Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity.

The molecular basis of the incomplete penetrance of monogenic disorders is unclear. We describe here eight related individuals with autosomal recessive TIRAP deficiency. Life-threatening staphylococcal disease occurred during childhood in the proband, but not in the other seven homozygotes. Responses to all Toll-like receptor 1/2 (TLR1/2), TLR2/6, and TLR4 agonists were impaired in the fibroblasts and leukocytes of all TIRAP-deficient individuals. However, the whole-blood response to the TLR2/6 agonist staphylococcal lipoteichoic acid (LTA) was abolished only in the index case individual, the only family member lacking LTA-specific antibodies (Abs). This defective response was reversed in the patient, but not in interleukin-1 receptor-associated kinase 4 (IRAK-4)-deficient individuals, by anti-LTA monoclonal antibody (mAb). Anti-LTA mAb also rescued the macrophage response in mice lacking TIRAP, but not TLR2 or MyD88. Thus, acquired anti-LTA Abs rescue TLR2-dependent immunity to staphylococcal LTA in individuals with inherited TIRAP deficiency, accounting for incomplete penetrance. Combined TIRAP and anti-LTA Ab deficiencies underlie staphylococcal disease in this patient.

Discovery and characterization of an acridine radical photoreductant.

Photoinduced electron transfer (PET) is a phenomenon whereby the absorption of light by a chemical species provides an energetic driving force for an electron-transfer reaction1-4. This mechanism is relevant in many areas of chemistry, including the study of natural and artificial photosynthesis, photovoltaics and photosensitive materials. In recent years, research in the area of photoredox catalysis has enabled the use of PET for the catalytic generation of both neutral and charged organic free-radical species. These technologies have enabled previously inaccessible chemical transformations and have been widely used in both academic and industrial settings. Such reactions are often catalysed by visible-light-absorbing organic molecules or transition-metal complexes of ruthenium, iridium, chromium or copper5,6. Although various closed-shell organic molecules have been shown to behave as competent electron-transfer catalysts in photoredox reactions, there are only limited reports of PET reactions involving neutral organic radicals as excited-state donors or acceptors. This is unsurprising because the lifetimes of doublet excited states of neutral organic radicals are typically several orders of magnitude shorter than the singlet lifetimes of known transition-metal photoredox catalysts7-11. Here we document the discovery, characterization and reactivity of a neutral acridine radical with a maximum excited-state oxidation potential of -3.36 volts versus a saturated calomel electrode, which is similarly reducing to elemental lithium, making this radical one of the most potent chemical reductants reported12. Spectroscopic, computational and chemical studies indicate that the formation of a twisted intramolecular charge-transfer species enables the population of higher-energy doublet excited states, leading to the observed potent photoreducing behaviour. We demonstrate that this catalytically generated PET catalyst facilitates several chemical reactions that typically require alkali metal reductants and can be used in other organic transformations that require dissolving metal reductants.

Genetic testing for familial hypercholesterolemia.

PURPOSE OF REVIEW: Despite familial hypercholesterolemia (FH) being the most common genetic cause of cardiovascular disease (CVD), genetic testing is rarely utilized in the US. This review summarizes what is known about the clinical utility of genetic testing and its role in the diagnosis and screening of FH. RECENT FINDINGS: The presence of an FH-causative variant is associated with a substantially higher risk of CVD, even when low-density lipoprotein cholesterol (LDL-C) levels are only modestly elevated. Genetic testing can facilitate the identification of FH cases who may be missed by clinical diagnostic criteria, improve risk stratification beyond LDL-C and family history, guide treatment decisions, and improve treatment initiation and adherence. Genetic testing can be incorporated into FH screening and diagnosis algorithms, including cascade, targeted, and universal screening. Integrating genetic testing into cascade screening can enhance the effectiveness of the process. Several models of universal FH screening with coordinated genetic and lipid testing are feasible and effective. SUMMARY: More systematic integration of genetic testing into FH diagnosis and screening can significantly reduce the burden of this condition through early detection and treatment. Further pragmatic implementation studies are needed to determine how to more effectively and affordably integrate genetic testing into clinical lipid screening programs.

Co-creation process of an intervention to implement a multiparameter point-of-care testing device in a primary healthcare setting for non-communicable diseases in Peru.

