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.

Accuracy of Noninvasive Blood Pressure Monitoring in Critically Ill Adults.

Background: Blood pressure (BP) is routinely invasively monitored by an arterial catheter in the intensive care unit (ICU). However, the available data comparing the accuracy of noninvasive methods to arterial catheters for measuring BP in the ICU are limited by small numbers and diverse methodologies. Purpose: To determine agreement between invasive arterial blood pressure monitoring (IABP) and noninvasive blood pressure (NIBP) in critically ill patients. Methods: This was a single center, observational study of critical ill adults in a tertiary care facility evaluating agreement (≤10% difference) between simultaneously measured IABP and NIBP. We measured clinical features at time of BP measurement inclusive of patient demographics, laboratory data, severity of illness, specific interventions (mechanical ventilation and dialysis), and vasopressor dose to identify particular clinical scenarios in which measurement agreement is more or less likely. Results: Of the 1852 critically ill adults with simultaneous IABP and NIBP readings, there was a median difference of 6 mm Hg in mean arterial pressure (MAP), interquartile range (1-12), P < .01. A logistic regression analysis identified 5 independent predictors of measurement discrepancy: increasing doses of norepinephrine (adjusted odds ratio [aOR] 1.10 [95% confidence interval, CI 1.08-1.12] P = .03 for every change in 5 µg/min), lower MAP value (aOR 0.98 [0.98-0.99] P < .01 for every change in 1 mm Hg), higher body mass index (aOR 1.04 [1.01-1.09] P = .01 for an increase in 1), increased patient age (aOR 1.31 [1.30-1.37] P < .01 for every 10 years), and radial arterial line location (aOR 1.74 [1.16-2.47] P = .04). Conclusions: There was broad agreement between IABP and NIBP in critically ill patients over a range of BPs and severity of illness. Several variables are associated with measurement discrepancy; however, their predictive capacity is modest. This may guide future study into which patients may specifically benefit from an arterial catheter.

Liquefied Petroleum Gas or Biomass Cooking and Severe Infant Pneumonia.

BACKGROUND: Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS: We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS: Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM2.5 among the children, with a median exposure of 24.2 µg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 µg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS: The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Effects of a household air pollution intervention using liquefied petroleum gas stoves, continuous fuel distribution and behavioural messaging on dietary and sodium intake of adult women in Puno, Peru: a randomised controlled trial.

OBJECTIVE: Household air pollution (HAP) is a widespread environmental exposure worldwide. While several cleaner fuel interventions have been implemented to reduce personal exposures to HAP, it is unclear if cooking with cleaner fuels also affects the choice of meals and dietary intake. DESIGN: Individually randomised, open-label controlled trial of a HAP intervention. We aimed to determine the effect of a HAP intervention on dietary and Na intake. Intervention participants received a liquefied petroleum gas (LPG) stove, continuous fuel delivery and behavioural messaging during 1 year whereas control participants continued with usual cooking practices that involved the use of biomass-burning stoves. Dietary outcomes included energy, energy-adjusted macronutrients and Na intake at baseline, 6 months and 12 months post-randomisation using 24-h dietary recalls and 24-h urine. We used t-tests to estimate differences between arms in the post-randomisation period. SETTING: Rural settings in Puno, Peru. PARTICIPANTS: One hundred women aged 25-64 years. RESULTS: At baseline, control and intervention participants were similar in age (47·4 v. 49·5 years) and had similar daily energy (8894·3 kJ v. 8295·5 kJ), carbohydrate (370·8 g v. 373·3 g) and Na intake (4·9 g v. 4·8 g). One year after randomisation, we did not find differences in average energy intake (9292·4 kJ v. 8788·3 kJ; P = 0·22) or Na intake (4·5 g v. 4·6 g; P = 0·79) between control and intervention participants. CONCLUSIONS: Our HAP intervention consisting of an LPG stove, continuous fuel distribution and behavioural messaging did not affect dietary and Na intake in rural Peru.

Lung Ultrasound Protocol and Quality Control of Image Interpretation Using an Adjudication Panel in the Household Air Pollution Intervention Network (HAPIN) Trial.

