Current World Health Organization Guidelines Research Articles

Association of nucleoside reverse transcriptase inhibitors with adverse perinatal outcomes in pregnant women living with HIV: systematic review and meta-analysis.

The World Health Organization (WHO) recommends antiretroviral therapy (ART) containing two nucleoside reverse transcriptase inhibitors (NRTIs) as backbone. WHO recommends tenofovir disoproxil fumarate combined with lamivudine or emtricitabine as first line in pregnancy, and zidovudine, abacavir or tenofovir alafenamide, combined with lamivudine or emtricitabine, as alternatives. Evaluate risk of adverse perinatal outcomes in pregnant women living with HIV (WLHIV) receiving different NRTIs. Medline, CINAHL, Global Health, EMBASE. Cohort studies. Pregnant WLHIV. ART regimes containing different NRTI drugs. Newcastle-Ottawa Scale and GRADE. Random-effects meta-analysis. 22 cohort studies including 124,478 WLHIV met the eligibility criteria. ART containing tenofovir disoproxil fumarate was associated with lower risk of preterm birth (Risk Ratio 0.89; 95% confidence interval 0.81-0.97), very preterm birth (0.58; 0.40-0.86), small for gestational age (0.76; 0.59-0.98), very small for gestational age (0.60; 0.48-0.73), stillbirth (0.49; 0.31-0.78), and neonatal death (0.61; 0.40-0.93), compared to ART not containing tenofovir disoproxil fumarate. ART containing zidovudine was associated with increased risk of very preterm birth (1.59; 1.01-2.49), small for gestational age (1.33; 1.03-1.70), very small for gestational age (1.63; 1.25-2.13), stillbirth (2.23; 1.10-4.55), and neonatal death (1.65; 1.08-2.52), compared to ART not containing zidovudine. For ART regimens also containing either lamivudine or emtricitabine, zidovudine was associated with increased risk of very preterm birth (1.62; 1.04-2.52), small for gestational age (1.52; 1.28-1.82), very small for gestational age (1.68; 1.36-2.06), stillbirth (2.19; 1.03-4.67), and neonatal death (1.65; 1.08-2.52), compared to ART containing tenofovir disoproxil fumarate. Abacavir was not associated with adverse perinatal outcomes. Tenofovir alafenamide was not associated with low birth weight compared to tenofovir disoproxil fumarate. Tenofovir disoproxil fumarate is associated with a lower risk of adverse perinatal outcomes, whereas zidovudine is associated with an increased risk of perinatal outcomes. Abacavir is not associated with adverse perinatal outcomes. Our findings support current WHO guidelines.

Pooled Analysis of Physical Activity, Sedentary Behavior, and Sleep Among Children From 33 Countries

The prevalence estimates of physical activity, sedentary behavior, and sleep (collectively known as movement behaviors) in 3- and 4-year-old children worldwide remains uncertain. To report the proportion of 3- and 4-year-old children who met the World Health Organization guidelines for physical activity, sedentary behavior, and sleep across 33 countries. Pooled analysis of data from 14 cross-sectional studies (July 2008 to September 2022) identified through systematic reviews and personal networks. Thirty-three countries of varying income levels across 6 geographical regions. Each study site needed to have at least 40 children aged 3.0 to 4.9 years with valid accelerometry and parent-/caregiver-reported screen time and sleep duration data. Data were analyzed from October 2022 to February 2023. Time spent in physical activity was assessed by reanalyzing accelerometry data using a harmonized data-processing protocol. Screen time and sleep duration were proxy reported by parents or caregivers. The proportion of children who met the World Health Organization guidelines for physical activity (≥180 min/d of total physical activity and ≥60 min/d of moderate- to vigorous-intensity physical activity), screen time (≤1 h/d), and sleep duration (10-13 h/d) was estimated across countries and by World Bank income group and geographical region using meta-analysis. Of the 7017 children (mean [SD] age, 4.1 [0.5] years; 3585 [51.1%] boys and 3432 [48.9%] girls) in this pooled analysis, 14.3% (95% CI, 9.7-20.7) met the overall guidelines for physical activity, screen time, and sleep duration. There was no clear pattern according to income group: the proportion meeting the guidelines was 16.6% (95% CI, 10.4-25.3) in low- and lower-middle-income countries, 11.9% (95% CI, 5.9-22.5) in upper-middle-income countries, and 14.4% (95% CI, 9.6-21.1) in high-income countries. The region with the highest proportion meeting the guidelines was Africa (23.9%; 95% CI, 11.6-43.0), while the lowest proportion was in North and South America (7.7%; 95% CI, 3.6-15.8). Most 3- and 4-year-old children in this pooled analysis did not meet the current World Health Organization guidelines for physical activity, sedentary behavior, and sleep. Priority must be given to understanding factors that influence these behaviors in this age group and to implementing contextually appropriate programs and policies proven to be effective in promoting healthy levels of movement behaviors.

