In Science Journals.

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Detection of Bronchiolitis Obliterans Syndrome Following Pediatric Hematopoietic Stem Cell Transplantation. An Official American Thoracic Society Clinical Practice Guideline.

BACKGROUND: Many children undergo allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for the treatment of malignant and non-malignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common non-infectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent National Institutes of Health workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. METHODS: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of post-HSCT BOS in children. Systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. RESULTS: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. CONCLUSIONS: This document provides an evidence-based approach to detection of post-HSCT BOS in children, while also highlighting considerations for implementation of each recommendation. Further, the document describes important areas for future research.

Diagnosis of Post-Hematopoietic Stem Cell Transplantation Bronchiolitis Obliterans Syndrome in Children: Time for a Rethink?

Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT. Unfortunately, during the development of a recent American Thoracic Society (ATS) Clinical Practice Guideline on this topic, it became apparent that the NIH criteria have significant limitations in the pediatric population, leading to late diagnosis of BOS. Specific limitations include use of an outdated pulmonary function testing reference equation, a reliance on spirometry, use of a fixed forced expiratory volume in 1 second (FEV1) threshold, focus on obstructive defects defined by FEV1/vital capacity, and failure to acknowledge that BOS and infection can coexist. In this review, we summarize the evidence regarding the limitations of the current criteria. We also suggest potential evidence-based ideas for improving these criteria. Finally, we highlight a new proposed criteria for post-HSCT BOS in children that were developed by the authors of the recently published ATS clinical practice guideline, along with a pathway forward for improving timely diagnosis of BOS in children post-HSCT.

Five-year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial.

Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone-naïve at baseline. The rate of 5-year TE-FS was 21.7% (95% confidence interval [CI]: 15.7%-28.7%) overall and 25.4% (95% CI: 18.1%-33.9%) in the hormone-naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4-5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05-2.01, p = .026), a higher baseline prostate-specific antigen (PSA) (HR = 1.06, 95% CI: 1.03-1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40-3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow-up, 18.9% (95% CI: 13.2%-25.7%) of participants were free from treatment escalation (median follow-up of 67.9 months) and two participants had an undetectable PSA level. No treatment-related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT-based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT-based MDT to standard-of-care ADT-based approaches are required to evaluate the impact of delaying ADT on survival.

Sudan virus disease super-spreading, Uganda, 2022.

BACKGROUND: On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this outbreak was 1.25. We described persons who were exposed to the virus, became infected, and they led to the infection of an unusually high number of cases during the outbreak. METHODS: In this descriptive cross-sectional study, we defined a super-spreader person (SSP) as any person with real-time polymerase chain reaction (RT-PCR) confirmed SVD linked to the infection of ≥ 13 other persons (10-fold the outbreak R). We reviewed illness narratives for SSPs collected through interviews. Whole-genome sequencing was used to support epidemiologic linkages between cases. RESULTS: Two SSPs (Patient A, a 33-year-old male, and Patient B, a 26-year-old male) were identified, and linked to the infection of one probable and 50 confirmed secondary cases. Both SSPs lived in the same parish and were likely infected by a single ill healthcare worker in early October while receiving healthcare. Both sought treatment at multiple health facilities, but neither was ever isolated at an Ebola Treatment Unit (ETU). In total, 18 secondary cases (17 confirmed, one probable), including three deaths (17%), were linked to Patient A; 33 secondary cases (all confirmed), including 14 (42%) deaths, were linked to Patient B. Secondary cases linked to Patient A included family members, neighbours, and contacts at health facilities, including healthcare workers. Those linked to Patient B included healthcare workers, friends, and family members who interacted with him throughout his illness, prayed over him while he was nearing death, or exhumed his body. Intensive community engagement and awareness-building were initiated based on narratives collected about patients A and B; 49 (96%) of the secondary cases were isolated in an ETU, a median of three days after onset. Only nine tertiary cases were linked to the 51 secondary cases. Sequencing suggested plausible direct transmission from the SSPs to 37 of 39 secondary cases with sequence data. CONCLUSION: Extended time in the community while ill, social interactions, cross-district travel for treatment, and religious practices contributed to SVD super-spreading. Intensive community engagement and awareness may have reduced the number of tertiary infections. Intensive follow-up of contacts of case-patients may help reduce the impact of super-spreading events.

