A consolidated and geolocated facility list in Senegal from triangulating secondary data.

Having a geolocated list of all facilities in a country - a "master facility list" (MFL) - can provide critical inputs for health program planning and implementation. To the best of our knowledge, Senegal has never had a centralized MFL, though many data sources currently exist within the broader Senegalese data landscape that could be leveraged and consolidated into a single database - a critical first step toward building a full MFL. We collated 12,965 facility observations from 16 separate datasets and lists in Senegal, and applied matching algorithms, manual checking and revisions as needed, and verification processes to identify unique facilities and triangulate corresponding GPS coordinates. Our resulting consolidated facility list has a total of 4,685 facilities, with 2,423 having at least one set of GPS coordinates. Developing approaches to leverage existing data toward future MFL establishment can help bridge data demands and inform more targeted approaches for completing a full facility census based on areas and facility types with the lowest coverage. Going forward, it is crucial to ensure routine updates of current facility lists, and to strengthen government-led mechanisms around such data collection demands and the need for timely data for health decision-making.

Innovations in social health delivery to advance equitable pediatric and adolescent life course health development: A review and roadmap forward.

Recognizing the influence of social determinants on health and development, health care has increasingly advocated for interventions that target upstream factors as part of routine pediatric care delivery. In response, clinic-based social risk screening and referral programs have proliferated wherein patients are screened for health-related social needs (HRSNs, such as food and housing insecurity) and referred to community-based organizations (CBOs) and social service providers to address those needs. In recent years, an array of digital platforms, known as Social Health Access and Referral Platforms (SHARPs), have emerged to facilitate the scale and implementation of these models amidst growing system demand. Recent evidence on the effectiveness of social risk screen and refer models and SHARPs has been mixed, giving researchers pause and calling for more nuanced understanding of the limitations of such models, especially for promoting child and family health. Design thinking informed by the Life-Course Health Development (LCHD) framework provides a particularly useful lens for synthesizing emerging limitations of such models in the pediatric context, given the dynamic and developmentally-driven circumstances that shape family health and well-being in the early life course. By (1) focusing on addressing deficits-based social risks, (2) scoping to act upon narrow, downstream needs, (3) timing to react to social needs that have already caused harm rather than preventing them, and (4) limiting scale to individual-by-individual responses rather than structural and population-wide interventions, the current design of prevailing social risk screen and refer programs fundamentally limits their potential impact and misses opportunities to improve health equity over the life course. How can health care, social care, and technology partners move forward in collaboration with families and communities to better support equitable lifelong health and social development? In this narrative review, we will summarize the current design, implementation, and limitations of the predominant social risk screen and refer approach in the context of early childhood and adolescent care delivery. We then will apply LCHD principles to advance and improve on this approach from a reactionary focus towards a Family Journey Model that better supports life course health development.

Increased posterior cingulate cortex blood flow in cancer-related fatigue.

Fatigue is a common symptom associated with cancer treatments. Brain mechanisms underlying cancer-related fatigue (CRF) and its progression following therapy are poorly understood. Previous studies have suggested a role of the default mode network (DMN) in fatigue. In this study we used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) and compared resting cerebral blood flow (CBF) differences in the posterior cingulate cortex (PCC), a core hub of the DMN, between 16 patients treated with radiation therapy (RAT) for prostate (9 males) or breast (7 females) cancer and 18 healthy controls (HC). Resting CBF in patients was also measured immediately after the performance of a fatiguing 20-min psychomotor vigilance task (PVT). Twelve of 16 cancer patients were further followed between 3 and 7 months after completion of the RAT (post-RAT). Patients reported elevated fatigue on RAT in comparison to post-RAT, but no change in sleepiness, suggesting that the underlying neural mechanisms of CRF progression are distinct from those regulating sleep drive progression. Compared to HC, patients showed significantly increased resting CBF in the PCC and the elevated PCC CBF persisted during the follow up visit. Post-PVT, but not pre-PVT, resting CBF changes in the PCC correlated with fatigue changes after therapy in patients with CRF, suggesting that PCC CBF following a fatiguing cognitive task may be a biomarker for CRF recovery.

Implementation of cross-sector partnerships: a description of implementation factors related to addressing social determinants to reduce racial disparities in adverse birth outcomes.