BACKGROUND: Point-of-care testing (POCT) devices are diagnostic tools that can provide quick and accurate results within minutes, making them suitable for diagnosing non-communicable diseases (NCDs). However, these devices are not widely implemented in healthcare systems and for this reason is relevant to understand the implementation process. AIM: To describe the process and define a strategy to implement a multiparameter POCT device for diagnosing and managing NCDs in one region of Peru. METHODS: A descriptive and non-experimental study, using the participatory methodologies of co-creation process. It was conducted in one region of Peru (Tumbes) to design an intervention for implementing a multiparameter POCT device. Two co-creation sessions were conducted involving five groups: community members, primary healthcare workers, these groups in both rural and urban settings, and regional decision-makers. These sessions included activities to understand patient journeys in receiving care for NCDs, identify facilitators and barriers to POCT devices usage, and define an implementation strategy for POCT devices in both rural and urban settings of Tumbes. The research team analysed the data and summarized key topics for discussion after each session. RESULTS: A total of 78 participants were enrolled across the five groups. Among community members: 22.2% had only diabetes, 24.1% had only hypertension, and 18.5% had both diagnoses. In the patient journey, community members mentioned that it took at least three days to receive a diagnosis and treatment for an NCD. Most of the participants agreed that the POCT devices would be beneficial for their communities, but they also identified some concerns. The strategy for POCT devices implementation included healthcare workers training, POCT devices must be placed in the laboratory area and must be able to perform tests for glucose, glycated haemoglobin, cholesterol, and creatinine. Advertising about POCT devices should be displayed at the healthcare centres and the municipality using billboards and flyers. CONCLUSIONS: The co-creation process was useful to develop strategies for the implementation of multiparameter POCT devices for NCDs, involving the participation of different groups of stakeholders guided by moderators in both, rural and urban, settings in Peru.

On-demand mobile hypertension training for primary health care workers in Nigeria: a pilot study.

BACKGROUND: Only one out of every ten Nigerian adults with hypertension has their blood pressure controlled. Health worker training is essential to improve hypertension diagnosis and treatment. In-person training has limitations that mobile, on-demand training might address. This pilot study evaluated a self-paced, case-based, mobile-optimized online training to diagnose and manage hypertension for Nigerian health workers. METHODS: Twelve hypertension training modules were developed, based on World Health Organization and Nigerian guidelines. After review by local academic and government partners, the course was piloted by Nigerian health workers at government-owned primary health centers. Primary care physician, nurse, and community health worker participants completed the course on their own smartphones. Before and after the course, hypertension knowledge was evaluated with multiple-choice questions. Learners provided feedback by responding to questions on a Likert scale. RESULTS: Out of 748 users who sampled the course, 574 enrolled, of whom 431 (75%) completed the course. The average pre-test score of completers was 65.4%, which increased to 78.2% on the post-test (P < 0.001, paired t-test). Health workers who were not part of existing hypertension control programs had lower pre-test scores and larger score gains. Most participants (96.1%) agreed that the training was applicable to their work, and nearly all (99.8%) agreed that they enjoyed the training. CONCLUSIONS: An on-demand mobile digital hypertension training increases knowledge of hypertension management among Nigerian health workers. If offered at scale, such courses can be a tool to build health workforce capacity through initial and refresher training on current clinical guidelines in hypertension and other chronic diseases in Nigeria as well as other countries.

Beyond 10-Year Risk: A Cost-Effectiveness Analysis of Statins for the Primary Prevention of Cardiovascular Disease.