Infrequent fractures and resilient bone mineral density: bone health in patients with Fanconi anemia.

Not available.

Individual and household risk factors for Ebola disease among household contacts in Mubende and Kassanda districts, Uganda, 2022.

BACKGROUND: In 2022, an Ebola disease outbreak caused by Sudan virus (SUDV) occurred in Uganda, primarily affecting Mubende and Kassanda districts. We determined risk factors for SUDV infection among household members (HHM) of cases. METHODS: We conducted a case-control and retrospective cohort study in January 2023. Cases were RT-PCR-confirmed SUDV infection in residents of Mubende or Kassanda districts during the outbreak. Case-households housed a symptomatic, primary case-patient for ≥ 24 h and had ≥ 1 secondary case-patient with onset < 2 weeks after their last exposure to the primary case-patient. Control households housed a case-patient and other HHM but no secondary cases. A risk factor questionnaire was administered to the primary case-patient or another adult who lived at home while the primary case-patient was ill. We conducted a retrospective cohort study among case-household members and categorized their interactions with primary case-patients during their illnesses as none, minimal, indirect, and direct contact. We conducted logistic regression to explore associations between exposures and case-household status, and Poisson regression to identify risk factors for SUDV infection among HHM. RESULTS: Case- and control-households had similar median sizes. Among 19 case-households and 51 control households, primary case-patient death (adjusted odds ratio [ORadj] = 7.6, 95% CI 1.4-41) and ≥ 2 household bedrooms (ORadj=0.19, 95% CI 0.056-0.71) were associated with case-household status. In the cohort of 76 case-HHM, 44 (58%) were tested for SUDV < 2 weeks from their last contact with the primary case-patient; 29 (38%) were positive. Being aged ≥ 18 years (adjusted risk ratio [aRRadj] = 1.9, 95%CI: 1.01-3.7) and having direct or indirect contact with the primary case-patient (aRRadj=3.2, 95%CI: 1.1-9.7) compared to minimal or no contact increased risk of Sudan virus disease (SVD). Access to a handwashing facility decreased risk (aRRadj=0.52, 95%CI: 0.31-0.88). CONCLUSION: Direct contact, particularly providing nursing care for and sharing sleeping space with SVD patients, increased infection risk among HHM. Risk assessments during contact tracing may provide evidence to justify closer monitoring of some HHM. Health messaging should highlight the risk of sharing sleeping spaces and providing nursing care for persons with Ebola disease symptoms and emphasize hand hygiene to aid early case identification and reduce transmission.

The 2023 Latin America report of the Lancet Countdown on health and climate change: the imperative for health-centred climate-resilient development.

