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Background Multi-month dispensing (MMD) for antiretroviral therapy (ART) is a promising care strategy to improve HIV treatment adherence. The effectiveness of MMD in routine settings has not yet been evaluated within a causal inference framework. We analyzed data from a robust clinical data system to evaluate MMD in Haiti. Methods We assessed 1-year retention in care among 21,880 ART-naive HIV-positive persons who started ART on or after January 1, 2017, up until November 1, 2018. We used an instrumental variable analysis to estimate the causal impact of MMD. This approach was used to address potential selection into specific dispensing intervals because MMD is not randomly applied to individuals. Findings We found that extending ART dispensing intervals increased the probability of retention at 12 months after ART initiation, with up to a 24·2%-point increase (95%CI: 21·9, 26·5) in the likelihood of retention with extending dispenses by 30 days for those receiving one-month dispenses. We observed statistically significant gains to retention with MMD with up to an approximately 4-month supply of ART; +5·1%-points (95%CI: 2·4,7·8). Increasing dispensing lengths for those already receiving ≥5-month supply of ART had a potentially negative effect on retention. Interpretation MMD for ART is an effective service delivery strategy that improves care retention for new ART recipients. There is a potentially negative effect of increasing prescription lengths for those new ART recipients already receiving longer ART supplies, though more research is needed to characterize this effect given medication supplies of this length are not common for newer ART recipients. Funding This research has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the US Centers for Disease Control and Prevention (https://www.cdc.gov/), under award number NU2GGH002226-02, made to the center Haitien de Renforcement du Systeme Sanitaire (CHARESS).

Background Beginning March 2020, the COVID-19 pandemic has disrupted different aspects of life. The impact on children's rate of weight gain has not been analysed. Methods In this retrospective cohort study, we used United States (US) Electronic Health Record (EHR) data from Optum® to calculate the age- and sex- adjusted change in BMI (∆BMIadj) in individual 6-to-17-year-old children between two well child checks (WCCs). The mean of individual ∆BMIadj during 2017–2020 was calculated by month. For September-December WCCs, the mean of individual ∆BMIadj (overall and by subgroup) was reported for 2020 and 2017–2019, and the impact of 2020 vs 2017–2019 was tested by multivariable linear regression. Findings The mean [95% Confidence Interval - CI] ∆BMIadj in September-December of 2020 was 0·62 [0·59,0·64] kg/m2, compared to 0·31 [0·29, 0·32] kg/m2 in previous years. The increase was most prominent in children with pre-existing obesity (1·16 [1·07,1·24] kg/m2 in 2020 versus 0·56 [0·52,0·61] kg/m2 in previous years), Hispanic children (0·93 [0·84,1·02] kg/m2 in 2020 versus 0·41 [0·36,0·46] kg/m2 in previous years), and children who lack commercial insurance (0·88 [0·81,0·95] kg/m2 in 2020 compared to 0·43 [0·39,0·47] kg/m2 in previous years). ∆BMIadj accelerated most in ages 8–12 and least in ages 15–17. Interpretation Children's rate of unhealthy weight gain increased notably during the COVID-19 pandemic across demographic groups, and most prominently in children already vulnerable to unhealthy weight gain. This data can inform policy decisions critical to child development and health as the pandemic continues to unfold. Funding Amgen, Inc.

Background: Cancer-related cognitive impairment (CRCI) is a prevalent source of comprised quality of life in cancer survivors. This study evaluated the efficacy of Emotional Freedom Techniques (EFT) on self-reported CRCI (sr-CRCI). Methods: In this prospective multicentre randomised wait-list controlled study (ClinicalTrials.gov Identifier: NCT02771028), eligible cancer survivors had completed curative treatment, were 18 years or older and screened positive for sr-CRCI with > 43 on the Cognitive Failures Questionnaire (CFQ). Participants were randomised to the immediate treatment group (ITG) or wait-list control (WLC) group, based on age (< or > 65 years), gender, treatment (chemotherapy or not), and centre. The ITG started to apply EFT after inclusion and performed this for 16 weeks. The WLC group could only start the application of EFT after 8 weeks of waiting. Evaluations took place at baseline (T0), 8 weeks (T1) and 16 weeks (T2). The primary outcome was the proportion of patients with sr-CRCI according to the CFQ score. Findings: Between October 2016 and March 2020, 121 patients were recruited with CFQ > 43 indicating sr-CRCI. At T1, the number of patients scoring positive on the CFQ was significantly reduced in the ITG compared to the WLC group (40.8% vs. 87.3% respectively; p

Background: Understanding the effect of early kangaroo mother care on survival of mild-moderately unstable neonates 24 h after admission (control) versus KMC initiated

Background: Interpretation of incidental findings on term neonatal MRI brain imaging can be challenging as there is a paucity of published normative data on asymptomatic term neonates. Reporting radiologists and clinicians need to be familiar with these incidental findings to avoid over-investigation and misinterpretation particularly in relation to neurodevelopmental outcome. This study aimed to determine the prevalence of incidental findings in a large group of asymptomatic term neonates participating in the Developing Human Connectome Project (dHCP) who were invited for neurodevelopmental assessment at 18 months. Methods: We retrospectively reviewed MRI brain scans performed on 500 term neonates enrolled in the dHCP study between 2015 and 2019 with normal clinical examination. We reviewed the results of the Bayley Scales of Infant and Toddler Development (Bayley III) applied to participants who attended for neurodevelopmental follow-up at 18 months. Scores considered “delayed” if

Background: Bacterial intestinal communities interact with the immune system and may contribute to protection against community-acquired pneumonia (CAP). Intestinal viruses are closely integrated with these bacterial communities, yet the composition and clinical significance of these communities in CAP patients are unknown. The aims of this exploratory study were to characterise the composition of the rectal bacteriome and virome at hospital admission for CAP, and to determine if microbiota signatures correlate with clinical outcomes., Methods: We performed a prospective observational cohort study in CAP patients, admitted to a university or community hospital in the Netherlands between October 2016 and July 2018, and controls. Rectal bacteriome and virome composition were characterised using 16S ribosomal RNA gene sequencing and virus discovery next-generation sequencing, respectively. Unsupervised multi-omics factor analysis was used to assess the co-variation of bacterial and viral communities, which served as primary predictor. The clinical outcomes of interest were the time to clinical stability and the length of hospital stay., Findings: 64 patients and 38 controls were analysed. Rectal bacterial alpha (p = 0•0015) and beta diversity (r2 =0•023, p = 0•004) of CAP patients differed from controls. Bacterial and viral microbiota signatures correlated with the time to clinical stability (hazard ratio 0•43, 95% confidence interval 0•20-0•93, p = 0•032) and the length of hospital stay (hazard ratio 0•37, 95% confidence interval 0•17-0•81, p = 0•012), although only the latter remained significant following p-value adjustment for examining multiple candidate cut-points (p = 0•12 and p = 0•046, respectively)., Interpretation: This exploratory study provides preliminary evidence that intestinal bacteriome and virome signatures could be linked with clinical outcomes in CAP. Such exploratory data, when validated in independent cohorts, could inform the development of a microbiota-based diagnostic panel used to predict clinical outcomes in CAP., Funding Netherlands Organization for Scientific Research and Netherlands Organization for Health Research and Development., peer-reviewed

Background:: There is a significant disparity in global cancer care and out-come between countries. We aimed to provide data on characteristics, average cost of treatment and survival estimates in patients with Hodgkin Lymphoma in Sri Lanka.Methods: All patients diagnosed with Hodgkin Lymphoma between 01.05.2013 and 01.10.2020 were included in the analysis.Findings: Classical Hodgkin Lymphoma(cHL) diagnosed in 85%; 68% presented with B symptoms and 61% had advanced stage of disease. Treatment was discontinued by 23% either before or just after starting treatment of whom 72% percent were females. The complete response (CR) rate of patients who continued treatment was 86% while the estimated five-year survival rate is 92%. Seventeen percent of these patients died but only two percent due to Hodgkin Lymphoma or associated treatment in the group which continued treatment compared to 45% in the group who defaulted treatment (p-value 0.0002). Five-year survival rate of patients who defaulted treatment was 50% while patients who continued treatment have an estimated five-year survival rate of 90%. Average cost of first line treatment was between US$ 2280 and US$ 7642. First treatment failure may incur substantially higher health care costs.Interpretation: This is the only well characterized study on long-term survival of patients with Hodgkin Lymphoma in Sri Lanka. We have shown that it is possible to successfully apply western treatment and supportive care protocols to the local population. This published data will help to bench mark and improve the treatment and develop blood cancer care in the local setting. Funding: None.