OBJECTIVE: Lung ultrasound (LUS) is an alternative to chest radiography to confirm a diagnosis of pneumonia. For research and disease surveillance, methods to use LUS to diagnose pneumonia are needed. METHODS: In the Household Air Pollution Intervention Network (HAPIN) trial, LUS was used to confirm a clinical diagnosis of severe pneumonia in infants. We developed a standardized definition of pneumonia, protocols for recruitment and training of sonographers, along with LUS image acquisition and interpretation. We use a blinded panel approach to interpretation with LUS cine-loops randomized to non-scanning sonographers with expert review. DISCUSSION: We obtained 357 lung ultrasound scans: 159, 8 and 190 scans were collected in Guatemala, Peru and Rwanda, respectively. The diagnosis of primary endpoint pneumonia (PEP) required an expert tie breaker in 181 scans (39%). PEP was diagnosed in 141 scans (40%), not diagnosed in 213 (60%), with 3 scans (<1%) deemed uninterpretable. Agreement among the two blinded sonographers and the expert reader in Guatemala, Peru and Rwanda was 65%, 62% and 67%, with a prevalence-and-bias-corrected kappa of 0.30, 0.24 and 0.33, respectively. CONCLUSION: Use of standardized imaging protocols, training and an adjudication panel resulted in high confidence for the diagnosis of pneumonia using LUS.

Health, social, and economic characteristics of patients enrolled in a COVID-19 recovery program.

At least one in five people who recovered from acute COVID-19 have persistent clinical symptoms, however little is known about the impact on quality-of-life (QOL), socio-economic characteristics, fatigue, work and productivity. We present a cross-sectional descriptive characterization of the clinical symptoms, QOL, socioeconomic characteristics, fatigue, work and productivity of a cohort of patients enrolled in the MedStar COVID Recovery Program (MSCRP). Our participants include people with mental and physical symptoms following recovery from acute COVID-19 and enrolled in MSCRP, which is designed to provide comprehensive multidisciplinary care and aid in recovery. Participants completed medical questionnaires and the PROMIS-29, Fatigue Severity Scale, Work and Productivity Impairment Questionnaire, and Social Determinants of Health surveys. Participants (n = 267, mean age 47.6 years, 23.2% hospitalized for COVID-19) showed impaired QOL across all domains assessed with greatest impairment in physical functioning (mean 39.1 ± 7.4) and fatigue (mean 60.6 ±. 9.7). Housing or "the basics" were not afforded by 19% and food insecurity was reported in 14% of the cohort. Participants reported elevated fatigue (mean 4.7 ± 1.1) and impairment with activity, work productivity, and on the job effectiveness was reported in 63%, 61%, and 56% of participants, respectively. Patients with persistent mental and physical symptoms following initial illness report impairment in QOL, socioeconomic hardships, increased fatigue and decreased work and productivity. Our cohort highlights that even those who are not hospitalized and recover from less severe COVID-19 can have long-term impairment, therefore designing, implementing, and scaling programs to focus on mitigating impairment and restoring function are greatly needed.

Economic Evaluation of Ultrasound-guided Central Venous Catheter Confirmation vs Chest Radiography in Critically Ill Patients: A Labor Cost Model.

INTRODUCTION: Despite evidence suggesting that point-of-care ultrasound (POCUS) is faster and non-inferior for confirming position and excluding pneumothorax after central venous catheter (CVC) placement compared to traditional radiography, millions of chest radiographs (CXR) are performed annually for this purpose. Whether the use of POCUS results in cost savings compared to CXR is less clear but could represent a relative advantage in implementation efforts. Our objective in this study was to evaluate the labor cost difference for POCUS-guided vs CXR-guided CVC position confirmation practices. METHODS: We developed a model to evaluate the per patient difference in labor cost between POCUS-guided vs CXR-guided CVC confirmation at our local urban, tertiary academic institution. We used internal cost data from our institution to populate the variables in our model. RESULTS: The estimated labor cost per patient was $18.48 using CXR compared to $14.66 for POCUS, resulting in a net direct cost savings of $3.82 (21%) per patient using POCUS for CVC confirmation. CONCLUSION: In this study comparing the labor costs of two approaches for CVC confirmation, the more efficient alternative (POCUS-guided) is not more expensive than traditional CXR. Performing an economic analysis framed in terms of labor costs and work efficiency may influence stakeholders and facilitate earlier adoption of POCUS for CVC confirmation.

Cross-sectional analysis of the association between personal exposure to household air pollution and blood pressure in adult women: Evidence from the multi-country Household Air Pollution Intervention Network (HAPIN) trial.

