and non-breastfeeding women, providing support to the case for FDA approval of over-the-counter use of 75 mg/day norgestrel. Most contraindications to use of combination estrogen-progestin contraceptives relate to the estrogen component. Over the counter availability of the norgestrel POP could enhance women’s access to hormonal contraception.  

Millions of women view YouTube videos on self-removal of long-acting contraception

This study reviewed 58 YouTube videos related to self-removal of long-acting reversible contraception (LARC)– namely intrauterine devices (IUD) and contraceptive implants. Video content was analyzed to explore demographic characteristics, method and duration of LARC use, and motivations and experiences of self-removal. There were 48 videos (83%) that featured individuals who self-removed an IUD and 10 videos (17%) that featured individuals who self-removed an implant. All videos were uploaded between 2012-2020 and had over 4 million collective views, with the median number of views being 10,473 per video. Although a much smaller proportion of videos featured the self-removal of an implant, these videos had a higher average number of views (median 23,097 vs, 9533) and comments (median 44 vs. 14) compared to videos of IUD self-removals. The video creators of 53% were identified as White, 31% as Black, and 14% as Latina. The top comments for each video were analyzed and three primary themes emerged: positive affirmations; the viewer’s consideration of or attempt at self-removal; and complaints about LARC. There were 25 videos (n = 25/58) that included a comment from a viewer who stated they had either removed their own LARC device after watching the video or intended to do so soon. Three main motivations for self-removal were identified. Roughly half the sample (n = 30/58) described a desire to remove their method at home out of personal preference or convenience (n = 28/48 IUD users and n = 2/10 implant users). Others noted the inconvenience of an in-clinic removal. A large proportion of LARC users described barriers to clinic-based removal, including cost, lack of insurance, and long waiting times for an appointment. Most individuals in the sample (n = 56/58) successfully removed their device and described their experience in positive terms related to the ease of removal. Roughly a third of all video creators encountered challenges, including difficulty grasping the strings of their IUD or challenges removing the implant (n = 17/48 IUD users and n = 3/10 implant users). Positive experiences of self-removal and high levels of viewer engagement with online videos suggest a need for provider counseling on LARC removal at the time of insertion. Providers should clearly describe any procedural or financial requirements of removal prior to LARC placement. Providers may also wish to proactively discuss the risks and best practices for safe self-removal of LARC, including a conversation about the desired length of the IUD strings, risks associated with self-removal, and available resources when the patient encounters barriers to clinic-based removal. This study provides important data about the characteristics, motivations, and experiences of a group of people that are often invisible to researchers and healthcare providers.

References:
Broussard K, Becker A. Self-removal of long-acting reversible contraception: A content analysis of YouTube videos. Contraception. 2021 Aug 13: S0010-7824(21)00346-2 (in press).

Chen C, Strasser J, Banawa R, Luo Q, Bodas M, Castruccio-Prince C, Das K, Pittman P. Who is providing contraception care in the United States? An observational study of the contraception workforce. Am J Obstet Gynecol. 2021 Aug 18:  S0002-9378(21)00883-8 (in press).

We’ve launched a new app designed to help AGA trainees and early career members navigate each step along their GI career path. Once users get started by setting up their professional profile, AGA Career Compass offers curated resources on topics like career planning, clinical education, and leadership skills.

The Connections Corner section hosts experienced mentors and matches them with users based on profile compatibility and shared topics of interest, such as grant writing, setting up a lab, navigating career options in academic medicine, managing burnout, and more. Download the app today to branch out from your institution or practice and receive personalized career guidance.

Now available in Apple and Google Play stores.

We’ve launched a new app designed to help AGA trainees and early career members navigate each step along their GI career path. Once users get started by setting up their professional profile, AGA Career Compass offers curated resources on topics like career planning, clinical education, and leadership skills.

The Connections Corner section hosts experienced mentors and matches them with users based on profile compatibility and shared topics of interest, such as grant writing, setting up a lab, navigating career options in academic medicine, managing burnout, and more. Download the app today to branch out from your institution or practice and receive personalized career guidance.

Now available in Apple and Google Play stores.

We’ve launched a new app designed to help AGA trainees and early career members navigate each step along their GI career path. Once users get started by setting up their professional profile, AGA Career Compass offers curated resources on topics like career planning, clinical education, and leadership skills.

The Connections Corner section hosts experienced mentors and matches them with users based on profile compatibility and shared topics of interest, such as grant writing, setting up a lab, navigating career options in academic medicine, managing burnout, and more. Download the app today to branch out from your institution or practice and receive personalized career guidance.

Now available in Apple and Google Play stores.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Junaid Beig, MBBS, FRACP wrote the following in “Subtherapeutic Azathioprine metabolites despite being adherent to medication”:

“I have an Ulcerative patient (Pancolitis) on Mesalazine and Azathioprine 150mg since 2018. His levels are subtherapeutic (6TGN 159 and 6MMP 70) despite being adherent to medication. He drinks 2 liters of wine per week.

“Questions: Is there any way we can find if he has high TPMT activity (Level is normal 6.1)? Does alcohol have an impact on TPMT activity? Does he warrant alternative treatment?”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/25109.
 

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Junaid Beig, MBBS, FRACP wrote the following in “Subtherapeutic Azathioprine metabolites despite being adherent to medication”:

“I have an Ulcerative patient (Pancolitis) on Mesalazine and Azathioprine 150mg since 2018. His levels are subtherapeutic (6TGN 159 and 6MMP 70) despite being adherent to medication. He drinks 2 liters of wine per week.

“Questions: Is there any way we can find if he has high TPMT activity (Level is normal 6.1)? Does alcohol have an impact on TPMT activity? Does he warrant alternative treatment?”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/25109.
 

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

Junaid Beig, MBBS, FRACP wrote the following in “Subtherapeutic Azathioprine metabolites despite being adherent to medication”:

“I have an Ulcerative patient (Pancolitis) on Mesalazine and Azathioprine 150mg since 2018. His levels are subtherapeutic (6TGN 159 and 6MMP 70) despite being adherent to medication. He drinks 2 liters of wine per week.

“Questions: Is there any way we can find if he has high TPMT activity (Level is normal 6.1)? Does alcohol have an impact on TPMT activity? Does he warrant alternative treatment?”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/25109.
 

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

A version of this article first appeared on Medscape.com.

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

A version of this article first appeared on Medscape.com.

