Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).

Eco-management of end-of-life tires: Advances and challenges for the Ecuadorian case.

The aim of this research is to analyse the performance of the extended producer responsibility model for the management of end-of-life tires (ELTs) in Ecuador that has been implemented since 2013. For this research, we conducted case studies of, and subsequently, a comparative analysis between, the ELT management system in Ecuador with respect to the ELT management models in Colombia and Brazil. Our findings show that although the programme implementation represented a significant advance in Ecuador's waste management system there are important challenges that should be considered in future adaptations of the programme. Among the measures that can be adopted to improve the ELT management system are the consolidation and stimulation of the market for products made from ELT waste; promotion of other productive sectors linked to the creation of new products and sectors that generate complementary products; enhancement of the generation, socialization and access to knowledge of the waste by-products for micro-, small- and medium-sized enterprises; increase the tire consumer fee, known as 'Ecovalor' and improvement of the quality and availability of information and indicators regarding ELT management. In this sense, the experiences of Colombia and Brazil show important lessons for the Ecuadorian case.

Impact of Molnupiravir Treatment on Patient-Reported COVID-19 Symptoms in the Phase 3 MOVe-OUT Trial: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Molnupiravir is an orally administered antiviral authorized for COVID-19 treatment in adults at high risk of progression to severe disease. Here, we report secondary and post hoc analyses of participants' self-reported symptoms in the MOVe-OUT trial, which evaluated molnupiravir initiated within 5 days of symptom onset in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19. METHODS: Eligible participants completed a 15-item symptom diary daily from day 1 (randomization) through day 29, rating symptom severity as "none," "mild," "moderate," or "severe"; loss of smell and loss of taste were rated as "yes" or "no." Time to sustained symptom resolution/improvement was defined as the number of days from randomization to the first of 3 consecutive days of reduced severity, without subsequent relapse. Time to symptom progression was defined as the number of days from randomization to the first of 2 consecutive days of worsening severity. The Kaplan-Meier method was used to estimate event rates at various time points. The Cox proportional hazards model was used to estimate the hazard ratio between molnupiravir and placebo. RESULTS: For most targeted COVID-19 symptoms, sustained resolution/improvement was more likely, and progression was less likely, in the molnupiravir versus placebo group through day 29. When evaluating 5 distinctive symptoms of COVID-19, molnupiravir participants had a shorter median time to first resolution (18 vs 20 d) and first alleviation (13 vs 15 d) of symptoms compared with placebo. CONCLUSIONS: Molnupiravir treatment in at-risk, unvaccinated patients resulted in improved clinical outcomes for most participant-reported COVID-19 symptoms compared with placebo. Clinical Trials Registration. ClinicalTrials.gov: NCT04575597.

Molnupiravir for the treatment of COVID-19 in immunocompromised participants: efficacy, safety, and virology results from the phase 3 randomized, placebo-controlled MOVe-OUT trial.

PURPOSE: Immunocompromised patients have a potentially increased risk for progression to severe COVID-19 and prolonged replication of SARS-CoV-2. This post hoc analysis examined outcomes among immunocompromised participants in the MOVe-OUT trial. METHODS: In phase 3 of MOVe-OUT, non-hospitalized at-risk adults with mild-to-moderate COVID-19 were randomized to receive molnupiravir 800 mg or placebo twice daily for 5 days. Immunocompromised participants were identified based on prior/concomitant medications and/or medical history. All-cause hospitalization/death, adverse events, SARS-CoV-2 titers, infectivity, and RNA sequences were compared between immunocompromised participants who received molnupiravir or placebo and with non-immunocompromised participants. RESULTS: Fifty-five of 1408 participants were considered immunocompromised. Compared to placebo, fewer molnupiravir-treated immunocompromised participants were hospitalized/died through Day 29 (22.6% [7/31] vs. 8.3% [2/24]), with fewer adverse events (45.2% [14/31] vs. 25.0% [6/24]). A larger mean change from baseline in SARS-CoV-2 RNA was observed with molnupiravir compared to placebo in non-immunocompromised participants (least squares mean [LSM] difference Day 5: - 0.31, 95% confidence interval [CI] - 0.47 to - 0.15), while the mean change was comparable between treatment groups in immunocompromised participants (LSM difference Day 5: 0.23, 95% CI - 0.71 to 1.17). Molnupiravir treatment was associated with increased clearance of infectious virus. Increased errors in viral nucleotide sequences in post-baseline samples compared to placebo support molnupiravir's mechanism of action and were not associated with observation of novel treatment-emergent amino acid substitutions in immunocompromised participants. CONCLUSION: Although the study population was small, these data suggest that molnupiravir treatment for mild-to-moderate COVID-19 in non-hospitalized immunocompromised adults is efficacious and safe and quickly reduces infectious SARS-CoV-2. GOV REGISTRATION NUMBER: NCT04575597.

Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche.

We have described multipotent progenitor-like cells within the major pancreatic ducts (MPDs) of the human pancreas. They express PDX1, its surrogate surface marker P2RY1, and the bone morphogenetic protein (BMP) receptor 1A (BMPR1A)/activin-like kinase 3 (ALK3), but not carbonic anhydrase II (CAII). Here we report the single-cell RNA sequencing (scRNA-seq) of ALK3bright+-sorted ductal cells, a fraction that harbors BMP-responsive progenitor-like cells. Our analysis unveiled the existence of multiple subpopulations along two major axes, one that encompasses a gradient of ductal cell differentiation stages, and another featuring cells with transitional phenotypes toward acinar tissue. A third potential ducto-endocrine axis is revealed upon integration of the ALK3bright+ dataset with a single-cell whole-pancreas transcriptome. When transplanted into immunodeficient mice, P2RY1+/ALK3bright+ populations (enriched in PDX1+/ALK3+/CAII- cells) differentiate into all pancreatic lineages, including functional ß-cells. This process is accelerated when hosts are treated systemically with an ALK3 agonist. We found PDX1+/ALK3+/CAII- progenitor-like cells in the MPDs of types 1 and 2 diabetes donors, regardless of the duration of the disease. Our findings open the door to the pharmacological activation of progenitor cells in situ.

Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19 : A Randomized, Placebo-Controlled Trial.

BACKGROUND: In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease. OBJECTIVE: To identify other potential clinical benefits of molnupiravir versus placebo. DESIGN: Secondary analysis of the randomized, double-blind, placebo-controlled phase 3 component of MOVe-OUT. (ClinicalTrials.gov: NCT04575597). SETTING: 107 sites globally. PARTICIPANTS: 1433 nonhospitalized adults aged 18 years or older with mild to moderate COVID-19. INTERVENTION: Molnupiravir, 800 mg, or placebo every 12 hours for 5 days. MEASUREMENTS: Changes from baseline in C-reactive protein (CRP) concentration and oxygen saturation (Spo 2), need for respiratory interventions (including invasive mechanical ventilation), and need for medical services in all randomly assigned participants through day 29, and need for respiratory interventions and time to discharge in the subgroup of participants who were hospitalized after randomization. RESULTS: Participants receiving molnupiravir showed faster normalization of CRP and Spo 2, with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19-related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants. LIMITATIONS: Some analyses were performed post hoc. Longer-term benefits of molnupiravir therapy were not evaluated. Participants were not immunized against SARS-CoV-2. CONCLUSION: The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization or death. PRIMARY FUNDING SOURCE: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

TRiCit: A High-Throughput Approach to Detect Trichomonas vaginalis from ITS1 Amplicon Sequencing.

Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common non-viral sexually transmitted infection (STI) worldwide, affecting over 174 million people annually and is frequently associated with reproductive co-morbidities. However, its detection can be time-consuming, subjective, and expensive for large cohort studies. This case-control study, conducted at the Mount Sinai Adolescent Health Center in New York City, involved 36 women with prevalent TV infections and 36 controls. The objective was to examine Internal Transcribed Spacer region-1 (ITS1) amplicon-derived communities for the detection of prevalent TV infections with the same precision as clinical microscopy and the independent amplification of the TV-specific TVK3/7 gene. DNA was isolated from clinician-collected cervicovaginal samples and amplified using ITS1 primers in a research laboratory. Results were compared to microscopic wet-mount TV detection of concurrently collected cervicovaginal samples and confirmed against TV-specific TVK3/7 gene PCR. The area under the receiver operating characteristics curve (AUC) for diagnosing TV using ITS1 communities was 0.92. ITS1 amplicons displayed an intra-class correlation coefficient (ICC) of 0.96 (95% CI: 0.93-0.98) compared to TVK3/7 PCR fragment testing. TV cases showed an increased risk of bacterial vaginosis (BV) compared to the TV-negative controls (OR = 8.67, 95% CI: 2.24-48.54, p-value = 0.0011), with no significant differences regarding genital yeast or chlamydia infections. This study presents a bioinformatics approach to ITS1 amplicon next-generation sequencing that is capable of detecting prevalent TV infections. This approach enables high-throughput testing for TV in stored DNA from large-scale epidemiological studies.