Background Children are frequently injured during major incidents (MI), including terrorist attacks, conflict and natural disasters. Triage facilitates healthcare resource allocation in order to maximise overall survival. A critical function of MI triage tools is to identify patients needing time-critical major resuscitative and surgical intervention (Priority 1 (P1) status). This study compares the performance of 11 MI triage tools in predicting P1 status in children from the UK Trauma Audit and Research Network (TARN) registry. Methods Patients aged

Background Osteoporosis affects over half of adults over 50 years worldwide. With an ageing population, osteoporosis, fractures and their associated costs are increasing. Unfortunately, despite effective therapies, many with osteoporosis remain undiagnosed and untreated. Models of care (MoC) to improve outcomes include fracture liaison services, screening, education, and exercise programs, however efficacy for these is mixed. The aim of this study is to summarise MoC in osteoporosis and describe implementation characteristics and evidence for improving outcomes. Methods This systematic scoping review identified articles via Ovid Medline and Embase, published in English between 01/01/2009 and 15/06/2021, describing MoC for adults aged ≥18 years with, or at risk of, osteoporosis and / or health professionals caring for this group. All included at least one of clinical, consumer or clinician outcomes, with fractures and bone mineral density (BMD) change the primary clinical outcomes. Exclusion criteria were studies assessing pharmaceuticals or procedures without other interventions, or insufficient operational details. All study designs were included, with no comparator necessary. Title and abstract were reviewed by two reviewers. Full text review and data extraction was performed by these reviewers for 20% of article and, thereafter by a single author. As the review was predominantly descriptive, no comparator statistics were used. Findings 314 articles were identified describing 289 MoC with fracture liaison services (n=89) and education programs (n=86) predominating. The population had prior fragility fracture in 77 studies, the median (IQR) patient number was 210 (87, 667) and the median (IQR) follow-up duration for outcome assessment was 12 (6, 12·5) months. Fracture reduction was reported by 65 studies, with 16 (37%) graded as high quality, and 19 / 47 studies with a comparator group found a reduction in fractures. BMD change was reported by 73 studies, with 41 finding improved BMD. Implementation characteristics including reach, fidelity and loss to follow-up were under-reported, and consumer and clinician perspectives rare. Interpretation This comprehensive review of MoC for osteoporosis demonstrated inconsistent evidence for improving outcomes despite similar types of models. Future studies should include implementation outcomes, consumer and clinician perspectives, and fracture or BMD outcomes with sufficient duration of follow-up. Authors should consider pragmatic trial designs and co-design with clinicians and consumers. Funding None.

Background A novel variant of SARS-CoV-2, the Delta variant of concern (VOC, also known as lineage B.1.617.2), is fast becoming the dominant strain globally. We reported the epidemiological, viral, and clinical characteristics of hospitalized patients infected with the Delta VOC during the local outbreak in Guangzhou, China. Methods We extracted the epidemiological and clinical information pertaining to the 159 cases infected with the Delta VOC across seven transmission generations between May 21 and June 18, 2021. The whole chain of the Delta VOC transmission was described. Kinetics of viral load and clinical characteristics were compared with a cohort of wild-type infection in 2020 admitted to the Guangzhou Eighth People's Hospital. Findings There were four transmission generations within the first ten days. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain. In cases with critical illness, the proportion of patients over the age of 60 was higher in the Delta VOC group than in the wild-type strain (100.0% vs. 69.2%, p = 0.03). The Delta VOC had a higher risk than wild-type infection in deterioration to critical status (hazards ratio 2.98 [95%CI 1.29-6.86]; p = 0.01). Interpretation Infection with the Delta VOC is characterized by markedly increased transmissibility, viral loads and risk of disease progression compared with the wild-type strain, calling for more intensive prevention and control measures to contain future outbreaks. Funding National Grand Program, National Natural Science Foundation of China, Guangdong Provincial Department of Science and Technology, Guangzhou Laboratory

Background Consistent guidance for choosing an appropriate probiotic for the treatment of irritable bowel syndrome is lacking. Methods Literature databases searched included: PubMed, Google Scholar and NIH registry of clinical trials from inception to June 2021. Inclusion criteria: randomized controlled trials (RCTs) enrolling adult or pediatric IBS patients comparing probiotics against controls and ≥ 2 RCTs with common IBS outcome measures within each type of probiotic. Five common measures of IBS symptoms (changes in global Irritable Bowel Syndrome Severity Scoring System or IBS-SSS scores, frequency of global responders, changes in bloating or abdominal pain scores and frequency of abdominal pain relief) were used. This study was registered at Prospero (#CRD42018109169). Findings We screened 521 studies and included 42 randomized controlled trials (45 treatment arms, N = 3856). Four probiotics demonstrated significant reduction in abdominal pain relief: B. coagulans MTCC5260 (RR= 4.9, 95% C.I. 3.3, 7.3), L. plantarum 299v (RR= 4.6, 95% CI 1.9, 11.0), S. boulardii CNCM I-745 (RR= 1.5, 95% C.I. 1.1, 2.1) and S. cerevisiae CNCM I-3856 (RR= 1.3, 95% C.I. 1.04, 1.6). Mild-moderate adverse events were reported in 51% of the trials, none were more associated with the probiotic compared to controls. Interpretation Although the analysis of probiotic efficacy was limited by the diversity of IBS outcomes used in trials and lack of confirmatory trials for some strains, six single-strain probiotics and three different types of probiotic mixtures showed significant efficacy for at least one IBS outcome measure. These results might be relevant to clinical practice and policy. Funding None.

Background Natural disasters, conflict, and terrorism are major global causes of death and disability. Central to the healthcare response is triage, vital to ensure the right care is provided to the right patient at the right time. The ideal triage tool has high sensitivity for the highest priority (P1) patients with acceptably low over-triage. This study compared the performance of major incident triage tools in predicting P1 casualty status in adults in the prospective UK Trauma Audit and Research Network (TARN) registry. Methods TARN patients aged 16+ years (January 2008-December 2017) were included. Ten existing triage tools were applied using patients’ first recorded pre-hospital physiology. Patients were subsequently assigned triage categories (P1, P2, P3, Expectant or Dead) based on pre-defined, intervention-based criteria. Tool performance was assessed by comparing tool-predicted and intervention-based priority status. Findings 195,709 patients were included; mortality was 7·0% (n=13,601); median Injury Severity Score (ISS) was 9 (IQR 9–17); 97·1% sustained blunt injuries. 22,144 (11·3%) patients fulfilled intervention-based criteria for P1 status, exhibiting higher mortality (12·8% vs. 5·0%, p

Summary: Background: We aimed to determine whether heart, stroke, and vascular disease (HSVD) prevalence and emergency primary evacuation (EPE), hospitalisation, and mortality differ by patient characteristics. Methods: An Australian-wide incidence population based study, with prospective data collected form the 1 July 2019 to the 30 October 2020. Findings: Indigenous Australians reported significantly higher prevalence of HSVD at 229.0 per-1000 as compared to 152.0 per-1000 non-Indigenous Australians: risk ratio 1.5 (95% CI 1.2-1.8). 583 remote patients received an EPE for HSVD, consisting of 388 (66.6%; 95% CI: 62.6-70.4) males and 195 (33.0%; 95% CI: 29.6-37.4) females. There were 289 (49.6%; 95% CI 45.4- 53.7) patients who identified as Indigenous, and 294 (50.4%; 95% CI 46.3- 54.6) as non-Indigenous. The mean Indigenous age during EPE was 48.0 (95% CI 45.9-50.1) years old, significantly lower than the non-Indigenous mean age of 55.6 (95% CI 53.8-57.4). Indigenous patients hospitalised for HSVD were younger, the majority younger than 65 years (n=21175; 73.7% 95% CI 73.2-74.2) as compared to non-Indigenous patients (n= 357654; 33.1% 95% CI 33.0-33.15). When adjusted for HSVD prevalence, remote Indigenous patients had a higher hospitalisation rate as compared to non-remote Indigenous patients (rate ratio: 1.6; 95% CI 1.3-2.0) and remote non-Indigenous patients (rate ratio: 1.2; 95% CI 1.0-1.5). More Indigenous patients died of HSVD before the age of 65 years (n=1875; 56.5% 95% CI 54.8-58.2) as compared to non-Indigenous patients (n= 16161; 10.6% 95% CI 10.45-10.8). Interpretation: Indigenous Australians have a higher prevalence, and younger age during EPE, and hospitalisation for HSVD than non-Indigenous Australians. Funding: This is a self/internally-funded study, with the lead organisation being the Royal Flying Doctor Service (RFDS) of Australia. For the duration of the study period, the RFDS provided in-kind support including one full-time equivalent (FTE) and resources (office space, computer, research software, and office equipment). There was no external funding source that had a role in study design or data analysis or interpretation.

Background Trials of the Pfizer-BioNTech BNT162b2 mRNA vaccine showed 95% efficacy in preventing symptomatic disease; however, the trials excluded immunocompromised patients (ICPs). We aim at analyzing antibody response in ICPs. Methods A prospective cohort study was conducted at Sheba Medical Center, Israel, between January and April 2020, in 1274 participants who received the vaccine, including 1002 ICPs and 272 immunocompetent healthcare workers (HCWs). Antibodies were measured two-four weeks after vaccination by SARS-CoV-2 anti–receptor binding domain IgG antibodies (RBD IgG) and pseudo-virus neutralization assays. Multivariable logistic regression analyses were used to identify factors associated with vaccine-induced antibody response. Adverse events (AEs) were monitored. Findings RBD-IgG antibodies were detected in 154/156 (98.7%) of patients with HIV, 75/90 (83.3%) with solid malignancies, 149/187 (79.7%) with myeloma, 83/111 (74.8%) following hematopoietic stem cell transplants, 25/36 (69.4%) following liver transplantation, 26/43 (60.5%) with myelodysplastic syndrome, 96/188 (51.0%) with chronic lymphocytic leukemia/non-Hodgkin's lymphoma, 50/110 (45.5%) following kidney transplantation, 15/80 (18.8%) following heart transplantation, and 269/272 (98.9%) in controls. There was a significant correlation r = 0.74 (95%CI 0.69,0.78) between RBD-binding IgG and neutralizing antibodies in all groups. Multivariate logistic regression analysis showed that age > 65 years (OR 0.41,95%CI 0.30,0.57) and underlying immunosuppression (OR 0.02,95%CI 0.01,0.07) were significantly associated with a non-reactive response of IgG antibodies. HIV patients showed a similar immunological response as healthy adults. The vaccine was safe without any episodes of rejection, graft-versus-host disease (GVHD) or allergy. Immunocompetent HCWs experienced significantly more AEs than ICPs. Interpretation Antibody response to the Pfizer-BioNTech vaccine was highly variable among different ICPs; thus, individual recommendations should be provided for the different immunosuppression states. Funding None.

