Impact of randomly assigned "pay-as-you-go" liquefied petroleum gas prices on energy use for cooking: Experimental pilot evidence from rural Rwanda.

The disease burden related to air pollution from traditional solid-fuel cooking practices in low- and middle-income countries impacts millions of people globally. Although the use of liquefied petroleum gas (LPG) fuel for cooking can meaningfully reduce household air pollution concentrations, major barriers, including affordability and accessibility, have limited widespread adoption. Using a randomized controlled trial, our objective was to evaluate the association between the cost and use of LPG among 23 rural Rwandan households. We provided a 2-burner LPG stove with accessories and incorporated a "pay-as-you-go" (PAYG) LPG service model that included fuel delivery. PAYG services remove the large up-front cost of cylinder refills by integrating "smart meter" technology that allows participants to pay in incremental amounts, as needed. We assigned three randomized discounted prices for LPG to each household at ~4-week intervals over a 12-week period. We modeled the relationship between randomized PAYG LPG price and use (standardized to monthly periods), analyzing effect modification by relative household wealth. A 1000 Rwandan Franc (about 1 USD at the time of the study) increase in LPG price/kg was associated with a 4.1 kg/month decrease in use (95% confidence interval [CI]: -6.7, -1.6; n=69 observations). Wealth modified this association; we observed a 9.7 kg/month reduction (95% CI: -14.8, -4.5) among wealthier households and a 2.5 kg/month reduction (95% CI: -5.3, 0.3) among lower-wealth households (p-interaction=0.01). The difference in price sensitivity was driven by higher LPG use among wealthier households at more heavily discounted prices; from an 80% to 10% discount, wealthy households used 17.5 to 5.3 kg/month and less wealthy households used 6.2 to 3.1 kg/month. Our pilot-level experimental evidence of PAYG LPG in a rural low-resource setting suggests that further exploration of subsidized pricing varied by household wealth is needed to ensure future policy initiatives can achieve targets without exacerbating inequities.

Unaddressed Uncertainties When Scaling Regional Aircraft Emission Surveys to Basin Emission Estimates.

Wide-area aerial methods provide comprehensive screening of methane emissions from oil and gas (O & G) facilities in production basins. Emission detections ("plumes") from these studies are also frequently scaled to the basin level, but little is known regarding the uncertainties during scaling. This study analyzed an aircraft field study in the Denver-Julesburg basin to quantify how often plumes identified maintenance events, using a geospatial inventory of 12,629 O & G facilities. Study partners (7 midstream and production operators) provided the timing and location of 5910 maintenance events during the 6 week study period. Results indicated three substantial uncertainties with potential bias that were unaddressed in prior studies. First, plumes often detect maintenance events, which are large, short-duration, and poorly estimated by aircraft methods: 9.2 to 46% (38 to 52%) of plumes on production were likely known maintenance events. Second, plumes on midstream facilities were both infrequent and unpredictable, calling into question whether these estimates were representative of midstream emissions. Finally, 4 plumes attributed to O & G (19% of emissions detected by aircraft) were not aligned with any O & G location, indicating that the emissions had drifted downwind of some source. It is unclear how accurately aircraft methods estimate this type of plume; in this study, it had material impact on emission estimates. While aircraft surveys remain a powerful tool for identifying methane emissions on O & G facilities, this study indicates that additional data inputs, e.g., detailed GIS data, a more nuanced analysis of emission persistence and frequency, and improved sampling strategies are required to accurately scale plume estimates to basin emissions.

AirPen: A Wearable Monitor for Characterizing Exposures to Particulate Matter and Volatile Organic Compounds.

Exposure to air pollution is a leading risk factor for disease and premature death, but technologies for assessing personal exposure to particulate and gaseous air pollutants, including the timing and location of such exposures, are limited. We developed a small, quiet, wearable monitor, called the AirPen, to quantify personal exposures to fine particulate matter (PM2.5) and volatile organic compounds (VOCs). The AirPen combines physical sample collection (PM onto a filter and VOCs onto a sorbent tube) with a suite of low-cost sensors (for PM, VOCs, temperature, pressure, humidity, light intensity, location, and motion). We validated the AirPen against conventional personal sampling equipment in the laboratory and then conducted a field study to measure at-work and away-from-work exposures to PM2.5 and VOCs among employees at an agricultural facility in Colorado, USA. The resultant sampling and sensor data indicated that personal exposures to benzene, toluene, ethylbenzene, and xylenes were dominated by a specific workplace location. These results illustrate how the AirPen can be used to advance our understanding of personal exposure to air pollution as a function of time, location, source, and activity, even in the absence of detailed activity diary data.