Mass drug administration to reduce malaria incidence in a low-to-moderate endemic setting: short-term impact results from a cluster randomised controlled trial in Senegal.

In Africa, the scale-up of malaria control interventions, including seasonal malaria chemoprevention (SMC), has dramatically reduced malaria burden, but progress toward malaria elimination has stalled. We evaluated mass drug administration (MDA) as a strategy to accelerate reductions in malaria incidence in Senegal. We conducted an open-label, cluster-randomised controlled trial in a low-to-moderate transmission setting of Tambacounda, Senegal. Eligible villages had a population size between 200-800. All villages received pyrethroid-piperonyl butoxide bednets and proactive community case management of malaria at baseline. Sixty villages were randomised 1:1 to either three cycles of MDA with dihydroartemisinin-piperaquine+single-low dose primaquine administered to individuals aged ≥3 months, six-weeks apart starting the third week of June (intervention), or standard-of-care, which included three monthly cycles of SMC with sulfadoxine-pyrimethamine+amodiaquine administered to children aged 3-120 months starting end of July (control). MDA and SMC were delivered door-to-door. The primary outcome was clinical malaria incidence in all ages assessed during the peak transmission season (July-December), the year after intervention. Here, we report safety, coverage, and impact outcomes during the intervention year. The trial is registered at ClinicalTrials.Gov (NCT04864444). Between June 21, 2021 and October 3, 2021, 6505, 7125, and 7250 participants were administered MDA and 3202, 3174, and 3146 participants were administered SMC across cycles. Coverage of ≥1 dose of MDA drugs was 79%, 82%, and 83% across cycles. During the transmission season of the intervention year, MDA was associated with a 55% [95% CI: 28%-72%] lower incidence of malaria compared to control (MDA: 93 cases/1000 population; control: 173 cases/1000 population). No serious adverse events were reported in either arm. In low-to-moderate malaria transmission settings with scaled-up malaria control interventions, MDA with dihydroartemisinin-piperaquine+single-low dose primaquine is effective and well-tolerated for reducing malaria incidence. Further analyses will focus on the sustainability of this reduction. United States President's Malaria Initiative.

"Our desire is to make this village intestinal worm free": Identifying determinants of high coverage of community-wide mass drug administration for soil transmitted helminths in Benin, India, and Malawi.

Soil-transmitted helminth infections (STH) are associated with substantial morbidity in low-and-middle-income countries, accounting for 2.7 million disability-adjusted life years annually. Current World Health Organization guidelines recommend controlling STH-associated morbidity through periodic deworming of at-risk populations, including children and women of reproductive age (15-49 years). However, there is increasing interest in community-wide mass drug administration (cMDA) which includes deworming adults who serve as infection reservoirs as a method to improve coverage and possibly to interrupt STH transmission. We investigated determinants of cMDA coverage by comparing high-coverage clusters (HCCs) and low-coverage clusters (LCCs) receiving STH cMDA in three countries. A convergent mixed-methods design was used to analyze data from HCCs and LCCs in DeWorm3 trial sites in Benin, India, and Malawi following three rounds of cMDA. Qualitative data were collected via 48 community-level focus group discussions. Quantitative data were collected via routine activities nested within the DeWorm3 trial, including annual censuses and coverage surveys. The Consolidated Framework for Implementation Research (CFIR) guided coding, theme development and a rating process to determine the influence of each CFIR construct on cMDA coverage. Of 23 CFIR constructs evaluated, we identified 11 constructs that differentiated between HCCs and LCCs, indicating they are potential drivers of coverage. Determinants differentiating HCC and LCC include participant experiences with previous community-wide programs, communities' perceptions of directly observed therapy (DOT), perceptions about the treatment uptake behaviors of neighbors, and women's agency to make household-level treatment decisions. The convergent mixed-methods study identified barriers and facilitators that may be useful to NTD programs to improve cMDA implementation for STH, increase treatment coverage, and contribute to the successful control or elimination of STH. The parent trial was registered at clinicaltrials.gov (NCT03014167).

Optimized strategy for real-time qPCR detection of Onchocerca volvulus DNA in pooled Simulium sp. blackfly vectors.

Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, with at least two African countries having now stopped MDA as they approach verification of elimination. It is essential that accurate data for active transmission are used to assist in making the critical decision to stop MDA, since missing low levels of transmission and infection can lead to continued spread or recrudescence of the disease. Current World Health Organization guidelines for MDA stopping decisions and post-treatment surveillance include screening pools of the Simulium blackfly vector for the presence of O. volvulus larvae using a PCR-ELISA-based molecular technique. In this study, we address the potential of an updated, practical, standardized molecular diagnostic tool with increased sensitivity and species-specificity by comparing several candidate qPCR assays. When paired with heat-stable reagents, a qPCR assay with a mitochondrial DNA target (OvND5) was found to be more sensitive and species-specific than an O150 qPCR, which targets a non-protein coding repetitive DNA sequence. The OvND5 assay detected 19/20 pools of 100 blackfly heads spiked with a single L3, compared to 16/20 for the O150 qPCR assay. Given the improved sensitivity, species-specificity and resistance to PCR inhibitors, we identified OvND5 as the optimal target for field sample detection. All reagents for this assay can be shipped at room temperature with no loss of activity. The qPCR protocol we propose is also simpler, faster, and more cost-effective than the current end-point molecular assays.

Improvements in patient-reported outcomes following initiation of dolutegravir- or low-dose efavirenz-based first-line antiretroviral therapy: A four-year longitudinal analysis in Cameroon (NAMSAL ANRS 12313 trial).

We provide new and comprehensive evidence on the evolution of a wide range of patient-reported outcomes (PROs) in the NAMSAL ANRS 12313 trial in Cameroon (2016-2021) - the first randomized comparison of dolutegravir 50 mg (DTG) and low-dose efavirenz (i.e., 400 mg; EFV400) in treatment-naive adults living with HIV-1 in sub-Saharan Africa. We first described the evolution of PROs between baseline and Week 192. We then used random-effects models to measure the effect of time since antiretroviral therapy (ART) initiation and the differential effect of DTG versus EFV400 on each PRO, adjusting for clinical, demographic, and socioeconomic factors, while accounting for unobserved heterogeneity and missing data. Among the 613 patients randomized (DTG arm, n=310; EFV400 arm, n=303), (i) physical and mental health-related quality of life improved by 13.3% and 6.8%, respectively, (ii) the percentage of patients with depression, anxiety, and stress decreased from 23.3%, 23.0%, and 7.7% to 3.1%, 3.5%, and 0.4%, respectively, and (iii) the mean number of HIV-related symptoms decreased from 7.2 to 3.0 (p<0.001). For most PROs, no significant difference was found between both arms, even when accounting for the effect of DTG on weight gain. Nevertheless, our results suggest smaller improvements in mental health outcomes in the DTG arm, with a 5 percentage-point higher adjusted probability of having anxiety at Week 192 (p<0.01). Although supporting the current WHO guidelines recommending DTG- and EFV400-based regimens as preferred and alternative first-line ART, further studies should investigate medium-term mental health outcomes in patients on DTG.

Medicine donations: a review of policies and practices

BackgroundTo help promote the effective delivery of drug donations, the World Health Organization (WHO) developed the Guidelines for Medicine Donations. The need for revisions is timely given the large-scale influx of medicine donations since the start of the COVID-19 pandemic. This study analyses current policies of donors and recipients that are commensurate with the recommendations in the Guidelines and examines current practices, challenges, and revision suggestions.ResultsA search for medicine donation policies of donors and recipients was conducted in May/June 2022 and repeated in January 2023. Potential donor countries were identified from the high-income countries on the United Nation’s (UN) List of G20 Countries. Potential pharmaceutical company donors were selected from those with 2021 revenue of $30 billion or greater. Potential non-government organization donors came from the WHO list of non-governmental organizations (NGOs) and two other sources. Potential recipient countries were those on the UN List of Least Developed Countries. These four lists were supplemented with actual donors and recipients identified from the literature. All policies retrieved were screened to identify which of the 12 recommendations from the WHO Guidelines were incorporated. We identified 38 policies from 1 donor country, 6 brand-name multinational pharmaceutical companies, 6 NGOs and 25 recipient countries. Most policies incorporated all 12 recommendations. Twenty-five of the 38 policies were developed in 2010 or later. The majority of actual donors and recipients did not have policies that were publicly available. A rapid literature review for publications from 2010 onwards identified challenges in implementing the WHO Guidelines and suggested for revisions. Challenges included: (1) information management; (2) medication presentation; (3) influence from the pharmaceutical industry; (4) donation sustainability; and (5) the belief that donations are inherently good.ConclusionsOur findings suggest that both donors and recipients could further align their policies with the existing Guidelines and both groups should be consulted on any revisions to ensure that their experiences are reflected and their needs are addressed. While the current WHO Guidelines for Medicine Donations are a solid base for medical humanitarian efforts, evidence points to the need for an update to meet current challenges.