In 2023, a series of climatological and political events unfolded, partly driving forward the global climate and health agenda while simultaneously exposing important disparities and vulnerabilities to climate-related events. On the policy front, a significant step forward was marked by the inaugural Health Day at COP28, acknowledging the profound impacts of climate change on health. However, the first-ever Global Stocktake showed an important gap between the current progress and the targets outlined in the Paris Agreement, underscoring the urgent need for further and decisive action. From a Latin American perspective, some questions arise: How do we achieve the change that is needed? How to address the vulnerabilities to climate change in a region with long-standing social inequities? How do we promote intersectoral collaboration to face a complex problem such as climate change? The debate is still ongoing, and in many instances, it is just starting. The renamed regional centre Lancet Countdown Latin America (previously named Lancet Countdown South America) expanded its geographical scope adding Mexico and five Central American countries: Costa Rica, El Salvador, Guatemala, Honduras, and Panama, as a response to the need for stronger collaboration in a region with significant social disparities, including research capacities and funding. The centre is an independent and multidisciplinary collaboration that tracks the links between health and climate change in Latin America, following the global Lancet Countdown's methodologies and five domains. The Lancet Countdown Latin America work hinges on the commitment of 23 regional academic institutions, United Nations agencies, and 34 researchers who generously contribute their time and expertise. Building from the first report, the 2023 report of the Lancet Countdown Latin America, presents 34 indicators that track the relationship between health and climate change up to 2022, aiming at providing evidence to public decision-making with the purpose of improving the health and wellbeing of Latin American populations and reducing social inequities through climate actions focusing on health. This report shows that Latin American populations continue to observe a growing exposure to changing climatic conditions. A warming trend has been observed across all countries in Latin America, with severe direct impacts. In 2022, people were exposed to ambient temperatures, on average, 0.38 °C higher than in 1986-2005, with Paraguay experiencing the highest anomaly (+1.9 °C), followed by Argentina (+1.2 °C) and Uruguay (+0.9 °C) (indicator 1.1.1). In 2013-2022, infants were exposed to 248% more heatwave days and people over 65 years old were exposed to 271% more heatwave days than in 1986-2005 (indicator 1.1.2). Also, compared to 1991-2000, in 2013-2022, there were 256 and 189 additional annual hours per person, during which ambient heat posed at least moderate and high risk of heat stress during light outdoor physical activity in Latin America, respectively (indicator 1.1.3). Finally, the region had a 140% increase in heat-related mortality from 2000-2009 to 2013-2022 (indicator 1.1.4). Changes in ecosystems have led to an increased risk of wildfires, exposing individuals to very or extremely high fire danger for more extended periods (indicator 1.2.1). Additionally, the transmission potential for dengue by Aedes aegypti mosquitoes has risen by 54% from 1951-1960 to 2013-2022 (indicator 1.3), which aligns with the recent outbreaks and increasing dengue cases observed across Latin America in recent months. Based on the 2023 report of the Lancet Countdown Latin America, there are three key messages that Latin America needs to further explore and advance for a health-centred climate-resilient development. Latin American countries require intersectoral public policies that simultaneously increase climate resilience, reduce social inequities, improve population health, and reduce greenhouse gas (GHG) emissions. The findings show that adaptation policies in Latin America remain weak, with a pressing need for robust vulnerability and adaptation (V&A) assessments to address climate risks effectively. Unfortunately, such assessments are scarce. Up to 2021, Brazil is the only country that has completed and officially reported a V&A to the 2021 Global Survey conducted by the World Health Organization (WHO). Argentina, Guatemala, and Panama have also conducted them, but they have not been reported (indicator 2.1.1). Similarly, efforts in developing and implementing Health National Adaptation Plans (HNAPs) are varied and limited in scope. Brazil, Chile, and Uruguay are the only countries that have an HNAP (indicator 2.1.2). Moreover, self-reported city-level climate change risk assessments are very limited in the region (indicator 2.1.3). The collaboration between meteorological and health sectors remains insufficient, with only Argentina, Brazil, Colombia, and Guatemala self-reporting some level of integration (indicator 2.2.1), hindering comprehensive responses to climate-related health risks in the region. Additionally, despite the urgent need for action, there has been minimal progress in increasing urban greenspaces across the region since 2015, with only Colombia, Nicaragua, and Venezuela showing slight improvements (indicator 2.2.2). Compounding these challenges is the decrease in funding for climate change adaptation projects in Latin America, as evidenced by the 16% drop in funds allocated by the Green Climate Fund (GCF) in 2022 compared to 2021. Alarmingly, none of the funds approved in 2022 were directed toward climate change and health projects, highlighting a critical gap in addressing health-related climate risks (indicator 2.2.3). From a vulnerability perspective, the Mosquito Risk Index (MoRI) indicates an overall decrease in severe mosquito-borne disease risk in the region due to improvements in water, sanitation, and hygiene (WASH) (indicator 2.3.1). Brazil and Paraguay were the only countries that showed an increase in this indicator. It is worth noting that significant temporal variation within and between countries still persists, suggesting inadequate preparedness for climate-related changes. Overall, population health is not solely determined by the health sector, nor are climate policies a sole responsibility of the environmental sector. More and stronger intersectoral collaboration is needed to pave development pathways that consider solid adaptation to climate change, greater reductions of GHG emissions, and that increase social equity and population health. These policies involve sectors such as finance, transport, energy, housing, health, and agriculture, requiring institutional structures and policy instruments that allow long-term intersectoral collaboration. Latin American countries need to accelerate an energy transition that prioritises people's health and wellbeing, reduces energy poverty and air pollution, and maximises health and economic gains. In Latin America, there is a notable disparity in energy transition, with electricity generation from coal increasing by an average of 2.6% from 1991-2000 to 2011-2020, posing a challenge to efforts aimed at phasing out coal (indicator 3.1.1). However, this percentage increase is conservative as it may not include all the fossil fuels for thermoelectric electricity generation, especially during climate-related events and when hydropower