Elevated blood pressure (BP) is a leading risk factor for the global burden of disease. Household air pollution (HAP), resulting from the burning of biomass fuels, may be an important cause of elevated BP in resource-poor communities. We examined the exposure-response relationship of personal exposures to HAP -fine particulate matter (PM2.5), carbon monoxide (CO), and black carbon (BC) - with BP measures in women aged 40-79 years across four resource-poor settings in Guatemala, Peru, India and Rwanda. BP was obtained within a day of 24-h personal exposure measurements at baseline, when participants were using biomass for cooking. We used generalized additive models to characterize the shape of the association between BP and HAP, accounting for the interaction of personal exposures and age and adjusting for a priori identified confounders. A total of 418 women (mean age 52.2 ± 7.9 years) were included in this analysis. The interquartile range of exposures to PM2.5 was 42.9-139.5 µg/m3, BC was 6.4-16.1 µg/m3, and CO was 0.5-2.9 ppm. Both SBP and PP were positively associated with PM2.5 exposure in older aged women, achieving statistical significance around 60 years of age. The exact threshold varied by BP measure and PM2.5 exposures being compared. For example, SBP of women aged 65 years was on average 10.8 mm Hg (95% CI 1.0-20.6) higher at 232 µg/m3 of PM2.5 exposure (90th percentile) when compared to that of women of the same age with personal exposures of 10 µg/m3. PP in women aged 65 years was higher for exposures ≥90 µg/m3, with mean differences of 6.1 mm Hg (95% CI 1.8-10.5) and 9.2 mm Hg (95% CI 3.3-15.1) at 139 (75th percentile) and 232 µg/m3 (90th percentile) respectively, when compared to that of women of the same age with PM2.5 exposures of 10 µg/m3. Our findings suggest that reducing HAP exposures may help to reduce BP, particularly among older women.

Facing the Realities of Pragmatic Design Choices in Environmental Health Studies: Experiences from the Household Air Pollution Intervention Network Trial.

Objective: Household Air Pollution Intervention Network (HAPIN) investigators tested a complex, non-pharmacological intervention in four low- and middle-income countries as a strategy to mitigate household air pollution and improve health outcomes across the lifespan. Intervention households received a liquefied petroleum gas (LPG) stove, continuous fuel delivery and regular behavioral reinforcements for 18 months, whereas controls were asked to continue with usual cooking practices. While HAPIN was designed as an explanatory trial to test the efficacy of the intervention on four primary outcomes, it introduced several pragmatic aspects in its design and conduct that resemble real-life conditions. We surveyed HAPIN investigators and asked them to rank what aspects of the design and conduct they considered were more pragmatic than explanatory. Methods: We used the revised Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2) to survey investigators on the degree of pragmatism in nine domains of trial design and conduct using a five-point Likert rank scale from very explanatory (1) to very pragmatic (5). We invited 103 investigators. Participants were given educational material on PRECIS-2, including presentations, papers and examples that described the use and implementation of PRECIS-2. Results: Thirty-five investigators (mean age 42 years, 51% female) participated in the survey. Overall, only 17% ranked all domains as very explanatory, with an average (±SD) rank of 3.2 ± 1.4 across domains. Fewer than 20% of investigators ranked eligibility, recruitment or setting as very explanatory. In contrast, ≥50% of investigators ranked the trial organization, delivery and adherence of the intervention and follow-up as very/rather explanatory whereas ≤17% ranked them as rather/very pragmatic. Finally, <25% of investigators ranked the relevance of outcomes to participants and analysis as very/rather explanatory whereas ≥50% ranked then as rather/very pragmatic. In-country partners were more likely to rank domains as pragmatic when compared to investigators working in central coordination (average rank 3.2 vs. 2.8, respectively; Wilcoxon rank-sum p < 0.001). Conclusion: HAPIN investigators did not consider their efficacy trial to be rather/very explanatory and reported that some aspects of the design and conduct were executed under real-world conditions; however, they also did not consider the trial to be overly pragmatic. Our analysis underscores the importance of using standardized tools such as PRECIS-2 to guide early discussions among investigators in the design of environmental health trials attempting to measure efficacy.

Resources and Geographic Access to Care for Severe Pediatric Pneumonia in Four Resource-limited Settings.