IntroductionSARS-CoV-2 serological studies have so far focused mainly on adults. Public Health England initiated prospective, longitudinal SARS-CoV-2 sero-surveillance in schools across England after the first national lockdown, which allowed comparison of child and adult responses to SARS-CoV-2 infection over time.MethodsStaff and students had venepuncture for SARS-CoV-2 antibodies in school during June, July and December 2020. Blood samples were tested for nucleocapsid (Abbott) and receptor binding domain (RBD) antibodies (in-house assay), and student samples were additionally assessed for live virus neutralising activity.ResultsIn June 2020, 1,344 staff and 835 students were tested. Overall, 11.5% (95% CI: 9.4-13.9) and 11.3% (95% CI: 9.2-13.6; p=0.88) of students had nucleoprotein and RBD antibodies, compared to 15.6% (95% CI: 13.7-17.6) and 15.3% (95% CI: 13.4-17.3; p=0.83) of staff. Live virus neutralising activity was detected in 79.8% (n=71/89) of nucleocapsid and 85.5% (71/83) of RBD antibody positive children. RBD antibodies correlated more strongly with neutralising antibodies (rs=0.7527; ps=0.3698; pConclusionRBD antibodies correlated more strongly with live virus neutralising activity. Most seropositive students and staff retained RBD antibodies for >6 months after SARS-CoV-2 infection.

Background: Advanced glycation end products (AGE), one of the main factors causing diabetic end-organ damage, accumulate in long half-life proteins, such as skin and cartilage collagen. AGE measurement may offer additional evidence to predict diabetic vascular complications. Skin autofluorescence (SAF) is suggested as a non-invasive, quick, and reliable method to measure tissue AGE level. The aim of this study was to review and evaluate evidence on the clinical validation of SAF measurement in diabetes mellitus (DM) patients. Methods: In this systematic review and meta-analysis, we searched ''PubMed'' (MEDLINE) and ''Cochrane'' databases from their inception to 10 August 2021 for observational studies concerning SAF measurement in diabetic patients. The following key terms were used in advanced searching: “Diabetes”, “Diabetes Mellitus”,” DM”, “Glycation “, “Advanced Glycation End product”, “AGE”, “skin autofluorescence”, “SAF”. Published studies that included DM patients and estimated their AGE using SAF were considered eligible for meta-analysis. Articles that were editorials, study proposals, congress posters, or case reports and were not on human subjects were excluded. We used a random-effect models for meta-analyzing the clinical validation of SAF in DM with particular emphasis on chronic diabetes complications. Findings: We identified 881 records and twenty-nine records fulfilled our eligibility criteria and were included in the systematic review and meta-analysis. A statistically significant correlation was found between SAF and diabetes last HbA1c 0.21(0.13,0.28) in studies with substantial heterogeneity (I2=77.99%, p

Background Disability-free life expectancy (DFLE) inequalities by socioeconomic deprivation are widening, alongside rising prevalence of multiple long-term conditions (MLTCs). We use longitudinal data to assess whether MLTCs contribute to the widening DFLE inequalities by socioeconomic deprivation. Methods The Cognitive Function and Ageing Studies (CFAS I and II) are large population-based studies of those ≥65 years, conducted in three areas in England. Baseline occurred in 1991 (CFAS I, n=7635) and 2011 (CFAS II, n=7762) with two-year follow-up. We defined disability as difficulty in activities of daily living, MLTCs as the presence of at least two of nine health conditions, and socioeconomic deprivation by area-level deprivation tertiles. DFLE and transitions between disability states and death were estimated from multistate models. Findings For people with MLTCs, inequalities in DFLE at age 65 between the most and least affluent widened to around 2.5 years (men:2.4 years, 95% confidence interval (95%CI) 0.4–4.4; women:2.6 years, 95%CI 0.7–4.5) by 2011. Incident disability reduced for the most affluent women (Relative Risk Ratio (RRR):0.6, 95%CI 0.4–0.9), and mortality with disability reduced for least affluent men (RRR:0.6, 95%CI 0.5–0.8). MLTCs prevalence increased only for least affluent men (1991: 58.8%, 2011: 66.9%) and women (1991: 60.9%, 2011: 69.1%). However, DFLE inequalities were as large in people without MLTCs (men:2.4 years, 95%CI 0.3–4.5; women:3.1 years, 95% CI 0.8–5.4). Interpretation Widening DFLE inequalities were not solely due to MLTCs. Reduced disability incidence with MLTCs is possible but was only achieved in the most affluent. Funding This work was supported by the Dunhill Medical Trust. CFAS II was supported by the UK Medical Research Council (MRC; research grant G0601022), Alzheimer's Society Grant Ref: 294, and received support from the UK National Institute for Health Research (NIHR) comprehensive clinical research networks in West Anglia and Trent, and the Dementias and Neurodegenerative Disease Research Network in Newcastle. HB is supported by the Dunhill Medical Trust (grant number RPGF1806\44), and AK by a Newcastle University Research Fellowship. This research was undertaken within the UK NIHR collaboration for leadership in applied health research and care for Cambridgeshire and Peterborough and the Cambridge Biomedical Research Centre infrastructures, Nottingham city and Nottinghamshire county NHS primary care trusts, and UK NIHR Policy Research Programme, conducted through the NIHR Older People and Frailty Policy Research Unit, PR-PRU-1217-21502.

Background: The World Health Assembly set a global target of increasing exclusive breastfeeding for infants under 6 months to at least 50% by year 2025. However, little is known about the current status of breastfeeding practice, as well as the trends in breastfeeding practices during recent years. We examined global prevalence of the World Health Organization (WHO) feeding practices in 57 low- and middle-income countries (LMICs) and time trends since 2000 for 44 selected countries. Methods: We included 57 eligible LMICs that had completed data on breastfeeding and complementary feeding in 2010–2018 from the Demographic and Health Surveys (DHS) for examining current feeding status. We further selected 44 LMICs that had two standard DHS surveys between 2000 and 2009 and 2010–2018 to examine time trends of feeding status. We calculated global, regional, and national weighted prevalence estimates and 95% confidence intervals (CIs) for five breastfeeding indicators and two complementary feeding indicators. Findings: In 57 LMICs during 2010–2018, global weighted prevalence was 51.9% for early initiation of breastfeeding, 45.7% for exclusive breastfeeding under 6 months, 32.0% for exclusive breastfeeding at 4–5 months, 83.1% for continued breastfeeding at 1 year, 56.2% for continued breastfeeding at 2 years, 14.9% for introduction of solid, semi-solid or soft foods under 6 months, and 63.1% for introduction of solid, semi-solid or soft foods at 6–8 months. Eastern Mediterranean (34.5%) and European regions (43.7%) (vs. South-East Asia/Western Pacific (55.2%)), and upper middle-income countries (38.4%) (vs. lower middle-income countries (47.4%)) had poorer performance of exclusive breastfeeding under 6 months. South-East Asia/Western Pacific regions (51.0%) (vs. other regions (68.3%-84.1%)) and low-income (66.4%) or lower middle-income countries (58.2%) (vs. upper middle-income countries (81.7%)) had lower prevalence of introduction of solid, semi-solid or soft foods at 6–8 months. In 44 selected LMICs from 2000 to 2009 to 2010–2018, total weighted prevalence presented an increase of 10.1% for exclusive breastfeeding under 6 months, but a 1.7% decrease for continued breastfeeding at 1 year. Over this period, the Eastern Mediterranean region had a 5.3% decrease of exclusive breastfeeding under 6 months, and the European region had a 2.0% increase for introduction of solid, semi-solid or soft foods under 6 months. The prevalence of introduction of solid, semi-solid or soft foods at 6–8 months decreased in South-East Asia/Western Pacific region by 15.2%, and in lower middle-income countries by 24.4%. Interpretation: Breastfeeding practices in LMICs have continued to improve in the past decade globally, but practices still lag behind the WHO feeding recommendations. Breastfeeding practices differed greatly across WHO regions, with the Eastern Mediterranean and European regions, and upper middle-income countries facing the greatest challenges in meeting targets. Continued efforts are needed to achieve the 2025 global breastfeeding target.