Profiles of Childhood Maltreatment: Associations with Sexual Risk Behavior during Adolescence in a Sample of Racial/Ethnic Minority Girls.

This study examines associations between childhood maltreatment and developmental trajectories of sexual risk behaviors (SRBs) in a sample of 882 sexually active adolescent girls, predominantly Hispanic or Black, assessed every 6 months between 13 and 23 years. Latent profile analyses revealed four distinct maltreatment profiles: Low Maltreatment (76%), Moderate Emotional Neglect Only (15%), Severe Physical/Emotional Abuse (3%), and Severe Sexual Abuse (6%). Multilevel growth analyses showed the Moderate Emotional Neglect Only and Severe Sexual Abuse profiles exhibited more SRBs starting in late adolescence, and the Severe Sexual Abuse profile also exhibited a faster increase than the Low Maltreatment profile. Understanding heterogeneity within maltreated populations may have important implications for healthy sexual development.

The interaction between pubertal timing and childhood maltreatment on the risk of human papillomavirus infection among adolescent girls and young women.

PURPOSE: The goal of this study was to evaluate the effect of pubertal timing, and its interaction with prior childhood maltreatment, on the risk of cervical human papillomavirus (HPV) among sexually active adolescent minority female adolescents and young adults. METHODS: This cross-sectional study includes 842 adolescent girls and young women (aged 12 to 20 years; predominately Black and Hispanic) enrolled in an HPV vaccine surveillance study at a large adolescent health clinic in New York City between 2007 and 2016. Pubertal timing was assessed by self-reported age at menarche at baseline, with "early" and "late" defined as one standard deviation below (<11 years) or above (>13 years) the mean. Childhood exposure to abuse (sexual, physical and emotional) and neglect (physical and emotional) was assessed using the Childhood Trauma Questionnaire. Over 40 types of HPV infection were detected using the polymerase chain reaction in cervical Pap specimens. RESULTS: Results from multivariable logistic regression showed that early and late pubertal timing were marginally associated with a higher risk of HPV infection, adjusting for demographic and health covariates. Childhood maltreatment moderated the association between early pubertal timing and HPV infection: early pubertal timing was associated with a higher risk for HPV infection among maltreated girls (OR = 3.32, 95%CI:1.61-6.85), but not among non-maltreated girls (OR = 0.96, 95%CI:0.61-1.50; p-interaction<0.01). CONCLUSIONS: Variation in the timing of puberty and history of childhood maltreatment may have implications for adolescent sexual and reproductive health. Findings suggest that clinicians need to assess the biological and psychosocial risks in caring for youth.

Military Service Members and Emergence Delirium Screening: An Evidence-Based Practice Project.

PURPOSE: Emergence delirium (ED) is a postoperative phenomenon characterized by agitation, confusion, and violent physical or verbal behavior that can occur after general anesthesia. Preoperative identification of patients at risk for ED may allow providers to take steps to minimize the incidence or severity of ED. Because no formal tool currently exists, the purpose of this project was to develop and evaluate a screening tool based on available evidence of ED risk factors. DESIGN: This quality improvement project used a preimplementation and postimplementation design. METHODS: One hundred consecutive adult patient charts were reviewed 2 months before implementation of the project questionnaire. These data were used to confirm preimplementation screening rates. Postimplementation, prospective data were gathered to test this newly developed assessment tool for usefulness in the clinical setting. FINDINGS: The use of this focused screening tool significantly increased preoperative identification of patients at risk for ED compared with the preimplementation preoperative screening routine. Identification rates for at-risk patients rose from 5% to 21%-22.5% using this tool. CONCLUSIONS: This project demonstrated that the use of a focused tool to identify risk factors for ED could significantly increase actual identification rates for at-risk patients in the clinical setting.

Vital Directions for Health and Health Care: Priorities From a National Academy of Medicine Initiative.

