Engineered tRNAs suppress nonsense mutations in cells and in vivo.

Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases1. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation2-7. However, tRNA-based gene therapy has not yielded an optimal combination of clinical efficacy and safety and there is presently no treatment for individuals with nonsense mutations. Here we introduce a strategy based on altering native tRNAs into  efficient suppressor tRNAs (sup-tRNAs) by individually fine-tuning their sequence to the physico-chemical properties of the amino acid that they carry. Intravenous and intratracheal lipid nanoparticle (LNP) administration of sup-tRNA in mice restored the production of functional proteins with nonsense mutations. LNP-sup-tRNA formulations caused no discernible readthrough at endogenous native stop codons, as determined by ribosome profiling. At clinically important PTCs in the cystic fibrosis transmembrane conductance regulator gene (CFTR), the sup-tRNAs re-established expression and function in cell systems and patient-derived nasal epithelia and restored airway volume homeostasis. These results provide a framework for the development of tRNA-based therapies with a high molecular safety profile and high efficacy in targeted PTC suppression.

ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime-boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans.

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation.

BACKGROUND: Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. METHODS: We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. FINDINGS: Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. INTERPRETATION: KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. FUNDING: Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Effectiveness of handwashing with soap for preventing acute respiratory infections in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality globally, with 83% of ARI mortality occurring in low-income and middle-income countries (LMICs) before the COVID-19 pandemic. We aimed to estimate the effect of interventions promoting handwashing with soap on ARI in LMICs. METHODS: In our systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, Global Health, and Global Index Medicus for studies of handwashing with soap interventions in LMICs from inception to May 25, 2021. We included randomised and non-randomised controlled studies of interventions conducted in domestic, school, or childcare settings. Interventions promoting hand hygiene methods other than handwashing with soap were excluded, as were interventions in health-care facilities or the workplace. The primary outcome was ARI morbidity arising from any pathogen for participants of any age. Secondary outcomes were lower respiratory infection, upper respiratory infection, influenza confirmed by diagnostic test, COVID-19 confirmed by diagnostic test, and all-cause mortality. We extracted relative risks (RRs), using random-effects meta-analysis to analyse study results, and metaregression to evaluate heterogeneity. We assessed risk of bias in individual studies using an adapted Newcastle-Ottawa scale, and assessed the overall body of evidence using a Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The study is registered with PROSPERO, CRD42021231414. FINDINGS: 26 studies with 161 659 participants met inclusion criteria, providing 27 comparisons (21 randomised). Interventions promoting handwashing with soap reduced any ARI compared with no handwashing intervention (RR 0·83 [95% CI 0·76-0·90], I2 88%; 27 comparisons). Interventions also reduced lower respiratory infections (0·78 [0·64-0·94], I2 64%; 12 comparisons) and upper respiratory infections (0·74 [0·59-0·93], I2 91%; seven comparisons), but not test-confirmed influenza (0·94 [0·42-2·11], I2 90%; three comparisons), test-confirmed COVID-19 (no comparisons), or all-cause mortality (prevalence ratio 0·95 [95% CI 0·71-1·27]; one comparison). For ARI, no heterogeneity covariates were significant at p<0·1 and the GRADE rating was moderate certainty evidence. INTERPRETATION: Interventions promoting handwashing with soap can reduce ARI in LMICs, and could help to prevent the large burden of respiratory disease. FUNDING: Bill & Melinda Gates Foundation, Reckitt Global Hygiene Institute, and UK FCDO.

How do we design a laboratory space for a hospital transfusion medicine service?

BACKGROUND: Transfusion service laboratories (TSL) often need to renovate or design new laboratory space, and their leaders must be involved in the complex and multifaceted design process. STUDY DESIGN AND METHODS: This manuscript outlines the design process and considerations for a dedicated TSL space. RESULTS: Proactive engagement with key collaborators throughout the design process is essential. Major design considerations include physical features such as location, size, service/equipment needs, and zones within the laboratory; intangible issues such as efficiency, well-being, and disaster planning; and adaptations for suboptimal space and changes over time. CONCLUSION: Investing in the design of the laboratory space facilitates high-quality TSL operations, productivity, customer satisfaction, regulatory compliance, staff well-being, and most importantly, patient safety.