Patient-reported impact of myasthenia gravis in the real world: findings from a digital observational survey-based study (MyRealWorld MG).

OBJECTIVES: This study aims to explore the impact of myasthenia gravis (MG) - in terms of treatments, side effects, comorbidities, psychological health and work or study- in the real world from a patient perspective. DESIGN AND PARTICIPANTS: This is a prospective, observational, digital, longitudinal study. Adults diagnosed with MG residing in the USA, Japan, Germany, the UK, Italy, Spain or Canada were eligible to participate in the study. There were no other exclusion criteria. Participants used a bespoke smartphone application to confirm eligibility, provide consent and enter data about their MG into a profile, a tracker to record MG-related events and a series of patient-reported outcome instruments. 1693 participants completed at least 1 survey and were included in this analysis. RESULTS: Results are presented as a percentage of respondents to each survey question. The study population was largely female (69% of 1586 respondents), with an average age of 49.9 years (SD 14.8). In the previous 12 months, 83.7% of 1412 respondents confirmed that they had received one or more routine treatments for MG, and 67.1% of 255 respondents confirmed that they had experienced a side effect in the previous month. Commonly experienced comorbidities reported by 966 respondents were thyroid problems, hypertension and anxiety, experienced by 37.5%, 31.4% and 28.0% of respondents, respectively.According to 889 respondents to the Hospital Anxiety and Depression Scale survey, 52.7% and 43.2% had a score indicative of at least mild anxiety and mild depression, respectively. Of 257 respondents, 33.0% reported experiencing a work or study impact in the past month. CONCLUSIONS: This analysis of baseline characteristics of the MyRealWorld MG study population indicates that, despite current treatments, patients experience notable burden. Further scheduled analyses will develop a longitudinal picture of MG burden. TRIAL REGISTRATION NUMBER: NCT04176211.

Factors affecting urinary organophosphate pesticide metabolite levels among Californian agricultural community members.

Organophosphate (OP) pesticides are widely used in California for agricultural pest and weed control despite their well-documented adverse health effects among infants, children, and adults. We sought to identify factors affecting urinary OP metabolites among families living in high-exposure communities. Our study included 80 children and adults who lived within 61 m (200 ft) of agricultural fields in the Central Valley of California in January and June 2019, which are pesticide non-spraying and spraying seasons, respectively. We collected one urine sample per participant during each visit to measure dialkyl phosphate (DAP) metabolites; these were coupled with in-person surveys to identify health, household, sociodemographic, pesticide exposure, and occupational risk factors. We used a data-driven, best subsets regression approach to identify key factors that influenced urinary DAPs. Participants were mostly Hispanic/Latino(a) (97.5 %), over half were female (57.5 %), and most households reported having a member who worked in agriculture (70.6 %). Among the 149 urine samples suitable for analysis, DAP metabolites were detected in 48.0 % and 40.5 % of samples during January and June, respectively. Total diethyl alkylphosphates (EDE) were only detected in 4.7 % (n = 7) of samples, but total dimethyl alkylphosphates (EDM) were detected in 41.6 % (n = 62) of samples. No differences were observed in urinary DAP levels by visit month or by occupational exposure to pesticides. Best subsets regression identified several individual- and household-level variables that influenced both urinary EDM and total DAPs: the number of years spent living at the current address, household use of chemical products to control mice/rodents, and seasonal employment status. Among adults only, we identified educational attainment (for total DAPs) and age category (for EDM) as significant factors. Our study found consistent urinary DAP metabolites among participants, regardless of spraying season, and identified potential mitigating factors that members of vulnerable populations can implement to protect their health against OP exposure.

Size-Resolved Field Performance of Low-Cost Sensors for Particulate Matter Air Pollution.