Introduction: Traditional perinatal care alone cannot address the social and structural determinants that drive disparities in adverse birth outcomes. Despite the wide acceptance of partnerships between healthcare systems and social service agencies to address this challenge, there needs to be more research on the implementation factors that facilitate (or hinder) cross-sector partnerships, particularly from the perspective of community-based organizations. This study aimed to integrate the views of healthcare staff and community-based partner organizations to describe the implementation of a cross-sector partnership designed to address social and structural determinants in pregnancy. Methods: We used a mixed methods design (in-depth interviews and social network analysis) to integrate the perspectives of healthcare clinicians and staff with those of community-based partner organizations to identify implementation factors related to cross-sector partnerships. Results: We identified seven implementation factors related to three overarching themes: relationship-centered care, barriers and facilitators of cross-sector partnerships, and strengths of a network approach to cross-sector collaboration. Findings emphasized establishing relationships between healthcare staff, patients, and community-based partner organizations. Conclusion: This study provides practical insights for healthcare organizations, policymakers, and community organizations that aim to improve access to social services among historically marginalized perinatal populations.

Triplin: Mechanistic Basis for Voltage Gating.

The outer membrane of Gram-negative bacteria contains a variety of pore-forming structures collectively referred to as porins. Some of these are voltage dependent, but weakly so, closing at high voltages. Triplin, a novel bacterial pore-former, is a three-pore structure, highly voltage dependent, with a complex gating process. The three pores close sequentially: pore 1 at positive potentials, 2 at negative and 3 at positive. A positive domain containing 14 positive charges (the voltage sensor) translocates through the membrane during the closing process, and the translocation is proposed to take place by the domain entering the pore and thus blocking it, resulting in the closed conformation. This mechanism of pore closure is supported by kinetic measurements that show that in the closing process the voltage sensor travels through most of the transmembrane voltage before reaching the energy barrier. Voltage-dependent blockage of the pores by polyarginine, but not by a 500-fold higher concentrations of polylysine, is consistent with the model of pore closure, with the sensor consisting mainly of arginine residues, and with the presence, in each pore, of a complementary surface that serves as a binding site for the sensor.

Association of Major Adverse Cardiac Events and Beta-Blockers in Patients with and without Atherosclerotic Cardiovascular Disease: Long-Term Follow-Up Results of the T-SPARCLE and T-PPARCLE Registry in Taiwan.

Beta-blockers are widely used, but the benefit is now challenged in patients at risk of atherosclerotic cardiovascular disease (ASCVD) in the present coronary reperfusion era. We aimed to identify the risk factors of a major adverse cardiac event (MACE) and the long-term effect of beta-blockers in two large cohorts in Taiwan. Two prospective observational cohorts, including patients with known atherosclerosis cardiovascular disease (T-SPARCLE) and patients with at least one risk factor of ASCVD but without clinically evident ASCVD (T-PPARCLE), were conducted in Taiwan. The primary endpoint is the time of first occurrence of a MACE (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and cardiac arrest with resuscitation). Between December 2009 and November 2014, with a median 2.4 years follow-up, 11,747 eligible patients (6921 and 4826 in T-SPARCLE and T-PPARCLE, respectively) were enrolled. Among them, 273 patients (2.3%) met the primary endpoint. With multivariate Cox PH model analysis, usage of beta-blocker was lower in patients with MACE (42.9% vs. 52.4%, p < 0.01). In patients with ASCVD, beta-blocker usage was associated with lower MACEs (hazard ratio 0.72; p < 0.001), but not in patients without ASCVD. The event-free survival of beta-blocker users remained higher during the follow-up period (p < 0.005) of ASCVD patients. In conclusion, in ASCVD patients, reduced MACE was associated with beta-blocker usage, and the effect was maintained during a six-year follow-up. Prescribing beta-blockers as secondary prevention is reasonable in the Taiwanese population.

A Framework for Cross-Sector Partnerships to Address Childhood Adversity and Improve Life Course Health.

