National Institutes Of Health Research Articles

Long-term survival after unrelated donor marrow transplantation for aplastic anaemia after optimized conditioning regimen: a retrospective multicentre cohort study

Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50mg/kg (150, 100, 50, 0mg/kg) in combination with total body irradiation (TBI) 2Gy, anti-thymocyte globulin (ATG) and fludarabine. Ninety-six patients with severe aplastic anaemia aged ≤65 years with adequate organ function enrolled on a trial of human leukocyte antigen (HLA)-matched or 1 HLA-locus mismatched unrelated donor marrow transplantation conducted between 02/2006 and 12/2013 in the United States (NCT00326417). Exclusion criteria were Karnofsky performance status of less than 60, clonal cytogenetic abnormalities and inherited marrow failure syndormes. The primary outcome was day-100 engraftment (achievement of absolute neutrophil recovery to at least 0.5×109/L without subsequent decline) and day-100 survival. The trial determined the lowest effective Cydose as 50mg/kg (n=38) for day-100 engraftment and survival. Cy dose 100mg/kg (n=41) was also acceptable. Accrual to Cy doses 150mg/kg (n=15) and 0mg/kg (n=3) was terminated early for toxicities. The current study is an extended follow up of patients enrolled on the trial (NCT00326477) and includes 76 of 96 patients alive ≥1 year after transplantation. There were 20 deaths in the first year after transplantation (Cy 0mg/kg [n=2], Cy 50mg/kg [n=1], Cy 100mg/kg [n=10], Cy 150mg/kg [n=7]). Patients were followed prospectively from transplantation and data reported using standardized data collection forms until death, loss to follow up or last contact through November 2023. The incidence of graft failure was calculated using the cumulative incidence estimator and the probability of survival using the Kaplan-Meier estimator. The median follow up of the cohort is 8.02 (IQR) 5.16-10.12) years. With Cy 50mg/kg, there was one graft failure and five deaths ≥1 year after transplantation. With Cy 100mg/kg there was only one late death and no graft failure. The 8-year probabilities of survival were 85.0% (95% CI 67.3-93.5) and 75.6% (95% CI 59.4-86.1) after Cy50mg/kg and 100mg/kg, respectively, P=0.31. With Cy 0mg/kg and 150mg/kg, there were no graft failures or death ≥1 year after transplantation. Regardless of Cy dose 12 of 15 patients aged ≥50 years died. Cy 50mg/kg or 100mg/kg with TBI 2Gy, ATG and fludarabine are effective conditioning regimens for unrelated donor marrow transplants for aplastic anaemia. Identification of an optimized transplantation approach for patients aged ≥50 years is needed. US National Institutes of Health.

The mutant mouse resource and research center (MMRRC) consortium: the US-based public mouse repository system

AbstractNow in its 25th year, the Mutant Mouse Resource and Research Center (MMRRC) consortium continues to serve the United States and international biomedical scientific community as a public repository and distribution archive of laboratory mouse models of human disease for research. Supported by the National Institutes of Health (NIH), the MMRRC consists of 4 regionally distributed and dedicated vivaria, offices, and specialized laboratory facilities and an Informatics Coordination and Service Center (ICSC). The overarching purpose of the MMRRC is to facilitate groundbreaking biomedical research by offering an extensive repertoire of mutant mice that are essential for advancing the understanding of human physiology and disease. The function of the MMRRC is to identify, acquire, evaluate, characterize, cryopreserve, and distribute mutant mouse strains to qualified biomedical investigators around the nation and the globe. Mouse strains accepted from the research community are held to the highest scientific standards to optimize reproducibility and enhance scientific rigor and transparency. All submitted strains are thoroughly reviewed, documented, and validated using extensive scientific quality control measures. In addition, the MMRRC conducts resource-related research on cryopreservation, mouse genetics, environmental conditions, and other topics that enhance operations of the MMRRC. Today, the MMRRC maintains an archive of mice, cryopreserved embryos and sperm, embryonic stem (ES) cell lines, and murine hybridomas for nearly 65,000 alleles. Since its inception, the MMRRC has fulfilled more than 20,000 orders from 13,651 scientists at 8441 institutions worldwide. The MMRRC also provides numerous services to assist researchers, including scientific consultation, technical assistance, genetic assays, microbiome analysis, analytical phenotyping, pathology, cryorecovery, husbandry, breeding and colony management, infectious disease surveillance, and disease modeling. The ICSC coordinates MMRRC operations, interacts with researchers, and manages the website (mmrrc.org) and online catalogue. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest scientific standards while submitting investigators benefit by having their mouse strains cryopreserved, protected, and distributed in compliance with NIH policies.