BACKGROUND: Cholesterol guidelines typically prioritize primary prevention statin therapy on the basis of 10-year risk of cardiovascular disease. The advent of generic pricing may justify expansion of statin eligibility. Moreover, 10-year risk may not be the optimal approach for statin prioritization. We estimated the cost-effectiveness of expanding preventive statin eligibility and evaluated novel approaches to prioritization from a Scottish health sector perspective. METHODS: A computer simulation model predicted long-term health and cost outcomes in Scottish adults ≥40 years of age. Epidemiologic analysis was completed using the Scottish Heart Health Extended Cohort, Scottish Morbidity Records, and National Records of Scotland. A simulation cohort was constructed with data from the Scottish Health Survey 2011 and contemporary population estimates. Treatment and cost inputs were derived from published literature and health service cost data. The main outcome measure was the lifetime incremental cost-effectiveness ratio, evaluated as cost (2020 GBP) per quality-adjusted life-year (QALY) gained. Three approaches to statin prioritization were analyzed: 10-year risk scoring using the ASSIGN score, age-stratified risk thresholds to increase treatment rates in younger individuals, and absolute risk reduction (ARR)-guided therapy to increase treatment rates in individuals with elevated cholesterol levels. For each approach, 2 policies were considered: treating the same number of individuals as those with an ASSIGN score ≥20% (age-stratified risk threshold 20, ARR 20) and treating the same number of individuals as those with an ASSIGN score ≥10% (age-stratified risk threshold 10, ARR 10). RESULTS: Compared with an ASSIGN score ≥20%, reducing the risk threshold for statin initiation to 10% expanded eligibility from 804 000 (32% of adults ≥40 years of age without CVD) to 1 445 500 individuals (58%). This policy would be cost-effective (incremental cost-effectiveness ratio, £12 300/QALY [95% CI, £7690/QALY-£26 500/QALY]). Incremental to an ASSIGN score ≥20%, ARR 20 produced ≈8800 QALYs and was cost-effective (£7050/QALY [95% CI, £4560/QALY-£10 700/QALY]). Incremental to an ASSIGN score ≥10%, ARR 10 produced ≈7950 QALYs and was cost-effective (£11 700/QALY [95% CI, £9250/QALY-£16 900/QALY]). Both age-stratified risk threshold strategies were dominated (ie, more expensive and less effective than alternative treatment strategies). CONCLUSIONS: Generic pricing has rendered preventive statin therapy cost-effective for many adults. ARR-guided therapy is more effective than 10-year risk scoring and is cost-effective.

The Health and Economic Impact of Using a Sugar Sweetened Beverage Tax to Fund Fruit and Vegetable Subsidies in New York City: A Modeling Study.

Low fruit and vegetable (FV) intake and high sugar-sweetened beverage (SSB) consumption are independently associated with an increased risk of developing cardiovascular disease (CVD). Many people in New York City (NYC) have low FV intake and high SSB consumption, partly due to high cost of fresh FVs and low cost of and easy access to SSBs. A potential implementation of an SSB tax and an FV subsidy program could result in substantial public health and economic benefits. We used a validated microsimulation model for predicting CVD events to estimate the health impact and cost-effectiveness of SSB taxes, FV subsidies, and funding FV subsidies with an SSB tax in NYC. Population demographics and health profiles were estimated using data from the NYC Health and Nutrition Examination Survey. Policy effects and price elasticity were derived from recent meta-analyses. We found that funding FV subsidies with an SSB tax was projected to be the most cost-effective policy from the healthcare sector perspective. From the societal perspective, the most cost-effective policy was SSB taxes. All policy scenarios could prevent more CVD events and save more healthcare costs among men compared to women, and among Black vs. White adults. Public health practitioners and policymakers may want to consider adopting this combination of policy actions, while weighing feasibility considerations and other unintended consequences.

Regression discontinuity design to evaluate the effect of statins on myocardial infarction in electronic health records.

Regression discontinuity design (RDD) is a quasi-experimental method intended for causal inference in observational settings. While RDD is gaining popularity in clinical studies, there are limited real-world studies examining the performance on estimating known trial casual effects. The goal of this paper is to estimate the effect of statins on myocardial infarction (MI) using RDD and compare with propensity score matching and Cox regression. For the RDD, we leveraged a 2008 UK guideline that recommends statins if a patient's 10-year cardiovascular disease (CVD) risk score > 20%. We used UK electronic health record data from the Health Improvement Network on 49,242 patients aged 65 + in 2008-2011 (baseline) without a history of CVD and no statin use in the two years prior to the CVD risk score assessment. Both the regression discontinuity (n = 19,432) and the propensity score matched populations (n = 24,814) demonstrated good balance of confounders. Using RDD, the adjusted point estimate for statins on MI was in the protective direction and similar to the statin effect observed in clinical trials, although the confidence interval included the null (HR = 0.8, 95% CI 0.4, 1.4). Conversely, the adjusted estimates using propensity score matching and Cox regression remained in the harmful direction: HR = 2.42 (95% CI 1.96, 2.99) and 2.51 (2.12, 2.97). RDD appeared superior to other methods in replicating the known protective effect of statins with MI, although precision was poor. Our findings suggest that, when used appropriately, RDD can expand the scope of clinical investigations aimed at causal inference by leveraging treatment rules from everyday clinical practice.