is affected (Panel 4). Yet, renewable energy sources have been growing, increasing by an average of 5.7% during the same period. Access to clean fuels for cooking remains a concern, with 46.3% of the rural population in Central America and 23.3% in South America lacking access to clean fuels in 2022 (indicator 3.1.2). It is crucial to highlight the concerning overreliance on fossil fuels, particularly liquefied petroleum gas (LPG), as a primary cooking fuel. A significant majority of Latin American populations, approximately 74.6%, rely on LPG for cooking. Transitioning to cleaner heating and cooking alternatives could also have a health benefit by reducing household air pollution-related mortality. Fossil fuels continue to dominate road transport energy in Latin America, accounting for 96%, although some South American countries are increasing the use of biofuels (indicator 3.1.3). Premature mortality attributable to fossil-fuel-derived PM2.5 has shown varied trends across countries, increasing by 3.9% from 2005 to 2020 across Latin America, which corresponds to 123.5 premature deaths per million people (indicator 3.2.1). The Latin American countries with the highest premature mortality rate attributable to PM2.5 in 2020 were Chile, Peru, Brazil, Colombia, Mexico, and Paraguay. Of the total premature deaths attributable to PM2.5 in 2020, 19.1% was from transport, 12.3% from households, 11.6% from industry, and 11% from agriculture. From emission and capture of GHG perspective, commodity-driven deforestation and expansion of agricultural land remain major contributors to tree cover loss in the region, accounting for around 80% of the total loss (indicator 3.3). Additionally, animal-based food production in Latin America contributes 85% to agricultural CO2 equivalent emissions, with Argentina, Brazil, Panama, Paraguay, and Uruguay ranking highest in per capita emissions (indicator 3.4.1). From a health perspective, in 2020, approximately 870,000 deaths were associated with imbalanced diets, of which 155,000 (18%) were linked to high intake of red and processed meat and dairy products (indicator 3.4.2). Energy transition in Latin America is still in its infancy, and as a result, millions of people are currently exposed to dangerous levels of air pollution and energy poverty (i.e., lack of access to essential energy sources or services). As shown in this report, the levels of air pollution, outdoors and indoors, are a significant problem in the wholeregion, with marked disparities between urban and rural areas. In 2022, Peru, Chile, Mexico, Guatemala, Colombia, El Salvador, Brazil, Uruguay, Honduras, Panama, and Nicaragua were in the top 100 most polluted countries globally. Transitioning to cleaner sources of energy, phasing out fossil fuels, and promoting better energy efficiency in the industrial and housing sectors are not only climate mitigation measures but also huge health and economic opportunities for more prosperous and healthy societies. Latin American countries need to increase climate finance through permanent fiscal commitments and multilateral development banks to pave climate-resilient development pathways. Climate change poses significant economic costs, with investments in mitigation and adaptation measures progressing slowly. In 2022, economic losses due to weather-related extreme events in Latin America were US$15.6 billion -an amount mainly driven by floods and landslides in Brazil-representing 0.28% of Latin America's Gross Domestic Product (GDP) (indicator 4.1.1). In contrast to high-income countries, most of these losses lack insurance coverage, imposing a substantial financial strain on affected families and governments. Heat-related mortality among individuals aged 65 and older in Latin America reached alarming levels, with losses exceeding the equivalent of the average income of 451,000 people annually (indicator 4.1.2). Moreover, the total potential income loss due to heat-related labour capacity reduction amounted to 1.34% of regional GDP, disproportionately affecting the agriculture and construction sectors (indicator 4.1.3). Additionally, the economic toll of premature mortality from air pollution was substantial, equivalent to a significant portion of regional GDP (0.61%) (indicator 4.1.4). On a positive note, clean energy investments in the region increased in 2022, surpassing fossil fuel investments. However, in 2020, all countries reviewed continued to offer net-negative carbon prices, revealing fossil fuel subsidies totalling US$23 billion. Venezuela had the highest net subsidies relative to current health expenditure (123%), followed by Argentina (10.5%), Bolivia (10.3%), Ecuador (8.3%), and Chile (5.6%) (indicator 4.2.1). Fossil fuel-based energy is today more expensive than renewable energy. Fossil fuel burning drives climate change and damages the environment on which people depend, and air pollution derived from the burning of fossil fuels causes seven million premature deaths each year worldwide, along with a substantial burden of disease. Transitioning to sustainable, zero-emission energy sources, fostering healthier food systems, and expediting adaptation efforts promise not only environmental benefits but also significant economic gains. However, to implement mitigation and adaptation policies that also improve social wellbeing and prosperity, stronger and solid financial systems are needed. Climate finance in Latin American countries is scarce and strongly depends on political cycles, which threatens adequate responses to the current and future challenges. Progress on the climate agenda is lagging behind the urgent pace required. While engagement with the intersection of health and climate change is increasing, government involvement remains inadequate. Newspaper coverage of health and climate change has been on the rise, peaking in 2022, yet the proportion of climate change articles discussing health has declined over time (indicator 5.1). Although there has been significant growth in the number of scientific papers focusing on Latin America, it still represents less than 4% of global publications on the subject (indicator 5.3). And, while health was mentioned by most Latin American countries at the UN General Debate in 2022, only a few addressed the intersection of health and climate change, indicating a lack of awareness at the governmental level (indicator 5.4). The 2023 Lancet Countdown Latin America report underscores the cascading and compounding health impacts of anthropogenic climate change, marked by increased exposure to heatwaves, wildfires, and vector-borne diseases. Specifically, for Latin America, the report emphasises three critical messages: the urgent action to implement intersectoral public policies that enhance climate resilience across the region; the pressing need to prioritise an energy transition that focuses on health co-benefits and wellbeing, and lastly, that need for increasing climate finance by committing to sustained fiscal efforts and engaging with multilateral development banks. By understanding the problems, addressing the gaps, and taking decisive action, Latin America can navigate the challenges of climate change, fostering a more sustainable and resilient future for its population. Spanish and Portuguese translated versions of this Summary can be found in Appendix B and C, respectively. The full translated report in Spanish is available in Appendix D.