Avanos medical to pay $22 million to resolve criminal charge for fraudulent misbranding of PPE

A U.S.-based multinational medical device corporation will pay more than $22 million to resolve a criminal charge regarding fraudulent misbranding of their surgical gowns.

Avanos Medical Inc, which as its U.S. headquarters in Alpharetta, Georgia, is charged with one count of introducing misbranded surgical gowns into interstate commerce with the intent to defraud and mislead.

According to the Department of Justice, the company knowingly falsely labeled its MicroCool surgical gowns as providing AAMI Level 4 protection (the highest level) against fluid and virus penetration. Under the standards set by the American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI), the highest protection level for surgical gowns is reserved for gowns intended to be used in surgeries and other high-risk medical procedures on patients suspected of having infectious diseases.

Avanos admitted to selling hundreds of thousands of MicroCool gowns that were falsely labeled as AAMI Level 4 between late 2014 and early 2015, as well as directly lying to customers about the gowns’ protective capacities. In total, Avanos sold almost $9 million of misbranded MicroCool gowns.

“The last thing health care workers should have to worry about is whether their personal protective equipment lives up to manufacturers’ claims,” said Acting U.S. Attorney Prerak Shah for the Northern District of Texas. “Misbranded PPE can pose serious risks to medical professionals and patients alike.”
 

Company pays $38.75 million to settle allegations of knowingly selling defective devices 

Medical device manufacturers Alere and Alere San Diego (collectively, Alere) have agreed to pay almost $39 million to resolve allegations that they violated the False Claims Act by billing, and causing others to bill, the Medicare program for defective rapid point-of-care testing devices. 

From 2008 to 2016, the Department of Justice alleges, Alere knowingly sold defective INRatio blood coagulation monitors used by Medicare beneficiaries who were taking anticoagulants. The software algorithms in the monitors contained a material defect, which Alere had found in their research, to cause inaccurate readings. Blood coagulation monitoring is essential for the safety of these patients, enabling them to maintain a safe dosage of their medications. Taking too much of an anticoagulant can cause major bleeding, while taking too little can cause blood clots that lead to strokes. 

While Alere was aware that these devices were linked to over a dozen deaths and hundreds of injuries, the company continued to conceal the defect and billed Medicare for the devices.

In 2016, the product was taken off the market at the request of the FDA.
 

Mass. doctor, wife charged in international money laundering, fraud scheme

Massachusetts psychiatrist Rahim Shafa, MD, and his wife and office manager, Nahid Tormosi Shafa, are charged in connection to an international money laundering scheme involving importing illegal and misbranded drugs. 

Through Shafa’s company, Novel Psychopharmacology, the two allegedly filed false and fraudulent Medicare reimbursement claims from 2016-2019, then deposited the money in their bank accounts, according to federal officials. From 2008-2018, the couple also engaged in an international money laundering scheme to purchase naltrexone pellet implants, disulfiram pellet implants, and injections from Hong Kong that were not approved by the FDA. According to officials, they falsified shipping documents, disguising the naltrexone pellet implants as “plastic beads in plastic tubes” to receive the drugs. They then offered to sell these drugs to patients of Novel Psychopharmacology. 

Rahim Shafa was indicted on conspiracies of international money laundering, health care fraud, and defrauding the United States, as well as illegally importing merchandise and purposely delivering misbranded drugs. His wife was indicted on one count each of health care fraud conspiracy and international money laundering conspiracy.
 

Jury convicts medical equipment company owners of $27 million fraud

A federal jury in Texas convicted the owners of two durable medical equipment (DME) companies linked to a scheme to defraud Medicare.

Leah Hagen, 49, and Michael Hagen, 54, were convicted of one count of conspiracy to defraud the United States and to pay and receive health care kickbacks and one count of conspiracy to commit money laundering. The defendants owned and operated Metro DME Supply and Ortho Pain Solutions. 

Ms. Hagen and Mr. Hagen paid a fixed rate per DME item in exchange for prescriptions and paperwork completed by telemedicine doctors that were used to submit false claims to Medicare, which totaled about $59 million. They were paid $27 million, and wired millions to their personal bank accounts. The defendants paid illegal bribes and kickbacks and wired money to their co-conspirator’s call center in the Philippines that provided signed doctor’s orders for orthotic braces. 

At trial, evidence showed emails between Leah and Michael Hagen and their co-conspirators outlining a per-product pricing structure for orthotic braces, but not disclosing their agreement as one for marketing and other services.

At sentencing, the Hagens each face a maximum sentence of 25 years in prison.

A version of this article first appeared on Medscape.com.

Once-daily dosing of poziotinib shows clinically meaningful efficacy for patients with treatment-naive non–small cell lung cancer (NSCLC) HER2 exon 20 mutations, according to results of the ZENITH20 trial presented at the 2021 European Society for Medical Oncology Congress. Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.

EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.

Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.

All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.

Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).

The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.

Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.

Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.

Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.

HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.

Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”

The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.

Once-daily dosing of poziotinib shows clinically meaningful efficacy for patients with treatment-naive non–small cell lung cancer (NSCLC) HER2 exon 20 mutations, according to results of the ZENITH20 trial presented at the 2021 European Society for Medical Oncology Congress. Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.

EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.

Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.

All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.

Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).

The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.

Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.

Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.

Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.

HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.

Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”

The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.

Once-daily dosing of poziotinib shows clinically meaningful efficacy for patients with treatment-naive non–small cell lung cancer (NSCLC) HER2 exon 20 mutations, according to results of the ZENITH20 trial presented at the 2021 European Society for Medical Oncology Congress. Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.

EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.

Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.

All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.

Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).

The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.

Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.

Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.

Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.

HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.

Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”

The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.

Weekly COVID-19 cases in children dropped again, but the count remained above 200,000 for the fifth consecutive week, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Over that 5-week span since the end of August, in fact, the United States has added over 1.13 million new cases, or just under 20% of all cases (5.7 million) in children during the entire pandemic, based on the data in the AAP/CHA joint weekly report on COVID in children.

In the most recent week, Sept. 17-23, there were almost 207,000 new cases of COVID-19 in children, which represented 26.7% of all cases reported in the 46 states that are currently posting data by age on their COVID dashboards, the AAP and CHA said. (New York has never reported such data by age, and Alabama, Nebraska, and Texas have not updated their websites since July 29, June 24, and Aug. 26, respectively.)

The decline in new vaccinations among children, however, began before the summer surge in new cases hit its peak – 251,781 during the week of Aug. 27 to Sept. 2 – and has continued for 7 straight weeks in children aged 12-17 years, based on data from the Centers for Disease Control and Prevention.