Rationale: Pneumonia is the leading cause of death in children worldwide. Identifying and appropriately managing severe pneumonia in a timely manner improves outcomes. Little is known about the readiness of healthcare facilities to manage severe pediatric pneumonia in low-resource settings. Objectives: As part of the HAPIN (Household Air Pollution Intervention Network) trial, we sought to identify healthcare facilities that were adequately resourced to manage severe pediatric pneumonia in Jalapa, Guatemala (J-GUA); Puno, Peru (P-PER); Kayonza, Rwanda (K-RWA); and Tamil Nadu, India (T-IND). We conducted a facility-based survey of available infrastructure, staff, equipment, and medical consumables. Facilities were georeferenced, and a road network analysis was performed. Measurements and Main Results: Of the 350 healthcare facilities surveyed, 13% had adequate resources to manage severe pneumonia, 37% had pulse oximeters, and 44% had supplemental oxygen. Mean (±SD) travel time to an adequately resourced facility was 41 ± 19 minutes in J-GUA, 99 ± 64 minutes in P-PER, 40 ± 19 minutes in K-RWA, and 31 ± 19 minutes in T-IND. Expanding pulse oximetry coverage to all facilities reduced travel time by 44% in J-GUA, 29% in P-PER, 29% in K-RWA, and 11% in T-IND (all P < 0.001). Conclusions: Most healthcare facilities in low-resource settings of the HAPIN study area were inadequately resourced to care for severe pediatric pneumonia. Early identification of cases and timely referral is paramount. The provision of pulse oximeters to all health facilities may be an effective approach to identify cases earlier and refer them for care and in a timely manner.

A risk assessment tool for resumption of research activities during the COVID-19 pandemic for field trials in low resource settings.

RATIONALE: The spread of severe acute respiratory syndrome coronavirus-2 has suspended many non-COVID-19 related research activities. Where restarting research activities is permitted, investigators need to evaluate the risks and benefits of resuming data collection and adapt procedures to minimize risk. OBJECTIVES: In the context of the multicountry Household Air Pollution Intervention (HAPIN) trial conducted in rural, low-resource settings, we developed a framework to assess the risk of each trial activity and to guide protective measures. Our goal is to maximize the integrity of reseach aims while minimizing infection risk based on the latest scientific understanding of the virus. METHODS: We drew on a combination of expert consultations, risk assessment frameworks, institutional guidance and literature to develop our framework. We then systematically graded clinical, behavioral, laboratory and field environmental health research activities in four countries for both adult and child subjects using this framework. National and local government recommendations provided the minimum safety guidelines for our work. RESULTS: Our framework assesses risk based on staff proximity to the participant, exposure time between staff and participants, and potential viral aerosolization while performing the activity. For each activity, one of four risk levels, from minimal to unacceptable, is assigned and guidance on protective measures is provided. Those activities that can potentially aerosolize the virus are deemed the highest risk. CONCLUSIONS: By applying a systematic, procedure-specific approach to risk assessment for each trial activity, we were able to protect our participants and research team and to uphold our ability to deliver on the research commitments we have made to our staff, participants, local communities, and funders. This framework can be tailored to other research studies conducted in similar settings during the current pandemic, as well as potential future outbreaks with similar transmission dynamics. The trial is registered with clinicaltrials.gov NCT02944682 on October 26. 2016 .

Ultrasound Core Laboratory for the Household Air Pollution Intervention Network Trial: Standardized Training and Image Management for Field Studies Using Portable Ultrasound in Fetal, Lung, and Vascular Evaluations.

Ultrasound Core Laboratories (UCL) are used in multicenter trials to assess imaging biomarkers to define robust phenotypes, to reduce imaging variability and to allow blinded independent review with the purpose of optimizing endpoint measurement precision. The Household Air Pollution Intervention Network, a multicountry randomized controlled trial (Guatemala, Peru, India and Rwanda), evaluates the effects of reducing household air pollution on health outcomes. Field studies using portable ultrasound evaluate fetal, lung and vascular imaging endpoints. The objective of this report is to describe administrative methods and training of a centralized clinical research UCL. A comprehensive administrative protocol and training curriculum included standard operating procedures, didactics, practical scanning and written/practical assessments of general ultrasound principles and specific imaging protocols. After initial online training, 18 sonographers (three or four per country and five from the UCL) participated in a 2 wk on-site training program. Written and practical testing evaluated ultrasound topic knowledge and scanning skills, and surveys evaluated the overall course. The UCL developed comprehensive standard operating procedures for image acquisition with a portable ultrasound system, digital image upload to cloud-based storage, off-line analysis and quality control. Pre- and post-training tests showed significant improvements (fetal ultrasound: 71% ± 13% vs. 93% ± 7%, p < 0.0001; vascular lung ultrasound: 60% ± 8% vs. 84% ± 10%, p < 0.0001). Qualitative and quantitative feedback showed high satisfaction with training (mean, 4.9 ± 0.1; scale: 1 = worst, 5 = best). The UCL oversees all stages: training, standardization, performance monitoring, image quality control and consistency of measurements. Sonographers who failed to meet minimum allowable performance were identified for retraining. In conclusion, a UCL was established to ensure accurate and reproducible ultrasound measurements in clinical research. Standardized operating procedures and training are aimed at reducing variability and enhancing measurement precision from study sites, representing a model for use of portable digital ultrasound for multicenter field studies.