Chest x-ray has low sensitivity to detect silicosis in artificial stone benchtop industry workers.

BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.

Public Perceptions of Opioid Use for Chronic Non-Cancer Pain.

Background: Chronic non-cancer pain affects 20% of Americans. This is significantly impacted by the ongoing opioid crisis and reduced opioid dispensing. Public perceptions additionally shape pain management strategies. Purpose: This study explores public attitudes toward prescription opioids for chronic non-cancer pain. We aim to understand how public attitudes are influenced by the evolving opioid crisis and shifting opioid use patterns. Methods: In Michigan, 823 adults participated in a Qualtrics survey on attitudes toward nonmedical and medical prescription opioid use. Multivariable logistic regression was performed to identify factors associated with beliefs that doctors prescribe opioids for too long (Model 1) and chronic pain patients should transition to alternative treatments (Model 2). Results: About half (49.4%) of respondents believed doctors keep patients on prescription opioids for too long, while two-thirds (65.7%) agreed chronic pain patients should be tapered off medications. Knowing someone who misused opioids and perceptions of substance use (e.g. perceived risk of prescription opioid misuse, stigma toward chronic pain patients, perceived prevalence of prescription opioid misuse, and awareness of fentanyl) were associated with greater odds of believing doctors keep patients on opioids too long. Demographics (age and education), substance use histories and perceptions (e.g. perceived risk and stigma) were associated with greater odds of believing patients should be tapered off their medication. Conclusions: These findings inform strategies to correct public misperceptions, emphasizing the importance of personal experience, perceived risks, and stigmatization of chronic pain patients. This insight can guide effective pain management for those with chronic non-cancer pain.

Rapid antiretroviral therapy initiation following rollout of point-of-care early infant diagnosis testing, Uganda, 2018-2021.