Access for ALL in ALS: A large-scale, inclusive, collaborative consortium to unlock the molecular and genetic mechanisms of amyotrophic lateral sclerosis.

Recent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persist. This unmet need remains a stark reminder that innovative paradigms are needed to invigorate ALS research. To move toward more informative, targeted, and personalized drug development, the National Institutes of Health (NIH) established a national ALS clinical research consortium called Access for ALL in ALS (ALL ALS). This new consortium is a multi-institutional effort that aims to organize the ALS clinical research landscape in the United States. ALL ALS is operating in partnership with several stakeholders to operationalize the recommendations of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) Public Private Partnership. ALL ALS will provide a large-scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers). Importantly, ALL ALS is designed to encourage community engagement, equity, and inclusion. The consortium is prioritizing the enrollment of geographically, ethnoculturally, and socioeconomically diverse participants. Collected data include longitudinal clinical data and biofluids, genomic, and digital biomarkers that will be harmonized and linked to the central Accelerating Medicines Partnership for ALS (AMP ALS) portal for sharing with the research community. The aim of ALL ALS is to deliver a comprehensive, inclusive, open-science dataset to help researchers answer important scientific questions of clinical relevance in ALS.

Pediatric calcaneal osteomyelitis: an analysis of literature-reported 128 cases

BackgroundCalcaneal osteomyelitis (CO) poses a formidable challenge in treatment due to the distinct anatomical structure and functional properties of the calcaneus. The present study endeavors to furnish a thorough and comprehensive understanding of the clinical manifestations, therapeutic strategies, and therapeutic outcomes pertaining to pediatric calcaneal osteomyelitis (PCO) by conducting a meticulous synthesis and analysis of cases reported in the literature.MethodsA systematic search of the PubMed, Embase, and Cochrane Library databases was conducted to identify English-language studies analyzing PCO between 2000 and 2021. The quality of the included studies was assessed using the National Institutes of Health (NIH) assessment scale. Effective data were extracted and analyzed.ResultsA total of 42 studies, encompassing 128 patients, fulfilled the established inclusion criteria. The gender distribution revealed a male-to-female ratio of 2:1 (81 boys and 40 girls). The median age at the time of diagnosis was 8 years, while the median duration of symptoms was 0.6 month. Trauma emerged as the primary etiology (41 cases, 54%), and limited activity was the most prevalent symptom (68 cases). The positive rate for pathogen culture was 75.4% (49/65), with Staphylococcus aureus being the most commonly isolated pathogen (28 cases, 57.1%). Surgical intervention was performed in 51% (64/126) of the patients, with debridement serving as the primary surgical strategy. The rate of infection recurrence was 6.8% (8/118), and the risk of below-knee amputation was 0.8% (1/124).ConclusionsPCO occurred more frequently in male patients, with trauma being the primary underlying cause and Staphylococcus aureus being the most prevalent bacterial pathogen isolated. Over half of the patients underwent surgical intervention. Nonetheless, it is imperative that treatment strategies undergo further refinement, as approximately 7% of patients experienced infection recurrence.

Data access arrangements in genomic research consortia

One of the most common terms that is used to describe entities responsible for sharing genomic data for research purposes is ‘genomic research consortium’. However, there is a lack of clarity around the language used by consortia to describe their data sharing arrangements. Calls have been made for more uniform terminology. This article reports on a review of the genomic research consortium literature illustrating a wide diversity in the language that has been used over time to describe the access arrangements of these entities. The second component of this research involved an examination of publicly available information from a dataset of 98 consortia. This analysis further illustrates the wide diversity in the access arrangements adopted by genomic research consortia. A total of 12 different access arrangements were identified, including four simple forms (open, consortium, managed and registered access) and eight more complex tiered forms (for example, a combination of consortium, managed and open access). The majority of consortia utilised some form of tiered access, often following the policy requirements of funders like the US National Institutes of Health and the UK Wellcome Trust. It was not always easy to precisely identify the access arrangements of individual consortia. Greater consistency, clarity and transparency is likely to be of benefit to donors, depositors and accessors alike. More work needs to be done to achieve this end.