Childhood adversity and its structural causes drive lifelong and intergenerational inequities in health and well-being. Health care systems increasingly understand the influence of childhood adversity on health outcomes but cannot treat these deep and complex issues alone. Cross-sector partnerships, which integrate health care, food support, legal, housing, and financial services among others, are becoming increasingly recognized as effective approaches address health inequities. What principles should guide the design of cross-sector partnerships that address childhood adversity and promote Life Course Health Development (LCHD)? The complex effects of childhood adversity on health development are explained by LCHD concepts, which serve as the foundation for a cross-sector partnership that optimizes lifelong health. We review the evolution of cross-sector partnerships in health care to inform the development of an LCHD-informed partnership framework geared to address childhood adversity and LCHD. This framework outlines guiding principles to direct partnerships toward life course-oriented action: (1) proactive, developmental, and longitudinal investment; (2) integration and codesign of care networks; (3) collective, community and systemic impact; and (4) equity in praxis and outcomes. Additionally, the framework articulates foundational structures necessary for implementation: (1) a shared cross-sector theory of change; (2) relational structures enabling shared leadership, trust, and learning; (3) linked data and communication platforms; and (4) alternative funding models for shared savings and prospective investment. The LCHD-informed cross-sector partnership framework presented here can be a guide for the design and implementation of cross-sector partnerships that effectively address childhood adversity and advance health equity through individual-, family-, community-, and system-level intervention.

Assessment of Hypothetical Out-of-Pocket Costs of Guideline-Recommended Medications for the Treatment of Older Adults With Multiple Chronic Conditions, 2009 and 2019.

IMPORTANCE: Most adults 65 years or older have multiple chronic conditions. Managing these conditions with prescription drugs can be costly, particularly for older adults with limited incomes. OBJECTIVE: To estimate hypothetical out-of-pocket costs associated with guideline-recommended outpatient medications for the initial treatment of 8 common chronic diseases among older adults with Medicare prescription drug plans (PDPs). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study used 2009 and 2019 Medicare prescription drug plan formulary files to estimate annual out-of-pocket costs among hypothetical patients enrolled in Medicare Advantage or stand-alone Medicare Part D plans. A total of 3599 PDPs in 2009 and 3618 PDPs in 2019 were included after inclusion and exclusion criteria were applied. Costs associated with guideline-recommended medications for 8 of the most common chronic diseases (atrial fibrillation, chronic obstructive pulmonary disease [COPD], heart failure with reduced ejection fraction, hypercholesterolemia, hypertension, osteoarthritis, osteoporosis, and type 2 diabetes), alone and in 2 clusters of commonly comorbid conditions, were examined. MAIN OUTCOMES AND MEASURES: Annual out-of-pocket costs for each chronic condition, inflation adjusted to 2019 dollars. RESULTS: Among 3599 Medicare PDPs in 2009, 1998 were Medicare Advantage plans and 1601 were stand-alone plans; among 3618 Medicare PDPs in 2019, 2719 were Medicare Advantage plans and 899 were stand-alone plans. For an older adult enrolled in any Medicare PDP in 2019, the median annual out-of-pocket costs for individual conditions varied, from a minimum of $32 (IQR, $6-$48) for guideline-recommended management of osteoporosis (a decrease from $128 [IQR, $102-$183] in 2009) to a maximum of $1579 (IQR, $1524-$2229) for guideline-recommended management of atrial fibrillation (an increase from $91 [IQR, $73-$124] in 2009). For an older adult with a cluster of 5 commonly comorbid conditions (COPD, hypertension, osteoarthritis, osteoporosis, and type 2 diabetes) enrolled in any PDP, the median out-of-pocket cost in 2019 was $1999 (IQR, $1630-$2564), a 12% decrease from $2284 (IQR, $1920-$3107) in 2009. For an older adult with all 8 chronic conditions (atrial fibrillation, COPD, diabetes, hypercholesterolemia, heart failure, hypertension, osteoarthritis, and osteoporosis) enrolled in any PDP, the median out-of-pocket cost in 2019 was $3630 (IQR, $3234-$5197), a 41% increase from $2571 (IQR, $2185-$3719) in 2009. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, out-of-pocket costs for guideline-recommended outpatient medications for the initial treatment of 8 common chronic diseases varied by condition. Although costs generally decreased between 2009 and 2019, particularly with regard to conditions for which generic drugs were available, out-of-pocket costs remained high and may have presented a substantial financial burden for Medicare beneficiaries, especially older adults with conditions for which brand-name drugs were guideline recommended.

