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RCT: Twice-Yearly Lenacapavir Reduces HIV Incidence in Men and Gender-Diverse Persons Background

28 Nov, 2024 | 12:38h | UTC

Background: Although preexposure prophylaxis (PrEP) effectively reduces HIV transmission, adherence to daily oral regimens is suboptimal among high-risk populations. Lenacapavir, a long-acting HIV-1 capsid inhibitor administered subcutaneously every six months, has shown efficacy in cisgender women, but its efficacy in men and gender-diverse individuals remains unclear.

Objective: To evaluate the safety and efficacy of twice-yearly subcutaneous lenacapavir compared to background HIV incidence and daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) in preventing HIV infection among men and gender-diverse persons.

Methods: In this phase 3, double-blind, randomized trial, 3,271 HIV-negative participants were assigned in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral F/TDF, with matching placebos. Participants were cisgender men, transgender women and men, and gender-nonbinary persons aged 16 or older who have sex with male-assigned partners. The primary endpoint compared HIV incidence in the lenacapavir group to background incidence; secondary analysis compared lenacapavir to F/TDF.

Results: In the modified intention-to-treat analysis (n=3,265), HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years) and 9 in the F/TDF group (0.93 per 100 person-years). The background HIV incidence was 2.37 per 100 person-years. Lenacapavir significantly reduced HIV incidence compared to background (incidence rate ratio [IRR], 0.04; 95% CI, 0.01–0.18; P<0.001) and F/TDF (IRR, 0.11; 95% CI, 0.02–0.51; P=0.002). No significant safety concerns emerged. Injection-site reactions led to discontinuation in 1.2% of lenacapavir recipients and 0.3% of F/TDF recipients.

Conclusions: Twice-yearly subcutaneous lenacapavir significantly reduced HIV incidence compared to both the background incidence and daily oral F/TDF among men and gender-diverse persons. These findings support lenacapavir as an effective PrEP option in this population.

Implications for Practice: The introduction of a long-acting, twice-yearly injectable PrEP option like lenacapavir could improve adherence and uptake among populations challenged by daily oral regimens.

Study Strengths and Limitations: Strengths include a large, diverse participant population with significant representation of transgender and gender-nonbinary persons, and the use of an active comparator. The novel counterfactual design estimating background HIV incidence avoided ethical issues of placebo controls but may have limitations in accuracy. Limitations include a relatively short follow-up and potential impact of injection-site reactions on adherence. The emergence of resistance mutations in participants who acquired HIV while on lenacapavir is a concern needing further investigation.

Future Research: Further studies should assess the long-term safety, efficacy, and resistance patterns associated with lenacapavir use. Research into optimizing injection techniques to minimize injection-site reactions and exploring lenacapavir’s applicability in other at-risk populations is recommended.

Reference: Kelley CF, et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. New England Journal of Medicine. Published November 27, 2024. DOI: http://doi.org/10.1056/NEJMoa2411858

Review: Chronic Low-Level Lead Poisoning

3 Nov, 2024 | 01:15h | UTC

Introduction: Lead poisoning, historically known as plumbism, remains a significant health concern despite reductions in lead use. Chronic low-level lead exposure has been identified as a critical risk factor for cardiovascular disease in adults and cognitive deficits in children, even at blood lead concentrations previously deemed safe. This review by Lanphear et al. explores the multifaceted effects of chronic, low-level lead poisoning, emphasizing its impact on neurodevelopment, kidney function, and cardiovascular health, and underscores the urgent need for effective prevention strategies.

Key Findings:

Exposure and Absorption: Lead exposure occurs primarily through ingestion and inhalation, with children absorbing lead more readily than adults. Absorption is enhanced in the presence of iron or calcium deficiency. Once absorbed, lead is predominantly stored in the skeleton, and factors altering bone metabolism can mobilize lead back into the bloodstream.
Neurodevelopmental Effects: Lead exposure is linked to preterm birth, cognitive deficits, attention deficit–hyperactivity disorder (ADHD), and behavioral disorders in children. Notably, cognitive deficits are proportionately larger at lower blood lead levels, with significant IQ reductions observed even at the lowest measurable concentrations.
Kidney Disease: Chronic lead exposure is a risk factor for chronic kidney disease. Higher blood lead levels are associated with reduced glomerular filtration rates and an increased risk of developing chronic kidney conditions.
Cardiovascular Disease: Lead induces hypertension and atherosclerosis through mechanisms such as oxidative stress and endothelial dysfunction. It is a leading risk factor for mortality from cardiovascular disease, with substantial risk increases even at low blood lead concentrations. Studies indicate that lead exposure may have contributed to historical trends in coronary heart disease mortality.
Global Burden: In 2019, lead exposure accounted for approximately 5.5 million deaths from cardiovascular disease and the loss of 765 million IQ points in children globally. The economic cost associated with lead-related health outcomes is estimated at $6 trillion annually, representing about 7% of the global gross domestic product.
Screening and Treatment: Screening high-risk populations is recommended, including children in older housing and workers in certain industries. While chelation therapy can reduce body lead burden, its effects on health outcomes are inconsistent, highlighting the importance of primary prevention.
Prevention Strategies: Eliminating environmental sources of lead through government-funded population strategies is essential. This includes replacing lead-containing infrastructure like water service lines, banning leaded aviation fuel, reducing lead in consumer products, and remediating contaminated soils and older housing with lead-based paints.

