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1.
J Biopharm Stat ; 33(2): 234-252, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36121193

ABSTRACT

Recently, retrieved-dropout-based multiple imputation has been used in some therapeutic areas to address the treatment policy estimand, mostly for continuous endpoints. In this approach, data from subjects who discontinued study treatment but remained in study were used to construct a model for multiple imputation for the missing data of subjects in the same treatment arm who discontinued study. We extend this approach to time-to-event endpoints and provide a practical guide for its implementation. We use a cardiovascular outcome trial dataset to illustrate the method and compare the results with those from Cox proportional hazard and reference-based multiple imputation methods.

2.
Front Public Health ; 10: 890381, 2022.
Article in English | MEDLINE | ID: mdl-35719655

ABSTRACT

The Kiribati 2019 Integrated Household Income and Expenditure Survey (Integrated HIES) embeds novel ecological and human health research into an ongoing social and economic survey infrastructure implemented by the Pacific Community in partnership with national governments. This study seeks to describe the health status of a large, nationally representative sample of a geographically and socially diverse I-Kiribati population through multiple clinical measurements and detailed socio-economic surveys, while also conducting supporting food systems research on ecological, social, and institutional drivers of change. The specific hypotheses within this research relate to access to seafood and the potential nutritional and health benefits of these foods. We conducted this research in 21 of the 23 inhabited islands of Kiribati, excluding the two inhabited islands-Kanton Islands in the Phoenix Islands group with a population of 41 persons (2020 census) and Banaba Island in the Gilbert Islands group with a population of 333 persons (2020 census)-and focusing exclusively on the remaining islands in the Gilbert and Line Islands groups. Within this sample, we focused our intensive human health and ecological research in 10 of the 21 selected islands to examine the relationship between ecological conditions, resource governance, food system dynamics, and dietary patterns. Ultimately, this research has created a baseline for future Integrated HIES assessments to simultaneously monitor change in ecological, social, economic, and human health conditions and how they co-vary over time.


Subject(s)
Coral Reefs , Fisheries , Ethnicity , Humans , Micronesia/epidemiology
3.
Am J Public Health ; 111(4): 663-666, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33600252

ABSTRACT

A safety-net hospital in Boston, Massachusetts, made adaptations to its Nourishing Our Community Program to accommodate restrictions brought on by the COVID-19 pandemic to continue providing food and education to patients. While participation in programs decreased overall, some of the adaptations made, including virtual classes and food pantry home delivery, were well received and are planned to be maintained after the pandemic subsides. By making adjustments to operational procedures, the Nourishing Our Community Program continued to reach its underserved population despite pandemic challenges.


Subject(s)
COVID-19 , Food Assistance , Medically Underserved Area , Resource Allocation , Safety-net Providers , Vulnerable Populations , Boston , Humans , Massachusetts , Poverty , Urban Population
4.
Am J Epidemiol ; 188(2): 382-388, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30407481

ABSTRACT

The US population aged 90 years or more is growing rapidly, and there are limited data on their health. The Cardiovascular Health Study is a prospective study of black and white adults aged ≥65 years recruited in 2 waves (1989-1990 and 1992-1993) from Medicare eligibility lists in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. We created a synthetic cohort of the 1,889 participants who had reached age 90 years at baseline or during follow-up through July 16, 2015. Participants entered the cohort at 90 years of age, and we evaluated their changes in health after age 90 years (median duration of follow-up, 3 years (interquartile range, 1.3-5)). Measures of health included cardiovascular events, cognitive function, depressive symptoms, prescription medications, self-rated health, and functional status. The mortality rate was high: 19.0 per 100 person-years (95% confidence interval : 17.8, 20.3) in women and 20.9 per 100 person-years (95% confidence interval: 19.2, 22.8) in men. Cognitive function and all measures of functional status declined with age; these changes were similar by sex. When we isolated period effects, we found that medication use increased over time. These estimates can help inform future research and can help health-care systems meet the needs of this growing population.


Subject(s)
Black or African American/statistics & numerical data , Health Status , Mental Health/ethnology , White People/statistics & numerical data , Activities of Daily Living , Age Factors , Aged, 80 and over , Cardiovascular Diseases/ethnology , Cognition , Cognition Disorders/ethnology , Depression/ethnology , Female , Humans , Male , Medicare/statistics & numerical data , Mortality/ethnology , Physical Functional Performance , Prescription Drugs/administration & dosage , Prospective Studies , Risk Factors , Sex Factors , Time Factors , United States
6.
J Am Heart Assoc ; 6(3)2017 Mar 13.
Article in English | MEDLINE | ID: mdl-28288973

ABSTRACT

BACKGROUND: Despite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density (BMD) and heart failure (HF) risk remains insufficiently studied. METHODS AND RESULTS: We investigated whether BMD measured by dual-energy x-ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55% women) developed HF during the median follow-up of 10.5 years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF, with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95% CI, 1.01-1.26] per 0.1 g/cm2 decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95% CI, 0.59-0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95% CI, 1.39-5.74]) compared with normal BMD. CONCLUSIONS: Among older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways.