Particulate matter (PM) air pollution is a major health hazard. The health effects of PM are closely linked to particle size, which governs its deposition in (and penetration through) the respiratory tract. In recent years, low-cost sensors that report particle concentrations for multiple-sized fractions (PM1.0, PM2.5, PM10) have proliferated in everyday use and scientific research. However, knowledge of how well these sensors perform across the full range of reported particle size fractions is limited. Unfortunately, erroneous particle size data can lead to spurious conclusions about exposure, misguided interventions, and ineffectual policy decisions. We assessed the linearity, bias, and precision of three low-cost sensor models, as a function of PM size fraction, in an urban setting. Contrary to manufacturers' claims, sensors are only accurate for the smallest size fraction (PM1). The PM1.0-2.5 and PM2.5-10 size fractions had large bias, noise, and uncertainty. These results demonstrate that low-cost aerosol sensors (1) cannot discriminate particle size accurately and (2) only report linear and precise measures of aerosol concentration in the accumulation mode size range (i.e., between 0.1 and 1 µm). We recommend that crowdsourced air quality monitoring networks stop reporting coarse (PM2.5-10) mode and PM10 mass concentrations from these sensors.

Value-based performance arrangements for chronic conditions: an economic simulation of Medicaid Drug Rebate Program reforms.

OBJECTIVE: Changes to the Medicaid Drug Rebate Program (MDRP) determination of Medicaid Best Price (MBP) enables Value-based purchasing arrangements (VBPAs) to address financial uncertainty. This study estimates the likely effectiveness of MDRP-enabled VBPAs for chronically dosed medicines. METHODS: Monte Carlo simulations examined: Multiple Best Prices and Bundled Sales MBP approaches authorized under MDRP and a third National Pooling approach using payment misalignment; needed payer size for practical participation; and the resulting potential number of covered lives under a VBPA as evaluation metrics. RESULTS: Both Multiple Best Prices and National Pooling enable VBPAs for 95% of scenarios (including all 5i chronic products with ≥1,000 treated patients per year), with 75% of those with payment misalignment ≤9%. National pooling for retail drugs has less participation and worse misalignment (5i: 95% contracted, 75% ≤9% misalignment; retail: 71%, 66%). Bundled Sales performed worst (5i: 40%, 75% ≤9%; retail: 31%, 88%) due to rebate volatility risk of breaking best price and Average Manufacturer Price impact. Medicaid sees worse misalignment for the 60% drug performance scenarios because of comparison to the statutory rebate (23.1%). CONCLUSION: The Multiple Best Prices approach has the lowest misalignment and could be applied to most chronic therapies, even rare ones.

Patient-reported burden of myasthenia gravis: baseline results of the international prospective, observational, longitudinal real-world digital study MyRealWorld-MG.

OBJECTIVES: Myasthenia gravis (MG) is a rare, chronic, autoimmune neuromuscular disease which can affect functional and mental aspects of health and health-related quality of life (HRQoL). This study aims to obtain detailed knowledge of the impact of MG on HRQoL in a broad population from the perspective of the patient. DESIGN: Prospective, observational, digital, longitudinal real-world study. SETTING: Adult patients with MG from seven countries (USA, Japan, Germany, UK, Italy, Spain and Canada) downloaded a mobile application onto their phones and entered data about themselves and their MG. OUTCOME MEASURES: Data was collected using the following general and disease-specific patient-reported outcome measurements: EuroQol 5 Domains Health-Related Quality of Life Questionnaire (EQ-5D-5L), Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Quality of Life 15-item revised scale (MG-QoL-15r), Hospital Anxiety and Depression Scale (HADS) and Health Utilities Index III (HUI3). Patients were categorised by their self-assessed Myasthenia Gravis Foundation of America (MGFA) class (I-V). RESULTS: Baseline results of 841 participants (mean age 47 years, 70% women) are reported . The distribution across the MGFA classes was: 13.9%, 31.0%, 38.1%, 15.5% and 1.6% for classes I-V. The MGFA class was a strong predictor of all aspects of HRQoL, measured with disease-specific and with generic instruments. The domains in which patients with MG most frequently mentioned problems were usual activities, anxiety and depression, tiredness, breathing and vision. The mean total MG-ADL Score was positively associated with increasing MGFA classes: 2.7, 4.4, 6.3 and 8.4 for MGFA classes I-IV. Mean baseline EQ-5D-5L utility was also associated with MGFA classes and was 0.817, 0.766, 0.648 and 0.530 for MGFA class I-IV. CONCLUSIONS: MG has a large impact on key aspects of health and HRQoL. The impact of this disease increases substantially with increasing disease severity.

Medicaid best price reforms to enable innovative payment models for cell and gene therapies.