Effects of a Household Air Pollution Intervention with Liquefied Petroleum Gas on Cardiopulmonary Outcomes in Peru. A Randomized Controlled Trial.

Rationale: Approximately 40% of people worldwide are exposed to household air pollution (HAP) from the burning of biomass fuels. Previous efforts to document health benefits of HAP mitigation have been stymied by an inability to lower emissions to target levels. Objectives: We sought to determine if a household air pollution intervention with liquefied petroleum gas (LPG) improved cardiopulmonary health outcomes in adult women living in a resource-poor setting in Peru. Methods: We conducted a randomized controlled field trial in 180 women aged 25-64 years living in rural Puno, Peru. Intervention women received an LPG stove, continuous fuel delivery for 1 year, education, and behavioral messaging, whereas control women were asked to continue their usual cooking practices. We assessed for stove use adherence using temperature loggers installed in both LPG and biomass stoves of intervention households. Measurements and Main Results: We measured blood pressure, peak expiratory flow (PEF), and respiratory symptoms using the St. George's Respiratory Questionnaire at baseline and at 3-4 visits after randomization. Intervention women used their LPG stove exclusively for 98% of days. We did not find differences in average postrandomization systolic blood pressure (intervention - control 0.7 mm Hg; 95% confidence interval, -2.1 to 3.4), diastolic blood pressure (0.3 mm Hg; -1.5 to 2.0), prebronchodilator peak expiratory flow/height2 (0.14 L/s/m2; -0.02 to 0.29), postbronchodilator peak expiratory flow/height2 (0.11 L/s/m2; -0.05 to 0.27), or St. George's Respiratory Questionnaire total score (-1.4; -3.9 to 1.2) over 1 year in intention-to-treat analysis. There were no reported harms related to the intervention. Conclusions: We did not find evidence of a difference in blood pressure, lung function, or respiratory symptoms during the year-long intervention with LPG. Clinical trial registered with www.clinicaltrials.gov (NCT02994680).

A Risk Assessment Tool for Resumption of Research Activities During the COVID-19 Pandemic.

RATIONALE: The spread of severe acute respiratory syndrome coronavirus-2 has suspended many non-COVID-19 related research activities. Where restarting research activities is permitted, investigators need to evaluate the risks and benefits of resuming data collection and adapt procedures to minimize risk. OBJECTIVES: In the context of the multicountry Household Air Pollution Intervention (HAPIN) trial, we developed a framework to assess the risk of each trial activity and to guide protective measures. Our goal is to maximize integrity of reseach aims while minimizing infection risk based on the latest understanding of the virus. METHODS: We drew on a combination of expert consultations, risk assessment frameworks, institutional guidance and literature to develop our framework. We then systematically graded clinical, behavioral, laboratory and field environmental health research activities in four countries for both adult and child subjects using this framework. RESULTS: Our framework assesses risk based on staff proximity to the participant, exposure time between staff and participants, and potential aerosolization while performing the activity. One of of four risk levels, from minimal to unacceptable, is assigned and guidance on protective measures is provided. Those activities which can potentially aerosolize the virus are deemed the highest risk. CONCLUSIONS: By applying a systematic, procedure-specific approach to risk assessment for each trial activity, we can compare trial activities using the same criteria. This approach allows us to protect our participants and research team and to uphold our ability to deliver on the research commitments we have made to our participants, local communities, and funders. The trial is registered with clinicaltrials.gov (NCT02944682).

Exploring the impact of a liquefied petroleum gas intervention on time use in rural Peru: A mixed methods study on perceptions, use, and implications of time savings.