Background: Viral infections of the respiratory tract represent a major global health concern. Co-infection with bacteria may contribute to severe disease and increased mortality in patients. Nevertheless, viral-bacterial co-infection patterns and their clinical outcomes have not been well characterized to date. This study aimed to evaluate the clinical features and outcomes of patients with viral-bacterial respiratory tract co-infections.Methods: We included 19,361 patients with respiratory infection due to respiratory viruses [influenza A and B, respiratory syncytial virus (RSV), parainfluenza] and/or bacteria in four tertiary hospitals in Hong Kong from 2013 to 2017 using a large territory-wide healthcare database. All microbiological tests were conducted within 48 h of hospital admission. Four etiological groups were included: (1) viral infection alone; (2) bacterial infection alone; (3) laboratory-confirmed viral-bacterial co-infection and (4) clinically suspected viral-bacterial co-infection who were tested positive for respiratory virus and negative for bacteria but had received at least four days of antibiotics. Clinical features and outcomes were recorded for laboratory-confirmed viral-bacterial co-infection patients compared to other three groups as control. The primary outcome was 30-day mortality. Secondary outcomes were intensive care unit (ICU) admission and length of hospital stay. Propensity score matching estimated by binary logistic regression was used to adjust for the potential bias that may affect the association between outcomes and covariates.Findings: Among 15,906 patients with respiratory viral infection, there were 8451 (53.1%) clinically suspected and 1,087 (6.8%) laboratory-confirmed viral-bacterial co-infection. Among all the bacterial species, Haemophilus influenzae (226/1,087, 20.8%), Pseudomonas aeruginosa (180/1087, 16.6%) and Streptococcus pneumoniae (123/1087, 11.3%) were the three most common bacterial pathogens in the laboratory-confirmed co-infection group. Respiratory viruses co-infected with non-pneumococcal streptococci or methicillin-resistant Staphylococcus aureus was associated with the highest death rate [9/30 (30%) and 13/48 (27.1%), respectively] in this cohort. Compared with other infection groups, patients with laboratory-confirmed co-infection had higher ICU admission rate (p < 0.001) and mortality rate at 30 days (p = 0.028), and these results persisted after adjustment for potential confounders using propensity score matching. Furthermore, patients with laboratory-confirmed co-infection had significantly higher mortality compared to patients with bacterial infection alone.Interpretation: In our cohort, bacterial co-infection is common in hospitalized patients with viral respiratory tract infection and is associated with higher ICU admission rate and mortality. Therefore, active surveillance for bacterial co-infection and early antibiotic treatment may be required to improve outcomes in patients with respiratory viral infection.

Background: The disease course of inflammatory bowel disease (IBD) following treatment with glucagon-like peptide (GLP)-1 based therapies is unclear. Objectives: To examine clinical outcomes of IBD in patients with IBD and type 2 diabetes treated with GLP-1 based therapies compared with treatment with other antidiabetics. Methods: Using nationwide Danish registries, we identified patients with IBD and type 2 diabetes who received antidiabetic treatment between 1 January 2007 and 31 March 2019. The primary outcome was a composite of the need for oral corticosteroids, tumour necrosis factor-α inhibitors, IBD-related hospitalisation, or IBD-related surgery. In the setting of a new-user active comparator design, we used Poisson regression to estimate incidence rate ratios (IRRs) comparing treatment with GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors with other antidiabetic therapies. The analyses were adjusted for age, sex, calendar year, IBD severity, and metformin use. Results: We identified 3751 patients with a diagnosis of IBD and type 2 diabetes and with a prescription of an antidiabetic drug (GLP-1 receptor agonists/DPP-4 inhibitors: 982 patients; other antidiabetic treatment: 2769 patients). The adjusted IRR of the composite outcome was 0.52 (95% CI: 0.42-0.65) for patients exposed to GLP-1 receptor agonists/DPP-4 inhibitors compared with patients exposed to other antidiabetics. Conclusion: In patients with IBD and type 2 diabetes, treatment with GLP-1 receptor agonists/DPP-4 inhibitors are associated with a lower risk of adverse clinical events compared with treatment with other antidiabetics. Funding Information: The study was funded by the Novo Nordisk Foundation [grant number NNF16OC0022586 and NNF17OC0029768]. Declaration of Interests: None of the authors have any conflicts of interest to disclose. Ethics Approval Statement: The study was approved by the Danish Data Protection Agency, and data were analysed on a secure research server at the Danish Health Data Authority. In Denmark, ethical approval is not required for research using pre-existing, routinely collected data.

Background There are growing concerns about the impact of the COVID-19 pandemic on mental health. With government-imposed restrictions as well as a general burden on healthcare systems, the pandemic has the potential to disrupt the access to, and delivery of, mental healthcare. Methods Electronic healthcare records from primary care psychological therapy services (Improving Access to Psychological Therapy) in England were used to examine changes in access to mental health services and service delivery during early stages of the COVID-19 pandemic. A descriptive time series was conducted using data from five NHS trusts to examine patterns in referrals to services (1st January 2019 to 24th May 2020) and appointments (1st January 2020 to 24th May 2020) taking place. Findings The number of patients accessing mental health services dropped by an average of 55% in the early weeks after the March 2020 lockdown was announced, reaching a maximum reduction of 74% in the initial 3 weeks after lockdown in the UK, which gradually recovered to a 28% reduction by May. We found some evidence suggesting changes in the sociodemographic and clinical characteristics of referrals. Despite a reduction in access, the impact on appointments appeared limited with service providers shifting to remote delivery of care. Interpretation Services appeared to adapt to provide continuity of care in mental healthcare. However, patients accessing services reduced, potentially placing a future burden on service. Despite the observational nature of the data, the present study can inform the planning of service provision and policy. Funding AD and TS were funded by Innovate UK (KTP #11,105).

Background The SARS-CoV-2 virus enters cells via Angiotensin-converting enzyme 2 (ACE2), disrupting the renin-angiotensin-aldosterone axis, potentially contributing to lung injury. Treatment with angiotensin receptor blockers (ARBs), such as losartan, may mitigate these effects, though induction of ACE2 could increase viral entry, replication, and worsen disease. Methods This study represents a placebo-controlled blinded randomized clinical trial (RCT) to test the efficacy of losartan on outpatients with COVID-19 across three hospital systems with numerous community sites in Minnesota, U.S. Participants included symptomatic outpatients with COVID-19 not already taking ACE-inhibitors or ARBs, enrolled within 7 days of symptom onset. Patients were randomized to 1:1 losartan (25 mg orally twice daily unless estimated glomerular filtration rate, eGFR, was reduced, when dosing was reduced to once daily) versus placebo for 10 days, and all patients and outcome assesors were blinded. The primary outcome was all-cause hospitalization within 15 days. Secondary outcomes included functional status, dyspnea, temperature, and viral load. (clinicatrials.gov, NCT04311177, closed to new participants) Findings From April to November 2020, 117 participants were randomized 58 to losartan and 59 to placebo, and all were analyzed under intent to treat principles. The primary outcome did not differ significantly between the two arms based on Barnard's test [losartan arm: 3 events (5.2% 95% CI 1.1, 14.4%) versus placebo arm: 1 event (1.7%; 95% CI 0.0, 9.1%)]; proportion difference -3.5% (95% CI -13.2, 4.8%); p = 0.32]. Viral loads were not statistically different between treatment groups at any time point. Adverse events per 10 patient days did not differ signifcantly [0.33 (95% CI 0.22–0.49) for losartan vs. 0.37 (95% CI 0.25–0.55) for placebo]. Due to a lower than expected hospitalization rate and low likelihood of a clinically important treatment effect, the trial was terminated early. Interpretation In this multicenter blinded RCT for outpatients with mild symptomatic COVID-19 disease, losartan did not reduce hospitalizations, though assessment was limited by low event rate. Importantly, viral load was not statistically affected by treatment. This study does not support initiation of losartan for low-risk outpatients. Funding This study was supported by Minnesota Partnership for Biotechnology and Medical Genomics (CON000000076883).

Background: Migrants globally, including refugees and asylum seekers, have experienced adverse clinical and socioeconomic impacts of the COVID-19 pandemic. For approximately 56,000 refugees and asylum seekers in Reception and Identification Centers (RICs) and Reception Sites (RS) in Greece, living in severely substandard living conditions, prevention measures have been impossible with limited provision in terms of routine testing, surveillance, and access to healthcare. These migrant populations have experienced prolonged lockdowns and restricted movement since the pandemic began. We aimed to assess the impact of COVID-19 on refugees and asylum seekers in reception facilities in Greece and explore implications for policy and practice. Methods: A retrospective analysis of policy documents and national surveillance data was conducted to identify COVID-19 outbreaks and estimate incidence among asylum seekers and refugees residing in these camps during the first 9 months of the epidemic in Greece (26th February – 15th November 2020). Incidence proportion (IP) of COVID-19 confirmed cases was calculated for three population groups (refugees and asylum seekers in RICs, refugees and asylum seekers in RSs, and the general population in Greece) during three time periods (first wave, second wave, and overall across the 9-month period). Findings: Twenty-five COVID-19 outbreaks were identified in refugee and asylum seeker reception facilities, with 6 (85.7%) of 7 RICs and 18 (56.3%) of 32 RSs reporting at least one outbreak during the study period. The overall 9-month COVID-19 IP among refugee and asylum seeker populations residing in RSs on the Greek mainland was 1758 cases per 100,000 population; in RICs the incidence was 2052 cases per 100,000 population. Compared to the general population the risk of COVID-19 infection among refugees and asylum seekers in reception facilities was 2.5 to 3 times higher (p-value

Background: Sickle cell anemia (SCA) is a severe monogenic disorder, caused by single nucleotide mutations in the hemoglobin (Hb) gene, that is prevalent in malaria endemic regions of the world. Sickle cell trait (SCT) individuals carry only one of the mutated alleles and were shown to be protected against malaria. However, defining the relative contribution of hematological, clinical, and environmental factors to the overall burden of malaria in individuals with hemoglobinopathies such as SCA has been challenging. Methods: We hypothesized that hematological differences, clinical presentations, and self-reported bed net usage among Plasmodium-infected and uninfected individuals may govern overall malaria burden in individuals with sickle cell disease (SCD). We conducted a cross-sectional study in Ghana from 2014 to 2019 and described clinical presentations, hematological characteristics, and bed net use based on a comprehensive questionnaire. Hematological characteristics were compared using a parametric or nonparametric ANOVA, pending if data passed D'Agostino & Pearson normality test. When comparing only two Hb genotypes hematological characteristics a Mann–Whitney U-test were used. Logistic regressions and Chi-squared tests were used to compare questionnaire responses between Hb genotypes. All statistical significance was set at p

Background: The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates’ drugs. Nitazoxanide (NTZ) has a broad antiviral effect. Methods: This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. Findings: Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for D-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+ T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+ T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01) Interpretation: Compared to placebo in clinical and virologic outcomes and improvement of inflammatory out comes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms. Funding: This study was supported by Farmoquimica (FQM), Brazil. Laboratory testing was partially sup ported by a grant from CNPq, Brazil (RD).

