Measuring the Impact of Biostatistical Methods on General Medical Research

Background: Novel statistical methods are constantly being developed within the context of biomedical research; however, the rate of diffusion of this knowledge into the field of general / internal medicine is unclear. This study highlights the statistical journal articles, the statistical journals, and the statistical methods that appear to be having the most direct impact on research in the field of general / internal medicine. Methods: Descriptive techniques, including analyses of articles’ keywords and controlled vocabulary terms, were used to characterize the articles published in statistics and probability journals that were subsequently referenced within general / internal medicine journal articles during a recent 10-year period (2000-2009). Results: From the 45 statistics and probability journals of interest, a total of 597 unique articles were identified as being cited by 900 (out of a total of about 10,501) unique general / internal medicine journal articles. The most frequently cited statistical topics included general/other statistical methods, followed by epidemiologic methods, randomized trials, generalized linear models, meta-analysis, and missing data. Conclusion: As statisticians continue to develop and refine techniques, the promotion and adoption of these methods should also be addressed so that their efforts spent in developing the methods are not done in vain

The Effect of Direct to Consumer Television Advertising on the Timing of Treatment

We examine how direct to consumer advertising (DCA) affects the delay between diagnosis and pharmacological treatment for patients suffering from a common chronic disease. The primary data for this study consist of patients diagnosed with osteoarthritis (N=18,235) taken from a geographically diverse national research network of 72 primary care practices with 348 physicians in 27 states over the 1999 to 2002 time period. Brand specific advertising data was collected for local and network television at the monthly-level for the nearest media markets to the practices. Results of duration models of delay to treatment suggest advertising does affect the length of time that patients and physicians wait to initiate therapy. This evidence suggests these effects may be welfare enhancing, in that advertising tends to encourage more rapid adoption among patients who are good clinical candidates for the therapy, and leads to less rapid adoption among some patients who are poor clinical candidates.Health and Safety, Technology and Industry

Fitting parametric random effects models in very large data sets with application to VHA national data

<p>Abstract</p> <p>Background</p> <p>With the current focus on personalized medicine, patient/subject level inference is often of key interest in translational research. As a result, random effects models (REM) are becoming popular for patient level inference. However, for very large data sets that are characterized by large sample size, it can be difficult to fit REM using commonly available statistical software such as SAS since they require inordinate amounts of computer time and memory allocations beyond what are available preventing model convergence. For example, in a retrospective cohort study of over 800,000 Veterans with type 2 diabetes with longitudinal data over 5 years, fitting REM via generalized linear mixed modeling using currently available standard procedures in SAS (e.g. PROC GLIMMIX) was very difficult and same problems exist in Stata’s gllamm or R’s lme packages. Thus, this study proposes and assesses the performance of a meta regression approach and makes comparison with methods based on sampling of the full data.</p> <p>Data</p> <p>We use both simulated and real data from a national cohort of Veterans with type 2 diabetes (n=890,394) which was created by linking multiple patient and administrative files resulting in a cohort with longitudinal data collected over 5 years.</p> <p>Methods and results</p> <p>The outcome of interest was mean annual HbA1c measured over a 5 years period. Using this outcome, we compared parameter estimates from the proposed random effects meta regression (REMR) with estimates based on simple random sampling and VISN (Veterans Integrated Service Networks) based stratified sampling of the full data. Our results indicate that REMR provides parameter estimates that are less likely to be biased with tighter confidence intervals when the VISN level estimates are homogenous.</p> <p>Conclusion</p> <p>When the interest is to fit REM in repeated measures data with very large sample size, REMR can be used as a good alternative. It leads to reasonable inference for both Gaussian and non-Gaussian responses if parameter estimates are homogeneous across VISNs.</p

ESTUDO LONGITUDINAL DE FATORES QUE AFETAM O RISCO DE FRATURA POR ESTRESSE EM DUAS POPULAÇÕES DE COLEGIAIS DO SEXO FEMININO

