Analysis of Binary Adherence Data in the Setting of Polypharmacy: A Comparison of Different Approaches

Older community dwelling adults often take multiple medications for numerous chronic diseases. Non-adherence to these medications can have a large public health impact. Therefore, the measurement and modeling of medication adherence in the setting of polypharmacy is an important area of research. We apply a variety of different modeling techniques (standard linear regression; weighted linear regression; adjusted linear regression; naïve logistic regression; beta-binomial (BB) regression; generalized estimating equations (GEE)) to binary medication adherence data from a study in a North Carolina based population of older adults, where each medication an individual was taking was classified as adherent or non-adherent. In addition, through simulation we compare these different methods based on Type I error rates, bias, power, empirical 95% coverage, and goodness of fit. We find that estimation and inference using GEE is robust to a wide variety of scenarios and we recommend using this in the setting of polypharmacy when adherence is dichotomously measured for multiple medications per person

Characterizing pre-dialysis care in the era of eGFR reporting: a cohort study

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is a common disorder associated with increased morbidity and mortality. Primary care physicians (PCPs) care for the majority of pre-dialysis CKD patients; however, PCPs often do not recognize the presence of CKD based on serum creatinine levels. Prior studies suggest that PCPs and nephrologists deliver suboptimal CKD care. One strategy to improve disease awareness and treatment is estimated glomerular filtration rate (eGFR) reporting. We examined PCP and nephrologist CKD practices before and after routine eGFR reporting.</p> <p>Methods</p> <p>We conducted a retrospective cohort study of patients with CKD 3b-4 (eGFR < 45) seen at a university-based, outpatient primary care clinic. Using a chi-square or Fisher's exact test, we compared co-management rates, renal protective strategies, CKD documentation, and laboratory processes of care in 274 patients and 266 patients seen in a 6-month period prior to and following eGFR implementation, respectively.</p> <p>Results</p> <p>CKD co-management increased from 22.6% pre-eGFR to 48.5% post-eGFR (P < 0.0001). eGFR reporting did not improve angiotensin converting enzyme inhibitor or angiotensin receptor blocker use or quantitative urinary testing. However, non-steroidal anti-inflammatory drug avoidance (pre-eGFR 81.8% vs. post- eGFR 90.6%, P = 0.003) and phosphorus and parathyroid hormone testing improved (pre-eGFR vs. post-eGFR: 32.5% vs. 51.5%, P < 0.0001; 12.4% vs. 36.1%, P < 0.0001 respectively).</p> <p>Conclusions</p> <p>A marked increase in CKD co-management was observed following eGFR implementation. Although some improvements in processes of care were noted, this did not include angiotensin converting enzyme inhibitor or angiotensin receptor blocker use. Overall care remained suboptimal despite eGFR reporting; further strategies are needed to improve PCP and nephrologist CKD care.</p

Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis

Pharmacologic treatments for Alzheimer’s disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 through 2007 (July) for placebo-controlled and comparative trials assessing cognition, function, behavior, global change, and safety. Thirty-three articles on 26 studies were included in the review. Meta-analyses of placebo-controlled data support the drugs’ modest overall benefits for stabilizing or slowing decline in cognition, function, behavior, and clinical global change. Three open-label trials and one double-blind randomized trial directly compared donepezil with galantamine and rivastigmine. Results are conflicting; two studies suggest no differences in efficacy between compared drugs, while one study found donepezil to be more efficacious than galantamine, and one study found rivastigmine to be more efficacious than donepezil. Adjusted indirect comparison of placebo-controlled data did not find statistically significant differences among drugs with regard to cognition, but found the relative risk of global response to be better with donepezil and rivastigmine compared with galantamine (relative risk = 1.63 and 1.42, respectively). Indirect comparisons also favored donepezil over galantamine with regard to behavior. Across trials, the incidence of adverse events was generally lowest for donepezil and highest for rivastigmine

Being More Realistic About Reasons: On Rationality and Reasons Perspectivism

This paper looks at whether it is possible to unify the requirements of rationality with the demands of normative reasons. It might seem impossible to do because one depends upon the agent’s perspective and the other upon features of the situation. Enter Reasons Perspectivism. Reasons perspectivists think they can show that rationality does consist in responding correctly to reasons by placing epistemic constraints on these reasons. They think that if normative reasons are subject to the right epistemic constraints, rational requirements will correspond to the demands generated by normative reasons. While this proposal is prima facie plausible, it cannot ultimately unify reasons and rationality. There is no epistemic constraint that can do what reasons perspectivists would need it to do. Some constraints are too strict. The rest are too slack. This points to a general problem with the reasons-first program. Once we recognize that the agent’s epistemic position helps determine what she should do, we have to reject the idea that the features of the agent’s situation can help determine what we should do. Either rationality crowds out reasons and their demands or the reasons will make unreasonable demands

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

Association of Physical Activity with Hormone Receptor Status: The Shanghai Breast Cancer Study