A Retrospective Genomic Landscape of 661 Young Adult Glioblastomas Diagnosed Using 2016 WHO Guidelines for Central Nervous System Tumors.

The authors present a cohort of 661 young adult glioblastomas diagnosed using 2016 WHO World Health Organization Classification of Tumors of the Central Nervous System, utilizing comprehensive genomic profiling (CGP) to explore their genomic landscape and assess their relationship to currently defined disease entities. This analysis explored variants with evidence of pathogenic function, common copy number variants (CNVs), and several novel fusion events not described in literature. Tumor mutational burden (TMB) mutational signatures, anatomic location, and tumor recurrence are further explored. Using data collected from CGP, unsupervised machine-learning techniques were leveraged to identify 10 genomic classes in previously assigned young adult glioblastomas. The authors relate these molecular classes to current World Health Organization guidelines and reference current literature to give therapeutic and prognostic descriptions where possible.

Long-term exposure to residential transportation noise and mortality: A nationwide cohort study

Studies have indicated that transportation noise is associated with higher cardiovascular mortality, whereas evidence of noise as a risk factor for respiratory and cancer mortality is scarce and inconclusive. Also, knowledge on effects of low-level noise on mortality is very limited. We aimed to investigate associations between road and railway noise and natural-cause and cause-specific mortality in the Danish population. We estimated address-specific road and railway noise at the most (LdenMax) and least (LdenMin) exposed façades for all residential addresses in Denmark from 1990 to 2017 using high-quality exposure models. Using these data, we calculated 10-year time-weighted mean noise exposure for 2.6 million Danes aged >50 years, of whom 600,492 died from natural causes during a mean follow-up of 11.7 years. We analyzed data using Cox proportional hazards models with adjustment for individual and area-level sociodemographic variables and air pollution (PM2.5 and NO2). We found that a 10-year mean exposure to road LdenMax and road LdenMin per 10 dB were associated with hazard ratios (95% confidence intervals) of, respectively, 1.09 (1.09; 1.10) and 1.10 (1.10; 1.11) for natural-cause mortality, 1.09 (1.08; 1.10) and 1.09 (1.08; 1.10) for cardiovascular mortality, 1.13 (1.12; 1.14) and 1.17 (1.16; 1.19) for respiratory mortality and 1.03 (1.02; 1.03) and 1.06 (1.05; 1.07) for cancer mortality. For LdenMax, the associations followed linear exposure-response relationships from 35 dB to 60–<65 dB, after which the function levelled off. For LdenMin, exposure-response relationships were linear from 35 dB and up, with some levelling off at high noise levels for natural-cause and cardiovascular mortality. Railway noise did not seem associated with higher mortality in an exposure-response dependent manner. In conclusion, road traffic noise was associated with higher mortality and the increase in risk started well below the current World Health Organization guideline limit for road traffic noise of 53 dB.

Short-Term Association between Sulfur Dioxide and Mortality: A Multicountry Analysis in 399 Cities.

Epidemiological evidence on the health risks of sulfur dioxide () is more limited compared with other pollutants, and doubts remain on several aspects, such as the form of the exposure-response relationship, the potential role of copollutants, as well as the actual risk at low concentrations and possible temporal variation in risks. Our aim was to assess the short-term association between exposure to and daily mortality in a large multilocation data set, using advanced study designs and statistical techniques. The analysis included 43,729,018 deaths that occurred in 399 cities within 23 countries between 1980 and 2018. A two-stage design was applied to assess the association between the daily concentration of and mortality counts, including first-stage time-series regressions and second-stage multilevel random-effect meta-analyses. Secondary analyses assessed the exposure-response shape and the lag structure using spline terms and distributed lag models, respectively, and temporal variations in risk using a longitudinal meta-regression. Bi-pollutant models were applied to examine confounding effects of particulate matter with an aerodynamic diameter of () and (), ozone, nitrogen dioxide, and carbon monoxide. Associations were reported as relative risks (RRs) and fractions of excess deaths. The average daily concentration of across the 399 cities was , with 4.7% of days above the World Health Organization (WHO) guideline limit (, 24-h average), although the exceedances occurred predominantly in specific locations. Exposure levels decreased considerably during the study period, from an average concentration of in 1980-1989 to in 2010-2018. For all locations combined, a increase in daily was associated with an RR of mortality of 1.0045 [95% confidence interval (CI): 1.0019, 1.0070], with the risk being stable over time but with substantial between-country heterogeneity. Short-term exposure to was associated with an excess mortality fraction of 0.50% [95% empirical CI (eCI): 0.42%, 0.57%] in the 399 cities, although decreasing from 0.74% (0.61%, 0.85%) in 1980-1989 to 0.37% (0.27%, 0.47%) in 2010-2018. There was some evidence of nonlinearity, with a steep exposure-response relationship at low concentrations and the risk attenuating at higher levels. The relevant lag window was 0-3 d. Significant positive associations remained after controlling for other pollutants. The analysis revealed independent mortality risks associated with short-term exposure to , with no evidence of a threshold. Levels below the current WHO guidelines for 24-h averages were still associated with substantial excess mortality, indicating the potential benefits of stricter air quality standards. https://doi.org/10.1289/EHP11112.