Measuring carrier diffusion in MAPbI3 solar cells with photocurrent-detected transient grating spectroscopy.

Conventional time-of-flight methods can be used to determine carrier mobilities for photovoltaic cells in which the transit time between electrodes is greater than the RC time constant of the device. To measure carrier drift on sub-ns timescales, we have recently developed a two-pulse time-of-flight technique capable of detecting drift velocities with 100-ps time resolution in perovskite materials. In this method, the rates of carrier transit across the active layer of a device are determined by varying the delay time between laser pulses and measuring the magnitude of the recombination-induced nonlinearity in the photocurrent. Here, we present a related experimental approach in which diffractive optic-based transient grating spectroscopy is combined with our two-pulse time-of-flight technique to simultaneously probe drift and diffusion in orthogonal directions within the active layer of a photovoltaic cell. Carrier density gratings are generated using two time-coincident pulse-pairs with passively stabilized phases. Relaxation of the grating amplitude associated with the first pulse-pair is detected by varying the delay and phase of the density grating corresponding to the second pulse-pair. The ability of the technique to reveal carrier diffusion is demonstrated with model calculations and experiments conducted using MAPbI3 photovoltaic cells.

Facilitators and barriers of the implementation of point-of-care devices for cardiometabolic diseases: a scoping review.

BACKGROUND: Point-of-care testing (POCT) devices may facilitate the delivery of rapid and timely results, providing a clinically important advantage in patient management. The challenges and constraints in the implementation process, considering different levels of actors have not been much explored. This scoping review aimed to assess literature pertaining to implementation facilitators and barriers of POCT devices for the diagnosis or monitoring of cardiometabolic diseases. METHODS: A scoping review of the literature was conducted. The inclusion criteria were studies on the inception, planning, or implementation of interventions with POCT devices for the diagnosis or monitoring of cardiometabolic diseases defined as dyslipidemia, cardiovascular diseases, type 2 diabetes, and chronic kidney disease. We searched MEDLINE, Embase, and Global Health databases using the OVID searching engine until May 2022. The Consolidated Framework of Implementation Research (CFIR) was used to classify implementation barriers and facilitators in five constructs. Also, patient, healthcare professional (HCP), and organization level was used. RESULTS: Twenty studies met the eligibility criteria for data extraction. All studies except two were conducted in high-income countries. Some findings are: 1) Intervention: the most widely recognized facilitator was the quick turnaround time with which results are obtained. 2) Outer setting: at the organizational level, the lack of clear regulatory and accreditation mechanisms has hindered the adoption and sustainability of the use of POCT. 3) Inner setting: for HCP, performing POCT during the consultation was both a facilitator and a barrier in terms of time, personnel, and service delivery. 4) Individuals: the implementation of POCT may generate stress and discomfort in some HCP in terms of training and new responsibilities. 5) Process: for patients, it is highly appreciated that obtaining the sample was simple and more comfortable if venipuncture was not used. CONCLUSION: This scoping review has described the facilitators and barriers of implementing a POCT device for cardiometabolic conditions using the CFIR. The information can be used to design better strategies to implement these devices and benefit more populations that have low access to cardiometabolic tests.

Understanding the Role of Staff Nurses in Hypertension Management in Primary Care Facilities in India: A Time-Motion Study.

INTRODUCTION: India is facing a shortage of staff nurses; thus, a better understanding of nurses' workloads is essential for improving and implementing noncommunicable disease (NCD) control strategies. We estimated the proportion of time spent by staff nurses on hypertension and other NCD activities in primary care facilities in 2 states in India. METHODS: We conducted a cross-sectional study in 6 purposively selected primary care facilities in Punjab and Madhya Pradesh during July through September 2021. We used a standardized stopwatch to collect data for time spent on direct hypertension activities (measuring blood pressure, counseling, recording blood pressure measurement, and other NCD-related activities), indirect hypertension activities (data management, patient follow-up calls), and non-NCD activities. We used the Mann-Whitney U test to compare the median time spent on activities between facilities using paper-based records and the Simple mobile device-based app (open-source software). RESULTS: Six staff nurses were observed for 213 person-hours. Nurses spent 111 person-hours (52%; 95% CI, 45%-59%) on direct hypertension activities and 30 person-hours (14%; 95% CI, 10%-19%) on indirect hypertension activities. The time spent on blood pressure measurement (34 minutes) and documentation (35 minutes) was the maximum time on any given day. Facilities that used paper records spent more median time (39 [IQR, 26-62] minutes) for indirect hypertension activities than those using the Simple app (15 [IQR, 11-19] minutes; P < .001). CONCLUSION: Our study found that hypertension activities required more than half of nurses' time in India's primary care facilities. Digital systems can help to reduce the time spent on indirect hypertension activities.