Evidence exists that breast tumors differing by estrogen receptor (ER) and progesterone receptor (PR) status may be phenotypically distinct diseases resulting from dissimilar etiologic processes. Few studies have attempted to examine the association of physical activity with breast cancer subtype. Such research may prove instructive into the biological mechanisms of activity. Consequently, this investigation was designed to assess the relationship between physical activity and hormone receptor-defined breast cancers in a population of Asian women in which the distribution of receptor types differed from traditional Western populations. Participants, ages 25 to 64 years, were recruited into this population-based, case-control study of breast cancer conducted in Shanghai, China from August 1996 to March 1998. Histologically confirmed breast cancer cases with available receptor status information (n = 1001) and age frequency-matched controls (n = 1,556) completed in-person interviews. Polytomous logistic regression was used to model the association between measures of activity with each breast cancer subtype (ER+/PR+, ER−/PR−, ER+/PR−, and ER−/PR+) using the control population as the reference group. Exercise in both adolescence and the last 10 years was associated with a decreased risk of both receptor-positive (ER+/PR+) and receptor-negative (ER−/PR−) breast cancers in both premenopausal and postmenopausal women (odds ratios, 0.44 and 0.51 and 0.43 and 0.21, respectively). Sweating during exercise within the last 10 years was also associated with decreased risk for receptor-positive and receptor-negative breast cancers among post-menopausal women (odds ratios, 0.58 and 0.28, respectively). These findings suggest that physical activity may reduce breast cancer risk through both hormonal and nonhormonal pathways

Coagulation activation and inflammation in sickle cell disease-associated pulmonary hypertension

BACKGROUND: Pulmonary hypertension (PHT) is common in sickle cell disease (SCD). The purpose of this study was to determine whether markers of coagulation activation and inflammation are associated with PHT in SCD. DESIGN AND METHODS: This cross-sectional study was performed using a cohort of patients followed at an adult Sickle Cell Clinic. Pulmonary artery systolic pressure was determined by Doppler echocardiography, and the diagnosis of PHT was defined using age, sex and body mass index-adjusted reference ranges. Clinical laboratory examinations, including hematologic studies and biochemical tests, as well as various measures of coagulation activation, endothelial activation and inflammation, were conducted on SCD subjects and on healthy, race-matched control subjects without SCD. RESULTS: Patients with SCD (n=76) had higher plasma levels of markers of coagulation (thrombin-antithrombin complex, prothrombin fragment F1+2, D-dimer) and endothelial (soluble vascular endothelial cell adhesion molecule, sVCAM) activation compared with control subjects (n=6). SCD patients with PHT (n=26) had significantly higher levels of sVCAM compared with those patients without PHT (n=50). Although PHT patients showed increased plasma measures of coagulation activation, the differences were not statistically significant when compared to those of patients without PHT. HbSS patients with PHT also had a trend towards higher levels of other inflammatory cytokines (interleukins 6, 8 and 10) than HbSS patients without PHT. There was a modest negative correlation between hemoglobin and plasma measures of coagulation and endothelial activation, and modest positive correlations between markers of hemolysis and plasma measures of coagulation and endothelial activation. CONCLUSIONS: SCD patients with PHT have higher levels of markers of endothelial activation and other inflammatory markers than patients without PHT. A trend towards an increased level of markers of coagulation activation was observed in SCD patients with PHT compared with that in patients without PHT. Markers of hemolysis are associated with coagulation activation and endothelial dysfunction in SCD patients. Clinical trials of anticoagulants and anti-inflammatory agents are warranted in SCD patients with PHT

Efficacy and tolerability of second-generation antidepressants in social anxiety disorder

A systematic review and meta-analysis was conducted to evaluate the comparative efficacy and tolerability of second-generation antidepressants in social anxiety disorder. Studies were identified by searching MEDLINE®, Embase, The Cochrane Library, PsychLit, and the International Pharmaceutical Abstracts from January 1980 through October 2006. Comparative evidence was summarized and indirect comparisons were made using network meta-analysis. Only three head-to-head trials were identified; comparative trials found only minimal differences in efficacy between escitalopram and paroxetine, and no statistically significant differences in efficacy between extended-release venlafaxine and paroxetine. Pooled evidence from 15 placebo-controlled trials suggests that escitalopram (relative benefit 1.3; 95% CI 1.2 to 1.5), paroxetine (relative benefit 1.9; 95% CI 1.5 to 2.3), sertraline (relative benefit 1.8; 95% CI 1.5 to 2.2), and venlafaxine (relative benefit 1.7; 95% CI 1.5 to 1.9) all produce significantly more responders than placebo; evidence favored fluvoxamine over placebo but was not significant (relative benefit 1.5; 95% CI 0.9 to 2.4). Network meta-analysis did not reveal differences in efficacy among drugs. Overall, fair evidence supports the efficacy of escitalopram, fluvoxamine, paroxetine, sertraline, and venlafaxine in social anxiety disorder. The drugs do not differ in efficacy, although their adverse event profiles do

Overlap Between Orofacial Pain and Vulvar Vestibulitis Syndrome

To explore the prevalence of Orofacial Pain (OFP) among patients with Vulvar Vestibulitis Syndrome (VVS) and to examine the relationship between signs and symptoms of OFP and clinical characteristics of women with VVS; we specifically sought to investigate differences in psychological characteristics and self-reported severity of painful intercourse

Resident Physicians' Life Expectancy Estimates and Colon Cancer Screening Recommendations in Elderly Patients

Colon cancer screening recommendations for patients aged 75 years and older should account for variation in older adults’ health states, life expectancies, and potential to benefit from screening