BACKGROUND: Cell and gene therapies promise durable benefits but face financial challenges from the uncertainty in their performance. Value-based purchasing arrangements (VBPAs) can address uncertainty but have been inhibited in the US by the Medicaid Drug Rebate Program (MDRP) approach to determining Medicaid Best Price (MBP) rebates. The likely effectiveness of MDRP reform proposals enabling VBPAs is examined in this study for durable cell and gene therapies. METHODS: Monte Carlo simulations examined three potential reforms (Multiple Best Prices, Bundled Sales, and National Pooling) to determine the impact on payment misalignment, the required payer size to participate, and the percentage of total lives covered by a VBPA. RESULTS: Simulation results suggest that 11% to 54% of commercial US lives would be feasibly covered by a VBPA depending on reform type and condition size. MPB reform achieved the highest commercial contracted percentage and lowest misalignment for commercial payers compared to National Pooling and Bundled Sales. State Medicaid plan results suggest lower extreme misalignment across all successfully contracted instances than commercial payers. CONCLUSIONS: The Multiple Best Prices will likely enable VBPAs for many durable cell and gene therapies and larger payers. Further reforms may be needed to extend VBPAs to ultra-orphan conditions.

Effects of household and participant characteristics on personal exposure and kitchen concentration of fine particulate matter and black carbon in rural Honduras.

Traditional cooking with solid fuels (biomass, animal dung, charcoals, coal) creates household air pollution that leads to millions of premature deaths and disability worldwide each year. Exposure to household air pollution is highest in low- and middle-income countries. Using data from a stepped-wedge randomized controlled trial of a cookstove intervention among 230 households in Honduras, we analyzed the impact of household and personal variables on repeated 24-h measurements of fine particulate matter (PM2.5) and black carbon (BC) exposure. Six measurements were collected approximately six-months apart over the course of the three-year study. Multivariable mixed models explained 37% of variation in personal PM2.5 exposure and 49% of variation in kitchen PM2.5 concentrations. Additionally, multivariable models explained 37% and 47% of variation in personal and kitchen BC concentrations, respectively. Stove type, season, presence of electricity, primary stove location, kitchen enclosure type, stove use time, and presence of kerosene for lighting were all associated with differences in geometric mean exposures. Stove type explained the most variability of the included variables. In future studies of household air pollution, tracking the cooking behaviors and daily activities of participants, including outdoor exposures, may explain exposure variation beyond the household and personal variables considered here.

Household air pollution from wood-burning cookstoves and C-reactive protein among women in rural Honduras.

Household air pollution from solid fuel combustion was estimated to cause 2.31 million deaths worldwide in 2019; cardiovascular disease is a substantial contributor to the global burden. We evaluated the cross-sectional association between household air pollution (24-h gravimetric kitchen and personal particulate matter (PM2.5) and black carbon (BC)) and C-reactive protein (CRP) measured in dried blood spots among 107 women in rural Honduras using wood-burning traditional or Justa (an engineered combustion chamber) stoves. A suite of 6 additional markers of systemic injury and inflammation were considered in secondary analyses. We adjusted for potential confounders and assessed effect modification of several cardiovascular-disease risk factors. The median (25th, 75th percentiles) 24-h-average personal PM2.5 concentration was 115 µg/m3 (65,154 µg/m3) for traditional stove users and 52 µg/m3 (39, 81 µg/m3) for Justa stove users; kitchen PM2.5 and BC had similar patterns. Higher concentrations of PM2.5 and BC were associated with higher levels of CRP (e.g., a 25% increase in personal PM2.5 was associated with a 10.5% increase in CRP [95% CI: 1.2-20.6]). In secondary analyses, results were generally consistent with a null association. Evidence for effect modification between pollutant measures and four different cardiovascular risk factors (e.g., high blood pressure) was inconsistent. These results support the growing evidence linking household air pollution and cardiovascular disease.

Data for modelling US projections of product approvals, patients treated, and product revenues for durable cell and gene therapies.

The recent marketing approval of several durable gene and cell therapies (2017-2020), together with observations that 7,000 monogenic indications and many cancers were potential targets, led to concern about the potential economic impact of such therapies on the US healthcare system. Using a Markov chain Monte Carlo simulation model, driven stochastically by our estimates of the time in phase of clinical trials and each clinical trial phase probability of success, we forecast the pattern of future US regulatory approvals for such therapies currently undergoing clinical trials. Using parameters of those trials, such as inclusion and exclusion criteria, and other epidemiological data we estimate potential treatable patient populations and use these together with pricing estimates to forecast a range for the potential future list price product revenues associated with these therapies.