There were about 172,000 COVID vaccine initiations in children aged 12-17 for the week of Sept. 21-27, the lowest number since April, before it was approved for use in 12- to 15-year-olds. That figure is down by almost a third from the previous week and by more than two-thirds since early August, just before the decline in vaccinations began, according to the CDC’s COVID Data Tracker.

The cumulative vaccine situation looks like this: Just over 13 million children under age 18 years have received at least one dose as of Sept. 27, and almost 10.6 million are fully vaccinated. By age group, 53.9% of 12- to 15-year-olds and 61.6% of 16- to 17-year-olds have received at least one dose, with corresponding figures of 43.3% and 51.3% for full vaccination, the CDC said.

COVID-related hospital admissions also continue to fall after peaking at 0.51 children aged 0-17 per 100,000 population on Sept. 4. The admission rate was down to 0.45 per 100,000 as of Sept. 17, and the latest 7-day average (Sept. 19-25) was 258 admissions, compared with a peak of 371 for the week of Aug. 29 to Sept. 4, the CDC reported.

“Although we have seen slight improvements in COVID-19 volumes in the past week, we are at the beginning of an anticipated increase in” multi-inflammatory syndrome in children, Margaret Rush, MD, president of Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn., said at a recent hearing of the House Committee on Energy and Commerce’s Oversight subcommittee. That increase would be expected to produce “a secondary wave of seriously ill children 3-6 weeks after acute infection peaks in the community,” the American Hospital Association said.

Meanwhile, Dr. Rush noted, there are signs that seasonal viruses are coming into play. “With the emergence of the Delta variant, we’ve experienced a steep increase in COVID-19 hospitalizations among children on top of an early surge of [respiratory syncytial virus], a serious respiratory illness we usually see in the winter months,” she said in a prepared statement before her testimony.

[email protected]

Weekly COVID-19 cases in children dropped again, but the count remained above 200,000 for the fifth consecutive week, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Over that 5-week span since the end of August, in fact, the United States has added over 1.13 million new cases, or just under 20% of all cases (5.7 million) in children during the entire pandemic, based on the data in the AAP/CHA joint weekly report on COVID in children.

In the most recent week, Sept. 17-23, there were almost 207,000 new cases of COVID-19 in children, which represented 26.7% of all cases reported in the 46 states that are currently posting data by age on their COVID dashboards, the AAP and CHA said. (New York has never reported such data by age, and Alabama, Nebraska, and Texas have not updated their websites since July 29, June 24, and Aug. 26, respectively.)

The decline in new vaccinations among children, however, began before the summer surge in new cases hit its peak – 251,781 during the week of Aug. 27 to Sept. 2 – and has continued for 7 straight weeks in children aged 12-17 years, based on data from the Centers for Disease Control and Prevention.

There were about 172,000 COVID vaccine initiations in children aged 12-17 for the week of Sept. 21-27, the lowest number since April, before it was approved for use in 12- to 15-year-olds. That figure is down by almost a third from the previous week and by more than two-thirds since early August, just before the decline in vaccinations began, according to the CDC’s COVID Data Tracker.

The cumulative vaccine situation looks like this: Just over 13 million children under age 18 years have received at least one dose as of Sept. 27, and almost 10.6 million are fully vaccinated. By age group, 53.9% of 12- to 15-year-olds and 61.6% of 16- to 17-year-olds have received at least one dose, with corresponding figures of 43.3% and 51.3% for full vaccination, the CDC said.

COVID-related hospital admissions also continue to fall after peaking at 0.51 children aged 0-17 per 100,000 population on Sept. 4. The admission rate was down to 0.45 per 100,000 as of Sept. 17, and the latest 7-day average (Sept. 19-25) was 258 admissions, compared with a peak of 371 for the week of Aug. 29 to Sept. 4, the CDC reported.

“Although we have seen slight improvements in COVID-19 volumes in the past week, we are at the beginning of an anticipated increase in” multi-inflammatory syndrome in children, Margaret Rush, MD, president of Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn., said at a recent hearing of the House Committee on Energy and Commerce’s Oversight subcommittee. That increase would be expected to produce “a secondary wave of seriously ill children 3-6 weeks after acute infection peaks in the community,” the American Hospital Association said.

Meanwhile, Dr. Rush noted, there are signs that seasonal viruses are coming into play. “With the emergence of the Delta variant, we’ve experienced a steep increase in COVID-19 hospitalizations among children on top of an early surge of [respiratory syncytial virus], a serious respiratory illness we usually see in the winter months,” she said in a prepared statement before her testimony.

[email protected]

Weekly COVID-19 cases in children dropped again, but the count remained above 200,000 for the fifth consecutive week, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Over that 5-week span since the end of August, in fact, the United States has added over 1.13 million new cases, or just under 20% of all cases (5.7 million) in children during the entire pandemic, based on the data in the AAP/CHA joint weekly report on COVID in children.

In the most recent week, Sept. 17-23, there were almost 207,000 new cases of COVID-19 in children, which represented 26.7% of all cases reported in the 46 states that are currently posting data by age on their COVID dashboards, the AAP and CHA said. (New York has never reported such data by age, and Alabama, Nebraska, and Texas have not updated their websites since July 29, June 24, and Aug. 26, respectively.)

The decline in new vaccinations among children, however, began before the summer surge in new cases hit its peak – 251,781 during the week of Aug. 27 to Sept. 2 – and has continued for 7 straight weeks in children aged 12-17 years, based on data from the Centers for Disease Control and Prevention.

There were about 172,000 COVID vaccine initiations in children aged 12-17 for the week of Sept. 21-27, the lowest number since April, before it was approved for use in 12- to 15-year-olds. That figure is down by almost a third from the previous week and by more than two-thirds since early August, just before the decline in vaccinations began, according to the CDC’s COVID Data Tracker.

The cumulative vaccine situation looks like this: Just over 13 million children under age 18 years have received at least one dose as of Sept. 27, and almost 10.6 million are fully vaccinated. By age group, 53.9% of 12- to 15-year-olds and 61.6% of 16- to 17-year-olds have received at least one dose, with corresponding figures of 43.3% and 51.3% for full vaccination, the CDC said.

COVID-related hospital admissions also continue to fall after peaking at 0.51 children aged 0-17 per 100,000 population on Sept. 4. The admission rate was down to 0.45 per 100,000 as of Sept. 17, and the latest 7-day average (Sept. 19-25) was 258 admissions, compared with a peak of 371 for the week of Aug. 29 to Sept. 4, the CDC reported.