Background Amyloid positron emission tomography (PET) can measure in-vivo demyelination in patients with multiple sclerosis (MS). However, the value of 18F-labeled amyloid PET tracer, 18F-florbetapir in the longitudinal study for monitoring myelin loss and recovery has not been confirmed. Methods From March 2019 to September 2020, twenty-three patients with MS and nine healthy controls (HCs) underwent a hybrid PET/MRI at baseline and expanded disability status scale (EDSS) assessment, and eight of 23 patients further underwent follow-up PET/MRI. The distribution volume ratio (DVR) and standard uptake value ratio (SUVR) of 18F-florbetapir in damaged white matter (DWM) and normal-appearance white matter (NAWM) were obtained from dynamic and static PET acquisition. Diffusion tensor imaging-derived parameters were also calculated. Data were expressed as mean ± standard deviation with 99% confidence interval (99%CI). Finding The mean DVR (1.08 ± 0.12, 99%CI [1.02 ~ 1.14]) but not the mean SUVR of DWM lesions was lower than that of NAWM in patients with MS (1.25 ± 0.10, 99%CI [1.20 ~ 1.31]) and HCs (1.29 ± 0.08, 99%CI [1.23 ~ 1.36]). A trend toward lower mean fractional anisotropy (374.95 ± 45.30 vs. 419.07 ± 4.83) and higher mean radial diffusivity (0.45 ± 0.05 vs. 0.40 ± 0.01) of NAWM in patients with MS than those in HCs was found. DVR decreased in DWM lesions with higher MD (rho = -0.261, 99%CI [-0.362 ~ -0.144]), higher AD (rho = -0.200, 99%CI [-0.318 ~ -0.070]) and higher RD (rho = -0.198, 99%CI [-0.313 ~ -0.075]). Patients’ EDSS scores were reduced (B = 0.04, 99%CI [-0.005 ~ 0.084]) with decreased index of global demyelination in the longitudinal study. Interpretation Our exploratory study suggests that dynamic 18F-florbetapir PET/MRI may be a very promising tool for quantitatively monitoring myelin loss and recovery in patients with MS. Funding Shanghai Pujiang Program, Shanghai Municipal Key Clinical Specialty, Shanghai Shuguang Plan Project, Shanghai Health and Family Planning Commission Research Project, Clinical Research Plan of SHDC, French-Chinese program "Xu Guangqi".

Background While the effects of prolonged sleep deprivation (≥24 h) on seizure occurrence has been thoroughly explored, little is known about the effects of day-to-day variations in the duration and quality of sleep on seizure probability. A better understanding of the interaction between sleep and seizures may help to improve seizure management. Methods To explore how sleep and epileptic seizures are associated, we analysed continuous intracranial electroencephalography (EEG) recordings collected from 10 patients with refractory focal epilepsy undergoing ordinary life activities between 2010 and 2012 from three clinical centres (Austin Health, The Royal Melbourne Hospital, and St Vincent's Hospital of the Melbourne University Epilepsy Group). A total of 4340 days of sleep-wake data were analysed (average 434 days per patient). EEG data were sleep scored using a semi-automated machine learning approach into wake, stages one, two, and three non-rapid eye movement sleep, and rapid eye movement sleep categories. Findings Seizure probability changes with day-to-day variations in sleep duration. Logistic regression models revealed that an increase in sleep duration, by 1·66 ± 0·52 h, lowered the odds of seizure by 27% in the following 48 h. Following a seizure, patients slept for longer durations and if a seizure occurred during sleep, then sleep quality was also reduced with increased time spent aroused from sleep and reduced rapid eye movement sleep. Interpretation Our results suggest that day-to-day deviations from regular sleep duration correlates with changes in seizure probability. Sleeping longer, by 1·66 ± 0·52 h, may offer protective effects for patients with refractory focal epilepsy, reducing seizure risk. Furthermore, the occurrence of a seizure may disrupt sleep patterns by elongating sleep and, if the seizure occurs during sleep, reducing its quality.

Background: Despite a significant shortage of kidneys for transplantation in the US, kidneys from older deceased donors are infrequently transplanted. This is primarily over concern of graft quality and transplant durability. Methods: The US national transplant database (2000–2018) was assessed for deceased donor kidney transplant patient and graft survival, graft durability and stratified by donor age (), Kidney Donor Profile Index (KDPI) and estimated glomerual filtration rate (GFR) one year post-transplantation (eGFR-1) were calculated. Findings: Recipients of kidneys transplanted from deceased donors >65 years had a lower eGFR-1, (median 39 ml/min) than recipients of younger donor kidneys (median 54 ml/min). However, death-censored graft survival, stratified by eGFR-1, demonstrated similar survival, irrespective of donor age or KDPI. The durability of kidney survival decreases as the achieved eGFR-1 declines. KDPI has a poor association with eGFR-1 and lesser for graft durability. While recipients of kidneys > 65 years had a higher one year mortality than younger kidney recipients, recipients of kidneys > 65 years and an eGFR-1

Background: Mandatory Day 2 and Day 8 PCR testing and variant sequencing of international arrivals has been recently introduced by the UK Government to mitigate against cross-border transmission of high-risk SARS-CoV-2 variants. Methods: SARS-CoV-2 testing and sequencing combines TaqPath CE-IVD COVID-19 RT-PCR with Ion AmpliSeq SARS-CoV-2 Next Generation Sequencing Assay. Retrospective analysis of test trending data was performed from initiation of testing on the 11th March through to the 14th April 2021. Findings: During this time interval, 203,065 SARS-CoV-2 PCR tests were performed, with 3,855 samples testing positive, giving a prevalence of 1.9%. In total 1,913 SARS-CoV-2 genomes were sequenced from positive cases with Ct values 60 with a single dose to 83% in

Background We provide the first post-approval safety analysis of COVISHIELD in health care workers (HCWs) in northern India. Methods This continuing prospective observational study (February 2021 to May 2022) enrolled participants ≥18 years receiving COVISHIELD vaccination. Primary outcome was safety and reactogenicity. Categories (FDA toxicity grading) and outcomes of adverse events following immunization (AEFIs) were recorded, causality assessment performed, and risk factors analysed. Findings We present the results of an interim analysis of 804 participants. AEFIs following first dose were reported in 321 (40%; systemic involvement in 248). Among 730 participants who completed a 7-day follow-up post second dose, AEFIs occurred in 115 (15.7%; systemic in 99). Majority of AEFIs were mild-moderate and resolved spontaneously. Serious AEFIs, leading to hospitalization was noticed in 1 (0.1%) participant with suspicion of immunization stress related response (ISRR). AEFIs of grade 3 severity (FDA) were recorded in 4 participants (0.5%). No deaths were recorded. Regression analysis showed increased risk of AEFIs in younger individuals, a two times higher odds in females, those with hypertension or with history of allergy; and three times higher odds in individuals with hypothyroidism. Interpretation COVISHIELD carries an overall favourable safety profile with AEFI rates much less than reported for other adenoviral vaccines. Females, those with hypertension, individuals with history of allergy and hypothyroidism may need watchful vaccine administration. This being an interim analysis and based on healthcare workers who may not reflect the general population demographics, larger inclusive studies are warranted for confirming the findings. Funding No funding support.

Background Non-Whites are more likely to suffer from cognitive impairment and complications of atrial fibrillation (AF) than Whites, though Whites are more likely to be diagnosed with AF. We examined whether non-Whites with AF are biologically older than Whites with AF and whether accelerated biological aging is associated with cognitive functioning. Methods We used baseline data from the ongoing Systematic Assessment of Geriatric Elements in Atrial Fibrillation prospective cohort study, collected 2016–2020 across ambulatory care practices in Massachusetts and Georgia. Of 1244 enrolled, 974 participants with full biological data were included in the present analysis. Accelerated aging (AccA) was calculated based on a combination of biomarkers associated with age and physiological “wear and tear.” Findings The main outcome was score on Montreal Cognitive Assessment (MoCA). Non-Whites had 2.9 years more AccA than Whites and higher AccA was associated with a lower MoCA score among both Whites (-0.06, 95% CI: -0.10, -0.03) and non-Whites (-0.14, 95% CI: -0.27, 0.02). This association was significantly greater among non-whites (-0.11, 95% CI: -0.20, -0.01). Interpretation Non-White AF patients are functionally “older” than their White counterparts and experience a stronger deleterious association between AccA and cognition. These findings underscore the importance of taking functional age into account when treating patients with AF, particularly non-White patients, to enhance treatment and improve AF outcomes. Funding The SAGE-AF study is supported by Grant R01HL126911 from the National Heart, Lung, and Blood Institute (NHLBI).