[Monitoring and evaluation platform for HEARTS in the Americas: improving population-based hypertension control programs in primary health carePlataforma de monitoramento e avaliação do programa HEARTS nas Américas: melhoria dos programas de controle da hipertensão de base populacional na atenção primária à saúde]. / Plataforma de monitoreo y evaluación para HEARTS en las Américas: hacia la mejora de los programas de control de la hipertensión a nivel poblacional en la atención primaria de salud.

HEARTS in the Americas is the Pan American Health Organization flagship program to accelerate the reduction of the cardiovascular disease (CVD) burden by improving hypertension control and CVD secondary prevention in primary health care. A monitoring and evaluation (M&E) platform is needed for program implementation, benchmarking, and informing policy-makers. This paper describes the conceptual bases of the HEARTS M&E platform including software design principles, contextualization of data collection modules, data structure, reporting, and visualization. The District Health Information Software 2 (DHIS2) web-based platform was chosen to implement aggregate data entry of CVD outcome, process, and structural risk factor indicators. In addition, PowerBI was chosen for data visualization and dashboarding for the analysis of performance and trends above the health care facility level. The development of this new information platform was focused on primary health care facility data entry, timely data reporting, visualizations, and ultimately active use of data to drive decision-making for equitable program implementation and improved quality of care. Additionally, lessons learnt and programmatic considerations were assessed through the experience of the M&E software development. Building political will and support is essential to developing and deploying a flexible platform in multiple countries which is contextually specific to the needs of various stakeholders and levels of the health care system. The HEARTS M&E platform supports program implementation and reveals structural and managerial limitations and care gaps. The HEARTS M&E platform will be central to monitoring and driving further population-level improvements in CVD and other noncommunicable disease-related health.

A iniciativa HEARTS nas Américas é o principal programa da Organização Pan-Americana da Saúde para acelerar a redução da carga de doenças cardiovasculares (DCV) por meio do melhoramento do controle da hipertensão e da prevenção secundária de DCV na atenção primária à saúde. Uma plataforma de monitoramento e avaliação (M&E, na sigla em inglês) é necessária para a implementação do programa, para fazer a avaliação comparativa e para informar os formuladores de políticas. Este documento descreve as bases conceituais da plataforma de M&E do HEARTS, incluindo princípios de design de software, contextualização dos módulos de coleta de dados, estrutura de dados, relatórios e visualização. A plataforma baseada na web do District Health Information Software 2 (DHIS2) foi escolhida para implementar a inserção de dados agregados de indicadores de fatores de risco estruturais, processos e desfechos de DCV. Além disso, o PowerBI foi escolhido para a visualização de dados e para fazer o dashboard da análise de desempenho e tendências para além do nível da unidade de saúde. O desenvolvimento desta nova plataforma de informações teve como foco a inserção de dados da unidade de atenção primária à saúde, a notificação oportuna de dados, visualizações e o uso ativo dos dados para orientar a tomada de decisões para a implementação equitativa do programa e a melhoria da qualidade do atendimento. Além disso, as lições aprendidas e as considerações programáticas foram avaliadas por meio da experiência do desenvolvimento do software de M&E. Fomentar vontade política e apoio é essencial para desenvolver e implantar uma plataforma flexível em vários países, que seja contextualmente específica para as necessidades das diferentes partes interessadas e níveis do sistema de saúde. A plataforma de M&E do HEARTS ampara a implementação do programa e revela limitações estruturais e gerenciais, bem como lacunas na atenção à saúde. A plataforma de M&E do HEARTS será central para monitorar e impulsionar mais melhorias no nível populacional em DCV e outras doenças não transmissíveis.

