[Posted 22/Feb/2023]

AUDIENCE: Family Medicine, Cardiology

KEY FINDINGS: Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.

BACKGROUND: Purpose of this study is to assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.

DETAILS: Cross-sectional study of a population-based cohort of women in Sweden (n = 10,528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected. A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.

Copyright © American Medical Association. All Rights Reserved.

Source: Lawesson, S. S., Swahn, E., Pihlsgard, M., et al. (2023). Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography. JAMA. 2023; 329(5): 393-404. Published: February 7, 2023. DOI: 10.1001/jama.2022.24093.

NIH-funded research effort identifies most common symptoms, potential subgroups, and initial symptom-based scoring system – with aim of improving future diagnostics and treatment.

[Posted 1/Jun/2023]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: Initial findings from a study of nearly 10,000 Americans, many of whom had COVID-19, have uncovered new details about long COVID, the post-infection set of conditions that can affect nearly every tissue and organ in the body. Clinical symptoms can vary and include fatigue, brain fog, and dizziness, and last for months or years after a person has COVID-19. The research team, funded by the National Institutes of Health, also found that long COVID was more common and severe in study participants infected before the 2021 Omicron variant.

The study, published in JAMA(link is external), is coordinated through the NIH’s Researching COVID to Enhance Recovery (RECOVER)(link is external) initiative, a nationwide effort dedicated to understanding why some people develop long-term symptoms following COVID-19, and most importantly, how to detect, treat, and prevent long COVID. The researchers hope this study is the next step toward potential treatments for long COVID, which affects the health and wellbeing of millions of Americans.

"Americans living with long COVID want to understand what is happening with their bodies," said ADM Rachel L. Levine, M.D., Assistant Secretary for Health. "RECOVER, as part of a broader government response, in collaboration with academia, industry, public health institutions, advocacy organizations and patients, is making great strides toward improving our understanding of long COVID and its associated conditions."

Researchers examined data from 9,764 adults, including 8,646 who had COVID-19 and 1,118 who did not have COVID-19. They assessed more than 30 symptoms across multiple body areas and organs and applied statistical analyses that identified 12 symptoms that most set apart those with and without long COVID: post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic cough, chest pain, and abnormal movements.

They then established a scoring system based on patient-reported symptoms. By assigning points to each of the 12 symptoms, the team gave each patient a score based on symptom combinations. With these scores in hand, researchers identified a meaningful threshold for identifying participants with long COVID. They also found that certain symptoms occurred together and defined four subgroups or "clusters" with a range of impacts on health.

Based on a subset of 2,231 patients in this analysis who had a first COVID-19 infection on or after Dec. 1, 2021, when the Omicron variant was circulating, about 10% experienced long-term symptoms or long COVID after six months. The results are based on a survey of a highly diverse set of patients and are not final. Survey results will next be compared for accuracy against an array of lab tests and imaging.

To date, more than 100 million Americans have been infected with SARS-CoV-2, the virus that causes COVID-19. As of April, the federal government’s Household Pulse survey(link is external) estimates that about 10% of adults infected with the virus continue to experience and suffer from the many symptoms termed together as long COVID. Patients and researchers have identified more than 200 symptoms associated with long COVID.

"This study is an important step toward defining long COVID beyond any one individual symptom," said study author Leora Horwitz, M.D., director of the Center for Healthcare Innovation and Delivery Science, and co-principal investigator for the RECOVER Clinical Science Core, at NYU Langone Health. "This approach — which may evolve over time — will serve as a foundation for scientific discovery and treatment design."

The researchers explain studying the underlying biological mechanisms of long COVID is central to advancing informed interventions and identifying effective treatment strategies.

In addition to establishing the scoring system, the researchers found that participants who were unvaccinated or who had COVID-19 before the Omicron strain emerged in 2021 were more likely to have long COVID and more severe cases of long COVID. Further, reinfections were also linked to higher long COVID frequency and severity, compared to people who only had COVID-19 once.

"While the score developed in this study is an important research tool and early step toward diagnosing and monitoring patients with long COVID, we recognize its limitations," said David C. Goff, M.D., Ph.D., director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute, part of NIH. Goff serves as an epidemiology lead for NIH RECOVER. "All patients suffering from long COVID deserve the attention and respect of the medical field, as well as care and treatment driven by their experiences. As treatments are developed, it will be important to consider the complete symptom profile."