Objetivos: As fraturas por estresse causam significante morbidade em mulheres. Diferenças no nível de atividades, valores hormonais e densidade mineral óssea (BMD) afetam diferentemente as taxas de fraturas por estresse. Os autores hipotetizaram que mulheres de um Colégio militar terão maior nível de atividade do que mulheres em colégios com um ambiente mais flexível, que correlacionará com mudanças nos valores hormonais, menor (BMD) e mais fraturas por estresse. Método: Nesse estudo prospectivo comparativo, 63 mulheres de duas Instituições (The Citadel: The Military College Of South Carolina And The College Of Cherleston) relataram detalhadamente suas atividades, dieta e lesões através de um questionário e tiveram sua BMB e os valores hormonais séricos medidos num intervalo de 06 meses, por um período de 2 anos; 38 sujeitos completaram o estudo. A análise estatística examinou diferenças e mudanças ao longo do tempo entre as duas amostras.Resultados: Uma fratura por estresse ocorreu em cada Instituição. As mulheres do Citadel tiveram maiores níveis de atividade, que as mulheres do College of Charleston no longo do estudo. As mulheres do Citadel tiveram menor nível de hormônio folículo estimulante, maior 17 Beta-Estradiol aos 24 meses e maior BMD na extremidade proximal femoral aos 18 meses da investigação (p< 0,05). Conclusões: Os valores séricos hormonais podem ser um indicador mais sensível de resposta ao nível da atividade física que o BMD dentro da amostra e duração deste estudo. Outros estudos são necessários para definir esta complexa interrelação. LONGITUDINAL STUDY OF FACTORS AFFECTING STRESS FRACTURE RISK IN TWO DISTINCT COLLEGE FEMALE POPULATIONS Abstract Objectives: Stress fractures cause significant morbidity in females. Differences in activity levels, hormone values, and bone mineral density (BMD) affect different rates of stress fracture. The authors hypothesized that females at a military college will have greater activity levels than females in a flexible college environment, which will correlate with greater changes in hormone values, lower BMD, and more stress fractures. Methods: In this prospective comparative study 63 females from two institutions (The Citadel: The Military College of South Carolina and the College of Charleston) self-reported on a detailed activity, diet, and injury questionnaire and had BMD and serum hormone values measured at 6- month intervals for a two year period; 38 completed the study. Statistical analysis was designed to examine differences and changes over time between the two samples. Results: One stress fracture occurred in each institution. Citadel females had higher activity levels than females at the College of Charleston throughout the study. Citadel females had lower follicle stimulating hormone levels at 24 months, greater 17 beta-estradiol at 24 months, and greater proximal femoral BMD at eighteen months (

Analyzing Adherence to Prenatal Supplement: Does Pill Count Measure Up?

Objective. To determine if adherence as measured by pill count would show a significant association with serum-based measures of adherence. Methods. Data were obtained from a prenatal vitamin D supplementation trial where subjects were stratified by race and randomized into three dosing groups: 400 (control), 2000, or 4000 IU vitamin D3/day. One measurement of adherence was obtained via pill counts remaining compared to a novel definition for adherence using serum 25-hydroxy-vitamin D (25-OH-D) levels (absolute change in 25(OH)D over the study period and the subject's steady-state variation in their 25(OH)D levels). A multivariate logistic regression model examined whether mean percent adherence by pill count was significantly associated with the adherence measure by serum metabolite levels. Results. Subjects' mean percentage of adherence by pill count was not a significant predictor of adherence by serum metabolite levels. This finding was robust across a series of sensitivity analyses. Conclusions. Based on our novel definition of adherence, pill count was not a reliable predictor of adherence to protocol, and calls into question how adherence is measured in clinical research. Our findings have implications regarding the determination of efficacy of medications under study and offer an alternative approach to measuring adherence of long half-life supplements/medications

Recommendations for Planning Pilot Studies in Clinical and Translational Research

Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase "pilot study" is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well-designed pilot studies play in the advancement of science and scientific careers

Effect of a Cognitive Aid on Adherence to Perioperative Assessment and Management Guidelines for the Cardiac Evaluation of Noncardiac Surgical Patients

The 2007 American College of Cardiologists/American Heart Association Guidelines on Perioperative Cardiac Evaluation and Care for Noncardiac Surgery is the standard for perioperative cardiac evaluation. Recent work has shown residents and anesthesiologists do not apply these guidelines when tested. This research hypothesized that a decision support tool would improve adherence to this consensus guideline

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

Stresses encountered during human islet isolation lead to unavoidable beta-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, beta-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less beta-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]