Background Chlorhexidine gluconate (CHG) body washes and emollient application may modulate bacterial pathogen colonization and prevent neonatal hospital-acquired infections. Methods This pilot, non-randomized, open-label trial, enrolled preterm neonates (1000-1500g; day 1-3 of life) at a tertiary hospital in Cape Town, South Africa. Participants were sequentially allocated to 4 trial arms (n=20 each): 1% aqueous CHG (CHG), 1% CHG plus emollient (CHG+EM), emollient only (EM) and standard of care (SOC: no antiseptic/emollient). Trial treatment/s were applied daily for 10 days (d) post-enrolment, documenting neonatal skin condition score. Anterior nose, neck, umbilical and perianal swabs for bacterial culture were collected at d1, d3, d10 and d16 post-enrolment, (±1 day), reporting pathogen acquisition rates and semi-quantitative bacterial colony counts. (ClinicalTrials.gov identifier: NCT03896893; trial status: closed). Findings Eighty preterm neonates (mean gestational age 30 weeks [SD 2]) were enrolled between 4 March and 26 August 2019. The bacterial pathogen acquisition rate (comparing d1 and d16 swabs) varied from 33·9% [95%CI 22·9-47·0] at the umbilicus, 39·3% [95%CI 27·6-52·4] at the neck, to 71·4% [95%CI 58·5-81·7] at both the nose and perianal region. At d10, CHG babies had reduced bacterial density detected from neck, umbilicus, and perianal swabs compared to other groups (see Table 3). Following intervention cessation, colonization density was similar across all trial arms, but S. aureus colonization was more prevalent among EM and CHG+EM babies. Neonatal skin condition score improved in babies receiving emollient application (EM: -0·87 [95%CI 0·69-1·06] and CHG+EM: -0·73 [0·45-0·99]), compared to the SOC and CHG arms (Table 2); no CHG-related skin reactions occurred. Interpretation Bacterial colonization density was significantly reduced in babies receiving 1% CHG washes but colonization levels rebounded rapidly post-intervention. Emollient application improved skin condition but was associated with higher rates of S. aureus colonization. Funding South African Medical Research Council; National Institutes of Health (TW010682).

Background: Low vitamin D (VitD) status is becoming a global health issue. Previous heterogenous results are urging a meta-analysis to delineate a panorama of VitD conditions in the general population in Mainland of China. Methods: We performed a systematic review and meta-analysis by searching PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, WanFang, and VIP databases up to June 4, 2021. The inclusion criteria were as follows: (1) original articles or dissertations focused on VitD status of people in Mainland of China; and (2) studies were population-based, cross-sectional, or longitudinal cohort with baseline data. The outcomes were serum 25(OH)D concentration and the prevalence of low VitD status. Low VitD status included VitD deficiency (

Background: There are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against SARSCoV-2 in vitro. This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma. Methods: Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0¢6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884. Findings: 45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59 77) versus untreated controls (42% IQR 31 73) (p = 0¢004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0¢47, p = 0¢02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed. Interpretation: A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19. Fil: Krolewiecki, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina Fil: Moragas, Matías. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Travacio, Marina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química General e Inorgánica; Argentina Fil: Valentini, Ricardo. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Solari, Rubén. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Tinelli, Marcelo Adrián. Laboratorio Elea/Phoenix; Argentina Fil: Cimino, Rubén Oscar. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Fleitas, Pedro Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Golemba, Marcelo Darío. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Fernández, Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Fernández de Oliveira, Diego. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: Astudillo, German. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Baeck, Inés. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: Farina, Javier. Hospital Cuenca Alta; Argentina Fil: Cardama, Georgina Alexandra. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mangano, Andrea María Mercedes. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Spitzer, Eduardo. Laboratorio Elea/phoenix; Argentina Fil: Gold, Silvia. Fundación Mundo Sano; Argentina Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina

Background Recent studies have suggested that gestational diabetes (GDM) is a heterogeneous condition with distinct subtypes determined by whether the predominant metabolic abnormality is impaired insulin sensitivity or deficient insulin secretion. However, it is not known if the elevated future risk of pre-diabetes/diabetes associated with GDM varies according to these subtypes. Thus, we sought to evaluate maternal metabolic function in the 1st year postpartum in relation to GDM subtypes. Methods In this prospective cohort study conducted in Toronto, Canada, 613 women underwent GDM screening by oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT at both 3-months and 12-months postpartum between 09/2003 and 03/2016. The antepartum OGTT identified 3 groups of women: GDM with predominant sensitivity defect (GDM-sensitivity), GDM with predominant secretion defect (GDM-secretion), and non-GDM. Findings Antepartum findings persisted after pregnancy, with lower insulin sensitivity in GDM-sensitivity (Matsuda index; HOMA-IR) and lower insulin secretion in GDM-secretion (Stumvoll first-phase; insulinogenic index (IGI)) at both 3-months and 12-months (all p

Background This study summarizes the experiences of patients, who have multiple comorbidities, with 15 mono-treated antidepressants. Methods This is a retrospective, observational, matched case control study. The cohort was organized using claims data available through OptumLabs for depressed patients treated with antidepressants between January 1, 2001 and December 31, 2018. The cohort included patients from all states within United States of America. The analysis focused on 3,678,082 patients with major depression who had 10,221,145 antidepressant treatments. Using the robust, and large predictors of remission, and propensity to prescribe an antidepressant, the study created 16,770 subgroups of patients. The study reports the remission rate for the antidepressants within the subgroups. The overall impact of antidepressant on remission was calculated as the common odds ratio across the strata. Findings The study accurately modelled clinicians’ prescription patterns (cross-validated Area under the Receiver Operating Curve, AROC, of 82.0%, varied from 77% to 90%) and patients’ remission (cross-validated AROC of 72.0%, varied from 69.5% to 78%). In different strata, contrary to published randomized studies, remission rates differed significantly and antidepressants were not equally effective. For example, in age and gender subgroups, the best antidepressant had an average remission rate of 50.78%, 1.5 times higher than the average antidepressant (30.30% remission rate) and 20 times higher than the worst antidepressant. The Breslow-Day chi-square test for homogeneity showed that across strata a homogenous common odds-ratio did not exist (alpha

Background: To explore the performance of quantitative morphological and functional analysis in meibography images by an automatic meibomian glands (MGs) analyser in diagnosis and grading Meibomian Gland Dysfunction (MGD). Methods: A cross-sectional study collected 256 subjects with symptoms related to dry eye and 56 healthy volunteers who underwent complete ocular surface examination was conducted between January 1, 2019, and December 31, 2020. The 256 symptomatic subjects were classified into MGD group (n = 195) and symptomatic non-MGD group (n = 61). An automatic MGs analyser was used to obtained multi-parametric measurements in meibography images including the MGs area ratio (GA), MGs diameter deformation index (DI), MGs tortuosity index (TI), and MGs signal index (SI). Adjusted odds ratios (ORs) of the multi-parametric measurements of MGs for MGD, and the area under the receiver operating characteristic (AUC-ROC) curves of multi-parametric measurements for MGD diagnosing and grading were conducted. Findings: When consider age, sex, ocular surface condition together, the estimated ORs for DI was 1.62 (95% CI, 1.29-2.56), low-level SI was 24.34 (95% CI, 2.73-217.3), TI was 0.76(95% CI, 0.54-0.90), and GA was 0.86 (95% CI, 0.74-0.92) for MGD. The combination of DI-TI-GA-SI showed an AUC = 0.82 (P < 0.001) for discriminating MGD from symptomatic subjects. The DI had a higher AUC in identifying early-stage MGD (grade 1-2), while TI and GA had higher AUCs in moderate and advanced stages (grade 3-5). Merging DI-TI-GA showed the highest AUCs in distinguish MGD severities. Interpretation: The MGs area ratio, diameter deformation, tortuosity and signal intensity could be considered promising biomarkers for MGD diagnosis and objective grading. Funding: This work was supported by the Key-Area Research and Development Program of Guangdong Province (No. 2019B010152001), the National Natural Science Foundation of China under Grant (81901788) and Guangzhou Science and Technology Program (202002030412).

Background Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. Methods We examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021. Findings Across data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May. Interpretation The outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control efforts Funding National Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open Philanthropy, Academy of Medical Sciences Bill,Melinda Gates Foundation, Imperial College Healthcare NHS Trust, The Novo Nordisk Foundation, MRC Centre for Global Infectious Disease Analysis, Community Jameel, Cancer Research UK, Imperial College COVID-19 Research Fund, Medical Research Council, Wellcome Sanger Institute.