Genetic Diversity in Schizophrenia: Developmental Implications of Ultra-Rare, Protein-Truncating Mutations

The genetic basis of schizophrenia (SZ) remains elusive despite its characterization as a highly heritable disorder. This incomplete understanding has led to stagnation in therapeutics and treatment, leaving many suffering with insufficient relief from symptoms. However, recent large-cohort genome- and exome-wide association studies have provided insights into the underlying genetic machinery. The scale of these studies allows for the identification of ultra-rare mutations that confer substantial disease risk, guiding clinicians and researchers toward general classes of genes that are central to SZ etiology. One such large-scale collaboration effort by the Schizophrenia Exome Sequencing Meta-Analysis consortium identified ten, high-risk, ultra-rare, protein-truncating variants, providing the clearest picture to date of the dysfunctional gene products that substantially increase risk for SZ. While genetic studies of SZ provide valuable information regarding “what” genes are linked with the disorder, it is an open question as to “when” during brain development these genetic mutations impose deleterious effects. To shed light on this unresolved aspect of SZ etiology, we queried the BrainSpan developmental mRNA expression database for these ten high-risk genes and discovered three general expression trajectories throughout pre- and postnatal brain development. The elusiveness of SZ etiology, we infer, is not only borne out of the genetic heterogeneity across clinical cases, but also in our incomplete understanding of how genetic mutations perturb neurodevelopment during multiple critical periods. We contextualize this notion within the National Institute of Mental Health’s Research Domain Criteria framework and emphasize the utility of considering both genetic variables and developmental context in future studies.

Transgender-Specific Differentiated HIV Service Delivery Models in the South African Public Primary Health Care System (Jabula Uzibone): Protocol for an Implementation Study.

Almost 60% of transgender people in South Africa are living with HIV. Ending the HIV epidemic will require that transgender people successfully access HIV prevention and treatment. However, transgender people often avoid health services due to facility-based stigma and lack of availability of gender-affirming care. Transgender-specific differentiated service delivery (TG-DSD) may improve engagement and facilitate progress toward HIV elimination. Wits RHI, a renowned South African research institute, established 4 TG-DSD demonstration sites in 2019, with funding from the US Agency for International Development. These sites offer unique opportunities to evaluate the implementation of TG-DSD and test their effectiveness. The Jabula Uzibone study seeks to assess the implementation, effectiveness, and cost of TG-DSD for viral suppression and prevention-effective adherence. The Jabula Uzibone study collects baseline and 12-month observation checklists at 8 sites and 6 (12.5%) key informant interviews per site at 4 TG-DSD and 4 standard sites (n=48). We seek to enroll ≥600 transgender clients, 50% at TG-DSD and 50% at standard sites: 67% clients with HIV and 33% clients without HIV per site type. Participants complete interviewer-administered surveys quarterly, and blood is drawn at baseline and 12 months for HIV RNA levels among participants with HIV and tenofovir levels among participants on pre-exposure prophylaxis. A subset of 30 participants per site type will complete in-depth interviews at baseline and 12 months: 15 participants will be living with HIV and 15 participants will be HIV negative. Qualitative analyses will explore aspects of implementation; regression models will compare viral suppression and prevention-effective adherence by site type. Structural equation modeling will test for mediation by stigma and gender affirmation. Microcosting approaches will estimate the cost per service user served and per service user successfully treated at TG-DSD sites relative to standard sites, as well as the budget needed for a broader implementation of TG-DSD. Funded by the US National Institutes of Mental Health in April 2022, the study was approved by the Human Research Ethics Committee at University of Witwatersrand in June 2022 and the Duke University Health System Institutional Review Board in June 2023. Enrollment began in January 2024. As of July 31, 2024, a total of 593 transgender participants have been enrolled: 348 are living with HIV and 245 are HIV negative. We anticipate baseline enrollment will be complete by August 31, 2024, and the final study visit will take place no later than August 2025. Jabula Uzibone will provide data to inform HIV policies and practices in South Africa and generate the first evidence for implementation of TG-DSD in sub-Saharan Africa. Study findings may inform the use of TG-DSD strategies to increase care engagement and advance global progress toward HIV elimination goals. DERR1-10.2196/64373.