Long-Term Clinical Outcomes of Fractional Flow Reserve-Guided Coronary Artery Revascularization in Chronic Kidney Disease.

Fractional flow reserve (FFR)-guided percutaneous coronary intervention has shown favorable long-term clinical outcomes. However, limited data exist evaluating the FFR assessment among the chronic kidney disease (CKD) population. The aim of this study was to evaluate the long-term clinical outcomes of FFR-guided coronary revascularization in patients with CKD. A total of 242 CKD patients who underwent FFR assessment were retrospectively analyzed. Patients were divided into two groups: revascularization (FFR ≤ 0.80) and non-revascularization (FFR > 0.80). The primary endpoint was the composite of cardiac death, non-fatal myocardial infarction, and target vessel failure (TVF). The key secondary endpoint was TVF. The Cox regression model was used for risk evaluation. With 91% of the ischemic vessels revascularized, the revascularization group had higher risks for both the primary endpoint (adjusted hazard ratio [aHR]: 2.06; 95% confidence interval [CI], 1.07-3.97; p = 0.030) and key secondary endpoint (aHR: 2.19, 95% CI: 1.10-4.37; p = 0.026), during a median follow-up of 2.9 years. This result was consistent among different CKD severities. In patients with CKD, functional ischemia in coronary artery stenosis was associated with poor clinical outcomes despite coronary revascularization.

Pediatric Household Transmission of Severe Acute Respiratory Coronavirus-2 Infection-Los Angeles County, December 2020 to February 2021.

This brief report presents transmission rates from a prospective study of 15 households with pediatric index cases of severe acute respiratory coronavirus-2 in Los Angeles County from December 2020 to February 2021. Our findings support ongoing evidence that transmission from pediatric index cases to household contacts is frequent but can be mitigated with practicing well-documented control measures at home, including isolation, masking and good hand hygiene.

Interest in Clinic-Based Financial Services among Low-Income Prenatal Patients and its Association with Health-Related Social Risk Factors.

BACKGROUND: Poverty and financial stress affect prenatal health and well-being as well as early childhood development. This study sought to examine interest in clinic-based financial services to address financial stress in low-income, Medicaid-enrolled prenatal patients and its relationship with self-reported social risks. METHODS: We conducted a cross-sectional study of patients at a large safety-net prenatal clinic. Participants completed a written survey on interest in linkage to financial services, poverty-related financial stress, difficulty affording social needs, and interest in services to address material hardships. We compared interest in financial and social needs services by level of financial stress using multivariate regression. RESULTS: Respondents (N = 108) were entirely Medicaid-enrolled, with a majority identifying as Hispanic/Latinx (57%) or Black/African American (20%). Sixty-four percent indicated interest in connection to any of the financial services surveyed. Interest was highest in employment (52%), savings and budgeting (49%), job training/adult education (49%), and financial counseling (48%) services. Individuals with high financial stress, compared to those with low financial stress, expressed a higher level of interest in financial services (aRR = 1.61 [95% CI 1.12-2.39]). Interest in financial services was associated with difficulty affording social needs (aRR = 2.24 [95% CI 1.33-4.43]) and interest in services addressing social needs (aRR = 1.45 [95% CI 1.13-1.92]). CONCLUSION: In this study of low-income, Medicaid-insured prenatal patients, there was a high degree of interest in clinic-based financial services. Integrating financial services into prenatal health care appears to be an approach that low-income patients would be interested in to directly address poverty and financial stress.

Predictive performance of international COVID-19 mortality forecasting models.

Forecasts and alternative scenarios of COVID-19 mortality have been critical inputs for pandemic response efforts, and decision-makers need information about predictive performance. We screen n = 386 public COVID-19 forecasting models, identifying n = 7 that are global in scope and provide public, date-versioned forecasts. We examine their predictive performance for mortality by weeks of extrapolation, world region, and estimation month. We additionally assess prediction of the timing of peak daily mortality. Globally, models released in October show a median absolute percent error (MAPE) of 7 to 13% at six weeks, reflecting surprisingly good performance despite the complexities of modelling human behavioural responses and government interventions. Median absolute error for peak timing increased from 8 days at one week of forecasting to 29 days at eight weeks and is similar for first and subsequent peaks. The framework and public codebase ( https://github.com/pyliu47/covidcompare ) can be used to compare predictions and evaluate predictive performance going forward.