A multi-institutional survey of apheresis services among institutions in the United States.

INTRODUCTION: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. METHODS: A multi-institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID-19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. RESULTS: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC-A) and red blood cell exchange (RCE). CAR-T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID-19 pandemic, were common and most often addressed using overtime. DISCUSSION: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. CONCLUSION: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers.

Violence outcomes in later adolescence with the Good School Toolkit-Primary: a nonrandomized controlled trial in Uganda.

BACKGROUND: We sought to determine whether the Good School Toolkit-Primary violence prevention intervention was associated with reduced victimisation and perpetration of peer and intimate partner violence four years later, and if any associations were moderated by sex and early adolescent: family connectedness, socio-economic status, and experience of violence outside of school. METHODS: Drawing on schools involved in a randomised controlled trial of the intervention, we used a quasi-experimental design to compare violence outcomes between those who received the intervention during our trial (n = 1388), and those who did not receive the intervention during or after the trial (n = 522). Data were collected in 2014 (mean age 13.4, SD 1.5 years) from participants in 42 schools in Luwero District, Uganda, and 2018/19 from the same participants both in and out of school (mean age 18, SD: 1.77 years). We compared children who received the Good School Toolkit-Primary, a whole school violence prevention intervention, during a randomised controlled trial, to those who did not receive the intervention during or after the trial. Outcomes were measured using items adapted from the International Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool-Child Institutional. We used mixed-effect multivariable logistic regression, with school fitted as a random-effect to account for clustering. RESULTS: 1910 adolescents aged about 16-19 years old were included in our analysis. We found no evidence of an average long-term intervention effect on our primary outcome, peer violence victimization at follow-up (aOR = 0.81, 95%CI = 0.59-1.11); or for any secondary outcome. However, exposure to the intervention was associated with: later reductions in peer violence, for adolescents with high family connectedness (aOR = 0.70, 95% CI 0.49 to 0.99), but not for those with low family connectedness (aOR = 1.07, 95% CI 0.69 to 1.6; p-interaction = 0.06); and reduced later intimate partner violence perpetration among males with high socio-economic status (aOR = 0.32, 95%CI 0.11 to 0.90), but not low socio-economic status (aOR = 1.01 95%CI 0.37 to 2.76, p-interaction = 0.05). CONCLUSIONS: Young adolescents in connected families and with higher socio-economic status may be better equipped to transfer violence prevention skills from primary school to new relationships as they get older. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01678846, registration date 24 August 2012. Protocol for this paper:  https://www.researchprotocols.org/2020/12/e20940 .

The Role of Community Health Agents in Promoting Social Change in Peru.

BACKGROUND: Community health agents (CHAs) provide basic health services and increase health care access thereby improving health outcomes for peri-urban regions in Peru. Few studies analyze the effect that becoming a CHA has on women's interpersonal interactions. We aim to explore the impact CHAs may have on gender and social norms through their roles as trusted leaders in male-dominated communities. METHODS: We conducted six 90-minute group discussions with CHAs working in Huancayo and Trujillo, Peru. We designed the discussions to extract data about family and community norms that changed as a result of working as a CHA. RESULTS: A total of 53 female CHAs participated in six discussion groups. CHAs reported shifting family support (a change in how their family supported them in their role as a CHA), gaining status within their family (feeling more valued for their knowledge and experience), and shifting family gender roles (men and boys taking on more household responsibilities) as a result of their work. CHAs also reported a change in community norms and felt they were more valued and respected within their communities as women leaders. CONCLUSIONS: Working as a CHA creates an opportunity to enact social change through altering family dynamics and community perceptions. Moreover, empowering women to become CHAs not only generates tangible benefits in community health, but can help create social change that ultimately improves the lives of women and realize their human rights.