A - 143 Organic Psychiatric Disorders Due to Frontal Lobe Neoplasms

Abstract Objective This current study seeks to explore the presentation of psychiatric disorders as a preliminary symptom in individuals who suffer from frontal lobe neoplasms. Data Selection The primary sources of information for this literature review were Google Scholar, PubMed, ScienceDirect, and the National Institute of Health (NIH). Search terms included frontal lobe tumors/neoplasms, primary brain tumors, psychiatric/psychological, acquired disorders, and pseudo-depression/mania. This search was limited to articles published in English from January 2014 to December 2023. Inclusion criteria were studies that focused on frontal lobe tumors and psychiatric manifestations as a result of illness. Exclusion criteria were studies older than nine years or studies that explored traits of psychiatric illness (i.e., aggression) as opposed to a psychiatric diagnosis. Data Synthesis Frontal lobe neoplasms, accounting for a significant percentage of PTBs, have been found to impact the psychological well-being of patients, leading to a range of psychiatric manifestations that may appear before physiological symptoms. These include mood disorders (i.e., depression, manic episodes), psychotic episodes, and personality disorders. Due to the complexities of the frontal lobe, these manifestations are not linearly linked to frontal lobe lesions. Conclusion This study’s findings advocate for a multidisciplinary approach to treatment, emphasizing the need for neuropsychological evaluations pre- and post-tumor resection. It calls for heightened awareness among clinicians to consider organic causes behind psychiatric presentations, especially in atypical cases or when traditional treatments fail. Ultimately, this research contributes to a deeper understanding of the neuropsychiatric consequences of frontal lobe neoplasms and paves the way for more targeted and effective interventions.

Mentalization-based interventions in schools for enhancing socio-emotional competencies and positive behaviour: a systematic review.

Mentalization-based interventions (MBIs) have been increasingly applied in school settings to support the social-emotional development and mental health of children and adolescents. This systematic review aimed to synthesize the evidence on the effectiveness of MBIs implemented in educational contexts for students aged 6-18 years. A comprehensive search was conducted in PsychInfo, MEDLINE, EMBASE, Web of Science, and ERIC databases from inception to October 2023. The search strategy combined terms related to mentalization, school-based interventions, and the target age group. The review protocol was registered with PROSPERO (CRD42022302757). Inclusion criteria included peer-reviewed publications in English, studies published between 1980 and 2023, interventions based on mentalization principles, and a primary focus on children aged 6 to 18 years. Exclusion criteria involved non-mentalization based interventions and research outside the 6-18 age range. The risk of bias was assessed using the Quality Assessment Tools from the National Institutes of Health (NIH). Data were synthesized narratively due to the heterogeneity of study designs and outcomes. Of the 5,250 articles screened, 21 studies met the inclusion criteria, comprising over 7,500 participants. The reviewed interventions targeted various aspects of mentalizing, such as emotion-understanding, empathy, perspective-taking, and Theory of Mind. Significant improvements were found in social-cognitive abilities, emotion regulation, and mental health outcomes, including reductions in disruptive behaviours. Interventions that combined mentalizing training for both students and teachers showed promising results. However, the long-term sustainability of these benefits remains unclear. Limitations of the reviewed studies include the lack of control groups, small sample sizes, and variations in outcome measures. The findings highlight the potential of MBIs as a promising approach to fostering socio-emotional competence, positive behaviour, and well-being in school-aged children. Future research should aim to establish the active components and optimal delivery of these interventions through well-designed randomized controlled trials with larger, more diverse samples and extended follow-up periods. The integration of MBIs within educational systems holds promise for promoting resilience and positive mental health outcomes in young people. Embedding MBIs within school curriculums and evaluating cost-effectiveness are important next steps to guide widespread implementation.

From palm to practice: prescription digital therapeutics for mental and brain health at the National Institutes of Health

Prescription Digital Therapeutics (PDTs) are emerging as promising tools for treating and managing mental and brain health conditions within the context of daily life. This commentary distinguishes PDTs from other Software as Medical Devices (SaMD) and explores their integration into mental and brain health treatments. We focus on research programs and support from the National Institutes of Health (NIH), discussing PDT research supported by the NIH’s National Institute on Child Health and Development (NICHD), National Institute of Mental Health (NIMH), and National Institute on Aging (NIA). We present a hierarchical natural language processing topic analysis of NIH-funded digital therapeutics research projects. We delineate the PDT landscape across different mental and brain health disorders while highlighting opportunities and challenges. Additionally, we discuss the research foundation for PDTs, the unique therapeutic approaches they employ, and potential strategies to improve their validity, reliability, safety, and effectiveness. Finally, we address the research and collaborations necessary to propel the field forward, ultimately enhancing patient care through innovative digital health solutions.

Applied research won't flourish without basic science.

Three senior figures at the US National Institutes of Health explain why the agency remains committed to supporting basic science and research.

Fifty Years of Psychiatric Classification and Epidemiology Interactions: What is a Mental Disorder?