Spending on Cardiovascular Disease and Cardiovascular Risk Factors in the United States: 1996 to 2016.

BACKGROUND: Spending on cardiovascular disease and cardiovascular risk factors (cardiovascular spending) accounts for a significant portion of overall US health care spending. Our objective was to describe US adult cardiovascular spending patterns in 2016, changes from 1996 to 2016, and factors associated with changes over time. METHODS: We extracted information on adult cardiovascular spending from the Institute for Health Metrics and Evaluation's disease expenditure project, which combines data on insurance claims, emergency department and ambulatory care visits, inpatient and nursing care facility stays, and drug prescriptions to estimate >85% of all US health care spending. Cardiovascular spending (2016 US dollars) was stratified by age, sex, type of care, payer, and cardiovascular cause. Time trend and decomposition analyses quantified contributions of epidemiology, service price and intensity (spending per unit of utilization, eg, spending per inpatient bed-day), and population growth and aging to the increase in cardiovascular spending from 1996 to 2016. RESULTS: Adult cardiovascular spending increased from $212 billion in 1996 to $320 billion in 2016, a period when the US population increased by >52 million people, and median age increased from 33.2 to 36.9 years. Over this period, public insurance was responsible for the majority of cardiovascular spending (54%), followed by private insurance (37%) and out-of-pocket spending (9%). Health services for ischemic heart disease ($80 billion) and hypertension ($71 billion) led to the most spending in 2016. Increased spending between 1996 and 2016 was primarily driven by treatment of hypertension, hyperlipidemia, and atrial fibrillation/flutter, for which spending rose by $42 billion, $18 billion, and $16 billion, respectively. Increasing service price and intensity alone were associated with a 51%, or $88 billion, cardiovascular spending increase from 1996 to 2016, whereas changes in disease prevalence were associated with a 37%, or $36 billion, spending reduction over the same period, after taking into account population growth and population aging. CONCLUSIONS: US adult cardiovascular spending increased by >$100 billion from 1996 to 2016. Policies tailored to control service price and intensity and preferentially reimburse higher quality care could help counteract future spending increases caused by population aging and growth.

Cost-Effectiveness of Hypertension Treatment by Pharmacists in Black Barbershops.

BACKGROUND: In LABBPS (Los Angeles Barbershop Blood Pressure Study), pharmacist-led hypertension care in Los Angeles County Black-owned barbershops significantly improved blood pressure control in non-Hispanic Black men with uncontrolled hypertension at baseline. In this analysis, 10-year health outcomes and health care costs of 1 year of the LABBPS intervention versus control are projected. METHODS: A discrete event simulation of hypertension care processes projected blood pressure, medication-related adverse events, fatal and nonfatal cardiovascular disease events, and noncardiovascular disease death in LABBPS participants. Program costs, total direct health care costs (2019 US dollars), and quality-adjusted life-years (QALYs) were estimated for the LABBPS intervention and control arms from a health care sector perspective over a 10-year horizon. Future costs and QALYs were discounted 3% annually. High and intermediate cost-effectiveness thresholds were defined as <$50 000 and <$150 000 per QALY gained, respectively. RESULTS: At 10 years, the intervention was projected to cost an average of $2356 (95% uncertainty interval, -$264 to $4611) more per participant than the control arm and gain 0.06 (95% uncertainty interval, 0.01-0.10) QALYs. The LABBPS intervention was highly cost-effective, with a mean cost of $42 717 per QALY gained (58% probability of being highly and 96% of being at least intermediately cost-effective). Exclusive use of generic drugs improved the cost-effectiveness to $17 162 per QALY gained. The LABBPS intervention would be only intermediately cost-effective if pharmacists were less likely to intensify antihypertensive medications when systolic blood pressure was ≥150 mm Hg or if pharmacist weekly time driving to barbershops increased. CONCLUSIONS: Hypertension care delivered by clinical pharmacists in Black barbershops is a highly cost-effective way to improve blood pressure control in Black men.

Factors associated with antihypertensive monotherapy among US adults with treated hypertension and uncontrolled blood pressure overall and by race/ethnicity, National Health and Nutrition Examination Survey 2013-2018.