BACKGROUND: Uganda Ministry of Health (MOH) recommends a first HIV DNA-PCR test at 4-6 weeks for early infant diagnosis (EID) of HIV-exposed infants (HEI) and immediate return of results. WHO recommends initiating antiretroviral therapy (ART) ≤ 7 days from HIV diagnosis. In 2019, MOH introduced point-of-care (POC) whole-blood EID testing in 33 health facilities and scaled up to 130 facilities in 2020. We assessed results turnaround time and ART linkage pre-POC and during POC testing. METHODS: We evaluated EID register data for HEI at 10 health facilities with POC and EID testing volume of ≥ 12 infants/month from 2018 to 2021. We abstracted data for 12 months before and after POC testing rollout and compared time to sample collection, results receipt, and ART initiation between periods using medians, Wilcoxon, and log-rank tests. RESULTS: Data for 4.004 HEI were abstracted, of which 1.685 (42%) were from the pre-POC period and 2.319 (58%) were from the period during POC; 3.773 (94%) had a first EID test (pre-POC: 1.649 [44%]; during POC: 2.124 [56%]). Median age at sample collection was 44 (IQR 38-51) days pre-POC and 42 (IQR 33-50) days during POC (p < 0.001). Among 3.773 HEI tested, 3.678 (97%) had test results. HIV-positive infants' (n = 69) median age at sample collection was 94 (IQR 43-124) days pre-POC and 125 (IQR 74-206) days during POC (p = 0.04). HIV positivity rate was 1.6% (27/1.617) pre-POC and 2.0% (42/2.061) during POC (p = 0.43). For all infants, median days from sample collection to results receipt by infants' caregivers was 28 (IQR 14-52) pre-POC and 1 (IQR 0-25) during POC (p < 0.001); among HIV-positive infants, median days were 23 (IQR 7-30) pre-POC and 0 (0-3) during POC (p < 0.001). Pre-POC, 4% (1/23) HIV-positive infants started ART on the sample collection day compared to 33% (12/37) during POC (p < 0.001); ART linkage ≤ 7 days from HIV diagnosis was 74% (17/23) pre-POC and 95% (35/37) during POC (p < 0.001). CONCLUSION: POC testing improved EID results turnaround time and ART initiation for HIV-positive infants. While POC testing expansion could further improve ART linkage and loss to follow-up, there is need to explore barriers around same-day ART initiation for infants receiving POC testing.

Uncommon BK polyomaviruses detected in allogeneic hematopoietic cell transplant recipients.

The role of viral diversity in the pathogenesis of BK polyomavirus (BKPyV)-associated disease is poorly understood. Here, we report near full-length BKPyV genome sequences from two allogeneic hematopoietic cell transplant recipients infected with BKPyV genotype II, which is uncommon in the USA.

Household Air Pollution Interventions to Improve Health in Low- and Middle-Income Countries: An Official American Thoracic Society Research Statement.

Background: An estimated 3 billion people, largely in low- and middle-income countries, rely on unclean fuels for cooking, heating, and lighting to meet household energy needs. The resulting exposure to household air pollution (HAP) is a leading cause of pneumonia, chronic lung disease, and other adverse health effects. In the last decade, randomized controlled trials of clean cooking interventions to reduce HAP have been conducted. We aim to provide guidance on how to interpret the findings of these trials and how they should inform policy makers and practitioners.Methods: We assembled a multidisciplinary working group of international researchers, public health practitioners, and policymakers with expertise in household air pollution from within academia, the American Thoracic Society, funders, nongovernmental organizations, and global organizations, including the World Bank and the World Health Organization. We performed a literature search, convened four sessions via web conference, and developed consensus conclusions and recommendations via the Delphi method.Results: The committee reached consensus on 14 conclusions and recommendations. Although some trials using cleaner-burning biomass stoves or cleaner-cooking fuels have reduced HAP exposure, the committee was divided (with 55% saying no and 45% saying yes) on whether the studied interventions improved measured health outcomes.Conclusions: HAP is associated with adverse health effects in observational studies. However, it remains unclear which household energy interventions reduce exposure, improve health, can be scaled, and are sustainable. Researchers should engage with policy makers and practitioners working to scale cleaner energy solutions to understand and address their information needs.

Time to care and factors influencing appropriate Sudan virus disease care among case patients in Uganda, September to November 2022.