The ongoing RECOVER research serves as the foundation for planned clinical trials, whose interventions are rooted in many of the symptoms outlined in this study. RECOVER clinical trials are expected to begin enrolling patient participants in 2023.

This research was funded by NIH agreements OT2HL161841, OT2HL161847, and OT2HL156812. Additional support came from grant R01 HL162373. For more information on RECOVER, visit https://recovercovid.org(link is external).

About RECOVER: The National Institutes of Health Researching COVID to Enhance Recovery (NIH RECOVER) Initiative is a $1.15 billion effort, including support through the American Rescue Plan Act of 2021, that seeks to identify how people recuperate from COVID-19, and who are at risk for developing post-acute sequelae of SARS-CoV-2 (PASC). Researchers are also working with patients, clinicians, and communities across the United States to identify strategies to prevent and treat the long-term effects of COVID – including long COVID. For more information, please visit recovercovid.org(link is external).

HHS Long COVID Coordination: This work is a part of the National Research Action Plan(link is external) (opens pdf), a broader government-wide effort in response to the Presidential Memorandum(link is external) directing the Secretary for the Department of Health and Human Services to mount a full and effective response to long COVID. Led by Assistant Secretary for Health Admiral Rachel Levine, the Plan and its companion Services and Supports for Longer-term Impacts of COVID-19(link is external) (opens pdf) report lay the groundwork to advance progress in the prevention, diagnosis, treatment, and provision of services for individuals experiencing long COVID.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference: Thaweethai T, Jolley SE, Karlson EW, et al. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA. Published online May 25, 2023. doi:10.1001/jama.2023.8823

Copyright © NIH. All rights reserved.

Source: Published: May, 2023. NIH.

[Posted 2/Jun/2023]

AUDIENCE: Psychiatry, Family Medicine

DETAILS: Today, the U.S. Food and Drug Administration approved Brixadi (buprenorphine) extended-release injection for subcutaneous use (under the skin) to treat moderate to severe opioid use disorder (OUD). Brixadi is available in two formulations, a weekly injection that can be used in patients who have started treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine, and a monthly version for patients already being treated with buprenorphine.

“Buprenorphine is an important treatment option for opioid use disorder. Today’s approval expands dosing options and provides people with opioid use disorder a greater opportunity to sustain long-term recovery,” said FDA Commissioner Robert M. Califf, M.D. “The FDA will continue to take the critical steps necessary to pursue efforts that advance evidence-based treatments for substance use disorders, which is a strategic priority under the FDA’s Overdose Prevention Framework.”

Buprenorphine is a safe and effective medication for the treatment of OUD. According to the Substance Abuse and Mental Health Services Administration (SAMHSA), patients receiving medication for their OUD cut their risk of death from all causes in half.

The FDA continues to implement a comprehensive approach to increase options to treat OUD. Earlier this month, the agency issued a joint letter with SAMHSA to clarify the importance of counseling and other services as part of a comprehensive treatment plan for OUD, and to also reiterate that supplying buprenorphine should not be made contingent upon participation in such services. The agency also held a virtual public workshop that highlighted the need for additional strengths and dosing regimens for extended-release formulations.

Brixadi is approved in both weekly and monthly subcutaneous injectable formulations at varying doses, including lower doses that may be appropriate for those who do not tolerate higher doses of extended-release buprenorphine that are currently available. The weekly doses are 8 milligrams (mg), 16 mg, 24 mg, 32 mg; and the monthly doses are 64 mg, 96 mg, 128 mg. The approved weekly formulation in various lower strengths offers a new option for people in recovery who may benefit from a weekly injection to maintain treatment adherence. Brixadi will be available through a Risk Evaluation and Mitigation Strategy (REMS) program and administered only by health care providers in a health care setting.

The most common adverse reactions (occurring in >=5% of patients) with Brixadi include injection-site pain, headache, constipation, nausea, injection-site erythema, itchy skin at the injection site (injection-site pruritus), insomnia and urinary tract infections.