Subject(s)
Black or African American , Bone Density , Health Status , Heart Failure/etiology , Osteoporosis/complications , Risk Assessment/methods , White People , Absorptiometry, Photon , Aged , Disease Progression , Female , Femur Neck/diagnostic imaging , Heart Failure/diagnosis , Heart Failure/ethnology , Humans , Longitudinal Studies , Male , Osteoporosis/diagnosis , Osteoporosis/ethnology , Pelvic Bones/diagnostic imaging , Prevalence , Proportional Hazards Models , Retrospective Studies , Risk Factors , Survival Rate/trends , United States/epidemiology
7.
Am J Cardiol ; 119(6): 923-928, 2017 03 15.
Article in English | MEDLINE | ID: mdl-28073429

ABSTRACT

We evaluated the association between 2-dimensional (2D) echocardiography (echo)-determined myocardial contraction fraction (MCF) and adverse cardiovascular outcomes including incident heart failure (HF), atherosclerotic cardiovascular disease (ASCVD), and mortality. The MCF, the ratio of left ventricular (LV) stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that can distinguish pathologic from physiological hypertrophy. Using 2D echo-guided M-mode data from the Cardiovascular Health Study, we calculated MCF in subjects with LV ejection fraction (EF) ≥55% and used Cox models to evaluate its association with incident HF, ASCVD, and all-cause mortality after adjusting for clinical and echo parameters. We assessed whether log2(SV) and log2(MV) were consistent with the expected 1:-1 ratio used in the definition of MCF. Among 2,147 participants (age 72 ± 5 years), average MCF was 59 ± 13%. After controlling for clinical and echo variables, each 10% absolute increment in MCF was associated with lower risk of HF (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82, 0.94), ASCVD (HR 0.90; 95% CI 0.85, 0.95), and death (HR 0.93; 95% CI 0.89, 0.97). Moreover, the MCF was still significantly associated with ASCVD and mortality, but not HF, after adjustment for percent-predicted LV mass. Significant departure from the 1:-1 ratio was not observed for ASCVD or death, but did occur for HF, driven by a stronger association for MV than SV. In conclusion, among older adults without CVD or low LV ejection fraction, 2D echo-guided M-mode-derived MCF was independently associated with lower risk of adverse cardiovascular outcomes, but this ratiometric index may not capture the full relation that is apparent when its components are modeled separately in the case of HF.


Subject(s)
Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Echocardiography , Heart Failure/diagnostic imaging , Heart Failure/mortality , Aged , Coronary Artery Disease/epidemiology , Coronary Artery Disease/physiopathology , Female , Heart Failure/epidemiology , Heart Failure/physiopathology , Humans , Incidence , Male , Myocardial Contraction/physiology , Stroke Volume/physiology , United States/epidemiology
8.
FASEB J ; 29(8): 3582-92, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25977255

ABSTRACT

The mitochondrial respiratory chain (RC) produces most of the cellular ATP and requires strict quality-control mechanisms. To examine RC subunit proteostasis in vivo, we measured RC protein half-lives (HLs) in mice by liquid chromatography-tandem mass spectrometry with metabolic [(2)H3]-leucine heavy isotope labeling under divergent conditions. We studied 7 tissues/fractions of young and old mice on control diet or one of 2 diet regimens (caloric restriction or rapamycin) that altered protein turnover (42 conditions in total). We observed a 6.5-fold difference in mean HL across tissues and an 11.5-fold difference across all conditions. Normalization to the mean HL of each condition showed that relative HLs were conserved across conditions (Spearman's ρ = 0.57; P < 10(-4)), but were highly heterogeneous between subunits, with a 7.3-fold mean range overall, and a 2.2- to 4.6-fold range within each complex. To identify factors regulating this conserved distribution, we performed statistical analyses to study the correlation of HLs to the properties of the subunits. HLs significantly correlated with localization within the mitochondria, evolutionary origin, location of protein-encoding, and ubiquitination levels. These findings challenge the notion that all subunits in a complex turnover at comparable rates and suggest that there are common rules governing the differential proteolysis of RC protein subunits under divergent cellular conditions.


Subject(s)
Electron Transport/physiology , Mitochondria/physiology , Proteins/metabolism , Animals , Biological Evolution , Caloric Restriction/methods , Female , Isotope Labeling/methods , Leucine/metabolism , Mass Spectrometry/methods , Mice , Mice, Inbred C57BL , Protein Subunits/metabolism , Proteolysis , Ubiquitination/physiology
9.
Technology (Singap World Sci) ; 3(4): 163-171, 2015 Dec.
Article in English | MEDLINE | ID: mdl-27158641

ABSTRACT

We developed micromolded microwell arrays to study the proliferation and senescence of single cells. Microwell arrays were designed to be compatible with conventional cell culture protocols to simplify cell loading, cell culture, and imaging. We demonstrated the utility of these arrays by measuring the proliferation and senescence of isogenic cells which expressed or had been depleted of the human Werner syndrome protein. Our results allowed us to reveal cell-to-cell heterogeneity in proliferation in WRN+ and WRN-depleted fibroblasts during clonal growth.

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