Background A significant proportion of individuals experience lingering and debilitating symptoms following acute COVID-19 infection. The National Institute for Health and Care Excellence (NICE) have coined the persistent cluster of symptoms as post-COVID syndrome. This has been further sub-categorised into acute post-COVID syndrome for symptoms persisting three weeks beyond initial infection and chronic post-COVID syndrome for symptoms persisting beyond twelve weeks. The aim of this review was to detail the prevalence of clinical features and identify potential predictors for acute and chronic post-COVID syndrome. Methods A systematic literature search, with no language restrictions, was performed to identify studies detailing characteristics and outcomes related to survivorship of post-COVID syndrome. The last search was performed on 6 March 2021 and all pre-dating published articles included. A means of proportion meta-analysis was performed to quantify characteristics of acute and chronic post-COVID syndrome. Study quality was assessed with a specific risk of bias tool. PROSPERO Registration: CRD42020222855 Findings A total of 43 studies met the eligibility criteria; of which, 38 allowed for meta-analysis. Fatigue and dyspnoea were the most prevalent symptoms in acute post-COVID (0·37 and 0·35) and fatigue and sleep disturbance in chronic post-COVID syndrome (0·48 and 0·44), respectively. The available evidence is generally of poor quality, with considerable risk of bias, and are of observational design. Interpretation In conclusion, this review highlights that flaws in data capture and interpretation, noted in the uncertainty within our meta-analysis, affect the applicability of current knowledge. Policy makers and researchers must focus on understanding the impact of this condition on individuals and society with appropriate funding initiatives and global collaborative research. Funding As stated in the Acknowledgements.

Background Guidelines to encourage responsible reporting of suicide in news media are a key component of suicide prevention strategies. Recent guidelines have been developed on portrayal of suicide in entertainment media although the relationship between these portrayals and subsequent suicidal behaviour has received considerably less attention in research. Methods We conducted a systematic review and meta-analysis to examine the association between portrayals of suicide and suicide attempt in entertainment media and suicidal behaviour in the population. We searched PubMed, Scopus, Embase, PsycInfo, Web of Science and Google Scholar until April 20, 2021. We included studies adopting interrupted time series or single/multiple arm pre-post designs. Separate analyses were undertaken for studies of suicide and suicide attempts. We synthesized studies at moderate risk of bias and included studies at serious risk in a sensitivity analysis. Using a random-effects meta-analysis, we synthesized studies at moderate risk of bias and included studies at serious risk in a sensitivity analysis. Study registration: PROSPERO (CRD42020221333). Findings Twelve studies met our inclusion criteria. Six studies were about suicide. Two of these were at moderate risk of bias and both examined the effects of the Netflix series 13 Reasons Why. The pooled rate ratio (RR) for these studies was 1·18 (95% CI 1·09 to 1·27, p

Background Fatal police violence in the United States disproportionately affects Black, Native American, and Hispanic people, and for these groups it is a racially oppressive population-level stressor that we hypothesize increases the risk of pregnancy loss. Focusing on core based statical areas (CBSAs) surrounding small and large urban centers, we accordingly tested whether gestational exposure to fatal police violence decreased the number of live births, which is reflective of a rise in lost pregnancies. Methods Our observational study linked microdata for all births (N = 7,709,300) in 520 CBSAs with at least one incident of fatal police violence in 2013–2015 to Fatal Encounters, a database that prospectively identified 2594 police-related fatalities using online media reports and public records. We estimated the association between month-to-month fatal police violence and conceptions resulting in live births using distributed lag quasi-Poisson models with CBSA-level fixed effects, adjusted for seasonality and stratified by maternal race/ethnicity. Findings For each additional police-related fatality that occurred in the first through sixth months of gestation, we observed a 0.14% decrease (95% confidence interval: 0.05%, 0.23%) in the total number of live births within CBSAs, and a 0.29% decrease in births to Black women (95% CI: 0.11%, 0.48%). The association was null for births to White women. Interpretation Our findings suggest fatal police violence may have population-level consequences for pregnancy loss and adds to the evidence regarding the importance of preventing these fatalities. Funding This study was supported in part by NIH grant P30ES00002 to MGW.

Background Angiotensin receptor blockers (ARBs), such as telmisartan, have been postulated to treat Covid-19-induced lung inflammation. Methods This is a parallel-group, randomized, two-arm, open-label, adaptive, multicenter superiority trial with 1:1 allocation ratio. Participants included patients from 18 years of age hospitalized with Covid-19 with 4 or fewer days since symptom onset enrolled at a university and a community hospital in Buenos Aires, Argentina. Exclusion criteria included prior intensive care unit (ICU) admission and use of ARBs/angiotensin converting enzyme inhibitors at randomization. Control arm received standard care alone and treatment arm telmisartan 80 mg twice daily for 14 days. Primary outcomes were C-reactive protein (CRP) plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge within 15 days, admission to ICU and death at 15- and 30-days. NCT04355936 (Completed). Findings A pragmatic decision to end the study before the third interim analysis was made on Oct. 30th due to sharp reduction in recruitment. A total of 162 patients were randomized. 158 patients enrolled between May 14 and October 30 2020, were included in the analysis, 80 in the standard care and 78 in the telmisartan added to standard care group. Baseline absolute CRP serum levels were 5.53 ± 6.19 mg/dL (95% CI 6.91 to 4.15, n = 80) and 9.04 ± 7.69 (95% CI 9.04 to 10.82, n = 74) in the standard care and telmisartan added to standard care groups, respectively. Day 5 control-group CRP levels were 6.06 ± 6.95 mg/dL (95% CI 7.79–4.35, n = 66) while telmisartan group were 3.83 ± 5.08 mg/dL (95% CI 5.08–2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 ± 8.19 mg/dL (95% CI 8.79–3.81, n = 44) and 2.37 ± 3.47 mg/dL (95% CI 3.44–1.30, n = 43, p = 0.0098) in the control and telmisartan groups, respectively (all values expressed as mean ± SD). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced in the telmisartan-treated group (control 22.54%, 16/71; telmisartan 4.29%, 3/70 participants; p = 0.0023). Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30. No adverse events were reported. Interpretation Our study suggests that the ARB telmisartan, a widely used antihypertensive drug, is safe and could reduce morbidity and mortality in hospitalized patients infected with SARS -CoV-2 by anti-inflammatory effects. Further studies employing telmisartan are needed for confirmation of our results and to define its true therapeutic value as a tool against Covid-19. Funding Facultad de Medicina (Universidad de Buenos Aires, Argentina), Hospital Espanol de Buenos Aires (Argentina) and Laboratorio Elea (Argentina).

Background Different physiologic changes that occur during pregnancy, such as Hydroureter, dilatation of the renal pelvis, glycosuria and aminoaciduria, and low urine production predispose pregnant women for ascending urinary tract infection. Globally, 2% to 15% of the pregnant women have urinary tract infection without specific symptoms. Therefore, this study aimed to estimate the prevalence of asymptomatic bacteriuria (ABU) in pregnant women in Africa. Methods Systematic search of published studies done on PubMed, EMBASE, Web of Science, SCOPUS, PsychInfo, CINAHL, and google scholar for gray literature. All published observational studies until October 30, 2020 were included. This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality of studies was assessed by modified Newcastle-Ottawa Scale (NOS). Meta-analysis was carried out using a random-effects method with the double arcsine transformation approach using the STATA™ Version 14 software. Trim and fill analysis was done to correct presence of significant publication bias. The study protocol is prospectively registered on PROSPERO, registration number CRD42020212601. Findings From 3393 obtained studies, 48 studies from 12 African countries involving 15, 664 pregnant women included in this Meta-analysis. The overall pooled prevalence of asymptomatic bacteriuria among pregnant women in Africa after correction for publication bias by trim and fill analysis was found to be 11.1% (95% CI: 7.8, 14.4). The most common bacterial isolates involved in the etiology of ABU was Escherichia coli with pooled prevalence 33.4% (95% CI: 27.3 - 39.4) Interpretation Asymptomatic bacteriuria is substantial among pregnant women in Africa. Therefore, all pregnant women should be tested for the presence of asymptomatic bacteriuria. A screening program must be based not only on the incidence but also on a cost-efficacy evaluation and a microbiological evaluation. Funding There was no funding source for this study.

Background: We evaluated features of HIV transmission networks involving persons diagnosed during incident HIV infection (IHI) to assess network-based opportunities to curtail onward transmission. Methods: Transmission networks were constructed using partial pol sequences reported to North Carolina surveillance among persons with recent (2014–2018) and past (90 days prior to an IHI were further characterized. We assessed named partner outcomes among IHI index persons using contact tracing data. Findings: Of 4,405 HIV diagnoses 2014–2018 with sequences, there were 323 (7%) IHI index persons; most were male (88%), Black (65%), young (68%