Importance: Recent discussion has focused on questions related to the repeal and replacement of portions of the Affordable Care Act (ACA). However, issues central to the future of health and health care in the United States transcend the ACA provisions receiving the greatest attention. Initiatives directed to certain strategic and infrastructure priorities are vital to achieve better health at lower cost. Objectives: To review the most salient health challenges and opportunities facing the United States, to identify practical and achievable priorities essential to health progress, and to present policy initiatives critical to the nation's health and fiscal integrity. Evidence Review: Qualitative synthesis of 19 National Academy of Medicine-commissioned white papers, with supplemental review and analysis of publicly available data and published research findings. Findings: The US health system faces major challenges. Health care costs remain high at $3.2 trillion spent annually, of which an estimated 30% is related to waste, inefficiencies, and excessive prices; health disparities are persistent and worsening; and the health and financial burdens of chronic illness and disability are straining families and communities. Concurrently, promising opportunities and knowledge to achieve change exist. Across the 19 discussion papers examined, 8 crosscutting policy directions were identified as vital to the nation's health and fiscal future, including 4 action priorities and 4 essential infrastructure needs. The action priorities-pay for value, empower people, activate communities, and connect care-recurred across the articles as direct and strategic opportunities to advance a more efficient, equitable, and patient- and community-focused health system. The essential infrastructure needs-measure what matters most, modernize skills, accelerate real-world evidence, and advance science-were the most commonly cited foundational elements to ensure progress. Conclusions and Relevance: The action priorities and essential infrastructure needs represent major opportunities to improve health outcomes and increase efficiency and value in the health system. As the new US administration and Congress chart the future of health and health care for the United States, and as health leaders across the country contemplate future directions for their programs and initiatives, their leadership and strategic investment in these priorities will be essential for achieving significant progress.

Risk of Delayed Human Papillomavirus Vaccination in Inner-City Adolescent Women.

BACKGROUND: Uptake of human papillomavirus (HPV) vaccine in the United States is slow, and the effectiveness of the vaccine has not been assessed in high-risk adolescent populations. METHODS: We conducted a longitudinal study of 1139 sexually active, inner-city adolescent women receiving the 3-dose quadrivalent (4vHPV) vaccine. Cervical and anal specimens collected semiannually were tested using an L1-specific polymerase chain reaction assay. Postvaccination incidence of 4vHPV vaccine and nonvaccine HPV types, and risk of cervical cytological abnormalities, were assessed in relation to time to completion of all 3 vaccine doses. RESULTS: Compared to vaccine naive women at enrollment, vaccinated women had significantly lower incidence rate ratios of cervical infection with HPV6/11/16/18 (0.2; 95% confidence interval [CI], .1-.4) and the related types HPV31 and HPV45 (0.4 [95% CI, .2-1.0] and 0.3 [95% CI, .1-.6], respectively), as well as significantly lower incidence rate ratios of anal infection with HPV6/11/16/18 (0.4; 95% CI, .2-.7). Notably, we observed higher risks of cervical HPV6/11/16/18 infection (hazards ratio [HR], 2.9; 95% CI, 1.0-8.0) and associated cytological abnormalities (HR, 4.5; 95% CI, .7-26.0) among women immunized at ≥15 years of age who took ≥12 months (vs <12 months) to complete the 3-dose regimen. CONCLUSIONS: Among adolescents immunized at ≥15 years of age, a longer time to complete the 3-dose schedule was associated with an increased risk of anogenital HPV6/11/16/18 infection and an increased incidence of associated cervical cytological abnormalities.

Cellular and Humoral Responses to a Second Dose of Herpes Zoster Vaccine Administered 10 Years After the First Dose Among Older Adults.

BACKGROUND: Herpes zoster vaccine (ZV) was administered as a second dose to 200 participants ≥ 70 years old who had received a dose of ZV ≥ 10 years previously (NCT01245751). METHODS: Varicella zoster virus (VZV) antibody titers (measured by a VZV glycoprotein-based enzyme-linked immunosorbent assay [gpELISA]) and levels of interferon γ (IFN-γ) and interleukin 2 (IL-2; markers of VZV-specific cell-mediated immunity [CMI], measured by means of ELISPOT analysis) in individuals aged ≥ 70 years who received a booster dose of ZV were compared to responses of 100 participants aged 50-59 years, 100 aged 60-69 years, and 200 aged ≥ 70 years who received their first dose of ZV. The study was powered to demonstrate noninferiority of the VZV antibody response at 6 weeks in the booster-dose group, compared with the age-matched first-dose group. RESULTS: Antibody responses were similar at baseline and after vaccination across all age and treatment groups. Both baseline and postvaccination VZV-specific CMI were lower in the older age groups. Peak gpELISA titers and their fold rise from baseline generally correlated with higher baseline and postvaccination VZV-specific CMI. IFN-γ and IL-2 results for subjects ≥ 70 years old were significantly higher at baseline and after vaccination in the booster-dose group, compared with the first-dose group, indicating that a residual effect of ZV on VZV-specific CMI persisted for ≥ 10 years and was enhanced by the booster dose. CONCLUSIONS: These findings support further investigation of ZV administration in early versus later age and of booster doses for elderly individuals at an appropriate interval after initial immunization against HZ. CLINICAL TRIALS REGISTRATION: NCT01245751.