OBJECTIVES: Early isolation and care for Ebola disease patients at Ebola Treatment Units (ETU) curb outbreak spread. We evaluated time to ETU entry and associated factors during the 2022 Sudan virus disease (SVD) outbreak in Uganda. METHODS: We included persons with RT-PCR-confirmed SVD with onset September 20-November 30, 2022. We categorized days from symptom onset to ETU entry ("delays") as short (≤2), moderate (3-5), and long (≥6); the latter two were "delayed isolation." We categorized symptom onset timing as "earlier" or "later," using October 15 as a cut-off. We assessed demographics, symptom onset timing, and awareness of contact status as predictors for delayed isolation. We explored reasons for early vs late isolation using key informant interviews. RESULTS: Among 118 case-patients, 25 (21%) had short, 43 (36%) moderate, and 50 (43%) long delays. Seventy-five (64%) had symptom onset later in the outbreak. Earlier symptom onset increased risk of delayed isolation (crude risk ratio = 1.8, 95% confidence interval (1.2-2.8]). Awareness of contact status and SVD symptoms, and belief that early treatment-seeking was lifesaving facilitated early care-seeking. Patients with long delays reported fear of ETUs and lack of transport as contributors. CONCLUSION: Delayed isolation was common early in the outbreak. Strong contact tracing and community engagement could expedite presentation to ETUs.

Cooking with liquefied petroleum gas or biomass and fetal growth outcomes: a multi-country randomised controlled trial.

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. We conducted ultrasound assessments at baseline, 24-28 weeks of gestation (the first pregnancy visit), and 32-36 weeks of gestation (the second pregnancy visit), to measure fetal size; we monitored 24 h personal exposures to household air pollutants during these visits; and we weighed children at birth. We conducted intention-to-treat analyses to estimate differences in fetal size between the intervention and control group, and exposure-response analyses to identify associations between household air pollutants and fetal size. This trial is registered with ClinicalTrials.gov (NCT02944682). FINDINGS: Between May 7, 2018, and Feb 29, 2020, we randomly assigned 3200 pregnant women (1593 to the intervention group and 1607 to the control group). The mean gestational age was 14·5 (SD 3·0) weeks and mean maternal age was 25·6 (4·5) years. We obtained ultrasound assessments in 3147 (98·3%) women at baseline, 3052 (95·4%) women at the first pregnancy visit, and 2962 (92·6%) at the second pregnancy visit, through to Aug 25, 2020. Intervention adherence was high (the median proportion of days with biomass stove use was 0·0%, IQR 0·0-1·6) and pregnant women in the intervention group had lower mean exposures to particulate matter with a diameter less than 2·5 µm (PM2·5; 35·0 [SD 37·2] µg/m3vs 103·3 [97·9] µg/m3) than did women in the control group. We did not find differences in averaged post-randomisation Z scores for head circumference (0·30 vs 0·39; p=0·04), abdominal circumference (0·38 vs 0·39; p=0·99), femur length (0·44 vs 0·45; p=0·73), and estimated fetal weight or birthweight (-0·13 vs -0·12; p=0·70) between the intervention and control groups. Personal exposures to household air pollutants were not associated with fetal size. INTERPRETATION: Although an LPG cooking intervention successfully reduced personal exposure to air pollution during pregnancy, it did not affect fetal size. Our findings do not support the use of unvented liquefied petroleum gas stoves as a strategy to increase fetal growth in settings were biomass fuels are used predominantly for cooking. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Kinyarwanda, Spanish and Tamil translations of the abstract see Supplementary Materials section.

Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant.

Reactivation or primary infection with double-stranded DNA viruses is common in recipients of solid organ transplants (SOTs) and is associated with significant morbidity and mortality. Treatment with conventional antiviral medications is limited by toxicities, resistance, and a lack of effective options for adenovirus (ADV) and BK polyomavirus (BKPyV). Virus-specific T cells (VSTs) have been shown to be an effective treatment for infections with ADV, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients, and no large studies have been published in the SOT population to date. In this study, we report on the outcome of quadrivalent third-party VST infusions in 98 recipients of SOTs in the context of an open-label phase 2 trial. The 98 patients received a total of 181 infusions, with a median of 2 infusions per patient. The overall response rate was 45% for BKPyV, 65% for cytomegalovirus, 68% for ADV, and 61% for Epstein-Barr virus. Twenty percent of patients with posttransplant lymphoproliferative disorder had a complete response and 40% of patients had a partial response. All the VST infusions were well tolerated. We conclude that VSTs are safe and effective in the treatment of viral infections in SOT recipients.

Trajectory of Sleep, Depression, and Quality of Life in Pediatric HSCT Recipients.