Conclusion: Chronic low-level lead poisoning continues to pose a significant global health threat, contributing to cardiovascular disease and neurodevelopmental deficits. The disproportionate effects at even the lowest exposure levels underscore the necessity for robust, population-wide prevention strategies. Implementing stringent regulatory actions to eliminate sources of lead exposure is imperative to reduce the substantial morbidity, mortality, and economic burdens associated with lead poisoning.

Reference: Lanphear B, Navas-Acien A, Bellinger DC. Lead Poisoning. New England Journal of Medicine. 2024;391(17):1621–1631. DOI: http://doi.org/10.1056/NEJMra2402527

RCT: Twice-Yearly Lenacapavir Prevents HIV Infections More Effectively Than Daily F/TAF in Women – N Engl J Med

18 Aug, 2024 | 13:56h | UTC

Study Design and Population: This phase 3, double-blind, randomized controlled trial included 5,338 adolescent girls and young women in South Africa and Uganda. Participants were assigned to receive either twice-yearly subcutaneous lenacapavir, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) as an active control, with corresponding placebos.

Main Findings: Lenacapavir demonstrated superior efficacy in HIV prevention, with zero infections observed among its recipients. In contrast, the F/TAF group experienced 39 HIV infections (2.02 per 100 person-years), while the F/TDF group had 16 infections (1.69 per 100 person-years). HIV incidence was significantly lower with lenacapavir compared to background incidence and F/TDF, while no significant difference was observed between F/TAF and F/TDF.

Implications for Practice: Twice-yearly lenacapavir could be a more effective and potentially easier-to-adopt HIV prevention strategy than daily oral F/TAF in cisgender women, though considerations of injection-site reactions are necessary. This approach could improve adherence and outcomes in populations with low persistence in daily PrEP use.

Reference: Bekker, L.-G., Das, M., Abdool Karim, Q., Ahmed, K., Batting, J., Brumskine, W., Gill, K., et al. (2024). Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. New England Journal of Medicine, 391(7), 648-659. DOI: 10.1056/NEJMoa2407001.

Erythritol Ingestion Increases Platelet Reactivity and Thrombosis Potential in Healthy Adults – Arterioscler Thromb Vasc Biol

10 Aug, 2024 | 21:11h | UTC

Study Design and Population: This interventional study evaluated the effects of erythritol versus glucose on platelet reactivity and thrombosis potential in 20 healthy volunteers, with 10 participants in each group. Researchers measured erythritol plasma levels and assessed platelet function through aggregometry and granule marker analysis both before and after ingestion of 30 g of erythritol or glucose.

Main Findings: Erythritol ingestion resulted in a more than 1000-fold increase in plasma erythritol concentration and significantly enhanced stimulus-dependent platelet aggregation and release of serotonin and CXCL4, markers of platelet activation. In contrast, glucose ingestion did not significantly alter platelet reactivity or granule marker release, highlighting erythritol’s unique pro-thrombotic effects.

Implications for Practice: These findings raise concerns regarding the safety of erythritol as a non-nutritive sweetener, particularly its potential to enhance thrombosis risk. The results suggest a need to reevaluate erythritol’s safety status and consider its impact on cardiovascular health in regulatory guidelines.

