INFERENCE FOR SURVIVAL CURVES WITH INFORMATIVELY COARSENED DISCRETE EVENT-TIME DATA: APPLICATION TO ALIVE

In many prospective studies, including AIDS Link to the Intravenous Experience (ALIVE), researchers are interested in comparing event-time distributions (e.g.,for human immunodeficiency virus seroconversion) between a small number of groups (e.g., risk behavior categories). However, these comparisons are complicated by participants missing visits or attending visits off schedule and seroconverting during this absence. Such data are interval-censored, or more generally,coarsened. Most analysis procedures rely on the assumption of non-informative censoring, a special case of coarsening at random that may produce biased results if not valid. Our goal is to perform inference for estimated survival functions across a small number of goups in the presence of informative coarsening. To do so, we propose methods for frequentist and Bayesian inference of ALIVE data utilizing information elicited from ALIVE scientists and an AIDS epidemiology expert about the visit compliance process

A Semi-Parametric Model Simultaneously Handling Unmeasured Confounding, Informative Cluster Size, and Truncation by Death with a Data Application in Medicare Claims

Nearly 300,000 older adults experience a hip fracture every year, the majority of which occur following a fall. Unfortunately, recovery after fall-related trauma such as hip fracture is poor, where older adults diagnosed with Alzheimer's Disease and Related Dementia (ADRD) spend a particularly long time in hospitals or rehabilitation facilities during the post-operative recuperation period. Because older adults value functional recovery and spending time at home versus facilities as key outcomes after hospitalization, identifying factors that influence days spent at home after hospitalization is imperative. While several individual-level factors have been identified, the characteristics of the treating hospital have recently been identified as contributors. However, few methodological rigorous approaches are available to help overcome potential sources of bias such as hospital-level unmeasured confounders, informative hospital size, and loss to follow-up due to death. This article develops a useful tool equipped with unsupervised learning to simultaneously handle statistical complexities that are often encountered in health services research, especially when using large administrative claims databases. The proposed estimator has a closed form, thus only requiring light computation load in a large-scale study. We further develop its asymptotic properties that can be used to make statistical inference in practice. Extensive simulation studies demonstrate superiority of the proposed estimator compared to existing estimators.Comment: Contact Emails: [email protected]

Seasonal and Temperature-Associated Increases in Gram-Negative Bacterial Bloodstream Infections among Hospitalized Patients

BACKGROUND: Knowledge of seasonal trends in hospital-associated infection incidence may improve surveillance and help guide the design and evaluation of infection prevention interventions. We estimated seasonal variation in the frequencies of inpatient bloodstream infections (BSIs) caused by common bacterial pathogens and examined associations of monthly BSI frequencies with ambient outdoor temperature, precipitation, and humidity levels. METHODS: A database containing blood cultures from 132 U.S. hospitals collected between January 1999 and September 2006 was assembled. The database included monthly counts of inpatient blood cultures positive for several clinically important Gram-negative bacteria (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Gram-positive bacteria (Enterococcus spp and Staphylococcus aureus). Monthly mean temperature, total precipitation, and mean relative humidity in the postal ZIP codes of participating hospitals were obtained from national meteorological databases. RESULTS: A total of 211,697 inpatient BSIs were reported during 9,423 hospital-months. Adjusting for long-term trends, BSIs caused by each gram-negative organism examined were more frequent in summer months compared with winter months, with increases ranging from 12.2% for E. coli (95% CI 9.2-15.4) to 51.8% for Acinetobacter (95% CI 41.1-63.2). Summer season was associated with 8.7% fewer Enterococcus BSIs (95% CI 11.0-5.8) and no significant change in S. aureus BSI frequency relative to winter. Independent of season, monthly humidity, monthly precipitation, and long-term trends, each 5.6°C (10°F) rise in mean monthly temperature corresponded to increases in gram-negative bacterial BSI frequencies ranging between 3.5% for E. coli (95% CI 2.1-4.9) to 10.8% for Acinetobacter (95% CI 6.9-14.7). The same rise in mean monthly temperature corresponded to an increase of 2.2% in S. aureus BSI frequency (95% CI 1.3-3.2) but no significant change in Enterococcus BSI frequency. CONCLUSIONS: Summer season and higher mean monthly outdoor temperature are associated with substantially increased frequency of BSIs, particularly among clinically important gram-negative bacteria

Factors that influence exercise activity among women post hip fracture participating in the Exercise Plus Program

Using a social ecological model, this paper describes selected intra- and interpersonal factors that influence exercise behavior in women post hip fracture who participated in the Exercise Plus Program. Model testing of factors that influence exercise behavior at 2, 6 and 12 months post hip fracture was done. The full model hypothesized that demographic variables; cognitive, affective, physical and functional status; pain; fear of falling; social support for exercise, and exposure to the Exercise Plus Program would influence self-efficacy, outcome expectations, and stage of change both directly and indirectly influencing total time spent exercising. Two hundred and nine female hip fracture patients (age 81.0 ± 6.9), the majority of whom were Caucasian (97%), participated in this study. The three predictive models tested across the 12 month recovery trajectory suggest that somewhat different factors may influence exercise over the recovery period and the models explained 8 to 21% of the variance in time spent exercising. To optimize exercise activity post hip fracture, older adults should be helped to realistically assess their self-efficacy and outcome expectations related to exercise, health care providers and friends/peers should be encouraged to reinforce the positive benefits of exercise post hip fracture, and fear of falling should be addressed throughout the entire hip fracture recovery trajectory

Application of Big Data to Support Evidence-Based Public Health Policy Decision-Making for Hearing