Psychiatric clinical diagnostic formulation has evolved over time. The changes alter our understanding and our ability to provide a public health perspective on the epidemiology of mental disorders in large populations. Epidemiology is an important perspective and set of tools to assess prevalence, treated prevalence, untreated prevalence, individual risks for mental disorders, and possible links to the etiology of disorders by following the trails of environmental exposures, biological measures, interpersonal dynamics, and genetic risk factors. As communities develop health-care services to treat individuals with mental disorders, knowledge about their prevalence and treatment requirements is also important. Since severe mental disorders may require institutional care, the diagnostic criteria used may either protect an individual’s liability for dangerous behavior (i.e. the insanity defense) or be used to control political and social dissidents. The criteria may also be used to determine evidence-based treatment options and eligibility for disability benefits. In this paper, using my vantage points as a physician scientist and public health officer, with leadership positions in national federal and professional mental health organizations, I address the developments in these areas over the past 50 years that have influenced institutional positions in the U.S. National Institute of Mental Health, the World Health Organization, the American Psychiatric Association, and the Center for the Study of Traumatic Stress. These perspectives may aid the next generation of investigators to advance the epidemiological and mental disorder classification scientific fields.

Acute and sub-chronic toxicity studies of methanol extract of Trema orientalis (Linn) blume in albino wistar rats

BackgroundThe safety potential of the methanol extract of Trema orientalis (TOM) leaf was evaluated in albino Wistar rats using biochemical, haematological, and histological indices in both acute and sub-chronic toxicity studies. MethodsThe animals were managed following the National Institute of Health (NIH) stipulated protocols for handling laboratory animals. The weight of each animal was recorded upon arrival and monitored throughout the study. The animals were allowed to acclimatize for 14 days, after which they were reweighed and randomly distributed into four groups of three female rats (n=12) for acute toxicity studies. Group A was given distilled water, and Groups B, C, and D were given a single dose of 2000, 4000, and 5000 mg/kg bw TOM extract, respectively. On day 15, each animal was anaesthetized and then euthanized. For the sub-chronic toxicity study, animals were randomly distributed into five groups of eight female rats (n=40). They were dosed daily for 28 days. Group A (Negative control group) was given distilled water. Groups B, C, and D had 200, 400, and 800 mg/kg bw TOM extract and Group E (Vehicle control group) were given 0.25 % of sodium carboxyl methyl cellulose (CMC). Five animals were anaesthetized and then euthanized on day 29, while three animals were kept for recovery evaluation for another two weeks without further administration of the extract. Ten organs were excised from each animal and weighed. The liver and kidney were processed for histopathological studies, while the blood samples were collected for biochemical and haematological assays. ResultsFrom acute toxicity studies, the LD50 value of TOM extract was estimated to exceed 5000 mg/kg bw via oral passage. From Sub-chronic toxicity studies, biochemical results showed a significant (p < 0.05) reduction in total protein, albumin, globulin, AST, ALP, and ALT in a dose-dependent manner. Histology of the liver and kidney tissues of all the animals except the kidney of the 800 mg/kg group had no visible lesions; this sets the safety dose for TOM at above 400 mg/kg but below 800 mg/kg. Recovery animals had significantly (p < 0.05) increased total protein, total bilirubin, and ALP and decreased albumin and direct bilirubin levels. ConclusionThis study reports the safety dose of TOM, a reputable medicinal plant extract. This is the first study reporting that the LD50 value of TOM extract exceeds 5000 mg/kg bw via oral passage.

Transdermal Fentanyl in Patients with Cachexia-A Scoping Review.

Cachectic patients frequently require transdermal fentanyl (TDF) for pain management, but data on its efficacy and safety are scarce and inconsistent. This scoping review aims to analyze the evidence concerning TDF administration in patients with cachexia irrespective of the underlying pathology. The primary objective is to assess the analgesic efficacy and tolerability of TDF in cachectic patients. The secondary objective is to identify cachexia characteristics that may influence fentanyl pharmacokinetics (PK). A comprehensive search of PubMed, Embase, and Web of Science databases was conducted up to March 2024. The review included observational and clinical studies on cachectic patients with moderate to severe pain treated with TDF patches at any dosage or frequency. Phase 1 trials, animal studies, case reports, preclinical studies and conference abstracts were excluded. Nine studies were included: four studies reported that cachexia negatively impacted TDF efficacy, increasing required doses and lowering plasma concentrations; three studies found minimal or no impact of cachexia on TDF efficacy and PK; two studies suggested that cachexia might improve TDF outcomes. Study quality ranged from moderate to high, according to the National Institutes of Health (NIH) Quality Assessment Tool. The current evidence is insufficient to provide any definitive recommendations for TDF prescribing in cachectic patients.