The safety and efficacy of Brixadi were evaluated in a behavioral pharmacology study assessing the ability of two weekly doses of Brixadi to block the subjective effects of opioids, and one randomized, double-blind, active-controlled clinical trial in 428 adults with a diagnosis of moderate-to-severe OUD. After an initial test dose of transmucosal buprenorphine, patients were randomized to treatment with Brixadi plus a sublingual placebo, or active sublingual buprenorphine plus placebo injections. After titration over the first week, patients were treated with weekly injections over 12 weeks and then transitioned to monthly injections for an additional 12 weeks. A response to treatment was measured by urine drug screening and self-reporting of illicit opioid use during the treatment period. Patients were considered responders if they had negative opioid assessments at the end of each of the two treatment phases. The proportion of patients meeting the responder definition was 16.9% in the Brixadi group and 14.0% in the sublingual buprenorphine group.

The FDA granted approval of Brixadi to Braeburn Inc.

The agency remains focused on responding to all facets of substance use, misuse, substance use disorders, overdose and death in the U.S. through its FDA Overdose Prevention Framework. The framework’s priorities include: supporting primary prevention by eliminating unnecessary initial prescription drug exposure and inappropriate prolonged prescribing; encouraging harm reduction through innovation and education; advancing development of evidence-based treatments for substance use disorders; and protecting the public from unapproved, diverted or counterfeit drugs presenting overdose risks.

Copyright © FDA. All rights reserved.

Source: FDA Approves New Buprenorphine Treatment Option for Opioid Use Disorder. FDA. Published: May 23, 2023.

[Posted 31/May/2023]

AUDIENCE: Hematology, Infectious Disease

DETAILS: The U.S. Food and Drug Administration finalized recommendations for assessing blood donor eligibility using a set of individual risk-based questions to reduce the risk of transfusion-transmitted HIV. These questions will be the same for every donor, regardless of sexual orientation, sex or gender. Blood establishments may now implement these recommendations by revising their donor history questionnaires and procedures.

This updated policy is based on the best available scientific evidence and is in line with policies in place in countries like the United Kingdom and Canada. It will potentially expand the number of people eligible to donate blood, while also maintaining the appropriate safeguards to protect the safety of the blood supply.

These final recommendations are consistent with the policy initially proposed in January. The FDA worked diligently to review and consider all comments submitted to the agency to finalize these recommendations as quickly as possible. "The FDA has worked diligently to evaluate our policies and ensure we had the scientific evidence to support individual risk assessment for donor eligibility while maintaining appropriate safeguards to protect recipients of blood products. The implementation of these recommendations will represent a significant milestone for the agency and the LGBTQI+ community," said Peter Marks, M.D., PhD., director of the FDA’s Center for Biologics Evaluation and Research. "The FDA is committed to working closely with the blood collection industry to help ensure timely implementation of the new recommendations and we will continue to monitor the safety of the blood supply once this individual risk-based approach is in place."

This policy eliminates time-based deferrals and screening questions specific to men who have sex with men (MSM) and women who have sex with MSM. Under the final guidance issued today, all prospective blood donors will answer a series of individual, risk-based questions to determine eligibility. All prospective donors who report having a new sexual partner, or more than one sexual partner in the past three months, and anal sex in the past three months, would be deferred to reduce the likelihood of donations by individuals with new or recent HIV infection who may be in the window period for detection of HIV by nucleic acid testing.

Additionally, under these final recommendations, those taking medications to treat or prevent HIV infection (e.g., antiretroviral therapy (ART), pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP)), will also be deferred. Though these antiretroviral drugs are safe, effective, and an important public health tool, the available data demonstrate that their use may delay detection of HIV by currently licensed screening tests for blood donations, which may potentially give false negative results. Although HIV is not transmitted sexually by individuals with undetectable viral levels, this does not apply to transfusion transmission of HIV because a blood transfusion is administered intravenously, and a transfusion involves a large volume of blood compared to exposure with sexual contact. As stated in the guidance, individuals should not stop taking their prescribed medications, including PrEP, or PEP, in order to donate blood. The FDA remains committed to evaluating additional data and new technological developments as they become available to inform our donor eligibility recommendations.

The FDA has been evaluating alternatives to time-based deferrals for MSM and helping to facilitate the generation of scientific evidence that would support an individual risk based- assessment blood donor questionnaire. This scientific information has given the agency a solid foundation to support this new policy. The FDA strongly believes the implementation of an individual risk-based approach will not adversely affect the safety or availability of the U.S. blood supply.