Comparison of Current World Health Organization Guidelines with Physiologically Based Serum Ferritin Thresholds for Iron Deficiency in Healthy Young Children and Nonpregnant Women Using Data from the Third National Health and Nutrition Examination Survey

BackgroundCurrent WHO serum ferritin (SF) thresholds for iron deficiency (ID) in children (<12 μg/L) and women (<15 μg/L) are derived from expert opinion based on radiometric assays in use decades ago. Using a contemporary immunoturbidimetry assay, higher thresholds (children, <20 μg/L; women, <25 μg/L) were identified from physiologically based analyses. ObjectiveWe examined relationships of SF measured using an immunoradiometric assay from the era of expert opinion with 2 independently measured indicators of ID, hemoglobin (Hb) and erythrocyte zinc protoporphyrin (eZnPP), using data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994). The SF at which circulating Hb begins to decrease and eZnPP begins to increase provides a physiological basis for identifying the onset of iron-deficient erythropoiesis. MethodsWe analyzed NHANES III cross-sectional data from 2616 apparently healthy children, aged 12-59 mo, and 4639 apparently healthy nonpregnant women, aged 15-49 y. We used restricted cubic spline regression models to determine SF thresholds for ID. ResultsSF thresholds identified by Hb and eZnPP did not differ significantly in children, 21.2 μg/L (95% confidence interval: 18.5, 26.5) and 18.7 μg/L (17.9, 19.7), and, in women, were similar although significantly different, 24.8 μg/L (23.4, 26.9) and 22.5 μg/L (21.7, 23.3). ConclusionsThese NHANES results suggest that physiologically based SF thresholds are higher than the thresholds from expert opinion established during the same era. SF thresholds found using physiological indicators detect the onset of iron-deficient erythropoiesis, whereas the WHO thresholds identify a later, more severe stage of ID.

Dyspnea: a map of Cochrane evidence relevant to rehabilitation for people with post COVID-19 condition.

Rehabilitation focuses on impairments, activity limitations and participation restrictions being informed by the underlying health condition. In the current absence of direct "evidence on" rehabilitation interventions for people with post COVID-19 condition (PCC), we can search and synthesize the indirect "evidence relevant to" coming from interventions effective on the symptoms of PCC in other health conditions. The World Health Organization (WHO) required this information to inform expert teams and provide specific recommendations in their Guidelines. With this overview of reviews with mapping we aimed to synthesize in a map the Cochrane evidence relevant to rehabilitation for dyspnea due to PCC. We searched the last five years' Cochrane Systematic Review (CSRs) using the terms "dyspnea" and its synonyms in the Cochrane Library. We extracted and summarized all the available evidence using a map. We grouped the included CSRs for health conditions and interventions, indicating the effect and the quality of evidence. We found 371 CSRs published between 2016 and 2021 and included 15 in this overview. We found eight studies on chronic obstructive pulmonary disease, two on cancer, and one for bronchiectasis, chronic respiratory disease, cystic fibrosis, idiopathic pulmonary fibrosis and interstitial lung disease. Effective interventions included pulmonary rehabilitation, also in combination with exercise training, non-invasive ventilation, upper limb training and multicomponent integrated interventions, with very low- to moderate-quality evidence. These results are the first step of indirect evidence to generate helpful hypotheses for clinical practice and future research on dyspnea in adults with PCC. They served as the basis for one recommendation on treatments for dyspnea as a PCC symptom published in the current WHO Guidelines for clinical practice.

Fatigue, post-exertional malaise and orthostatic intolerance: a map of Cochrane evidence relevant to rehabilitation for people with post COVID-19 condition.