“Although we have seen slight improvements in COVID-19 volumes in the past week, we are at the beginning of an anticipated increase in” multi-inflammatory syndrome in children, Margaret Rush, MD, president of Monroe Carell Jr. Children’s Hospital at Vanderbilt University, Nashville, Tenn., said at a recent hearing of the House Committee on Energy and Commerce’s Oversight subcommittee. That increase would be expected to produce “a secondary wave of seriously ill children 3-6 weeks after acute infection peaks in the community,” the American Hospital Association said.

Meanwhile, Dr. Rush noted, there are signs that seasonal viruses are coming into play. “With the emergence of the Delta variant, we’ve experienced a steep increase in COVID-19 hospitalizations among children on top of an early surge of [respiratory syncytial virus], a serious respiratory illness we usually see in the winter months,” she said in a prepared statement before her testimony.

[email protected]

A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.

Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA  vaccines, according to a report in JAMA Network Open.

In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.

Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.

PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.

No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.

This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.

“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.

In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).

“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.

The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.

Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.

A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.

Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.

High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.

The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.

“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”

The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.

Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA  vaccines, according to a report in JAMA Network Open.

In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.

Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.

PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.

No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.

This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.

“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.

In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).

“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.

The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.

Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.

A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.

Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.

High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.

The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.

“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”

The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A common inert ingredient may be the culprit behind the rare allergic reactions reported among individuals who have received mRNA COVID-19 vaccines, according to investigators at a large regional health center that was among the first to administer the shots.

Blood samples from 10 of 11 individuals with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of both the Pfizer and Moderna mRNA  vaccines, according to a report in JAMA Network Open.

In total, only 22 individuals had suspected allergic reactions out of nearly 39,000 mRNA COVID-19 vaccine doses administered, the investigators reported, noting that the reactions were generally mild and all fully resolved.

Those findings should be reassuring to individuals who are reticent to sign up for a COVID-19 vaccine because of fear of an allergic reaction, said study senior author Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.

“We’re hoping that this word will get out and then that the companies could also think about making vaccines that have other products in them that don’t include polyethylene glycol,” Dr. Nadeau said in an interview.

PEG is a compound used in many products, including pharmaceuticals, cosmetics, and food. In the mRNA COVID-19 vaccines, PEG serves to stabilize the lipid nanoparticles that help protect and transport mRNA. However, its use in this setting has been linked to allergic reactions in this and previous studies.

No immunoglobulin E (IgE) antibodies to PEG were detected among the 22 individuals with suspected allergic reactions to mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. That suggests non-IgE mediated allergic reactions to PEG may be implicated for the majority of cases, Dr. Nadeau said.

This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic response is behind the suspected allergic reactions that are occurring after mRNA COVID-19 vaccine, said Aleena Banerji, MD, associate professor at Harvard Medical School, Boston, and clinical director of the Drug Allergy Program at Massachusetts General Hospital.

“We need to further understand the mechanism of these reactions, but what we know is that IGE mediated allergy to excipients like PEG is probably not the main cause,” Dr. Banerji, who was not involved in the study, said in an interview.

In a recent research letter published in JAMA Internal Medicine, Dr. Banerji and coauthors reported that all individuals with immediate suspected allergic reactions to mRNA COVID-19 vaccine went on to tolerate the second dose, with mild symptoms reported in the minority of patients (32 out of 159, or about 20%).

“Again, that is very consistent with not having an IgE-mediated allergy, so it seems to all be fitting with that picture,” Dr. Banerji said.

The case series by Dr. Nadeau and coauthors was based on review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most mRNA vaccine recipients were Stanford-affiliated health care workers, according to the report.

Among recipients of those doses, they identified 148 individuals who had anaphylaxis-related ICD-10 codes recorded over the same time period. In a review of medical records, investigators pinpointed 22 individuals as having suspected allergy and invited them to participate in follow-up allergy testing.

A total of 11 individuals underwent skin prick testing, but none of them tested positive to PEG or to polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients tested positive to the same mRNA vaccine they had previously received, according to the report.

Those same 11 individuals also underwent basophil activation testing (BAT). In contrast to the skin testing results, BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for their administered vaccine in all 11 cases, the report shows.

High levels of IgG to PEG were identified in blood samples of individuals with an allergy to the vaccine. Investigators said it’s possible that the BAT results were activated due to IgG via complement activation–related pseudoallergy, or CARPA, as has been hypothesized by some other investigators.

The negative skin prick testing results for PEG, which contrast with the positive BAT results to PEG, suggest that the former may not be appropriate for use as a predictive marker of potential vaccine allergy, according to Dr. Nadeau.

“The take-home message for doctors is to be careful,” she said. “Don’t assume that just because the person skin-tests negative to PEG or to the vaccine itself that you’re out of the woods, because the skin test would be often negative in those scenarios.”

The study was supported by a grants from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation. Dr. Nadeau reports numerous conflicts with various sources in the industry. Dr. Banerji has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

On Sept. 1, Texas enacted astonishing legislation that effectively bans abortion after a fetal heartbeat is detected. In addition, it further empowers private citizens to sue anyone “aiding and abetting” patients who seek abortion services. Many organizations, including Planned Parenthood and the American College of Obstetricians and Gynecologists, have issued formalized statements condemning the bill. While we as obstetrician/gynecologists try to remain as nonpartisan as humanly possible in our patient care, unfortunately our specialty is inarguably one of the few in the medical field that is routinely significantly affected by federal and state politics.

It is no secret that Texas Senate Bill 8, otherwise referred to the “Texas Heartbeat Act,” will have devastating consequences for women, particularly women of color, but it will also have potentially catastrophic repercussions for patients who identify as LGBTQ. Overall, the LGBTQ population faces higher rates of poverty, unemployment, insurance coverage barriers, and provider discrimination because of their gender identity or sexual orientation, which can make access to abortion services challenging. Furthermore, they are more susceptible to hate-motivated violence and sexual assault and as a result, may seek to terminate pregnancies that result from these traumatic experiences.