BACKGROUND: Treating hypertension with antihypertensive medications combinations, rather than one medication (ie, monotherapy), is underused in the United States, particularly in certain race/ethnic groups. Identifying factors associated with monotherapy use despite uncontrolled blood pressure (BP) overall and within race/ethnic groups may elucidate intervention targets in under-treated populations. METHODS: Cross-sectional analysis of National Health and Nutrition Examination Surveys (NHANES; 2013-2014 through 2017-2018). We included participants age ≥20 years with hypertension, taking at least one antihypertensive medication, and uncontrolled BP (systolic BP [SBP] ≥ 140 mmHg or diastolic BP [DBP] ≥ 90 mmHg). Demographic, clinical, and healthcare-access factors associated with antihypertensive monotherapy were determined using multivariable-adjusted Poisson regression. RESULTS: Among 1,597 participants with hypertension and uncontrolled BP, age- and sex- adjusted prevalence of monotherapy was 42.6% overall, 45.4% among non-Hispanic White, 31.9% among non-Hispanic Black, 39.6% among Hispanic, and 50.9% among non-Hispanic Asian adults. Overall, higher SBP was associated with higher monotherapy use, while older age, having a healthcare visit in the previous year, higher body mass index, and having heart failure were associated with lower monotherapy use. CONCLUSION: Clinical and healthcare-access factors, including a healthcare visit within the previous year and co-morbid conditions were associated with a higher likelihood of combination antihypertensive therapy.

Estimating the optimal individualized treatment rule from a cost-effectiveness perspective.

Optimal individualized treatment rules (ITRs) provide customized treatment recommendations based on subject characteristics to maximize clinical benefit in accordance with the objectives in precision medicine. As a result, there is growing interest in developing statistical tools for estimating optimal ITRs in evidence-based research. In health economic perspectives, policy makers consider the tradeoff between health gains and incremental costs of interventions to set priorities and allocate resources. However, most work on ITRs has focused on maximizing the effectiveness of treatment without considering costs. In this paper, we jointly consider the impact of effectiveness and cost on treatment decisions and define ITRs under a composite-outcome setting, so that we identify the most cost-effective ITR that accounts for individual-level heterogeneity through direct optimization. In particular, we propose a decision-tree-based statistical learning algorithm that uses a net-monetary-benefit-based reward to provide nonparametric estimations of the optimal ITR. We provide several approaches to estimating the reward underlying the ITR as a function of subject characteristics. We present the strengths and weaknesses of each approach and provide practical guidelines by comparing their performance in simulation studies. We illustrate the top-performing approach from our simulations by evaluating the projected 15-year personalized cost-effectiveness of the intensive blood pressure control of the Systolic Blood Pressure Intervention Trial (SPRINT) study.

Physical activity from young adulthood to middle age and premature cardiovascular disease events: a 30-year population-based cohort study.

BACKGROUND: Although physical activity is generally protective of cardiovascular disease (CVD), less is known about how young adult physical activity relates to premature CVD events. The objective of this study was to determine the association between level and change in physical activity from young adulthood to middle age and incidence of premature CVD events before age 60. METHODS: We analyzed data collected across four urban sites from nine visits over 30 years of follow-up (1985-2016) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective community-based cohort study of 5115 Black and White women and men aged 18-30 years at baseline (1985-1986). Linear mixed models were used to develop individualized moderate-to-vigorous intensity self-reported physical activity trajectories per participant. Fatal and nonfatal coronary heart disease (CHD), heart failure, and stroke outcomes were analyzed separately and as a combined CVD event outcome. RESULTS: Overall, physical activity declined in young adults as they progressed through middle age. Lower physical activity scores (per 100 exercise units) in 18 year-olds were associated with higher odds of premature CHD (AOR 1.14, 95% CI 1.02-1.28), heart failure (AOR 1.21, 95% CI 1.05-1.38), stroke (AOR 1.20, 95% CI 1.04-1.39), and any CVD (AOR 1.15, 95% CI 1.06-1.24) events. Each additional annual 1-unit reduction in the physical activity score was associated with a higher annual odds of incident heart failure (1.07, 95% CI 1.02-1.13), stroke (1.06, 95% CI 1.00-1.13), and CVD (1.04, 95% CI 1.01-1.07) events. Meeting the minimum (AOR 0.74, 95% CI 0.0.57-0.96) and twice the minimum (AOR 0.55, 95% CI 0.34-0.91) Department of Health and Human Services physical activity guidelines through follow up was protective of premature CVD events. CONCLUSIONS: Given recent trends in declining physical activity with age and associated premature CVD events, the transition from young adult to midlife is an important time period to promote physical activity.