Rehabilitation focuses on impairments, activity limitations and participation restrictions being informed by the underlying health condition. In the current absence of direct "evidence on" rehabilitation interventions for people with post-COVID-19 condition (PCC), we can search and synthesize the indirect "evidence relevant to" coming from interventions effective for the symptoms of PCC in other health conditions. The World Health Organization (WHO) required this information to inform expert teams and provide specific recommendations in their Guidelines. With this overview of reviews with mapping, we aimed to synthesize in a map the Cochrane evidence relevant to rehabilitation for fatigue, post-exertional malaise and orthostatic intolerance due to PCC. We searched the last five years' Cochrane Systematic Review (CSRs) using the terms "fatigue," "orthostatic intolerance," "rehabilitation" and their synonyms in the Cochrane Library. We extracted and summarized the available evidence using a map. We grouped the included CSRs for health conditions and interventions, indicating the effect and the quality of evidence. Out of 1397 CSRs published between 2016 and 2021, we included 32 for fatigue and 4 for exercise intolerance. They provided data from 13 health conditions, with cancer (11 studies), chronic obstructive pulmonary disease (7 studies), fibromyalgia (4 studies), and cystic fibrosis (3 studies) being the most studied. Effective interventions for fatigue included exercise training and physical activities, telerehabilitation and multicomponent and educational interventions. Effective interventions for exercise intolerance included combined aerobic/anaerobic training and integrated disease rehabilitation management. The overall quality of evidence was low to very low and moderate in very few cases. We did not identify CSRs that specifically addressed post-exertional malaise or orthostatic intolerance. These results are the first step of indirect evidence able to generate helpful hypotheses for clinical practice and future research. They served as the basis for the three recommendations on treatments for these PCC symptoms published in the current WHO Guidelines for clinical practice.

Joint associations of social health and movement behaviours with mortality and cardiovascular disease: an analysis of 497,544 UK biobank participants

BackgroundPoor physical activity and excessive sedentary behaviour are well-established risk factors for morbidity and mortality. In the presence of emerging social problems, including loneliness and social isolation, these risks may be even greater. We aimed to investigate the joint effects of social health and movement behaviours on mortality and cardiovascular disease (CVD).Methods497,544 UK Biobank participants were followed for an average of 11 years. Loneliness and social isolation were measured via self-report. Physical activity was categorised around current World Health Organisation (WHO) guidelines as low (< 600 metabolic equivalent of task [MET]-mins/week), moderate (600 < 1200) and high (≥ 1200). Sedentary behaviour was classified as low (≤ 3.5 h/day), moderate (3.5 ≤ 5) and high (> 5.5). We derived 24 social health–movement behaviour combinations, accordingly. Mortality and hospitalisations were ascertained to May 2020 for all-cause and CVD mortality, and non-fatal cardiovascular events.ResultsSocial isolation amplified the risk of both all-cause and CVD death across all physical activity and sedentary levels (hazard ratio, 95% confidence interval [HR, 95% CIs] for all-cause mortality; 1.58 [1.49 to 1.68] for low active-isolated vs. 1.26 [1.22 to 1.30] for low active-not isolated). Loneliness was only found to amplify the risk of death from cardiovascular disease among the high active and low sedentary participants. Loneliness and social isolation did not add to the risk of non-fatal cardiovascular events across most activity levels.ConclusionThe detrimental associations of poor physical activity and sedentary behaviour with mortality were consistently amplified by social isolation. Our study supports the need to target the socially isolated as a priority group in preventive public health strategies.

Can the history of empiric antibiotic treatment for neonatal sepsis inform future global trials?

Antimicrobial resistance is a major threat to the Sustainable Development Goal to reduce neonatal mortality to 12 per 1000 live births [1]. Current global rates are at 17 per 1000 live births with variation between <1 and 50 per 1000 live births [2]. There are many contributing factors limiting the success of reaching this target including preterm birth, intrapartum-related complications, and birth defects. However, one of the other leading causes of mortality is neonatal sepsis. Current World Health Organization (WHO) guidelines recommend using a combination of ampicillin (or penicillin) and gentamicin for the empiric treatment of neonatal sepsis [3].

Multiple Plasmodium falciparum drug resistance polymorphisms identified in a pregnant woman with severe malaria and a concomitant spontaneous abortion in Cross River, Nigeria, West Africa