An exploration of potential pressures to engage in parenting accommodation of PTSD symptoms for military couples.

In the context of service member posttraumatic stress disorder (PTSD) symptoms, intimate partners may experience pressure to take over parenting roles and run interference between the service member and the children; that is, to engage in partner accommodation focal to parenting. The current study quantitatively assessed potential pressures to engage in parenting accommodation (PPEPA) in a sample of 207 female partners married to male service members with at least one child in the home and the convergence of PPEPA with service member PTSD symptoms, general partner accommodation, couple functioning, parenting, and child functioning. Partners' reports of PPEPA were associated with higher levels of service member PTSD symptoms and partners' general accommodation of PTSD symptoms. When controlling for service member PTSD symptoms and general partner accommodation, partner reports of PPEPA still accounted for unique variance in lower parenting alliance (as reported by both service member and partner), lower levels of service members' reports of closeness with children in the home, higher levels of harsh parenting by both the service member and partner, and greater child behavioral difficulties. Findings support PPEPA as related to partners' accommodative responses to PTSD but demonstrating unique associations with parenting alliance, parenting, and child outcomes. Parenting interventions in the context of PTSD may benefit from conjoint or family approaches that attend to the intersection of PTSD and broader family functioning, including pressures to engage in accommodation focal to the parenting domain.

Before and after study of a national complementary and supplementary feeding programme in Rwanda, 2017-2021.

To address high rates of malnutrition among children from vulnerable households in Rwanda, the government initiated a national food supplementation programme. A before and after evaluation, using repeat cross-sectional surveys in randomly selected villages was conducted; aimed at assessing the effectiveness of providing fortified blended food (FBF) to children 18-23 months of age, pregnant and lactating women in the lowest tier of Rwanda's social support system. Data were collected in 2017, 2018 and 2021 through interviews with caregivers; anthropometric measurements and a capillary blood sample were obtained from children. The primary statistical analysis compared the nutritional status of children before and after the introduction of FBF. We enroled 724 children during each survey. The prevalence of stunting declined from 47% to 35% between 2017 and 2021; in 2018, the prevalence of stunting was 43%. Children had a 42% reduction in the odds of being stunted (adjusted odds ratio [AOR]: 0.58, 95% confidence interval [CI]: 0.47-0.74, p < 0.001) from 2017 to 2021 even after adjusting for inherent, distal, proximal, and intermediate covariates. The reduction in stunting observed within the first year of the programme was not statistically significant (AOR: 0.83, 95% CI: 0.67-1.03, p < 0.091). We observed meaningful reductions in the prevalence of stunting among children which coincided with the introduction of Government-led initiative to reduce malnutrition. The Rwandan Government has committed to improving the living conditions of vulnerable households and has made strong investments in reducing malnutrition. The impact of these investments can be seen in the overall trend towards improved nutritional status highlighted in this evaluation.

Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial.

BACKGROUND: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection. CLINICAL TRIALS REGISTRATION: NCT04323800.

Epidemiological and clinical features, therapeutic strategies and outcomes in patients with hyperhaemolysis: A systematic review.

Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves destruction of both donor and recipient red blood cells (RBCs). As the epidemiology and underlying pathophysiology have yet to be definitively elucidated, recognition can be challenging. We systematically reviewed PubMed and EMBASE to identify all cases of post-transfusion hyperhaemolysis and characterized the epidemiological, clinical and immunohaematological characteristics and treatments of HHS. We identified 51 patients (33 females and 18 males), including 31 patients with SCD (HbSS, HbSC and HbS/ß-thalassaemia). The median haemoglobin nadir (3.9 g/dL) occurred a median of 10 days post-transfusion. 32.6% and 45.7% of patients had a negative indirect anti-globulin test and a negative direct anti-globulin test, respectively. The most common therapies included corticosteroids and intravenous immune globulin. 66.0% of patients received ≥1 supportive transfusion, which was associated with a longer median hospital stay/time to recovery (23 days vs. 15 days; p = 0.015) compared to no supportive transfusion. These findings illustrate that HHS that often results in marked anaemia 10 days post-transfusion is not restricted to patients with haemoglobinopathies, and additional transfused RBCs may be associated with a longer time-to-recovery.