Reference: Witkowski, M., Wilcox, J., Province, V., Wang, Z., Nemet, I., Tang, W. H. W., & Hazen, S. L. (2024). Ingestion of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity and thrombosis potential in healthy volunteers. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.124.321019

USPSTF Guideline: Biennial screening mammography recommended for women aged 40-74 to reduce breast cancer morbidity and mortality

1 May, 2024 | 21:45h | UTC

Study Design and Population:

The US Preventive Services Task Force (USPSTF) performed a systematic review and collaborated on modeling studies to evaluate the effectiveness of various mammography-based breast cancer screening strategies. This assessment included factors such as age of initiation and cessation of screening, screening intervals, modalities, and the use of supplemental imaging. The population studied consisted of cisgender women and all other persons assigned female at birth who are 40 years or older and at average risk of breast cancer.

Main Findings:

The USPSTF concludes with moderate certainty that biennial screening mammography for women aged 40 to 74 years provides a moderate net benefit in reducing the incidence of and progression to advanced breast cancer, as well as in decreasing breast cancer morbidity and mortality. However, the evidence is insufficient to assess the benefits and harms of mammography screening in women aged 75 and older, as well as the use of supplemental screening with ultrasound or MRI in women with dense breasts.

Implications for Practice:

Based on these findings, the USPSTF recommends biennial screening mammography for women aged 40 to 74 years. This recommendation aims to optimize breast cancer outcomes while considering the balance of benefits and harms of screening. There is a need for further research to clarify the benefits and risks associated with mammography in women older than 75 and for those with dense breasts considering supplemental screening.

Commentary on X (thread – click for more)

???? Just published: USPSTF recommends all women undergo routine #breastcancer screening every other year beginning at age 40, an update from the 2016 recommendation to start at age 50.
https://t.co/xDPK4qu7JH pic.twitter.com/3zVBMWeuKb

— JAMA (@JAMA_current) April 30, 2024

Reference (link to free full-text):

Screening for Breast Cancer US Preventive Services Task Force Recommendation Statement. JAMA. Published online April 30, 2024. doi:10.1001/jama.2024.5534

Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021

21 Mar, 2024 | 11:10h | UTC

Study Design and Population

This study, a systematic analysis conducted by the Global Burden of Disease Study 2021, aimed to estimate the global, regional, and national health loss attributable to 37 unique nervous system conditions from 1990 to 2021. The researchers estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) across 204 countries. The analysis included morbidity and deaths directly resulting from damage to the central or peripheral nervous system, as well as neurological health loss from conditions where nervous system morbidity is a secondary outcome.

Main Findings

The collective global burden of these nervous system conditions emerged as the leading cause of DALYs in 2021, affecting approximately 3.40 billion individuals (43.1% of the global population) and resulting in 443 million DALYs. Although global DALY counts for these conditions increased by 18.2% from 1990 to 2021, there was a notable decrease in the age-standardised rates of deaths and DALYs by 33.6% and 27.0%, respectively. The conditions contributing most significantly to the age-standardised DALYs were stroke, neonatal encephalopathy, migraine, and Alzheimer’s disease among others.

Implications for Practice

This analysis underscores the critical need for effective prevention, treatment, and rehabilitation strategies for nervous system disorders, which now lead the global disease burden. Highlighting an 18.2% increase in DALY counts over the study period, it calls for heightened public health attention and resource allocation towards these conditions. The findings support the prioritization of nervous system health on the global health agenda and stress the importance of further research into modifiable risk factors and equitable access to care.

Reference

GBD 2021 Nervous System Disorders Collaborators (2024). Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021. The Lancet Neurology, Volume(issue), Pages. DOI: https://doi.org/10.1016/S1474-4422(24)00038-3. Access the study here: Link

Meta-Analysis: Effectiveness of therapist-guided remote vs. in-person cognitive behavioral therapy

20 Mar, 2024 | 19:32h | UTC

Study Design and Population: This systematic review and meta-analysis investigated the efficacy of therapist-guided remote cognitive behavioral therapy (CBT) compared to traditional in-person CBT. The authors conducted a comprehensive search across several databases, including MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials, up to July 4, 2023. A total of 54 randomized controlled trials (RCTs) were included, encompassing 5463 adult patients presenting with various clinical conditions. The study meticulously assessed the risk of bias and extracted data using a standardized approach, and outcomes were analyzed using a random-effects model.

Main Findings: The primary analysis focused on patient-important outcomes, comparing the effectiveness of remote and in-person CBT across diverse conditions such as anxiety and related disorders, depressive symptoms, insomnia, chronic pain or fatigue syndromes, body image or eating disorders, tinnitus, alcohol use disorder, and mood and anxiety disorders. The meta-analysis, based on moderate-certainty evidence, found little to no difference in effectiveness between remote and in-person CBT (standardized mean difference [SMD] −0.02, 95% confidence interval −0.12 to 0.07), suggesting that both delivery methods are comparably effective across a range of disorders.