A survey conducted by the Centers for Disease Control and Prevention examining rates of intimate partner violence and sexual violence found that 44% of lesbians and 61% of bisexual women experience rape and physical violence, compared with 35% of straight women.¹ A separate survey revealed that 47% of transgender people are sexually assaulted at some point in their lifetime, with rates reaching as high as 65% among transgender people of color.² Furthermore, many members of the LGBTQ population are misinformed or have misconceptions regarding their need for contraceptives and experience unintended pregnancies. As discussed in a previous column, one-third of pregnancies in transgender men were unplanned, and 20% of those patients were amenorrheic on testosterone at the time of conception.³

Current studies estimate that approximately 25% of all cisgender women will have an abortion. No corresponding data exist to describe the abortion rates of transgender and gender diverse patients.^4,5 Bills such as Texas SB8 make accessing safe abortions for patients virtually impossible and interferes with the ability for physicians to provide patients with much needed health care services. It further delegitimizes rape and incest victims and is almost punitive in requiring such victims to carry the unintended pregnancies resulting from these heinous acts to term.

Regardless of a provider’s feelings toward abortion or even gender-affirming care, it is undeniable that access to these services is necessary and should be readily available to patients seeking them. As we all took an oath in medical school to “do no harm,” we must not only abide by that solemn decree in everyday patient interactions, but also live by those words to advocate for our patients when politics prohibit appropriate care. While discussions surrounding abortion are often limited to cisgender, heterosexual patients, providers must also be aware that abortion access spans across a wider spectrum that includes the LGBTQ community. Our patients, and all patients, deserve equal access to abortion. This harmful law sets a dangerous precedent that could continue to threaten these services with detrimental effects to our patients.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Black MC et al. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 Summary Report. Atlanta, GA: National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; 2011.

2. James SE et al. The Report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality; 2016.

3. Abern L, Maguire K. Obstet Gynecol 2018;131:65S.

4. Jones RK et al. Abortion incidence and service availability in the Unites States, 2017. New York, NY: Guttmacher Institute: 2019.

5. Moseson H et al. Am J Obstet Gynecol 2021;224:376.e1-11.

On Sept. 1, Texas enacted astonishing legislation that effectively bans abortion after a fetal heartbeat is detected. In addition, it further empowers private citizens to sue anyone “aiding and abetting” patients who seek abortion services. Many organizations, including Planned Parenthood and the American College of Obstetricians and Gynecologists, have issued formalized statements condemning the bill. While we as obstetrician/gynecologists try to remain as nonpartisan as humanly possible in our patient care, unfortunately our specialty is inarguably one of the few in the medical field that is routinely significantly affected by federal and state politics.

It is no secret that Texas Senate Bill 8, otherwise referred to the “Texas Heartbeat Act,” will have devastating consequences for women, particularly women of color, but it will also have potentially catastrophic repercussions for patients who identify as LGBTQ. Overall, the LGBTQ population faces higher rates of poverty, unemployment, insurance coverage barriers, and provider discrimination because of their gender identity or sexual orientation, which can make access to abortion services challenging. Furthermore, they are more susceptible to hate-motivated violence and sexual assault and as a result, may seek to terminate pregnancies that result from these traumatic experiences.

A survey conducted by the Centers for Disease Control and Prevention examining rates of intimate partner violence and sexual violence found that 44% of lesbians and 61% of bisexual women experience rape and physical violence, compared with 35% of straight women.¹ A separate survey revealed that 47% of transgender people are sexually assaulted at some point in their lifetime, with rates reaching as high as 65% among transgender people of color.² Furthermore, many members of the LGBTQ population are misinformed or have misconceptions regarding their need for contraceptives and experience unintended pregnancies. As discussed in a previous column, one-third of pregnancies in transgender men were unplanned, and 20% of those patients were amenorrheic on testosterone at the time of conception.³

Current studies estimate that approximately 25% of all cisgender women will have an abortion. No corresponding data exist to describe the abortion rates of transgender and gender diverse patients.^4,5 Bills such as Texas SB8 make accessing safe abortions for patients virtually impossible and interferes with the ability for physicians to provide patients with much needed health care services. It further delegitimizes rape and incest victims and is almost punitive in requiring such victims to carry the unintended pregnancies resulting from these heinous acts to term.

Regardless of a provider’s feelings toward abortion or even gender-affirming care, it is undeniable that access to these services is necessary and should be readily available to patients seeking them. As we all took an oath in medical school to “do no harm,” we must not only abide by that solemn decree in everyday patient interactions, but also live by those words to advocate for our patients when politics prohibit appropriate care. While discussions surrounding abortion are often limited to cisgender, heterosexual patients, providers must also be aware that abortion access spans across a wider spectrum that includes the LGBTQ community. Our patients, and all patients, deserve equal access to abortion. This harmful law sets a dangerous precedent that could continue to threaten these services with detrimental effects to our patients.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Black MC et al. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 Summary Report. Atlanta, GA: National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; 2011.

2. James SE et al. The Report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality; 2016.

3. Abern L, Maguire K. Obstet Gynecol 2018;131:65S.

4. Jones RK et al. Abortion incidence and service availability in the Unites States, 2017. New York, NY: Guttmacher Institute: 2019.

5. Moseson H et al. Am J Obstet Gynecol 2021;224:376.e1-11.

On Sept. 1, Texas enacted astonishing legislation that effectively bans abortion after a fetal heartbeat is detected. In addition, it further empowers private citizens to sue anyone “aiding and abetting” patients who seek abortion services. Many organizations, including Planned Parenthood and the American College of Obstetricians and Gynecologists, have issued formalized statements condemning the bill. While we as obstetrician/gynecologists try to remain as nonpartisan as humanly possible in our patient care, unfortunately our specialty is inarguably one of the few in the medical field that is routinely significantly affected by federal and state politics.

It is no secret that Texas Senate Bill 8, otherwise referred to the “Texas Heartbeat Act,” will have devastating consequences for women, particularly women of color, but it will also have potentially catastrophic repercussions for patients who identify as LGBTQ. Overall, the LGBTQ population faces higher rates of poverty, unemployment, insurance coverage barriers, and provider discrimination because of their gender identity or sexual orientation, which can make access to abortion services challenging. Furthermore, they are more susceptible to hate-motivated violence and sexual assault and as a result, may seek to terminate pregnancies that result from these traumatic experiences.

A survey conducted by the Centers for Disease Control and Prevention examining rates of intimate partner violence and sexual violence found that 44% of lesbians and 61% of bisexual women experience rape and physical violence, compared with 35% of straight women.¹ A separate survey revealed that 47% of transgender people are sexually assaulted at some point in their lifetime, with rates reaching as high as 65% among transgender people of color.² Furthermore, many members of the LGBTQ population are misinformed or have misconceptions regarding their need for contraceptives and experience unintended pregnancies. As discussed in a previous column, one-third of pregnancies in transgender men were unplanned, and 20% of those patients were amenorrheic on testosterone at the time of conception.³

Current studies estimate that approximately 25% of all cisgender women will have an abortion. No corresponding data exist to describe the abortion rates of transgender and gender diverse patients.^4,5 Bills such as Texas SB8 make accessing safe abortions for patients virtually impossible and interferes with the ability for physicians to provide patients with much needed health care services. It further delegitimizes rape and incest victims and is almost punitive in requiring such victims to carry the unintended pregnancies resulting from these heinous acts to term.