BackgroundThe development of resistance by Plasmodium falciparum to anti-malarial drugs impedes any benefits of the drug. In addition, absence or delayed availability of current anti-malarial drugs in remote areas has the potential to results to parasite escape and continuous transmission.Case presentationThe case of a 29-year old pregnant woman from Biase Local Government Area in Cross River State Nigeria presenting with febrile illness and high body temperature of 38.7 °C was reported. She looked pale and vomited twice on arrival at the health facility. Her blood smear on the first day of hospitalization was positive for P. falciparum by RDT, microscopy (21,960 parasite/µl) and real-time PCR, with a PCV of 18%. She was treated with 600 mg intravenous quinine in 500 ml of 5% Dextrose/0.9% Saline 8-hourly for 24 h. On the second day of hospitalization, she complained of weakness, persistent high-grade fever and vaginal bleeding. A bulging amnion from an extended cervix was observed. Following venous blood collection for laboratory investigations, 600 µg of misoprostol was inserted into the posterior fornix of her vagina as part of her obstetric care. Parenteral quinine was discontinued, and she was given full therapeutic regimen of artemether-lumefantrine 80/480 mg tablets to be taken for 3 days beginning from the second day. Her blood samples on the second and third day of hospitalization remained positive for P. falciparum by all three diagnostic methods. Single nucleotide polymorphism (SNP) assay on all three P. falciparum isolates revealed the presence of variants associated with multiple drug resistant markers.DiscussionInfecting P. falciparum isolates may have been resistant to initial quinine treatment resulting from parasite cross-resistance with other quinoline associated resistant markers such as 86Y and 184 F.ConclusionsTherefore, the likely transmission of similarly resistant parasites in the study area calls for reinforcement of interventions and adherence to current World Health Organization guidelines in administering only approved drugs to individuals in order to mitigate parasite escape and eventual transmission to other susceptible individuals.

Simulating PM2.5 Concentrations during New Year in Cuenca, Ecuador: Effects of Advancing the Time of Burning Activities.

Fine particulate matter (PM2.5) is dangerous to human health. At midnight on 31 December, in Ecuadorian cities, people burn puppets and fireworks, emitting high amounts of PM2.5. On 1 January 2022, concentrations between 27.3 and 40.6 µg m−3 (maximum mean over 24 h) were measured in Cuenca, an Andean city located in southern Ecuador; these are higher than 15 µg m−3, the current World Health Organization guideline. We estimated the corresponding PM2.5 emissions and used them as an input to the Weather Research and Forecasting with Chemistry (WRF-Chem 3.2) model to simulate the change in PM2.5 concentrations, assuming these emissions started at 18:00 LT or 21:00 LT on 31 December 2021. On average, PM2.5 concentrations decreased by 51.4% and 33.2%. Similar modeling exercises were completed for 2016 to 2021, providing mean decreases between 21.4% and 61.0% if emissions started at 18:00 LT. Lower mean reductions, between 2.3% and 40.7%, or even local increases, were computed for emissions beginning at 21:00 LT. Reductions occurred through better atmospheric conditions to disperse PM2.5 compared to midnight. Advancing the burning time can help reduce the health effects of PM2.5 emissions on 31 December.

Physical activity engagement in Eldoret, Kenya, during COVID-19 pandemic.

The World Health Organization (WHO) recommends that individuals of all ages participate in regular physical activity (PA) for optimal health and to support with the control of multiple non-communicable diseases. In Kenya however, involvement in PA across the general population is low and there is an increase in sedentary lifestyles in both rural and urban areas. An inverse relationship exists between socioeconomic status and involvement in PA. The novel COVID-19 ushered in associated control measures to limit the spread of the virus. These measures included staying at home, social distancing, and closure of physical spaces such as gyms, public parks, sports grounds, outdoor playing areas and schools. The impact was immediate, impacting patterns and routines of PA in Kenya. The primary aim of this study was to verify if COVID-19 affected PA prevalence and patterns amongst adults in Eldoret, Kenya. The secondary aim was to ascertain if the modification in behaviour is consistent amongst individuals from different socioeconomic backgrounds. We used a cross-sectional study to examine self-reported PA data amongst 404 participants. All participants were ≥18 years and resided in Eldoret, Kenya. Data were collected using a self-administered, structured questionnaire adapted from the WHO Global Physical Activity Questionnaire (WHO GPAQ). The characteristics of participants' is summarized using descriptive statistics, and bivariate analyses for measures of associations of variables was done using Chi-squared and Fishers exact tests. Binary logistic regressions were performed to adjust for the various factors and report associations between variables. The p-value considered for significant differences was set at <0.05. Participants in this study had mean age of 30.2±9.8 years. Almost 90% of the participants were not aware of the current WHO guidelines on PA, 9% stopped PA engagement after COVID-19 was first reported in Kenya, and only 25% continued regular PA. Less than half maintained PA intensity after the advent of COVID-19, with almost half reporting a drop. Males had a drop in time taken per PA session while females maintained session lengths after COVID-19 (p = 0.03). Males preferred gym-setup or mixed-type PA while females opted for indoor (home) aerobics before and after COVID-19 (p = 0.01, p = 0.02 respectively). Compared to males, females were less likely to achieve both vigorous- and moderate-intensity PA recommendations (p<0.01 and p = 0.02 respectively). Zone of residence was associated with participation in aerobic PA (p = 0.04; 95% CI = 0.02499-0.96086) and, similarly, level of education was associated with knowledge of WHO recommendations for PA (p = 0.01; 95% CI = -1.7544 - -0.2070). A majority of the urban population of Eldoret, Kenya and especially those with lower level of education are unaware of WHO recommendations for PA, and 30% of them have not engaged in any form of PA for many years. The majority that report involvement in PA do not achieve the WHO recommended threshold levels of PA. The results also indicated that COVID-19 has negatively affected intensity of PA, and that there has been an increase in time spent sitting/reclining amongst individuals in the higher socio-economic classes and specifically amongst females.