International COVID-19 mortality forecast visualization: covidcompare.io.

COVID-19 mortality forecasting models provide critical information about the trajectory of the pandemic, which is used by policymakers and public health officials to guide decision-making. However, thousands of published COVID-19 mortality forecasts now exist, many with their own unique methods, assumptions, format, and visualization. As a result, it is difficult to compare models and understand under which circumstances a model performs best. Here, we describe the construction and usability of covidcompare.io, a web tool built to compare numerous forecasts and offer insight into how each has performed over the course of the pandemic. From its launch in December 2020 to June 2021, we have seen 4600 unique visitors from 85 countries. A study conducted with public health professionals showed high usability overall as formally assessed using a Post-Study System Usability Questionnaire. We find that covidcompare.io is an impactful tool for the comparison of international COVID-19 mortality forecasting models.

The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1.

Myotonic dystrophy type I (DM1) is a multisystemic autosomal-dominant inherited human disorder that is caused by CTG microsatellite repeat expansions (MREs) in the 3' untranslated region of DMPK. Toxic RNAs expressed from such repetitive sequences can be eliminated using CRISPR-mediated RNA targeting, yet evidence of its in vivo efficacy and durability is lacking. Here, using adult and neonatal mouse models of DM1, we show that intramuscular or systemic injections of adeno-associated virus (AAV) vectors encoding nuclease-dead Cas9 and a single-guide RNA targeting CUG repeats results in the expression of the RNA-targeting Cas9 for up to three months, redistribution of the RNA-splicing protein muscleblind-like splicing regulator 1, elimination of foci of toxic RNA, reversal of splicing biomarkers and amelioration of myotonia. The sustained reversal of DM1 phenotypes provides further support that RNA-targeting Cas9 is a viable strategy for treating DM1 and other MRE-associated diseases.

Predictive performance of international COVID-19 mortality forecasting models.

Forecasts and alternative scenarios of COVID-19 mortality have been critical inputs into a range of policies and decision-makers need information about predictive performance. We identified n=386 public COVID-19 forecasting models and included n=8 that were global in scope and provided public, date-versioned forecasts. For each, we examined the median absolute percent error (MAPE) compared to subsequently observed mortality trends, stratified by weeks of extrapolation, world region, and month of model estimation. Models were also assessed for ability to predict the timing of peak daily mortality. The MAPE among models released in July rose from 1.8% at one week of extrapolation to 24.6% at twelve weeks. The MAPE at six weeks were the highest in Sub-Saharan Africa (34.8%), and the lowest in high-income countries (6.3%). At the global level, several models had about 10% MAPE at six weeks, showing surprisingly good performance despite the complexities of modelling human behavioural responses and government interventions. The framework and publicly available codebase presented here ( https://github.com/pyliu47/covidcompare ) can be routinely used to compare predictions and evaluate predictive performance in an ongoing fashion.

High dose escalation of intracoronary adenosine in the assessment of fractional flow reserve: A retrospective cohort study.

Maximal hyperaemia for fractional flow reserve (FFR) may not be achieved with the current recommended doses of intracoronary adenosine. Higher doses (up to 720 µg) have been reported to optimize hyperaemic stimuli in small dose-response studies. Real-world data from a large cohort of patients is needed to evaluate FFR results and the safety of high-dose escalation. This is a retrospective study aimed to evaluate the safety and frequency of FFR ≤0.8 after high-dose escalation of intracoronary adenosine. Data were extracted from the medical databases of two university hospitals. Increasing doses (100, 200, 400, 600, and 800 µg) of adenosine were administered as intracoronary boluses until FFR ≤0.8 was achieved or heart block developed. The percentage of FFR ≤0.8 after higher-dose escalation was compared with those at conventional doses, and the predictors for FFR ≤0.8 after higher doses were analysed. In the 1163 vessels of 878 patients, 402 vessels (34.6%) achieved FFR ≤0.8 at conventional doses and 623 vessels (53.6%) received high-dose escalation. An additional 84 vessels (13.5%) achieved FFR ≤0.8 after high-dose escalation. No major complications developed during high-dose escalation. Borderline FFR (0.81-0.85) at the conventional dose, stenosis >60%, and triple-vessel disease increased the likelihood of FFR ≤0.8 after high-dose escalation, but chronic kidney disease decreased it. For vessels of borderline FFR at conventional doses, 46% achieved FFR ≤0.8 after high-dose escalation. In conclusion, High-dose escalation of intracoronary adenosine increases the frequency of FFR ≤0.8 without major complications. It could be especially feasible for borderline FFR values near the 0.8 diagnostic threshold.