Safety and efficacy comparison of Tenecteplase and Alteplase for clinically suspected large vessel occlusion strokes without thrombectomy.

Tenecteplase is a thrombolytic with higher fibrin affinity, and is potentially better in clot lysis. A higher spontaneous recanalization rate for large vessel occlusions strokes (LVO) had been shown in comparison studies with Alteplase. Results of the LVO studies reflect the composite effect of the thrombolytic and thrombectomy, as patients would be treated by thrombectomy had they not been recanalized by intravenous thrombolysis alone. Thrombectomy is not readily available in many parts of the world. Our study aimed to compare the outcomes of suspected LVO patients treated with Tenecteplase versus Alteplase only, without the confounding effect of thrombectomy. This is a retrospective review. Data of patients given Tenecteplase from May 2020 to August 2023, and those given Alteplase 0.9 mg/kg from January 2019 to August 2023 were retrieved. (Due to fluctuation in supply of Tenecteplase during the COVID pandemic, some large vessel occlusion patients were given Alteplase.) Patients with anterior circulation, clinically suspected large vessel occlusion strokes (defined as National Institutes Health Stroke Scale (NIHSS) score &gt;= 6, plus cortical signs or hyperdense vessel sign), with thrombolysis given within 4.5 hours of stroke onset were analyzed. Patients with thrombectomy done were excluded. Safety and efficacy outcomes were compared. There were 245 Tenecteplase treated patients treated between 1st May 2020 and 31st August 2023, and 732 patients were treated with Alteplase between 1st January 2019 to 31st August 2023. Out of these, 148 Tenecteplase patients and 138 Alteplase 0.9 mg/kg patients fulfilled the study criteria. The symptomatic intracerebral haemorrhage rate was non-significantly lower in the Tenecteplase group (2.1% versus 5.8%, p=0.13). There were no significant differences in the rate of &gt;=8 points NIHSS improvement (23.6% versus 23.7%, p=1) or the &gt;= 4 points improvement (40.5% versus 40.7%, p=1) at 24 hours. At 3 months, 21.6% of Tenecteplase patients had good functional outcome (modified Rankin scale (mRS) 0-2), compared to 26.3% in the Alteplase group (p=0.40). In this pragmatic study of clinically suspected anterior circulation LVO patients without thrombectomy, outcome solely reflects the effects of Tenecteplase. Tenecteplase showed comparable safety and efficacy to Alteplase. But the result should be interpreted with caution in view of its small sample size and non-randomized study design.

Population size, HIV prevalence, and antiretroviral therapy coverage among key populations in sub-Saharan Africa: collation and synthesis of survey data, 2010–23

Key population HIV programmes in sub-Saharan Africa require epidemiological information to ensure equitable and universal access to effective services. We aimed to consolidate and harmonise survey data among female sex workers, men who have sex with men, people who inject drugs, and transgender people to estimate key population size, HIV prevalence, and antiretroviral therapy (ART) coverage for countries in mainland sub-Saharan Africa. Key population size estimates, HIV prevalence, and ART coverage data from 39 sub-Saharan Africa countries between 2010 and 2023 were collated from existing databases and verified against source documents. We used Bayesian mixed-effects spatial regression to model urban key population size estimates as a proportion of the gender-matched, year-matched, and area-matched population aged 15-49 years. We modelled subnational key population HIV prevalence and ART coverage with age-matched, gender-matched, year-matched, and province-matched total population estimates as predictors. We extracted 2065 key population size data points, 1183 HIV prevalence data points, and 259 ART coverage data points. Across national urban populations, a median of 1·65% (IQR 1·35-1·91) of adult cisgender women were female sex workers, 0·89% (0·77-0·95) were men who have sex with men, 0·32% (0·31-0·34) were men who injected drugs, and 0·10% (0·06-0·12) were women who were transgender. HIV prevalence among key populations was, on average, four to six times higher than matched total population prevalence, and ART coverage was correlated with, but lower than, the total population ART coverage with wide heterogeneity in relative ART coverage across studies. Across sub-Saharan Africa, key populations were estimated as comprising 1·2% (95% credible interval 0·9-1·6) of the total population aged 15-49 years but 6·1% (4·5-8·2) of people living with HIV. Key populations in sub-Saharan Africa experience higher HIV prevalence and lower ART coverage, underscoring the need for focused prevention and treatment services. In 2024, limited data availability and heterogeneity constrain precise estimates for programming and monitoring trends. Strengthening key population surveys and routine data within national HIV strategic information systems would support more precise estimates. UNAIDS, Bill & Melinda Gates Foundation, and US National Institutes of Health.