Probing drift velocity dispersion in MAPbI3 photovoltaic cells with nonlinear photocurrent spectroscopy.

Conventional time-of-flight (TOF) measurements yield charge carrier mobilities in photovoltaic cells with time resolution limited by the RC time constant of the device, which is on the order of 0.1-1 µs for the systems targeted in the present work. We have recently developed an alternate TOF method, termed nonlinear photocurrent spectroscopy (NLPC), in which carrier drift velocities are determined with picosecond time resolution by applying a pair of laser pulses to a device with an experimentally controlled delay time. In this technique, carriers photoexcited by the first laser pulse are "probed" by way of recombination processes involving carriers associated with the second laser pulse. Here, we report NLPC measurements conducted with a simplified experimental apparatus in which synchronized 40 ps diode lasers enable delay times up to 100 µs at 5 kHz repetition rates. Carrier mobilities of ∼0.025 cm2/V/s are determined for MAPbI3 photovoltaic cells with active layer thicknesses of 240 and 460 nm using this instrument. Our experiments and model calculations suggest that the nonlinear response of the photocurrent weakens as the carrier densities photoexcited by the first laser pulse trap and broaden while traversing the active layer of a device. Based on this aspect of the signal generation mechanism, experiments conducted with co-propagating and counter-propagating laser beam geometries are leveraged to determine a 60 nm length scale of drift velocity dispersion in MAPbI3 films. Contributions from localized states induced by thermal fluctuations are consistent with drift velocity dispersion on this length scale.

Origin of layered perovskite device efficiencies revealed by multidimensional time-of-flight spectroscopy.

Mixtures of layered perovskite quantum wells with different sizes form prototypical light-harvesting antenna structures in solution-processed films. Gradients in the bandgaps and energy levels are established by concentrating the smallest and largest quantum wells near opposing electrodes in photovoltaic devices. Whereas short-range energy and charge carrier funneling behaviors have been observed in layered perovskites, our recent work suggests that such light-harvesting processes do not assist long-range charge transport due to carrier trapping at interfaces between quantum wells and interstitial organic spacer molecules. Here, we apply a two-pulse time-of-flight technique to a family of layered perovskite systems to explore the effects that interstitial organic molecules have on charge carrier dynamics. In these experiments, the first laser pulse initiates carrier drift within the active layer of a photovoltaic device, whereas the second pulse probes the transient concentrations of photoexcited carriers as they approach the electrodes. The instantaneous drift velocities determined with this method suggest that the rates of trap-induced carrier deceleration increase with the concentrations of organic spacer cations. Overall, our experimental results and model calculations suggest that the layered perovskite device efficiencies primarily reflect the dynamics of carrier trapping at interfaces between quantum wells and interstitial organic phases.

A quantitative model of charge injection by ruthenium chromophores connecting femtosecond to continuous irradiance conditions.

A kinetic framework for the ultrafast photophysics of tris(2,2-bipyridine)ruthenium(II) phosphonated and methyl-phosphonated derivatives is used as a basis for modeling charge injection by ruthenium dyes into a semiconductor substrate. By including the effects of light scattering, dye diffusion, and adsorption kinetics during sample preparation and the optical response of oxidized dyes, quantitative agreement with multiple transient absorption datasets is achieved on timescales spanning femtoseconds to nanoseconds. In particular, quantitative agreement with important spectroscopic handles-the decay of an excited state absorption signal component associated with charge injection in the UV region of the spectrum and the dynamical redshift of a ∼500 nm isosbestic point-validates our kinetic model. Pseudo-first-order rate coefficients for charge injection are estimated in this work, with an order of magnitude ranging from 1011 to 1012 s-1. The model makes the minimalist assumption that all excited states of a particular dye have the same charge injection coefficient, an assumption that would benefit from additional theoretical and experimental exploration. We have adapted this kinetic model to predict charge injection under continuous solar irradiation and find that as many as 68 electron transfer events per dye per second take place, significantly more than prior estimates in the literature.