Implications for Practice: The findings indicate that therapist-guided remote CBT is nearly as effective as in-person CBT for treating a variety of mental health and somatic disorders. This supports the potential for remote CBT to significantly increase access to evidence-based care, especially in settings where in-person therapy is not feasible or is limited by geographic, economic, or social barriers. Future research should explore optimizing remote CBT delivery methods to further enhance accessibility and efficacy.

Reference: Zandieh, S. et al (2024). Therapist-guided remote versus in-person cognitive behavioural therapy: a systematic review and meta-analysis of randomized controlled trials. CMAJ, 196(10), E327-E340. [Link]

Meta-Analysis: Efficacy of exercise modalities in major depressive disorder treatment

20 Mar, 2024 | 17:54h | UTC

Study Design and Population: This article presents a systematic review and network meta-analysis of randomized controlled trials to assess the optimal dose and modality of exercise for treating major depressive disorder, comparing its effects to psychotherapy, antidepressants, and control conditions such as usual care or placebo. The review included 218 unique studies encompassing 495 arms with a total of 14,170 participants who met the clinical cutoffs for major depression.

Main Findings: The findings revealed moderate reductions in depression symptoms for several exercise modalities when compared to active controls. Notably, walking or jogging, yoga, and strength training demonstrated the most significant effects. The effectiveness of exercise was found to be proportional to the intensity of the activity prescribed. Among these, yoga and strength training were identified as the most acceptable modalities for participants. However, the overall confidence in these results is low due to the high risk of bias in the included studies, with only one study meeting the criteria for a low risk of bias.

Implications for Practice: The study concludes that exercise, particularly walking or jogging, yoga, and strength training at sufficient intensities, can be an effective treatment for major depressive disorder. These modalities could be recommended alongside traditional treatments such as psychotherapy and antidepressants. Future research should focus on blinding participants and staff to mitigate expectancy effects and improve the reliability of findings. The inclusivity of exercise as a core treatment for depression could significantly impact treatment strategies and patient outcomes.

Reference: Noetel, M., et al. (2024). Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ, 384, e075847. DOI: https://doi.org/10.1136/bmj-2023-075847. Access the study here: [Link]

RCT | Field sobriety tests display insufficient accuracy for detecting THC-specific driving impairment

11 Aug, 2023 | 15:14h | UTC

Evaluation of Field Sobriety Tests for Identifying Drivers Under the Influence of Cannabis: A Randomized Clinical Trial – JAMA Psychiatry

See also: Visual Abstract

News Release: Can field sobriety tests identify drivers under the influence of cannabis? – University of California – San Diego

Commentary: Trained Officers Using Current Field Sobriety Tests May Misclassify Cannabis-Impaired Drivers – Psychiatric News Alert

Commentary on Twitter

This randomized clinical trial investigates the accuracy of field sobriety tests administered by law enforcement officers to assess functional impairment and driving performance among individuals who have smoked cannabis. https://t.co/pThOOdZGUh

— JAMA Psychiatry (@JAMAPsych) August 2, 2023

M-A | Community-based interventions using holistic assessment and care planning improve independent living in older adults

9 Aug, 2023 | 15:13h | UTC

Complex interventions for improving independent living and quality of life amongst community-dwelling older adults: a systematic review and meta-analysis – Age and Ageing

Global prevalence, years lived with disability, and trends in anemia burden by severity and cause, 1990–2021

3 Aug, 2023 | 13:43h | UTC

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990–2021: findings from the Global Burden of Disease Study 2021 – The Lancet Haematology

News Release: New study reveals global anemia cases remain persistently high among women and children. Anemia rates decline for men – Institute for Health Metrics and Evaluation

Commentary on Twitter

NEW #GBD study by @IHME_UW on the #anaemia burden by severity and cause, 1990–2021?https://t.co/NbiEDSkbGI

Despite a decrease in prevalence, the number of people with anaemia increased globally

In every region females had a higher #anemia YLDs than males pic.twitter.com/oFx4vHRhs1

— The Lancet Haematology (@TheLancetHaem) August 1, 2023

WHO | Seven out of 10 people protected by at least one tobacco control measure

2 Aug, 2023 | 14:14h | UTC

News Release: Seven out of 10 people protected by at least one tobacco control measure – World Health Organization

See also: MPOWER measures

Report: WHO report on the global tobacco epidemic, 2023: protect people from tobacco smoke – World Health Organization

Commentaries:

While Anti-Smoking Policies Cover 70% of Global Population, Taxation is Under-Utilised – Health Policy Watch

Expert reaction to WHO report on the global tobacco epidemic 2023 – Science Media Centre

Commentary on Twitter

The MPOWER measures include?