The FDA carefully reviewed numerous data sources, including data from countries with similar HIV epidemiology that have implemented an individual risk-based approach for assessing donor eligibility, surveillance information obtained from the Transfusion Transmissible Infections Monitoring System, performance characteristics of nucleic acid testing for HIV and the FDA-funded Assessing Donor Variability And New Concepts in Eligibility study. The ADVANCE study examined the rates of HIV risk factors, such as anal sex and rates of HIV infection, as well as the usage of medications to treat or prevent HIV infection, among MSM study participants.

Copyright © FDA. All rights reserved.

Source: FDA Finalizes Move to Recommend Individual Risk Assessment to Determine Eligibility for Blood Donations. FDA. Published: May 11, 2023.

[Posted 26/May/2023]

AUDIENCE: Dermatology, Oncology

KEY FINDINGS: Patients with second primary melanomas demonstrated a significant survival advantage and thinner lesions compared with those with single primary melanomas. The reported tumor distributions support the role of full body skin examinations, with attention to the region of initial diagnosis.

BACKGROUND: Patients with single primary melanomas have an increased risk of developing subsequent melanomas. Secondary tumors diagnosed within and after 3 months are termed "synchronous" and "asynchronous," respectively. Purpose of the study is to compare tumor distributions and survival characteristics between patients with second primary melanomas and those with single primary melanomas.

DETAILS: Retrospective cohort study. Data were collected from an institutional database from 14,029 patients with a diagnosis of a primary melanoma seen between 1970 and 2004. The synchronous and asynchronous cohorts demonstrated significantly improved survival probabilities compared with the single primary cohort (P = .04 and .002, respectively). Single primary lesions (2.2 ± 2.3 mm) were significantly thicker than the first-identified synchronous (2.0 ± 1.7 mm) and asynchronous (1.7 ± 1.3 mm) lesions. Synchronous lesions were more likely to be anatomically concordant compared with asynchronous lesions (55.7% vs 38.2%, P < .001).

Copyright © Elsevier Ltd. All rights reserved.

Source: Sarver, M. M., Rames, J. D., Beasley, G. M., et al. (2023). Survival and Tumor Characteristics Of Patients Presenting With Single Primary Versus Second Primary Melanoma Lesions. Journal of the American Academy of Dermatology. 2023; 88(5): 1033-1039. Published: May, 2023. DOI: 10.1016/j.jaad.2022.04.046.

[Posted 26/May/2023]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: This study found that memantine treatment resulted in statistically significant reductions in hair pulling and skin-picking symptoms compared with placebo, with relatively high efficacy (based on number needed to treat), and was well tolerated. The glutamate system may prove to be a beneficial target in the treatment of compulsive behaviors.

BACKGROUND: Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin, leading to noticeable hair loss or tissue damage. To date there is a severe paucity of evidence-based treatments for these conditions. In this study, the authors sought to determine whether memantine, a glutamate modulator, is more effective than placebo in reducing hair-pulling and skin-picking behavior.

DETAILS: One hundred adults with trichotillomania or skin-picking disorder (86 women; mean age, 31.4 years [SD=10.2]) were enrolled in a double-blind trial of memantine (dosing range, 10-20 mg/day) or placebo for 8 weeks. Participants were assessed with measures of pulling and picking severity. Outcomes were examined using a linear mixed-effects model. The prespecified primary outcome measure was treatment-related change on the NIMH Trichotillomania Symptom Severity Scale, modified to include skin picking. Compared with placebo, memantine treatment was associated with significant improvements in scores on the NIMH scale, Sheehan Disability Scale, and Clinical Global Impressions severity scale in terms of treatment-by-time interactions. At study endpoint, 60.5% of participants in the memantine group were "much or very much improved," compared with 8.3% in the placebo group (number needed to treat=1.9). Adverse events did not differ significantly between the treatment arms.

Copyright © American Psychiatric Association. All rights reserved.

Source: Grant, J. E., Chesivoir, E., Valle, S., et al. (2023). Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder. Am J Psychiatry. 2023; 180(5): 348-356. Published: May, 2023. DOI: 10.1176/appi.ajp.20220737.