Objective and subjective experiences of childhood maltreatment and their relationships with cognitive deficits: a cohort study in the USA

Cognitive deficits might contribute to the elevated risk of life-course psychopathology observed in maltreated children. Leading theories about the links between childhood maltreatment and cognitive deficits focus on documented exposures (objective experience), but empirical research has largely relied on retrospective self-reports of these experiences (subjective experience), and the two measures identify largely non-overlapping groups. We aimed to test the associations of objective and subjective measures of maltreatment with cognitive abilities within the same individuals. We studied a cohort of individuals from the US Midwest with both objective, court-documented evidence of childhood maltreatment and subjective self-reports of individuals' histories at age 29 years. Between the ages of 29 years and 41 years, participants were assessed with a comprehensive set of cognitive tests, including tests of general verbal intelligence (Quick Test and Wide Range Achievement Test-Revised [WRAT]), non-verbal intelligence (Matrix Reasoning Test [MRT]), executive function (Stroop Test and Trail Making Test Part B [TMT-B]), and processing speed (Trail Making Test Part A [TMT-A]). Participants were also assessed for psychopathology (Center for Epidemiologic Studies Depression Scale and Beck Anxiety Inventory). We tested the associations between objective or subjective measures of childhood maltreatment with cognitive functions using ordinary least squares regression. To test whether cognitive deficits could explain previously described associations between different measures of maltreatment and subsequent psychopathology, we re-ran the analyses accounting for group differences in the Quick Test. People with lived experience were not involved in the research or writing process. The cohort included 1196 individuals (582 [48·7%] female, 614 [51·3%] male; 752 [62·9%] White, 417 [34·9%] Black, 36 [3·8%] Hispanic) who were assessed between 1989 and 2005. Of the 1179 participants with available data, 173 had objective-only measures of childhood maltreatment, 492 had objective and subjective measures, 252 had subjective-only measures, and 262 had no measures of childhood maltreatment. Participants with objective measures of childhood maltreatment showed pervasive cognitive deficits compared with those without objective measures (Quick Test: β=-7·97 [95% CI -9·63 to -6·30]; WRAT: β=-7·41 [-9·09 to -5·74]; MRT: β=-3·86 [-5·86 to -1·87]; Stroop Test: β=-1·69 [-3·57 to 0·20]; TMT-B: β=3·66 [1·67 to 5·66]; TMT-A: β=2·92 [0·86 to 4·98]). The associations with cognitive deficits were specific to objective measures of neglect. In contrast, participants with subjective measures of childhood maltreatment did not differ from those without subjective measures (Quick Test: β=1·73 [95% CI -0·05 to 3·50]; WRAT: β=1·62 [-0·17 to 3·40]; MRT: β=0·19 [-1·87 to 2·24]; Stroop Test: β=-1·41 [-3·35 to 0·52]; TMT-B: β=-0·57 [-2·69 to 1·55]; TMT-A: β=-0·36 [-2·38 to 1·67]). Furthermore, cognitive deficits did not explain associations between different measures of maltreatment and subsequent psychopathology. Previous studies based on retrospective reports of childhood maltreatment have probably grossly underestimated the extent of cognitive deficits in individuals with documented experiences of childhood maltreatment, particularly neglect. Psychopathology associated with maltreatment is unlikely to emerge because of cognitive deficits, but might instead be driven by individual appraisals, autobiographical memories, and associated schemas. National Institute of Justice, National Institute of Mental Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Aging, Doris Duke Charitable Foundation, and National Institute for Health and Care Research.

Frequency of Phenotypes and their Clinical and Hormonal Characteristics of Polycystic Ovarian Syndrome.

To determine the frequency of phenotypes of polycystic ovarian syndrome (PCOS) in patients presenting with sub-fertility, and to compare the clinical and hormonal characteristics among them. Descriptive cross-sectional study. Place and Duration of the Study: Department of Obstetrics and Gynaecology, Forest View Specialist Clinic, Peshawar, Pakistan, from August 2022 to January 2023. The study included 662 female patients presenting with menstrual irregularities, hyperandrogenism, and infertility to the clinic. PCOS was diagnosed on the basis of the Rotterdam criterion and clinical features and classified into different phenotypes on the basis of the National Institute of Health (NIH) panel criteria. Data were entered and analysed by IBM SPSS VERSION 23.0. The frequency of four phenotypes was calculated and phenotypes were compared for age, weight, hormonal profiles, and history of miscarriages. A p <0.05 was considered statistically significant. Frequency of PCOS in patients with infertility was 59.76%. Phenotype A was seen in 58.2%, phenotype D in 23.3%, phenotype C in 16.9%, and phenotype B in 1.7% of cases. The LH/FSH ratio was statistically significant in phenotype A as compared to other phenotypes, while other parameters were non-significant. The frequency of PCOS is high in patients with infertility. Phenotype A is the most common variant and is associated with significant impairment of the LH/FSH ratio. Polycystic ovarian syndrome, Subfertility, Phenotypes of PCOS, Hyperandrogenism, Anovulation, R-C1.