The Discrepancy Between Standard Histologic WHO Grading of Meningioma and Molecular Profile: A Single Institution Series.

IntroductionMeningiomas are the most common primary central nervous system (CNS) tumor. They are most often benign, but a subset of these can behave aggressively. Current World Health Organization (WHO) guidelines classify meningiomas into three grades based on the histologic findings and presence or absence of brain invasion. These grades are intended to guide treatment, but meningiomas can behave inconsistently with regard to their assigned histopathological grade, influencing patient expectations and management. Advanced molecular profiling of meningiomas has led to the proposal of alternative molecular grading schemes that have shown superior predictive power. These include methylation patterns, copy number alterations, and mutually exclusive driver mutations affecting oncogenes, including BAP1, CDKN2A/B, and the TERT promoter, which are associated with particularly aggressive tumor biology. Despite the evident clinical value, advanced molecular profiling methods are not widely incorporated in routine clinical practice for meningiomas.ObjectiveTo assess the degree of concordance between the molecular profile of meningiomas and the histopathologic WHO classification, the current method of predicting meningioma behavior.MethodsIn a two-year single-institution experience, we used commercially available resources to determine molecular profiles of all resected meningiomas. Copy number aberrations and oncogenic driver mutations were identified and compared with the histopathologic grade.ResultsOne hundred fifty-one total meningioma cases were included for analysis (85.4% WHO grade 1, 13.3% WHO grade 2, and 1.3% grade 3). Chromosomal analysis of 124 of these samples showed that 29% of WHO grade 1 tumor featured copy number profiles consistent with higher grade meningioma, and 25% of WHO grade 2 meningiomas had copy number profiles consistent with less aggressive tumors. Furthermore, 8% harbored mutations in TERT, CDKN2A/B, or BAP1 of which 6% occurred in grade 1 meningiomas.ConclusionsRoutine advanced molecular profiling of all resected meningiomas using commercially available resources allowed for identification of a significant number of meningiomas whose molecular profiles were inconsistent with WHO grade. Our work shows the clinical value of integrating routine molecular profiling with histopathologic grading to guide clinical decision making.

The Effect of Arthrospira platensis (Phormidiaceae) on the Acute Toxicity of Artemeter Lumefantrine in Malaria Patients

Malaria has remained one of the leading causes of morbidity and mortality in most developing countries. This pathology is caused by the Plasmodium spp. Current World Health Organization (WHO) guidelines for the treatment of uncomplicated falciparum malaria recommends the use of artemisinin-based combination therapy (ACT). Arthrospira platensis is a microscopic filamentous alga that is rich in proteins, vitamins, essential amino acids, minerals and essential fatty acids like -linolenic acid (GLA). The current study was carried out to evaluate the effect of Arthrospira platensis on the liver and kidney toxicity induced by ACT. Malaria patients were randomized into two groups to receive therapeutic dose of either artemether-lumefantrine 20/120 mg (group 1) or artemether-lumefantrine 20/120 mg + Arthrospira platensis 8 g daily (group 2) as an adjunct therapy and follow-up for 7 days (D). After treatment, the activity levels/concentrations of liver and kidney biochemical markers (ALT, AST, ALB, UREA, CREAT) were analyzed. Both pre- and post-treatment samples were analyzed, and the results gotten compared with control group made up of malaria negative patients. Serum activity of selected biomarkers (ALT, AST, ALB, UREA) of malaria patients were statistically significant (P&lt;0.05) on D0 when compared to that of malaria negative patients. The serum activity of CREAT though not statistically significant (P&gt;0.05), increased compared to malaria negative patients. The serum level of ALT, AST, UREA and CREAT increased from D0 to D3 and decreased on D7 after treatment while ALB decreased from D0 to D3 and increased on D7 in both groups when compared with the negative control group. The concentration of these biochemical markers varied across the groups from D0 to D7. The results obtained from this study indicate that Arthrospira platensis has a positive effect on the liver and kidney toxicity induced by ACT and hence could be administered together with ACT in malaria treatment.