Factors Associated with Levels of Organophosphate Pesticides in Household Dust in Agricultural Communities.

Organophosphate (OP) pesticides are associated with numerous adverse health outcomes. Pesticide use data are available for California from the Pesticide Use Report (PUR), but household- and individual-level exposure factors have not been fully characterized to support its refinement as an exposure assessment tool. Unique exposure pathways, such as proximity to agricultural operations and direct occupational contact, further complicate pesticide exposure assessment among agricultural communities. We sought to identify influencing factors of pesticide exposure to support future exposure assessment and epidemiological studies. Household dust samples were collected from 28 homes in four California agricultural communities during January and June 2019 and were analyzed for the presence of OPs. Factors influencing household OPs were identified by a data-driven model via best subsets regression. Key factors that impacted dust OP levels included household cooling strategies, secondary occupational exposure to pesticides, and geographic location by community. Although PUR data demonstrate seasonal trends in pesticide application, this study did not identify season as an important factor, suggesting OP persistence in the home. These results will help refine pesticide exposure assessment for future studies and highlight important gaps in the literature, such as our understanding of pesticide degradation in an indoor environment.

Reduced Black Carbon Concentrations following a Three-Year Stepped-Wedge Randomized Trial of the Wood-Burning Justa Cookstove in Rural Honduras.

Introduction: Household air pollution from cooking-related biomass combustion remains a leading risk factor for global health. Black carbon (BC) is an important component of particulate matter (PM) in household air pollution. We evaluated the impact of the engineered, wood-burning Justa stove intervention on BC concentrations. Methods: We conducted a 3-year stepped-wedge randomized controlled trial with 6 repeated visits among 230 female primary cooks in rural Honduras. Participants used traditional stoves at baseline and were randomized to receive the Justa after visit 2 or after visit 4. At each visit, we measured 24-hour gravimetric personal and kitchen fine PM (PM2.5) concentrations and estimated BC mass concentrations (Sootscan Transmissometer). We conducted intent-to-treat analyses using linear mixed models with natural log-transformed 24-hour personal and kitchen BC. Results: BC concentrations were reduced for households assigned to the Justa vs. traditional stoves: e.g., personal BC geometric mean (GSD), 3.6 µg/m3 (6.4) vs. 11.5 µg/m3 (4.6), respectively. Following the intervention, we observed 53% (95% CI: 35-65%) lower geometric mean personal BC concentrations and 76% (95% CI: 66-83%) lower geometric mean kitchen BC concentrations. Conclusions: The Justa stove intervention substantially reduced BC concentrations, mitigating household air pollution and potentially benefitting human and climate health.

Durable cell and gene therapy potential patient and financial impact: US projections of product approvals, patients treated, and product revenues.

Durable cell and gene therapies potentially transform patient lives, but payers fear unsustainable costs arising from the more than 1000 therapies in the development pipeline. A novel multi-module Markov chain Monte Carlo-based model projects product-indication approvals, treated patients, and product revenues. We estimate a mean 63.5 (54-74 5th to 95th percentile range) cumulative US product-indication approvals through 2030, with a mean 93000 patients treated in 2030 generating a mean US$24.4 billion (US$17.0B-35.0B, US$73.0B extreme) list price product revenues not including ancillary medical costs or cost offsets. Thus, the likely dozens of durable cell and gene therapies developed through 2030 are unlikely to threaten US health system financial sustainability.

Fidelity and Adherence to a Liquefied Petroleum Gas Stove and Fuel Intervention during Gestation: The Multi-Country Household Air Pollution Intervention Network (HAPIN) Randomized Controlled Trial.