Regardless of a provider’s feelings toward abortion or even gender-affirming care, it is undeniable that access to these services is necessary and should be readily available to patients seeking them. As we all took an oath in medical school to “do no harm,” we must not only abide by that solemn decree in everyday patient interactions, but also live by those words to advocate for our patients when politics prohibit appropriate care. While discussions surrounding abortion are often limited to cisgender, heterosexual patients, providers must also be aware that abortion access spans across a wider spectrum that includes the LGBTQ community. Our patients, and all patients, deserve equal access to abortion. This harmful law sets a dangerous precedent that could continue to threaten these services with detrimental effects to our patients.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Black MC et al. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 Summary Report. Atlanta, GA: National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; 2011.

2. James SE et al. The Report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality; 2016.

3. Abern L, Maguire K. Obstet Gynecol 2018;131:65S.

4. Jones RK et al. Abortion incidence and service availability in the Unites States, 2017. New York, NY: Guttmacher Institute: 2019.

5. Moseson H et al. Am J Obstet Gynecol 2021;224:376.e1-11.

The investigational oral, neuroactive, steroid-positive allosteric modulator SAGE-324/BIIB124 (SAGE-324) is effective for treating essential tremor – but problems with tolerability may limit its usefulness, new research suggests.

The phase 2 KINETIC trial involved patients with essential tremor. Among patients treated with SAGE-324 for 28 days, there was a statistically significant reduction in upper-limb tremors on day 29 – meeting the primary endpoint of the study.

However, moderate to severe treatment-emergent adverse events (TEAEs) led to many treatment and/or study discontinuations, the investigators reported.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Mechanism of action

Essential tremor affects an estimated 6.4 million adults in the United States. Available drugs are not helpful for 30%-50% of these patients. No new drug for this condition has been approved by the Food and Drug Administration for the past 50 years. Of the several drugs used to treat essential tremor, propranolol is the only one that has been approved, according to the American Academy of Neurology.

Deficits in inhibitory signaling via the gamma-aminobutyric acid system may have a role in the pathophysiology of essential tremor because the GABAergic system is the major neuroinhibitory system in the brain.

SAGE-324 is a steroid-positive allosteric modulator of the GABAA receptor. It acts on the receptor distant from the neuronal synapse to enhance GABAergic (inhibitory) signaling.

In the phase 2 multicenter KINETIC trial, investigators enrolled 69 patients aged 18-80 years. The patients had moderate to severe essential tremor, as determined on the basis of their having a score of 10 or higher on item 4 of the Essential Tremor Rating Assessment Scale (TETRAS) on screening day and at baseline/day 1 of the trial.

Participants did not take medications for essential tremor during the 28-day washout period. They were randomly assigned in a 1:1 ratio to receive SAGE-324 60 mg (n = 34) or placebo (n = 35) once daily. Dose reductions were allowed.

The groups were reasonably matched for age (mean, 69.4 years for SAGE-324 vs. 64.7 years for placebo) and dominant hand (right, 85.3% for SAGE-324 vs. 88.6% for placebo). Women composed 35.3% of the drug group and 57.1% of the placebo group.

The primary endpoint of the trial was change from baseline for the active drug in comparison with placebo on day 29 (1 day after the final dose) for upper-limb tremor, as measured by item 4 of TETRAS. There was also a 2-week follow-up with assessments on day 42.
 

Primary endpoint met, high dropout rate

Baseline mean TETRAS Performance Subscale item 4 scores were 12.82 for the SAGE-324 group and 12.28 for the placebo group.

On day 29, the least squares mean difference from baseline was –2.31 with SAGE-324 (n = 21) versus –1.24 with placebo (n = 33; P = .049). There was no difference between the SAGE-324 and placebo groups on day 42.

“Their significant reduction in upper-limb tremor score at day 29 corresponds to a 36% reduction from baseline in tremor amplitude in patients receiving SAGE-324, compared with a 21% reduction in tremor amplitude in patients receiving a placebo,” said lead investigator Kemi Bankole, MBBCh, of Sage Therapeutics.

“A reduction in tremor amplitude of 36% is a clinically significant improvement for most patients with essential tremor. For patients with moderate-severe tremor, a 41% improvement would be clinically noticeable and appreciated,” said Helen Colquhoun, MBChB, vice president at Sage.

“We believe patients with more severe tremor, that is, a TETRAS score of greater than 12, represent the majority of [essential tremor] patients getting diagnosed and seeking treatment today,” Dr. Colquhoun said.

There was an even greater reduction in tremor amplitude for the subgroup of patients with more severe tremor at baseline, meaning those with a median TETRAS score of 12 or greater (–2.75 for SAGE-324 vs. –1.05 for placebo; P = .0066).

These figures represented a 41% reduction from baseline in tremor amplitude for the SAGE-324 group, versus an 18% reduction in the placebo group. Again, the effect had disappeared in comparison with placebo at the 2-week off-drug follow-up on day 42.

Tolerability of SAGE-324 was a major problem, leading to dose reductions, treatment discontinuations, and study discontinuations. Of the 34 patients who received SAGE-324, 13 dropped out of the study, compared with 2 of 35 patients who received placebo.

Most TEAEs were moderate or severe in the SAGE-324 group, whereas most were mild in the placebo group.

The most common TEAEs for participants who received SAGE-324 were somnolence (67.6%) and dizziness (38.2%), followed by balance problems, diplopia, dysarthria, and gait disturbance. In the placebo group, somnolence affected 5.7%, and dizziness affected 11.4%. There were no deaths in either group.

Dr. Colquhoun said these findings “are in line with our expectations for the 60-mg dose.”

More than one-third of the SAGE-324 group discontinued treatment before the end of the trial, and continuing treatment often required dose reductions. Only 24% completed the trial while taking the 60-mg dose; 15% completed the trial while taking 45 mg; and 24% did so while taking 30 mg.

Dr. Colquhoun noted that the company plans to initiate a phase 2b dose-ranging study later this year to optimize the dosing regimen with regard to tolerability and sustained tremor control.
 