Knowledge about Human Papillomavirus and Time to Complete Vaccination among Vulnerable Female Youth.

OBJECTIVE: To examine the association of knowledge about human papillomavirus (HPV) on the time to completion of the 3-dose quadrivalent vaccine series in an inner-city population of adolescent female subjects at high risk for infection. STUDY DESIGN: We prospectively followed 139 female subjects aged 14-20 years enrolled in a vaccine surveillance study in New York City during a period of at least 24 months. Participants were given a 30-item true or false survey on HPV at enrollment and ranked according to the number of correct responses. Multivariate Cox regression was used to examine the association between level of knowledge about HPV and time to completion (in days) of vaccine dose 1-3, dose 1-2, and dose 2-3. RESULTS: Overall time to completion of the 3-dose vaccine ranged from 158 days to 1114 days. Participants in the high knowledge group (top quartile) were significantly more likely to complete the 3-dose series earlier (hazard ratio 1.69, 95% CI 1.03-2.77; P = .04), in particular doses 2-3 (hazard ratio 1.71, 95% CI 1.02-2.89; P = .04), than those with low-to-moderate knowledge (bottom 3 quartiles). CONCLUSIONS: These findings suggest that knowledge of HPV is associated with shorter time to complete the 3-dose HPV vaccine series. Educational campaigns at time of vaccination may be important to improve vaccine adherence.

Distinct Ecological Niche of Anal, Oral, and Cervical Mucosal Microbiomes in Adolescent Women.

Human body sites represent ecological niches for microorganisms, each providing variations in microbial exposure, nutrient availability, microbial competition, and host immunological responses. In this study, we investigated the oral, anal, and cervical microbiomes from the same 20 sexually active adolescent females, using culture-independent, next-generation sequencing. DNA from each sample was amplified for the bacterial 16S rRNA gene and sequenced on an Illumina platform using paired-end reads. Across the three anatomical niches, we found significant differences in bacterial community composition and diversity. Overall anal samples were dominated with Prevotella and Bacteriodes, oral samples with Streptococcus and Prevotella, and cervical samples with Lactobacillus. The microbiomes of a few cervical samples clustered with anal samples in weighted principal coordinate analyses, due in part to a higher proportion of Prevotella in those samples. Additionally, cervical samples had the lowest alpha diversity. Our results demonstrate the occurrence of distinct microbial communities across body sites within the same individual.

[Gender violence: Knowledge and attitudes of nurses in Primary Care]. / Violencia de género: conocimientos y actitudes de las enfermeras en atención primaria.

AIM: To determine the knowledge and attitudes of nurses in Primary Care as regards gender violence and their relationship with socio-demographic factors and cases detected. DESIGN: Cross-sectional, descriptive study. LOCATION: Urban health centres. PARTICIPANTS: A total of 167 nurses working in Primary Care. MAIN MEASUREMENTS: A questionnaire was used that included questions related to knowledge, knowledge perception and attitudes to gender violence attitudes. Variables such as age, gender, marital status, work place and health area were also analysed. RESULTS: The response rate was 114 (68.26%). The percentage of correct responses in the knowledge questions was 62.2%, with a medium level of knowledge being observed. Married nurses or couples living in a stable relationship obtained a higher score (95.2%, P=.077). The low detection (29%) is associated with marital status (P=.004), low knowledge (P=0,008), low knowledge perception (P=.001), lack of training (P=.03) and non-implementation of the gender violence protocol (P=.001). Nurses with low self-perception of their knowledge implement the protocol less often (OR=0.26; 95% CI: 0.1-0.7), and they consider that the lack of training is the main problem in determining the diagnosis (OR=11.24; 95% CI: 1.5-81.1). CONCLUSIONS: The level of knowledge was adequate. Nurses have a lack of confidence in terms of their knowledge about gender violence. The detection and diagnosis attitudes are more related to self-perception of levels of knowledge than their real knowledge. Marital status influences the level of knowledge. Professionals state that the lack of training is the main problem to give an efficient healthcare response.

Global prevalence of violence against children and adolescents during COVID-19: A meta-analysis.