BACKGROUND: Clean cookstove interventions can theoretically reduce exposure to household air pollution and benefit health, but this requires near-exclusive use of these types of stoves with the simultaneous disuse of traditional stoves. Previous cookstove trials have reported low adoption of new stoves and/or extensive continued traditional stove use. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3195 pregnant women in Guatemala, India, Peru, and Rwanda to either a liquefied petroleum gas (LPG) stove and fuel intervention (n = 1590) or to a control (n = 1605). The intervention consisted of an LPG stove and two initial cylinders of LPG, free fuel refills delivered to the home, and regular behavioral messaging. We assessed intervention fidelity (delivery of the intervention as intended) and adherence (intervention use) through to the end of gestation, as relevant to the first primary health outcome of the trial: infant birth weight. Fidelity and adherence were evaluated using stove and fuel delivery records, questionnaires, visual observations, and temperature-logging stove use monitors (SUMs). RESULTS: 1585 women received the intervention at a median (interquartile range) of 8.0 (5.0-15.0) days post-randomization and had a gestational age of 17.9 (15.4-20.6) weeks. Over 96% reported cooking exclusively with LPG at two follow-up visits during pregnancy. Less than 4% reported ever running out of LPG. Complete abandonment of traditional stove cooking was observed in over 67% of the intervention households. Of the intervention households, 31.4% removed their traditional stoves upon receipt of the intervention; among those who retained traditional stoves, the majority did not use them: traditional stove use was detected via SUMs on a median (interquartile range) of 0.0% (0.0%, 1.6%) of follow-up days (median follow-up = 134 days). CONCLUSIONS: The fidelity of the HAPIN intervention, as measured by stove installation, timely ongoing fuel deliveries, and behavioral reinforcement as needed, was high. Exclusive use of the intervention during pregnancy was also high.

Design and Testing of a Low-Cost Sensor and Sampling Platform for Indoor Air Quality.

Americans spend most of their time indoors at home, but comprehensive characterization of in-home air pollution is limited by the cost and size of reference-quality monitors. We assembled small "Home Health Boxes" (HHBs) to measure indoor PM2.5, PM10, CO2, CO, NO2, and O3 concentrations using filter samplers and low-cost sensors. Nine HHBs were collocated with reference monitors in the kitchen of an occupied home in Fort Collins, Colorado, USA for 168 h while wildfire smoke impacted local air quality. When HHB data were interpreted using gas sensor manufacturers' calibrations, HHBs and reference monitors (a) categorized the level of each gaseous pollutant similarly (as either low, elevated, or high relative to air quality standards) and (b) both indicated that gas cooking burners were the dominant source of CO and NO2 pollution; however, HHB and reference O3 data were not correlated. When HHB gas sensor data were interpreted using linear mixed calibration models derived via collocation with reference monitors, root-mean-square error decreased for CO2 (from 408 to 58 ppm), CO (645 to 572 ppb), NO2 (22 to 14 ppb), and O3 (21 to 7 ppb); additionally, correlation between HHB and reference O3 data improved (Pearson's r increased from 0.02 to 0.75). Mean 168-h PM2.5 and PM10 concentrations derived from nine filter samples were 19.4 µg m-3 (6.1% relative standard deviation [RSD]) and 40.1 µg m-3 (7.6% RSD). The 168-h PM2.5 concentration was overestimated by PMS5003 sensors (median sensor/filter ratio = 1.7) and underestimated slightly by SPS30 sensors (median sensor/filter ratio = 0.91).

Air versus Water Chilling of Chicken: a Pilot Study of Quality, Shelf-Life, Microbial Ecology, and Economics.

The United States' large-scale poultry meat industry is energy and water intensive, and opportunities may exist to improve sustainability during the broiler chilling process. By USDA regulation, after harvest the internal temperature of the chicken must be reduced to 40°F or less within 16 h to inhibit bacterial growth that would otherwise compromise the safety of the product. This step is accomplished most commonly by water immersion chilling in the United States, while air chilling methods dominate other global markets. A comprehensive understanding of the differences between these chilling methods is lacking. Therefore, we assessed the meat quality, shelf-life, microbial ecology, and techno-economic impacts of chilling methods on chicken broilers in a university meat laboratory setting. We discovered that air chilling methods resulted in superior chicken odor and shelf-life, especially prior to 14 days of dark storage. Moreover, we demonstrated that air chilling resulted in a more diverse microbiome that we hypothesize may delay the dominance of the spoilage organism Pseudomonas Finally, a techno-economic analysis highlighted potential economic advantages to air chilling compared to water chilling in facility locations where water costs are a more significant factor than energy costs.IMPORTANCE As the poultry industry works to become more sustainable and to reduce the volume of food waste, it is critical to consider points in the processing system that can be altered to make the process more efficient. In this study, we demonstrate that the method used during chilling (air versus water chilling) influences the final product microbial community, quality, and physiochemistry. Notably, the use of air chilling appears to delay the bloom of Pseudomonas spp. that are the primary spoilers in packaged meat products. By using air chilling to reduce carcass temperatures instead of water chilling, producers may extend the time until spoilage of the products and, depending on the cost of water in the area, may have economic and sustainability advantages. As a next step, a similar experiment should be done in an industrial setting to confirm these results generated in a small-scale university lab facility.