How do we ensure a safe ABO recheck process?

BACKGROUND: Collecting a patient's blood in a correctly labeled pretransfusion specimen tube is essential for accurate ABO typing and safe transfusion. Noncompliance with specimen collection procedures can lead to wrong blood in tube (WBIT) incidents with potentially fatal consequences. Recent WBIT events inspired the investigation of how various institutions currently reduce the risk of these errors and ensure accurate ABO typing of patient samples. MATERIALS AND METHODS: This article describes the techniques employed at various institutions across the United States to mitigate the risk of misidentified pretransfusion patient specimens. Details and considerations for each of these measures are provided. RESULTS: Several institutions require the order for an ABO confirmation specimen, if indicated, to be generated from the transfusion medicine (TM) laboratory. Others issue a dedicated collection tube that is available exclusively from the TM service. Many institutions employ barcoding for electronic positive patient identification. Some use a combination of these strategies, depending on the locations or service lines from which the specimens are collected. CONCLUSION: The description of various WBIT mitigation strategies will inform TM services on practices that may be effective at their respective institutions. Irrespective of the method(s) utilized, institutions should continue to monitor and mitigate specimen misidentification errors to promote sustained safe transfusion practices.

Socioeconomic inequity in coverage and quality of maternal postnatal care in Ethiopia.

OBJECTIVE: High-quality postnatal care is vital for improving maternal health. This study examined the relationship between household socioeconomic status and both coverage and quality of postnatal care in Ethiopia. METHOD: Cross-sectional household survey data were collected in October-November 2013 from 12 zones in 4 regions of Ethiopia. Women reporting a live birth in the 3-24 months prior to the survey were interviewed about the care they received before, during and after delivery and their demographic characteristics. Using mixed effect logistic and linear regression, the associations between household socioeconomic status and receiving postnatal care, location of postnatal care (health facility vs. non-health facility), cadre of person providing care and the number of seven key services (including physical checks and advice) provided at a postnatal visit, were estimated. RESULTS: A total of 16% (358/2189) of women interviewed reported receiving at least one postnatal care visit within 6 weeks of delivery. Receiving a postnatal care visit was strongly associated with socioeconomic status with women from the highest socioeconomic group having twice the odds of receiving postnatal care compared to women in the poorest quintile (OR [95% CI]: 1.98 [1.29, 3.05]). For each increasing socioeconomic status quintile there was a mean increase of 0.24 postnatal care services provided (95% CI: 0.06-0.43, p = 0.009) among women who did not give birth in a facility. There was no evidence that number of postnatal care services was associated with socioeconomic status for women who gave birth in a facility. There was no evidence that socioeconomic status was associated with the provider or location of postnatal care visits. CONCLUSION: Postnatal care in Ethiopia shows evidence of socio-economic inequity in both coverage and quality. This demonstrates the need to focus on quality improvement as well as coverage, particularly among the poorest women who did not deliver in a facility.

Predicting emergency department visits among children with asthma in two academic medical systems.