?-onitoring tobacco use
?-rotecting people from tobacco smoke
?-ffering support to quit smoking
?-arning about the dangers of tobacco
?-nforcing tobacco advertising, promotion & sponsorship bans
?-aising taxes on Tobacco

Learn more.… pic.twitter.com/ImfGsL8in1

— World Health Organization (WHO) (@WHO) July 31, 2023

New WHO lists of essential medicines

28 Jul, 2023 | 14:23h | UTC

News Release: WHO endorses landmark public health decisions on Essential Medicines for Multiple Sclerosis – World Health Organization

Lists of Essential Medicines

Model Lists of Essential Medicines – World Health Organization

Model Lists of Essential Medicines for Children – World Health Organization

Commentary on Twitter

OUT TODAY: New editions of the WHO Model Lists of Essential Medicines and Essential Medicines for Children which include important new medicines for the treatment of multiple sclerosis, cancer, infectious diseases and cardiovascular conditions, among others… pic.twitter.com/RZYdgc0i65

— World Health Organization (WHO) (@WHO) July 26, 2023

WHO world drowning prevention day 2023

27 Jul, 2023 | 13:12h | UTC

World Drowning Prevention Day 2023 – World Health Organization

Report: Hidden depths: the global investment case for drowning prevention – World Health Organization

Tracing the emergence of drowning prevention on the global health and development agenda: a policy analysis – The Lancet Global Health

WHO Guideline on the prevention of drowning through provision of day-care and basic swimming and water safety skills – World health Organization

Wilderness Medical Society Clinical Practice Guidelines for the Treatment and Prevention of Drowning: 2019 Update

Prevention of Drowning – Pediatrics

The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study – Injury Prevention

Preventing drowning: an implementation guide – World Health Organization

Global report on drowning: preventing a leading killer – World Health Organization

Hidden Hazards: An Exploration of Open Water Drowning and Risks for Children – Safe Kids Worldwide

Commentary on Twitter (thread – click for more)

It's #WorldDrowningPreventionDay
Every year, drowning claims at least 236,000 lives. It's one of the leading causes of death ? for children & people aged 1-24 years. We can all take action to end drowning ?‍ https://t.co/7CSUGYBk49 pic.twitter.com/r64dbsLnHn

— World Health Organization (WHO) (@WHO) July 25, 2023

Global, regional, and national burden of meningitis and its etiologies, 1990–2019

25 Jul, 2023 | 13:55h | UTC

Global, regional, and national burden of meningitis and its aetiologies, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 – The Lancet Neurology

Commentary on Twitter

Although largely preventable, meningitis still causes hundreds of thousands of deaths globally each year.

New @IHME_UW #GBDStudy in @TheLancetNeuro assesses incident cases and deaths due to acute infectious meningitis by aetiology and age from 1990–2019. https://t.co/S3KtMA7DMs pic.twitter.com/AYuSJHsNwK

— The Lancet (@TheLancet) July 20, 2023

Key factors associated with quality of postnatal care: a pooled analysis of 23 countries

25 Jul, 2023 | 13:50h | UTC

Key factors associated with quality of postnatal care: a pooled analysis of 23 countries – eClinicalMedicine

New WHO guidance on the role of HIV viral suppression in improving individual health and reducing transmission

24 Jul, 2023 | 13:17h | UTC

News Release: New WHO guidance on HIV viral suppression and scientific updates released at IAS 2023 – World Health Organization

WHO Guidance: The role of HIV viral suppression in improving individual health and reducing transmission – Word Health Organization

Related WHO Guidelines:

WHO recommends optimizing HIV testing services – World Health Organization

Primary health care and HIV: convergent actions – World Health Organization

Systematic Review | Low-level HIV viremia (below 1000 copies/mL) linked to minimal sexual transmission risk

24 Jul, 2023 | 13:15h | UTC

The risk of sexual transmission of HIV in individuals with low-level HIV viraemia – The Lancet

Editorial: HIV is sexually untransmittable when viral load is undetectable – The Lancet

Commentary on Twitter

People on ART with low but detectible levels of HIV viral load have almost zero risk of sexually transmitting the virus to others, in-depth review suggests #IAS2023 https://t.co/wU26C8cEMK pic.twitter.com/hQHLDqPxO6

— The Lancet (@TheLancet) July 22, 2023