Ideally, public health policies are formulated from scientific data; however, policy-specific data are often unavailable. Big data can generate ecologically-valid, high-quality scientific evidence, and therefore has the potential to change how public health policies are formulated. Here, we discuss the use of big data for developing evidence-based hearing health policies, using data collected and analyzed with a research prototype of a data repository known as EVOTION (EVidence-based management of hearing impairments: public health pOlicy-making based on fusing big data analytics and simulaTION), to illustrate our points. Data in the repository consist of audiometric clinical data, prospective real-world data collected from hearing aids and an app, and responses to questionnaires collected for research purposes. To date, we have used the platform and a synthetic dataset to model the estimated risk of noise-induced hearing loss and have shown novel evidence of ways in which external factors influence hearing aid usage patterns. We contend that this research prototype data repository illustrates the value of using big data for policy-making by providing high-quality evidence that could be used to formulate and evaluate the impact of hearing health care policies

Child stunting is associated with low circulating essential amino acids

AbstractBackgroundStunting affects about one-quarter of children under five worldwide. The pathogenesis of stunting is poorly understood. Nutritional interventions have had only modest effects in reducing stunting. We hypothesized that insufficiency in essential amino acids may be limiting the linear growth of children.MethodsWe used a targeted metabolomics approach to measure serum amino acids, glycerophospholipids, sphingolipids, and other metabolites using liquid chromatography-tandem mass spectrometry in 313 children, aged 12–59months, from rural Malawi. Children underwent anthropometry.FindingsSixty-two percent of the children were stunted. Children with stunting had lower serum concentrations of all nine essential amino acids (tryptophan, isoleucine, leucine, valine, methionine, threonine, histidine, phenylalanine, lysine) compared with nonstunted children (p<0.01). In addition, stunted children had significantly lower serum concentrations of conditionally essential amino acids (arginine, glycine, glutamine), non-essential amino acids (asparagine, glutamate, serine), and six different sphingolipids compared with nonstunted children. Stunting was also associated with alterations in serum glycerophospholipid concentrations.InterpretationOur findings support the idea that children with a high risk of stunting may not be receiving an adequate dietary intake of essential amino acids and choline, an essential nutrient for the synthesis of sphingolipids and glycerophospholipids

An Evidence-Based Comparison of Operational Criteria for the Presence of Sarcopenia

Background. Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia. Methods. The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed. Results. The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all >95%). Conclusions. The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment

Non‐response adjustment of survey estimates based on auxiliary variables subject to error

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96670/1/j.1467-9876.2012.01058.x.pd

The FNIH Sarcopenia Project: Rationale, Study Description, Conference Recommendations, and Final Estimates

Background. Low muscle mass and weakness are common and potentially disabling in older adults, but in order to become recognized as a clinical condition, criteria for diagnosis should be based on clinically relevant thresholds and independently validated. The Foundation for the National Institutes of Health Biomarkers Consortium Sarcopenia Project used an evidence-based approach to develop these criteria. Initial findings were presented at a conference in May 2012, which generated recommendations that guided additional analyses to determine final recommended criteria. Details of the Project and its findings are presented in four accompanying manuscripts. Methods. The Foundation for the National Institutes of Health Sarcopenia Project used data from nine sources of community-dwelling older persons: Age, Gene/Environment Susceptibility-Reykjavik Study, Boston Puerto Rican Health Study, a series of six clinical trials, Framingham Heart Study, Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men Study, Rancho Bernardo Study, and Study of Osteoporotic Fractures. Feedback from conference attendees was obtained via surveys and breakout groups. Results. The pooled sample included 26,625 participants (57% women, mean age in men 75.2 [±6.1 SD] and in women 78.6 [±5.9] years). Conference attendees emphasized the importance of evaluating the influence of body mass on cutpoints. Based on the analyses presented in this series, the final recommended cutpoints for weakness are grip strength <26kg for men and <16kg for women, and for low lean mass, appendicular lean mass adjusted for body mass index <0.789 for men and <0.512 for women. Conclusions. These evidence-based cutpoints, based on a large and diverse population, may help identify participants for clinical trials and should be evaluated among populations with high rates of functional limitations

Grip Strength Cutpoints for the Identification of Clinically Relevant Weakness

Background. Weakness is common and contributes to disability, but no consensus exists regarding a strength cutpoint to identify persons at high risk. This analysis, conducted as part of the Foundation for the National Institutes of Health Sarcopenia Project, sought to identify cutpoints that distinguish weakness associated with mobility impairment, defined as gait speed less than 0.8 m/s. Methods. In pooled cross-sectional data (9,897 men and 10,950 women), Classification and Regression Tree analysis was used to derive cutpoints for grip strength associated with mobility impairment. Results. In men, a grip strength of 26–32 kg was classified as “intermediate” and less than 26 kg as “weak”; 11% of men were intermediate and 5% were weak. Compared with men with normal strength, odds ratios for mobility impairment were 3.63 (95% CI: 3.01–4.38) and 7.62 (95% CI 6.13–9.49), respectively. In women, a grip strength of 16–20 kg was classified as “intermediate” and less than 16 kg as “weak”; 25% of women were intermediate and 18% were weak. Compared with women with normal strength, odds ratios for mobility impairment were 2.44 (95% CI 2.20–2.71) and 4.42 (95% CI 3.94–4.97), respectively. Weakness based on these cutpoints was associated with mobility impairment across subgroups based on age, body mass index, height, and disease status. Notably, in women, grip strength divided by body mass index provided better fit relative to grip strength alone, but fit was not sufficiently improved to merit different measures by gender and use of a more complex measure. Conclusions. Cutpoints for weakness derived from this large, diverse sample of older adults may be useful to identify populations who may benefit from interventions to improve muscle strength and function