Objective: To develop and validate a predictive algorithm that identifies pediatric patients at risk of asthma-related emergencies, and to test whether algorithm performance can be improved in an external site via local retraining.Methods: In a retrospective cohort at the first site, data from 26 008 patients with asthma aged 2-18 years (2012-2017) were used to develop a lasso-regularized logistic regression model predicting emergency department visits for asthma within one year of a primary care encounter, known as the Asthma Emergency Risk (AER) score. Internal validation was conducted on 8634 patient encounters from 2018. External validation of the AER score was conducted using 1313 pediatric patient encounters from a second site during 2018. The AER score components were then reweighted using logistic regression using data from the second site to improve local model performance. Prediction intervals (PI) were constructed via 10 000 bootstrapped samples.Results: At the first site, the AER score had a cross-validated area under the receiver operating characteristic curve (AUROC) of 0.768 (95% PI: 0.745-0.790) during model training and an AUROC of 0.769 in the 2018 internal validation dataset (p = 0.959). When applied without modification to the second site, the AER score had an AUROC of 0.684 (95% PI: 0.624-0.742). After local refitting, the cross-validated AUROC improved to 0.737 (95% PI: 0.676-0.794; p = 0.037 as compared to initial AUROC).Conclusions: The AER score demonstrated strong internal validity, but external validity was dependent on reweighting model components to reflect local data characteristics at the external site.

Process and costs for readiness to safely implement immediate kangaroo mother care: a mixed methods evaluation from the OMWaNA trial at five hospitals in Uganda.

BACKGROUND: Preterm birth complications result in > 1 million child deaths annually, mostly in low- and middle-income countries. A World Health Organisation (WHO)-led trial in hospitals with intensive care reported reduced mortality within 28 days among newborns weighing 1000-1799 g who received immediate kangaroo mother care (iKMC) compared to those who received standard care. Evidence is needed regarding the process and costs of implementing iKMC, particularly in non-intensive care settings. METHODS: We describe actions undertaken to implement iKMC, estimate financial and economic costs of essential resources and infrastructure improvements, and assess readiness for newborn care after these improvements at five Ugandan hospitals participating in the OMWaNA trial. We estimated costs from a health service provider perspective and explored cost drivers and cost variation across hospitals. We assessed readiness to deliver small and sick newborn care (WHO level-2) using a tool developed by Newborn Essential Solutions and Technologies and the United Nations Children's Fund. RESULTS: Following the addition of space to accommodate beds for iKMC, floor space in the neonatal units ranged from 58 m2 to 212 m2. Costs of improvements were lowest at the national referral hospital (financial: $31,354; economic: $45,051; 2020 USD) and varied across the four smaller hospitals (financial: $68,330-$95,796; economic: $99,430-$113,881). In a standardised 20-bed neonatal unit offering a level of care comparable to the four smaller hospitals, the total financial cost could be in the range of $70,000 to $80,000 if an existing space could be repurposed or remodelled, or $95,000 if a new unit needed to be constructed. Even after improvements, the facility assessments demonstrated broad variability in laboratory and pharmacy capacity as well as the availability of essential equipment and supplies. CONCLUSIONS: These five Ugandan hospitals required substantial resource inputs to allow safe implementation of iKMC. Before widespread scale-up of iKMC, the affordability and efficiency of this investment must be assessed, considering variation in costs across hospitals and levels of care. These findings should help inform planning and budgeting as well as decisions about if, where, and how to implement iKMC, particularly in settings where space, devices, and specialised staff for newborn care are unavailable. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02811432 . Registered: 23 June 2016.

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma.

DESCRIPTION: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP. METHODS: These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations. RECOMMENDATION 1 (OUTPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence). RECOMMENDATION 2 (INPATIENT): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. RECOMMENDATION 3 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence). RECOMMENDATION 4 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence). RECOMMENDATION 5 (PROPHYLAXIS): The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence). GOOD CLINICAL PRACTICE STATEMENT: CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

PH WINS 2021 Methodology Report.