No advantage over older drugs?

Commenting on the findings, Michele Tagliati, MD, director of the movement disorders program at Cedars-Sinai Medical Center, Los Angeles, said he had been aware of the study and was interested in seeing the results. However, he does not see an advantage with this drug, compared with what is already used for essential tremor.

“The response of people is not that different than when we treat them with the old barbiturates and benzodiazepines,” said Dr. Tagliati, who was not involved with the research.

He also noted the high rate of adverse events, particularly somnolence, and said that in his experience with current treatments, some patients prefer to live with their tremors rather than be sleepy and not thinking well.

Dr. Tagliati said he thinks use of SAGE-324 is going to be limited to patients who can tolerate it, “which was not that many.”

In addition, the trial was limited by its relatively small size, a “huge placebo effect,” and a high dropout rate in the active treatment arm, he concluded.

The study was funded by Sage Therapeutics and Biogen. Dr. Bankole and Dr. Calquhoun are employees of Sage. Dr. Tagliati reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The investigational oral, neuroactive, steroid-positive allosteric modulator SAGE-324/BIIB124 (SAGE-324) is effective for treating essential tremor – but problems with tolerability may limit its usefulness, new research suggests.

The phase 2 KINETIC trial involved patients with essential tremor. Among patients treated with SAGE-324 for 28 days, there was a statistically significant reduction in upper-limb tremors on day 29 – meeting the primary endpoint of the study.

However, moderate to severe treatment-emergent adverse events (TEAEs) led to many treatment and/or study discontinuations, the investigators reported.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Mechanism of action

Essential tremor affects an estimated 6.4 million adults in the United States. Available drugs are not helpful for 30%-50% of these patients. No new drug for this condition has been approved by the Food and Drug Administration for the past 50 years. Of the several drugs used to treat essential tremor, propranolol is the only one that has been approved, according to the American Academy of Neurology.

Deficits in inhibitory signaling via the gamma-aminobutyric acid system may have a role in the pathophysiology of essential tremor because the GABAergic system is the major neuroinhibitory system in the brain.

SAGE-324 is a steroid-positive allosteric modulator of the GABAA receptor. It acts on the receptor distant from the neuronal synapse to enhance GABAergic (inhibitory) signaling.

In the phase 2 multicenter KINETIC trial, investigators enrolled 69 patients aged 18-80 years. The patients had moderate to severe essential tremor, as determined on the basis of their having a score of 10 or higher on item 4 of the Essential Tremor Rating Assessment Scale (TETRAS) on screening day and at baseline/day 1 of the trial.

Participants did not take medications for essential tremor during the 28-day washout period. They were randomly assigned in a 1:1 ratio to receive SAGE-324 60 mg (n = 34) or placebo (n = 35) once daily. Dose reductions were allowed.

The groups were reasonably matched for age (mean, 69.4 years for SAGE-324 vs. 64.7 years for placebo) and dominant hand (right, 85.3% for SAGE-324 vs. 88.6% for placebo). Women composed 35.3% of the drug group and 57.1% of the placebo group.

The primary endpoint of the trial was change from baseline for the active drug in comparison with placebo on day 29 (1 day after the final dose) for upper-limb tremor, as measured by item 4 of TETRAS. There was also a 2-week follow-up with assessments on day 42.
 

Primary endpoint met, high dropout rate

Baseline mean TETRAS Performance Subscale item 4 scores were 12.82 for the SAGE-324 group and 12.28 for the placebo group.

On day 29, the least squares mean difference from baseline was –2.31 with SAGE-324 (n = 21) versus –1.24 with placebo (n = 33; P = .049). There was no difference between the SAGE-324 and placebo groups on day 42.

“Their significant reduction in upper-limb tremor score at day 29 corresponds to a 36% reduction from baseline in tremor amplitude in patients receiving SAGE-324, compared with a 21% reduction in tremor amplitude in patients receiving a placebo,” said lead investigator Kemi Bankole, MBBCh, of Sage Therapeutics.

“A reduction in tremor amplitude of 36% is a clinically significant improvement for most patients with essential tremor. For patients with moderate-severe tremor, a 41% improvement would be clinically noticeable and appreciated,” said Helen Colquhoun, MBChB, vice president at Sage.

“We believe patients with more severe tremor, that is, a TETRAS score of greater than 12, represent the majority of [essential tremor] patients getting diagnosed and seeking treatment today,” Dr. Colquhoun said.

There was an even greater reduction in tremor amplitude for the subgroup of patients with more severe tremor at baseline, meaning those with a median TETRAS score of 12 or greater (–2.75 for SAGE-324 vs. –1.05 for placebo; P = .0066).

These figures represented a 41% reduction from baseline in tremor amplitude for the SAGE-324 group, versus an 18% reduction in the placebo group. Again, the effect had disappeared in comparison with placebo at the 2-week off-drug follow-up on day 42.

Tolerability of SAGE-324 was a major problem, leading to dose reductions, treatment discontinuations, and study discontinuations. Of the 34 patients who received SAGE-324, 13 dropped out of the study, compared with 2 of 35 patients who received placebo.

Most TEAEs were moderate or severe in the SAGE-324 group, whereas most were mild in the placebo group.

The most common TEAEs for participants who received SAGE-324 were somnolence (67.6%) and dizziness (38.2%), followed by balance problems, diplopia, dysarthria, and gait disturbance. In the placebo group, somnolence affected 5.7%, and dizziness affected 11.4%. There were no deaths in either group.

Dr. Colquhoun said these findings “are in line with our expectations for the 60-mg dose.”

More than one-third of the SAGE-324 group discontinued treatment before the end of the trial, and continuing treatment often required dose reductions. Only 24% completed the trial while taking the 60-mg dose; 15% completed the trial while taking 45 mg; and 24% did so while taking 30 mg.

Dr. Colquhoun noted that the company plans to initiate a phase 2b dose-ranging study later this year to optimize the dosing regimen with regard to tolerability and sustained tremor control.
 

No advantage over older drugs?

Commenting on the findings, Michele Tagliati, MD, director of the movement disorders program at Cedars-Sinai Medical Center, Los Angeles, said he had been aware of the study and was interested in seeing the results. However, he does not see an advantage with this drug, compared with what is already used for essential tremor.

“The response of people is not that different than when we treat them with the old barbiturates and benzodiazepines,” said Dr. Tagliati, who was not involved with the research.