BACKGROUND: Recent studies suggest that children and adolescents are at an increased risk of experiencing violence during the COVID-19 pandemic. However, there is limited knowledge about the prevalence of violence against children and adolescents across different regions in the world. OBJECTIVE: To estimate the pooled prevalence of violence against children and adolescents during the COVID-19 pandemic and explore how geographical and methodological factors explain the variation across studies. METHODS: We conducted a systematic search of MEDLINE, Embase, and PsycInfo databases for articles published from January 1, 2020 to October 1, 2022. The study protocol was pre-registered with PROSPERO (CRD42022338181). We included published and unpublished studies available in English that reported the prevalence of violence (e.g., physical, emotional, or sexual violence, neglect, bullying) against children and adolescents (age <18 years) during the pandemic. Data extraction followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A total of 2740 nonduplicate titles and abstracts were screened, and 217 full-text articles were reviewed for eligibility. RESULTS: Twenty-five studies with 66,637 participants met inclusion criteria. Based on random-effects meta-analysis, the pooled prevalence of violence against children and adolescents was 24 % (95%CI 18 %-30 %). The reported prevalence was higher in studies conducted in low- and middle-income countries compared to high-income countries. CONCLUSIONS: Over one in five children and adolescents globally reported ever experiencing violence during the COVID-19 pandemic. Our findings highlight the urgent need for effective child protection policies and interventions, as well as multisectoral collaboration, to reduce violence against children and adolescents.

Characterizing models of adolescent and youth-friendly health services in sub-Saharan Africa: a scoping review.

This scoping review provides an up-to-date overview of the evidence on adolescent and youth-friendly health services (AYFHS) in sub-Saharan African countries. We conducted a search of four databases and grey literature sources to identify English language publications from January 1, 2005, to December 14th, 2022. The review synthesized evidence on the models and characteristics of AYFHS, the application of World Health Organization (WHO) standards, and whether AYFHS have improved young people's health outcomes. In total, 77 sources were included in the review, representing 47 AYFHS initiatives spanning 19 countries, and three multi-country reports. Most commonly, AYFHS were delivered in public health facilities and focused on sexual and reproductive health, with limited application of WHO standards. Some evidence suggested that AYFHS increased young people's health service utilization and contraceptives uptake. There is a clear need to strengthen and develop innovative and multi-pronged approaches to delivering and evaluating AYFHS in this region.

Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation.

Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.

Respiratory virus coinfections during the COVID-19 pandemic: epidemiologic analysis and clinical outcomes from the Phase 2/3 molnupiravir trial (MOVe-OUT).

This exploratory post hoc analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with mild-to-moderate coronavirus disease-2019 (COVID-19) treated with molnupiravir versus placebo for 5 days in the Phase 2/3 MOVe-OUT trial (NCT04575597), which took place in October 2020 to January 2021 (Phase 2, n = 302) and May 2021 to October 2021 (Phase 3, n = 1,433). Among 1,735 total randomized participants, 1,674 had a baseline respiratory pathogen panel (NxTAG Respiratory Pathogen Panel for the Luminex MAGPIX instrument) performed and 69 (4.1%) were coinfected with at least one additional respiratory viral pathogen. Human rhinovirus/enterovirus (39/69, 56.5%) was the most common coinfection detected at baseline. In the modified intention-to-treat population, two participants with coinfecting respiratory RNA viruses were hospitalized and received respiratory interventions through Day 29, and none died; one participant in the molnupiravir group was coinfected with human rhinovirus/enterovirus, and one participant in the placebo group was coinfected with human metapneumovirus. Hospitalization or death occurred in 6.2% and 9.0% of non-coinfected participants in the molnupiravir versus placebo group, respectively, and over 90% did not require respiratory interventions. Most coinfecting respiratory RNA viruses detected at baseline were not detected at the end of therapy in both the molnupiravir and placebo groups. In summary, participants coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to be hospitalized or die, or require respiratory interventions, compared to participants who were not coinfected with another respiratory RNA virus at baseline in both groups. IMPORTANCE: Respiratory viral coinfections are known to occur with coronavirus disease-2019 (COVID-19). In a cohort of non-hospitalized adults with mild-to-moderate COVID-19 treated with molnupiravir versus placebo in the MOVe-OUT trial during October 2020 to October 2021, 4.1% of participants had a documented viral coinfection; human rhinovirus/enterovirus was the most common pathogen detected with the NxTAG Respiratory Pathogen Panel assay. Participants who had a coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to have worse clinical outcomes compared to those participants without a viral coinfection, and many coinfecting respiratory RNA viruses were no longer detected at the end of the 5-day treatment period in both groups.