Prostaglandin Coverage and Costs to Medicare and Medicare Beneficiaries, 2009-2017.

BACKGROUND: Prostaglandin analogs are the most effective treatment for glaucoma, a common condition among older adults. Despite the availability of generic drugs, the costs associated with these prescription drugs are rising. OBJECTIVE: To characterize Medicare prescription drug plan (PDP) formulary coverage and beneficiary out-of-pocket cost for prostaglandin analogs from 2009 to 2017 and Medicare spending on prostaglandin analogs from 2013 to 2017. METHODS: This study was a retrospective analysis. We used 2009, 2013, and 2017 Medicare PDP formulary, beneficiary cost, and pricing files to determine beneficiary first-prescription out-of-pocket costs and plan coverage (unrestricted, restricted, or not covered) of branded latanoprost 0.005%, travoprost 0.004%, bimatoprost 0.03% and 0.01%, and tafluprost 0.0015% and of generic latanoprost 0.005% and generic bimatoprost 0.03%. We also used Medicare Part D spending data to determine aggregate spend in 2013 and 2017. RESULTS: In 2009, 92% of plans covered branded latanoprost, 83% covered branded bimatoprost; and 49% covered branded travoprost, whereas in 2017, 6% of plans covered branded latanoprost; 95% covered branded bimatoprost; and 96% covered branded travoprost. Although generic latanoprost was universally covered, generic bimatoprost was only covered by 35% of plans in 2017. Median out-of-pocket cost of branded prostaglandins without generic equivalents was $35 (IQR = $29-$40) in 2009, $45 (IQR = $42-$101) in 2013, and $90 (IQR = $45-$159) in 2017. Median out-of-pocket cost of all available generic prostaglandins was $10 (IQR = $5-$33) in 2013 and $10 (IQR = $4-$15) in 2017. In 2013, Medicare spent $733 million on prostaglandin analogs; in 2017, this increased to $1.09 billion, with $943 million (86%) spent on branded prostaglandins and $148 million (14%) spent on generics. CONCLUSIONS: Medicare PDP coverage of branded prostaglandins remained stable from 2009 to 2017. While median beneficiary out-of-pocket costs associated with generic prostaglandins remained stable, those associated with branded prostaglandins increased nearly 3-fold. DISCLOSURES: Research reported in this publication was supported by National Heart, Lung and Blood Institute of the National Institutes of Health under Award Number T35HL007649. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. Shah has received research support through Mayo Clinic from the U.S. Food and Drug Administration (FDA) to establish Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation (CERSI) program (U01FD005938); the Centers of Medicare and Medicaid Innovation under the Transforming Clinical Practice Initiative (TCPI); the Agency for Healthcare Research and Quality (U19HS024075, R01HS025164, R01HS025402, R03HS025517); and the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R56HL130496, R01HL131535), National Science Foundation, and the Patient Centered Outcomes Research Institute to develop a clinical data research network. Ross has received research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing; Medtronic and the FDA to develop methods for postmarket surveillance of medical devices (U01FD004585); the FDA to establish Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (U01FD005938); the Blue Cross Blue Shield Association to better understand medical technology evaluation; the Centers of Medicare & Medicaid Services to develop and maintain performance measures that are used for public reporting (HHSM-500-2013-13018I); the Agency for Healthcare Research and Quality (R01HS022882); the National Heart, Lung and Blood Institute of the NIH (R01HS025164); and the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International and the Collaboration on Research Integrity and Transparency at Yale. The other authors have nothing to disclose.