He also noted the high rate of adverse events, particularly somnolence, and said that in his experience with current treatments, some patients prefer to live with their tremors rather than be sleepy and not thinking well.

Dr. Tagliati said he thinks use of SAGE-324 is going to be limited to patients who can tolerate it, “which was not that many.”

In addition, the trial was limited by its relatively small size, a “huge placebo effect,” and a high dropout rate in the active treatment arm, he concluded.

The study was funded by Sage Therapeutics and Biogen. Dr. Bankole and Dr. Calquhoun are employees of Sage. Dr. Tagliati reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The investigational oral, neuroactive, steroid-positive allosteric modulator SAGE-324/BIIB124 (SAGE-324) is effective for treating essential tremor – but problems with tolerability may limit its usefulness, new research suggests.

The phase 2 KINETIC trial involved patients with essential tremor. Among patients treated with SAGE-324 for 28 days, there was a statistically significant reduction in upper-limb tremors on day 29 – meeting the primary endpoint of the study.

However, moderate to severe treatment-emergent adverse events (TEAEs) led to many treatment and/or study discontinuations, the investigators reported.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Mechanism of action

Essential tremor affects an estimated 6.4 million adults in the United States. Available drugs are not helpful for 30%-50% of these patients. No new drug for this condition has been approved by the Food and Drug Administration for the past 50 years. Of the several drugs used to treat essential tremor, propranolol is the only one that has been approved, according to the American Academy of Neurology.

Deficits in inhibitory signaling via the gamma-aminobutyric acid system may have a role in the pathophysiology of essential tremor because the GABAergic system is the major neuroinhibitory system in the brain.

SAGE-324 is a steroid-positive allosteric modulator of the GABAA receptor. It acts on the receptor distant from the neuronal synapse to enhance GABAergic (inhibitory) signaling.

In the phase 2 multicenter KINETIC trial, investigators enrolled 69 patients aged 18-80 years. The patients had moderate to severe essential tremor, as determined on the basis of their having a score of 10 or higher on item 4 of the Essential Tremor Rating Assessment Scale (TETRAS) on screening day and at baseline/day 1 of the trial.

Participants did not take medications for essential tremor during the 28-day washout period. They were randomly assigned in a 1:1 ratio to receive SAGE-324 60 mg (n = 34) or placebo (n = 35) once daily. Dose reductions were allowed.

The groups were reasonably matched for age (mean, 69.4 years for SAGE-324 vs. 64.7 years for placebo) and dominant hand (right, 85.3% for SAGE-324 vs. 88.6% for placebo). Women composed 35.3% of the drug group and 57.1% of the placebo group.

The primary endpoint of the trial was change from baseline for the active drug in comparison with placebo on day 29 (1 day after the final dose) for upper-limb tremor, as measured by item 4 of TETRAS. There was also a 2-week follow-up with assessments on day 42.
 

Primary endpoint met, high dropout rate

Baseline mean TETRAS Performance Subscale item 4 scores were 12.82 for the SAGE-324 group and 12.28 for the placebo group.

On day 29, the least squares mean difference from baseline was –2.31 with SAGE-324 (n = 21) versus –1.24 with placebo (n = 33; P = .049). There was no difference between the SAGE-324 and placebo groups on day 42.

“Their significant reduction in upper-limb tremor score at day 29 corresponds to a 36% reduction from baseline in tremor amplitude in patients receiving SAGE-324, compared with a 21% reduction in tremor amplitude in patients receiving a placebo,” said lead investigator Kemi Bankole, MBBCh, of Sage Therapeutics.

“A reduction in tremor amplitude of 36% is a clinically significant improvement for most patients with essential tremor. For patients with moderate-severe tremor, a 41% improvement would be clinically noticeable and appreciated,” said Helen Colquhoun, MBChB, vice president at Sage.

“We believe patients with more severe tremor, that is, a TETRAS score of greater than 12, represent the majority of [essential tremor] patients getting diagnosed and seeking treatment today,” Dr. Colquhoun said.

There was an even greater reduction in tremor amplitude for the subgroup of patients with more severe tremor at baseline, meaning those with a median TETRAS score of 12 or greater (–2.75 for SAGE-324 vs. –1.05 for placebo; P = .0066).

These figures represented a 41% reduction from baseline in tremor amplitude for the SAGE-324 group, versus an 18% reduction in the placebo group. Again, the effect had disappeared in comparison with placebo at the 2-week off-drug follow-up on day 42.

Tolerability of SAGE-324 was a major problem, leading to dose reductions, treatment discontinuations, and study discontinuations. Of the 34 patients who received SAGE-324, 13 dropped out of the study, compared with 2 of 35 patients who received placebo.

Most TEAEs were moderate or severe in the SAGE-324 group, whereas most were mild in the placebo group.

The most common TEAEs for participants who received SAGE-324 were somnolence (67.6%) and dizziness (38.2%), followed by balance problems, diplopia, dysarthria, and gait disturbance. In the placebo group, somnolence affected 5.7%, and dizziness affected 11.4%. There were no deaths in either group.

Dr. Colquhoun said these findings “are in line with our expectations for the 60-mg dose.”

More than one-third of the SAGE-324 group discontinued treatment before the end of the trial, and continuing treatment often required dose reductions. Only 24% completed the trial while taking the 60-mg dose; 15% completed the trial while taking 45 mg; and 24% did so while taking 30 mg.

Dr. Colquhoun noted that the company plans to initiate a phase 2b dose-ranging study later this year to optimize the dosing regimen with regard to tolerability and sustained tremor control.
 

No advantage over older drugs?

Commenting on the findings, Michele Tagliati, MD, director of the movement disorders program at Cedars-Sinai Medical Center, Los Angeles, said he had been aware of the study and was interested in seeing the results. However, he does not see an advantage with this drug, compared with what is already used for essential tremor.

“The response of people is not that different than when we treat them with the old barbiturates and benzodiazepines,” said Dr. Tagliati, who was not involved with the research.

He also noted the high rate of adverse events, particularly somnolence, and said that in his experience with current treatments, some patients prefer to live with their tremors rather than be sleepy and not thinking well.

Dr. Tagliati said he thinks use of SAGE-324 is going to be limited to patients who can tolerate it, “which was not that many.”

In addition, the trial was limited by its relatively small size, a “huge placebo effect,” and a high dropout rate in the active treatment arm, he concluded.

The study was funded by Sage Therapeutics and Biogen. Dr. Bankole and Dr. Calquhoun are employees of Sage. Dr. Tagliati reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.