CONTEXT: The Public Health Workforce Interests and Needs Survey (PH WINS) was fielded in 2014 and 2017 and is the largest survey of the governmental public health workforce. It captures individual employees' perspectives on key issues such as workplace engagement and satisfaction, intention to leave, training needs, ability to address public health issues, as well as collects demographic information. This article describes the methods used for the 2021 PH WINS fielding. PH WINS: PH WINS 2021 was fielded to a nationally representative sample of staff in State Health Agency-Central Offices (SHA-COs) and local health departments (LHDs) from September 13, 2021, to January 14, 2022. The instrument was revised to assess the pandemic's potential toll on the workforce, including deployment to COVID-19 response roles and well-being, and the country's renewed focus on health equity and "Racism as a Public Health Crisis." PH WINS 2021 had 3 sampling frames: SHAs, Big Cities Health Coalition (BCHC) members, and LHDs. All participating agencies were surveyed using a census approach. PARTICIPATION: Overall, staff lists for 47 SHAs, 29 BCHC members, and 259 LHDs were collected, and the survey was sent to 137 446 individuals. PH WINS received a total of 44 732 responses, 35% of eligible respondents. The nationally representative SHA-CO frame includes a total of 14 957 individuals, and the nationally representative LHD frame includes 26 933 individuals from 439 LHDs (decentralized and nondecentralized). CONSIDERATIONS FOR ANALYSIS: PH WINS now offers a multiyear, nationally representative sample of both SHA-CO and LHD staff. Both practice and academia can use PH WINS to better understand the strengths, needs, and opportunities of the workforce. When using PH WINS for additional data analysis, there are a number of considerations both within the 2021 data set and when conducting multiyear and multiple cross-sectional analyses.

Intrahousehold power inequalities and cooperation: Unpacking household responses to nutrition-sensitive agriculture interventions in rural India.

Nutrition-sensitive agriculture (NSA) interventions offer a means to improve the dietary quality of rural, undernourished populations. Their effectiveness could be further increased by understanding how household dynamics enable or inhibit the uptake of NSA behaviours. We used a convergent parallel mixed-methods design to describe the links between household dynamics-specifically intrahousehold power inequalities and intrahousehold cooperation-and dietary quality and to explore whether household dynamics mediated or modified the effects of NSA interventions tested in a cluster-randomized trial, Upscaling Participatory Action and Videos for Agriculture and Nutrition (UPAVAN). We use quantitative data from cross-sectional surveys in 148 village clusters at UPAVAN's baseline and 32 months afterwards (endline), and qualitative data from family case studies and focus group discussions with intervention participants and facilitators. We found that households cooperated to grow and buy nutritious foods, and gendered power inequalities were associated with women's dietary quality, but cooperation and women's use of power was inhibited by several interlinked factors. UPAVAN interventions were more successful in more supportive, cooperative households, and in some cases, the interventions increased women's decision-making power. However, women's decisions to enter into negotiations with family members depended on whether women deemed the practices promoted by UPAVAN interventions to be feasible, as well as women's confidence and previous cultivation success. We conclude that interventions may be more effective if they can elicit cooperation from the whole household. This will require a move towards more family-centric intervention models that empower women while involving other family members and accounting for the varied ways that families cooperate and negotiate.

Communicating Effectively With People Experiencing Homelessness to Prevent Infectious Diseases.

BACKGROUND: People experiencing homelessness (PEH) are disproportionately affected by many infectious diseases, including coronavirus disease 2019 (COVID-19). However, communication efforts during public health emergencies like the COVID-19 pandemic often do not consider the unique needs of PEH. We examined how PEH seek and receive health information and how traditional health communication methods resonate with them. METHODS: We conducted in-person focus groups with PEH in 4 jurisdictions (Cincinnati, Ohio; Denver, Colorado; Sacramento, California; and the Bronx, New York) during July 2021. RESULTS: Findings from 15 focus groups with PEH (n = 53) revealed the need for trusted messengers and consistent messaging across local organizations, as PEH seek to verify information they receive from multiple sources. PEH overwhelmingly preferred to receive health information through face-to-face conversations, especially with healthcare providers with whom they had an established relationship, but they also cited news media, the internet, and social media as their main sources for obtaining health information. PEH reported that effective communication products pair a recommended action with instructions and resources about how to take that action within their community. CONCLUSIONS: These findings support healthcare providers collaborating with public health agencies to ensure that infectious disease prevention messages for PEH are provided by trusted messengers, multimodal, paired with resources, and consistent.