BACKGROUND: Efforts to promote clean cooking through adoption of clean-burning fuels such as liquefied petroleum gas (LPG) are often based on the idea that near-exclusive use of LPG could lead to health improvements. However, benefits beyond health, such as time savings, could be more tangible and meaningful to LPG users. OBJECTIVES: This study investigated the effect of an LPG intervention on time spent cooking and collecting fuel, using objective measures of stove temperatures combined with self-reports under conditions of near-exclusive LPG use. We also investigated the perceived value of any time savings and potential economic and quality of life implications. METHODS: We analyzed data from the Cardiopulmonary outcomes and Household Air Pollution trial in Puno, Peru, a randomized controlled trial with 180 participants assessing exposure and health impacts of an LPG stove, fuel, and behavioral intervention. Surveys conducted with 90 intervention women receiving free LPG and 90 control women cooking primarily with biomass assessed time spent cooking and collecting biomass fuel and use of time savings. Cooking time was objectively measured with temperature sensors on all stoves. Qualitative interviews explored perceptions and use of time savings in more depth. RESULTS: Intervention women spent 3.2 fewer hours cooking and 1.9 fewer hours collecting fuel per week compared to control women, but cooked on average 1.0 more meals per day. Participants perceived time saved from LPG positively, reporting more time for household chores, leisure activities, and activities with income-generating potential such as caring for animals and working in fields. DISCUSSION: This paper suggests that the benefits of LPG extend beyond health and the environment. LPG use could also lead to economic and quality of life gains, through increased time for work, rest, and consumption of hot meals, and reduced arduous biomass fuel collection.

Indwelling Pleural Catheter Drainage Strategy for Malignant Effusion: A Cost-Effectiveness Analysis.

Rationale: The likelihood of achieving pleurodesis after indwelling pleural catheter (IPC) placement for malignant pleural effusion varies with the specific drainage strategy used: symptom-guided drainage, daily drainage, or talc instillation through the IPC (IPC + talc). The relative cost-effectiveness of one strategy over the other is unknown.Objectives: We performed a decision tree model-based analysis to ascertain the cost-effectiveness of each IPC drainage strategy from a healthcare system perspective.Methods: We developed a decision tree model using theoretical event probability data derived from three randomized clinical trials and used 2019 Medicare reimbursement data for cost estimation. The primary outcome was incremental cost-effectiveness ratio (ICER) over an analytical horizon of 6 months with a willingness-to-pay threshold of $100,000/quality-adjusted life-year (QALY). Monte Carlo probabilistic sensitivity analysis and one-way sensitivity analyses were conducted to measure the uncertainty surrounding base case estimates.Results: IPC + talc was a cost-effective alternative to symptom-guided drainage, with an ICER of $59,729/QALY. Monte Carlo probabilistic sensitivity analysis revealed that this strategy was favored in 54% of simulations. However, symptom-guided drainage was cost effective for pleurodesis rates >20% and for life expectancy <4 months. Daily drainage was not cost effective in any scenario, including for patients with nonexpandable lung, in whom it had an ICER of $2,474,612/QALY over symptom-guided drainage.Conclusions: For patients with malignant pleural effusion and an expandable lung, IPC + talc may be cost effective relative to symptom-guided drainage, although considerable uncertainty exists around this estimation. Daily IPC drainage is not a cost-effective strategy under any circumstance.

Design and conduct of facility-based surveillance for severe childhood pneumonia in the Household Air Pollution Intervention Network (HAPIN) trial.

Pneumonia is both a treatable and preventable disease but remains a leading cause of death in children worldwide. Household air pollution caused by burning biomass fuels for cooking has been identified as a potentially preventable risk factor for pneumonia in low- and middle-income countries. We are conducting a randomised controlled trial of a clean energy intervention in 3200 households with pregnant women living in Guatemala, India, Peru and Rwanda. Here, we describe the protocol to ascertain the incidence of severe pneumonia in infants born to participants during the first year of the study period using three independent algorithms: the presence of cough or difficulty breathing and hypoxaemia (≤92% in Guatemala, India and Rwanda and ≤86% in Peru); presence of cough or difficulty breathing along with at least one World Health Organization-defined general danger sign and consolidation on chest radiography or lung ultrasound; and pneumonia confirmed to be the cause of death by verbal autopsy. Prior to the study launch, we identified health facilities in the study areas where cases of severe pneumonia would be referred. After participant enrolment, we posted staff at each of these facilities to identify children enrolled in the trial seeking care for severe pneumonia. To ensure severe pneumonia cases are not missed, we are also conducting home visits to all households and providing education on pneumonia to the mother. Severe pneumonia reduction due to mitigation of household air pollution could be a key piece of evidence that sways policymakers to invest in liquefied petroleum gas distribution programmes.