Impact of the wood-burning Justa cookstove on fine particulate matter exposure: A stepped-wedge randomized trial in rural Honduras.

TRIAL DESIGN: We evaluated the impact of a biomass stove intervention on fine particulate matter (PM2.5) concentrations using an individual-level, stepped-wedge randomized trial. METHODS: We enrolled 230 women in rural Honduran households using traditional biomass stoves and randomly allocated them to one of two study arms. The Justa stove, the study intervention, was locally-sourced, wood-burning, and included an engineered combustion chamber and chimney. At each of 6 visits over 3 years, we measured 24-hour gravimetric personal and kitchen PM2.5 concentrations. Half of the households received the intervention after Visit 2 and half after Visit 4. We conducted intent-to-treat analyses to evaluate the intervention effect using linear mixed models with log-transformed kitchen or personal PM2.5 (separately) as the dependent variable, adjusting for time. We also compared PM2.5 concentrations to World Health Organization (WHO) guidelines. RESULTS: Arms 1 and 2 each had 115 participants with 664 and 632 completed visits, respectively. Median 24-hour average personal PM2.5 exposures were 81 µg/m3 (25th-75th percentile: 50-141 µg/m3) for the traditional stove condition (n=622) and 43 µg/m3 (25th-75th percentile: 27-73 µg/m3) for the Justa stove condition (n=585). Median 24-hour average kitchen concentrations were 178 µg/m3 (25th-75th percentile: 69-440 µg/m3; n=629) and 53 µg/m3 (25th-75th percentile: 29-103 µg/m3; n=578) for the traditional and Justa stove conditions, respectively. The Justa intervention resulted in a 32% reduction in geometric mean personal PM2.5 (95% confidence interval [CI]: 20-43%) and a 56% reduction (95% CI: 46-65%) in geometric mean kitchen PM2.5. During rainy and dry seasons, 53% and 41% of participants with the Justa intervention had 24-hour average personal PM2.5 exposures below the WHO interim target-3 guideline (37.5 µg/m3), respectively. CONCLUSION: The Justa stove intervention substantially lowered personal and kitchen PM2.5 and may be a provisional solution that is feasible for Latin American communities where cleaner fuels may not be available, affordable, or acceptable for some time. Clinicaltrials.gov: NCT02658383.

Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: a multi-stakeholder perspective.

Immuno-oncologics (IOs) differ from chemotherapies as they prime the patient's immune system to attack the tumor, rather than directly destroying cancer cells. The IO mechanism of action leads to durable responses and prolonged survival in some patients. However, providing robust evidence of the long-term benefits of IOs at health technology assessment (HTA) submission presents several challenges for manufacturers. The aim of this article was to identify, analyze, categorize, and further explore the key challenges that regulators, HTA agencies, and payers commonly encounter when assessing the long-term benefits of IO therapies. Insights were obtained from an international, multi-stakeholder steering committee (SC) and expert panels comprising of payers, economists, and clinicians. The selected individuals were tasked with developing a summary of challenges specific to IOs in demonstrating their long-term benefits at HTA submission. The SC and expert panels agreed that standard methods used to assess the long-term benefit of anticancer drugs may have limitations for IO therapies. Three key areas of challenges were identified: (1) lack of a disease model that fully captures the mechanism of action and subsequent patient responses; (2) estimation of longer-term outcomes, including a lack of agreement on ideal methods of survival analyses and extrapolation of survival curves; and (3) data limitations at the time of HTA submission, for which surrogate survival end points and real-world evidence could prove useful. A summary of the key challenges facing manufacturers when submitting evidence at HTA submission was developed, along with further recommendations for manufacturers in what evidence to produce. Despite almost a decade of use, there remain significant challenges around how best to demonstrate the long-term benefit of checkpoint inhibitor-based IOs to HTA agencies, clinicians, and payers. Manufacturers can potentially meet or mitigate these challenges with a focus on strengthening survival analysis methodology. Approaches to doing this include identifying reliable biomarkers, intermediate and surrogate end points, and the use of real-world data to inform and validate long-term survival projections. Wider education across all stakeholders-manufacturers, payers, and clinicians-in considering the long-term survival benefit with IOs is also important.