Long-term life expectancy in severe traumatic brain injury: a systematic review.

Traumatic brain injuries (TBIs) pose significant challenges to public health, medicine, and society due to their substantial impact on victims, caregivers, and the community. While indicators like life expectancy or death rates provide insights into mortality and long-term outcomes, they fail to address how TBIs affect aging, neurological sequelae, cognitive impairment, and psychological or psychiatric disorders. Moreover, most studies are limited to North America, limiting the generalizability of findings across different social welfare systems. As a result, clinicians face difficulties in providing optimal care and prognosis, hindering the improvement of life quality for victims and caregivers and efficient public health service planning. This study aims to address these limitations by examining life expectancy, mortality rates, and long-term outcomes in severely injured individuals. PubMed/Medline, Web of Science, Cochrane Library, Google Scholar, and PEDro search engines were systematically searched for studies investigating life expectancy and long-term outcomes in severe traumatic brain injuries. The final search date for all sources/databases was July 31, 2023. We conducted a systematic review, and only original research articles published in English were eligible for inclusion. After the screening process, data were extracted about life expectancy, follow-up, and conclusions. This study analyzed 24 studies out of 343 identified. Life expectancy in the TBI population is lower than that of the general population. Older age and severity of functional impairments are major risk factors for mortality. Mortality rates are particularly high in the first two months. Mortality trends suggest a bimodal distribution, with a peak in the first five years followed by no further deaths until nine years after injury. The most influential factors include age, sex, trauma severity, independence in walking and feeding, time since injury, ventilator dependence, and cognitive and communication impairments. Respiratory and circulatory complications are among the leading causes of TBI-related deaths, followed by epilepsy, suicide, and respiratory infections. Further research is required, considering the different long-term outcomes after TBI and their impact on families and society, to accurately estimate the life expectancy necessary for clinicians, caregivers, national health institutions, and medico-legal settlements.

Ethion food poisoning outbreak in Pereira, Colombia, 2022

Introduction Ethion is an organophosphate used as an acaricide and insecticide, that is restricted worldwide. In Colombia, pesticide poisoning is the third most common cause of chemical intoxication. On 9 October 2022, an outbreak of ethion poisoning occurred in Pereira. The aim of this study was to describe the clinical and epidemiological characteristics of the outbreak. Methods This is a descriptive study of an outbreak of organophosphate poisoning. The onset of symptoms occurred on 9 October 2022, following the consumption of empanadas. Information was collected on sociodemographic characteristics and clinical manifestations, as well as from paraclinical examinations. Data were obtained from clinical histories, field epidemiological investigations, and inspection visits. Food samples were collected for analysis by gas chromatography-mass spectrometry. Attack rates, proportions, and measures of central tendency, dispersion, and position were calculated. Results The case definition was met by 37 individuals with a median age of 30 years; all presented with muscarinic symptoms, 29 patients presented with nicotinic symptoms, and 20 patients presented with neurological symptoms. Males were the most affected (57%), and the most common time of symptom onset was 10:00 am. Twenty-three patients (62%) required intensive care unit admission, of whom 14 (38%) required mechanical ventilation. No deaths were reported. Erythrocyte acetylcholinesterase activity was reduced in all patients. Ethion was detected in mass-prepared maize and empanadas at concentrations greater than 0.1 mg/kg. The consumption of empanadas was identified as the common source. Discussion In Colombia, pesticide poisonings are the third most common type of poisoning caused by chemical substances reported to the National Health Institute through the National Public Health Surveillance System. In the present outbreak, ethion was in empanadas, likely due to contamination of cooking oil. Conclusions We describe a large ethion-contaminated food poisoning outbreak reported in Colombia. The main symptoms were muscarinic, and the main treatment measures employed were atropine and respiratory support. Increased awareness of pesticide poisoning and training for food handlers are needed.