SummaryBackgroundEffective home treatment algorithms implemented based on a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalisation of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health system.MethodsThis academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians between October 2020 and January 2021, according to the proposed recommendation algorithm, with outcomes for 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalisation. Analyses were by intention-to-treat.FindingsAll patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the ‘recommended’ schedule cohort and 14 [7-30] days in the matched ‘control’ cohort (p=0·033). Other symptoms persisted in a lower percentage of patients in the ‘recommended’ than in the ‘control’ cohort (23·3% versus 73·3%, respectively, p90% (from 481 to 44 days and from €296.000 to €28.000, respectively. 1.2 patients had to be treated to prevent one hospitalisation event.InterpretationImplementation of an early home treatment algorithm failed to accelerate recovery from major symptoms of COVID 19, but almost eliminated the risk of hospitalisation and related treatment costs.Research inContextEvidence before this studyWe searched PubMed and the Cochrane Library for peer-reviewed articles published in any language up to March 19, 2021, using the search terms “2019-nCoV” or “SARS-CoV-2” or “COVID-19” and “early” or “outpatient” or “treatment” or “home”. Our search did not identify any randomised clinical trials or observational studies that assessed the effectiveness of treatment regimens targeting early, mild symptoms of COVID-19 in the outpatient setting.Added value of this studyIn this fully academic, observational matched-cohort study, we found that early home treatment of 90 consecutive patients with mild COVID-19 by their family physicians according to the proposed recommendation algorithm, designed based on a pathophysiologic and pharmacologic rationale, required few more days to achieve resolution of major symptoms including fever, dyspnea, musculoskeletal pain, headache and cough compared to 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens (primary outcome). Nonetheless, it is noteworthy that the home treatment of COVID-19 patients according to the proposed recommendation algorithm significantly reduced the risk of hospitalization compared to the other treatments in the ‘control’ cohort. Days of hospitalization and related treatment costs were reduced by over 90% in the ‘recommended’ cohort as compared to ‘control’ cohort. Just 1.2 patients needed to be treated according to the recommendation algorithm to prevent one hospitalization event. We also found that symptoms such as anosmia and ageusia/dysgeusia were less persistent and lasted a shorter time in the ‘recommendation’ than in the ‘control’ cohort.Implications of the available evidenceThe finding that the implementation of the proposed simple treatment algorithm during the initial, mild phase of COVID-19 has the potential to prevent disease progression, potentially limiting the need for hospital admission, may have major implications for patients and health care providers. Indeed, preventing hospitalisations due to the worsening of COVID-19 will not only save lives, but will also contribute to remarkably reduced treatment costs and to streamlining health care systems that are overburdened by the effects of the pandemic. However, time to hospitalization was a secondary outcome of the study and the possibility of a casual finding cannot be definitely excluded. Thus, the observed reduction in patients hospitalizations should be considered as an hypothesis generating finding that could provide a robust background for a prospective trial primarily aimed to test treatment effect on this outcome.

BackgroundThis first report of the Linköping Covid-19 Study (LinCoS) aimed at determination of Covid-19-associated mortality, impairments, activity and participation limitations denoting rehabilitation needs four months after discharge from hospital.MethodsAn ambidirectional population-based cohort study including all confirmed Covid-19 cases admitted to hospital during 1/03-31/05 and those living in home healthcare settings identified through a regional registry and evaluated through medical records, including WHO Clinical Progression Scale (CPS). All patients discharged from hospital were followed-up by structured telephone interview at 4 months post-discharge. Respondents indicated any new or aggravated persisting problems in any of 25 body functions and 12 activity/participation items and rated them for impact on daily life.FindingsOut of 734 hospitalised patients, 149 were excluded, 125 died, and 460 were alive at 4-month follow-up of whom 433 (94.1%) were interviewed. In total, 40% reported impairments and activity/participation limitations affecting daily life and warranted further multi-professional rehabilitation assessment, predominantly those with severe disease and a considerable proportion of those with moderate disease. Cognitive and affective impairments were equally common in all groups and were reported by 20-40% of cases. Limb weakness was reported by 31%, with CPS 7-9 being four times more likely to report this problem as compared to CPS 4-5. 26% of those working or studying reported difficulties returning to these activities, this being 3.5 times more likely in CPS 7-9 as compared to CPS 4-5. 25% reported problems walking >1 km, with CPS 7-9 over three times more likely to report this as compared to the other two sub-groups. 90-day mortality rate of Covid-19 associated deaths was 15.1%.InterpretationMost rehabilitation needs after Covid-19 involved higher cerebral dysfunction both in patients with moderate and severe disease. This should be considered when designing services aiming at minimizing long-term disability.FundingALF grant and Region Östergötland.

Background The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. Methods Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. Findings Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

Background Chlamydia trachomatis (CT) is one of the most prevalent bacterial sexually transmitted infections (STIs) globally but has been inadequately detected for intervention. Introduction of point-of-care tests (POCTs) for CT is critical for filling the intervention gaps. We conducted a systematical review and meta-analysis on diagnostic performance of POCTs for CT to assist in guiding the application of these assays in CT screening and detection. Methods We searched PubMed/Medline and Embase databases, from January 2004 to May 2021, for studies reporting the performance of POCTs for identifying CT using specimens collected from urethral, vaginal, cervical, anorectal, or pharyngeal site or of urine. Two investigators independently screened and extracted data for controlling the quality of data extraction. Any discrepancies in study selection and data extraction were resolved through consensus. We only included studies with sufficient data to estimate sensitivity and specificity, and used laboratory-based nucleic acid amplification test (NAAT) as the reference standard. The main outcomes were pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs). Summary estimates were calculated using a random-effects model and summary receiver operator curves (SROCs) were generated using the Moses-Littenberg method. STATA 14.0 and Meta-DiSc 1.4 were used for statistical analysis. The study protocol is registered with PROSPERO, number CRD42019140544. Findings Of 3,038 records identified, 39 studies (42,336 specimens) were included in the study, including 14 studies on evaluation of antigen detection (AD)-based and 25 on NAAT-based POCTs. The overall pooled sensitivity, specificity and DOR were 56% (95% CI 45%–67%), 99% (95% CI 98%–99%) and 86 (95% CI 46–163), respectively, for AD-based POCTs and corresponding values for NAAT-based POCTs were 94% (95% CI 91%–96%), 99% (95% CI 99%–99%) and 1,933(95% CI 1,018–3,669), respectively. The pooled sensitivity of AD-based POCTs varied across the types of specimens, indicating 46% for cervical swabs (95% CI 37%–56%; range 22.7%–71.4%), 52% for vaginal swabs (95% CI 34%–70%; range 17.1%–86.8%) and 57% for male urine (95% CI 36%–75%; range 20.0%–82.6%). For NAAT-based POCTs, the pooled sensitivity was 94% (95% CI 90%–96%) for cervical swabs, 94% (95% CI 86%–98%) for vaginal swabs, 95% (95% CI 91%–97%) for urine specimens and 93% (95% CI 87%–96%) for anorectal swabs. Interpretation NAAT-based POCTs for CT have a significantly better performance particularly in sensitivity for diagnosing the infection with CT than the AD-based POCTs. Screening strategy with AD-based POCTs may potentially result in a substantial under-detection of the infections.

Background Older children have higher SARS-CoV-2 infection rates than younger children. We investigated SARS-CoV-2 infection, seroprevalence and seroconversion rates in staff and students following the full reopening of all secondary schools in England. Methods Public Health England (PHE) invited secondary schools in six regions (East and West London, Hertfordshire, Derbyshire, Manchester and Birmingham) to participate in SARS-CoV-2 surveillance during the 2020/21 academic year. Participants had nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term. Multivariable logistic regression was used to assess independent risk factors for seropositivity and seroconversion. Findings Eighteen schools in six regions enrolled 2,209 participants, including 1,189 (53.8%) students and 1,020 (46.2%) staff. SARS-CoV-2 infection rates were not significantly different between students and staff in round one (5/948; [0.53%] vs. 2/876 [0.23%]; p = 0.46) or round two (10/948 [1.05%] vs. 7/886 [0.79%]; p = 0.63), and similar to national prevalence. None of four and 7/15 (47%) sequenced strains in rounds 1 and 2 were the highly transmissible SARS-CoV-2 B.1.1.7 variant. In round 1, antibody seropositivity was higher in students than staff (114/893 [12.8%] vs. 79/861 [9.2%]; p = 0.016), but similar in round 2 (117/893 [13.1%] vs.117/872 [13.3%]; p = 0.85), comparable to local community seroprevalence. Between the two rounds, 8.7% (57/652) staff and 6.6% (36/549) students seroconverted (p = 0.16). Interpretation In secondary schools, SARS-CoV-2 infection, seropositivity and seroconversion rates were similar in staff and students, and comparable to local community rates. Ongoing surveillance will be important for monitoring the impact of new variants in educational settings.

Background The prevalence of chronic hepatitis C (CHC) in People Who Inject Drugs (PWID) is 8-10% as compared to 3·6% in the general population in Punjab, India. We assessed the real-world efficacy and safety of free-of-charge generic direct-acting antivirals (DAAs), sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir)±ribavirin in the microelimination of CHC in PWID in a public health setting. Methods An integrated care team at 25 sites provided algorithm based DAAs treatment to PWID supervised by telemedicine clinics between 18th June 2016 and 31st July 2019. The primary endpoint was sustained virological response at 12 weeks (SVR-12); the secondary endpoints were treatment completion, adherence, safety, and adverse events. ClinicalTrials.gov number: NCT01110447. Findings We enrolled 3477 PWID (87·2% men; mean age 33·6±12·5 years; 83·8% rural; 6·8% compensated cirrhosis). While 2280 (65·5%) patients completed treatment, 1978 patients completed 12 weeks of follow up for SVR-12. SVR-12 was achieved in 91·1% of patients per protocol, 49.5% as per intention to treat (ITT) and 90·1% in a modified ITT analysis. Of 546 (15·7%) patients with treatment interruptions, 99 (19·7%) could be traced to test for SVR-12 with a cure rate of 77·8%. There were no major adverse events or consequent treatment discontinuation. Interpretation Integrated care of PWID with CHC with DAAs is safe and effective. Measures for reducing treatment interruptions will further improve outcomes. Funding The Government of the state of Punjab, India under the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) project, funds the project.