Disrupted sleep is commonly reported during hematopoietic stem cell transplant. In this study, we use actigraphy to measure sleep parameters, and qualitative measures of quality of life, depression, and sleep in pediatric and young adult transplant recipients to describe their time course through transplant. Eight patients had evaluable actigraphy data, and 10 patients completed the surveys. The median age of the 6 male and 7 female participants was 13.94 years old. Sleep duration and efficiency measured by actigraphy were suboptimal prior to transplant, then declined to a nadir between Day +7 to +14. Self-reported sleep quality, depression, and quality of life were worst at Day +14 to +30 but improved by Day +100. Findings support efforts to improve sleep, which may improve recovery, mental health and quality of life.

Attitudes toward medications for opioid use disorder among peer recovery specialists.

Background: Peer recovery specialists (PRSs) are substance use service providers with lived experience in recovery. Although a large body of research demonstrates the efficacy of medications for opioid use disorder (MOUD), emerging research suggests PRSs' attitudes toward MOUD are ambivalent or mixed. Few studies have quantitatively assessed factors influencing PRSs' attitudes.Objectives: This study identifies personal and professional characteristics associated with attitudes toward MOUD among PRSs.Methods: PRSs working at publicly funded agencies in Michigan completed a self-administered web-based survey (N = 266, 60.5% women). Surveys assessed socio-demographics, treatment and recovery history, attitudes toward clients, and attitudes toward MOUD. Multiple linear regression was used to identify factors associated with attitudes toward MOUD.Results: A minority of PRSs (21.4%) reported a history of treatment with MOUD, while nearly two-thirds reported current 12-step involvement (62.5%). Compared to PRSs without a history of MOUD treatment, PRSs who had positive (b = 4.71, p < .001) and mixed (b = 3.36, p = .010) experiences with MOUD had more positive attitudes; PRSs with negative experiences with MOUD had less positive attitudes (b = -3.16, p = .003). Current 12-step involvement (b = -1.63, p = .007) and more stigmatizing attitudes toward clients (b = -.294, p < .001) were associated with less positive attitudes toward MOUD. Black PRSs had less positive attitudes than White PRSs (b = -2.50, p = .001), and women had more positive attitudes than men (b = 1.19, p = .038).Conclusion: PRSs' attitudes toward MOUD varied based on the nature of their lived experience. Findings highlight considerations for training and supervising PRSs who serve individuals with opioid use disorder.

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Trends and geospatial distribution of stillbirths in Uganda, 2014-2020.

INTRODUCTION: Uganda with 17.8 stillbirths per 1,000 deliveries in 2021, is among the countries with a high burden of stillbirths globally. In 2014, Uganda adopted the World Health Organization Every New-born Action Plan (ENAP), which targets < 10 stillbirths per 1,000 deliveries by 2035. Little is known about the trends of stillbirth burden since ENAP was introduced. We assessed the temporal, and spatial distribution of stillbirths, in Uganda, 2014-2020, to inform programming for safe pregnancies and deliveries. METHODS: We obtained and analysed stillbirth surveillance data from the District Health Information System, 2014-2020. A stillbirth was defined as the death of a foetus > 28 weeks of pregnancy or weighing > 1000 g before or during birth and reported to a health facility. We calculated annual incidence rates of stillbirths per 1,000 deliveries at district, regional, and national levels. We used logistic regression to determine the significance of trends. RESULTS: The overall national annual incidence of stillbirths decreased from 24/1,000 deliveries in 2014 to 17/1,000 deliveries in 2020. During the same period, reporting rates declined from 71% in 2014 to 46% in 2020. The central region continuously had the highest incidence rate for the past 5 years despite the largest decline (OR = 0.79; CI = 0.77-0.83, P < 0.001) while the eastern region had the smallest decline (OR = 0.59; CI = 0.57-0.61, P < 0.001). Districts with persistently high annual incidence rates of stillbirths (> 30/1000) included Mubende, Kalangala, Hoima, and Nebbi. There was no difference in the reporting rates of the most- vs. least-affected districts. CONCLUSION: Even with suboptimal reporting, the incidence of stillbirths remained above the national target. Specific areas in the country appear to have particularly high stillbirth rates. We recommend continuous capacity building in managing pregnant women with an emphasis on the most affected districts, and investigation into the reasons for low reporting.