Effects of high altitude on respiratory rate and oxygen saturation reference values in healthy infants and children younger than 2 years in four countries: a cross-sectional study.

BACKGROUND: In resource-limited settings, pneumonia diagnosis and management are based on thresholds for respiratory rate (RR) and oxyhaemoglobin saturation (SpO2) recommended by WHO. However, as RR increases and SpO2 decreases with elevation, these thresholds might not be applicable at all altitudes. We sought to determine upper thresholds for RR and lower thresholds for SpO2 by age and altitude at four sites, with altitudes ranging from sea level to 4348 m. METHODS: In this cross-sectional study, we enrolled healthy children aged 0-23 months who lived within the study areas in India, Guatemala, Rwanda, and Peru. Participants were excluded if they had been born prematurely (<37 weeks gestation); had a congenital heart defect; had history in the past 2 weeks of overnight admission to a health facility, diagnosis of pneumonia, antibiotic use, or respiratory or gastrointestinal signs; history in the past 24 h of difficulty breathing, fast breathing, runny nose, or nasal congestion; and current runny nose, nasal congestion, fever, chest indrawing, or cyanosis. We measured RR either automatically with the Masimo Rad-97, manually, or both, and measured SpO2 with the Rad-97. Trained staff measured RR in duplicate and SpO2 in triplicate in children who had no respiratory symptoms or signs in the past 2 weeks. We estimated smooth percentiles for RR and SpO2 that varied by age and site using generalised additive models for location, shape, and scale. We compared these data with WHO RR and SpO2 thresholds for tachypnoea and hypoxaemia to determine agreement. FINDINGS: Between Nov 24, 2017, and Oct 10, 2018, we screened 2027 children for eligibility. 335 were ineligible, leaving 1692 eligible participants. 30 children were excluded because of missing values and 92 were excluded because of measurement or data entry errors, leaving 1570 children in the final analysis. 404 participants were from India (altitude 1-919 m), 389 were from Guatemala (1036-2017 m), 341 from Rwanda (1449-1644 m), and 436 from Peru (3827-4348 m). Mean age was 7·2 months (SD 7·2) and 796 (50·7%) of 1570 participants were female. Although average age was mostly similar between settings, the average participant age in Rwanda was noticeably younger, at 5·5 months (5·9). In the 1570 children included in the analysis, mean RR was 31·9 breaths per min (SD 7·1) in India, 41·5 breaths per min in Guatemala (8·4), 44·0 breaths per min in Rwanda (10·8), and 48·0 breaths per min in Peru (9·4). Mean SpO2 was 98·3% in India (SD 1·5), 97·3% in Guatemala (2·4), 96·2% in Rwanda (2·6), and 89·7% in Peru (3·5). Compared to India, mean RR was 9·6 breaths per min higher in Guatemala, 12·1 breaths per min higher in Rwanda, and 16·1 breaths per min higher in Peru (likelihood ratio test p<0·0001). Smooth percentiles for RR and SpO2 varied by site and age. When we compared age-specific and site-specific 95th percentiles for RR and 5th percentiles for SpO2 against the WHO cutoffs, we found that the proportion of false positives for tachypnoea increased with altitude: 0% in India (95% CI 0-0), 7·3% in Guatemala (4·1-10·4), 16·8% in Rwanda (12·9-21·1), and 28·9% in Peru (23·7-33·0). We also found a high proportion of false positives for hypoxaemia in Peru (11·6%, 95% CI 7·0-14·7). INTERPRETATION: WHO cutoffs for fast breathing and hypoxaemia overlap with RR and SpO2 values that are normal for children in different altitudes. Use of WHO definitions for fast breathing could result in misclassification of pneumonia in many children who live at moderate to high altitudes and show acute respiratory signs. The 5th percentile for SpO2 was in reasonable agreement with the WHO definition of hypoxaemia in all regions except for Peru (the highest altitude site). Misclassifications could result in inappropriate management of paediatric respiratory illness and misdirection of potentially scarce resources such as antibiotics and supplemental oxygen. Future studies at various altitudes are needed to validate our findings and recommend a revision to current guidelines. Substantiating research in sick children is still needed. FUNDING: US National Institutes of Health, Bill & Melinda Gates Foundation.