Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease

BACKGROUND: The objective of this study was to develop and psychometrically evaluate a general measure of patients' satisfaction with medication, the Treatment Satisfaction Questionnaire for Medication (TSQM). METHODS: The content and format of 55 initial questions were based on a formal conceptual framework, an extensive literature review, and the input from three patient focus groups. Patient interviews were used to select the most relevant questions for further evaluation (n = 31). The psychometric performance of items and resulting TSQM scales were examined using eight diverse patient groups (arthritis, asthma, major depression, type I diabetes, high cholesterol, hypertension, migraine, and psoriasis) recruited from a national longitudinal panel study of chronic illness (n = 567). Participants were then randomized to complete the test items using one of two alternate scaling methods (Visual Analogue vs. Likert-type). RESULTS: A factor analysis (principal component extraction with varimax rotation) of specific items revealed three factors (Eigenvalues > 1.7) explaining 75.6% of the total variance; namely Side effects (4 items, 28.4%, Cronbach's Alpha = .87), Effectiveness (3 items, 24.1%, Cronbach's Alpha = .85), and Convenience (3 items, 23.1%, Cronbach's Alpha = .87). A second factor analysis of more generally worded items yielded a Global Satisfaction scale (3 items, Eigenvalue = 2.3, 79.1%, Cronbach's Alpha = .85). The final four scales possessed good psychometric properties, with the Likert-type scaling method performing better than the VAS approach. Significant differences were found on the TSQM by the route of medication administration (oral, injectable, topical, inhalable), level of illness severity, and length of time on medication. Regression analyses using the TSQM scales accounted for 40–60% of variation in patients' ratings of their likelihood to persist with their current medication. CONCLUSION: The TSQM is a psychometrically sound and valid measure of the major dimensions of patients' satisfaction with medication. Preliminary evidence suggests that the TSQM may also be a good predictor of patients' medication adherence across different types of medication and patient populations

Hierarchical Construct Validity of the Treatment Satisfaction Questionnaire for Medication (TSQM Version II) among Outpatient Pharmacy Consumers

AbstractObjectivesThe objectives of this study were twofold: 1) to evaluate the construct validity of the Treatment Satisfaction Questionnaire for Medication (TSQM v. II) using structural equation modeling (SEM); and 2) to assess its concurrent validity using medication adherence criteria.MethodsPharmacy patients filling a new medication prescription (n = 342) were recruited from 14 Michigan pharmacies to participate in a 4-week treatment satisfaction study. The TSQM v. II was tested for model fit against an established theoretical model (the Decisional Balance Model of Treatment Satisfaction) using hierarchical confirmatory factor analysis (HCFA). Regression and discriminant analytic models were used to examine the criterion-related validity of the measure.ResultsAn exploratory factor analysis, used for TSQM v. II item reduction, revealed a strongly dimensional instrument (Effectiveness, Side Effects, and Convenience) and explained 88% of total pooled variance. Results of an HCFA using the final TSQM v. II items suggested a good model fit with the data (P > 0.54). In support of concurrent validity, the TSQM scales explained between 9% and 20% of the variance in dosing adherence and 60% of the variance in the likelihood of future use. Discriminant analysis demonstrated the superior classification power of the hierarchical model of treatment satisfaction over the discrete attribute model when predicting medication discontinuation.ConclusionsThe TSQM v. II has equivalent measurement characteristics as the TSQM v. I, yet uses four fewer items and more consistent wording. The value of the Decisional Balance Model for estimation of dosing adherence and medication persistence over time is discussed

Presenilin Controls CBP Levels in the Adult Drosophila Central Nervous System

Background: Dominant mutations in both human Presenilin (Psn) genes have been correlated with the formation of amyloid plaques and development of familial early-onset Alzheimer’s disease (AD). However, a definitive mechanism whereby plaque formation causes the pathology of familial and sporadic forms of AD has remained elusive. Recent discoveries of several substrates for Psn protease activity have sparked alternative hypotheses for the pathophysiology underlying AD. CBP (CREB-binding protein) is a haplo-insufficient transcriptional co-activator with histone acetly-transferase (HAT) activity that has been proposed to be a downstream target of Psn signaling. Individuals with altered CBP have cognitive deficits that have been linked to several neurological disorders. Methodology/Principal Findings: Using a transgenic RNA-interference strategy to selectively silence CBP, Psn, and Notch in adult Drosophila, we provide evidence for the first time that Psn is required for normal CBP levels and for maintaining specific global acetylations at lysine 8 of histone 4 (H4K8ac) in the central nervous system (CNS). In addition, flies conditionally compromised for the adult-expression of CBP display an altered geotaxis behavior that may reflect a neurological defect. Conclusions/Significance: Our data support a model in which Psn regulates CBP levels in the adult fly brain in a manner that is independent of Notch signaling. Although we do not understand the molecular mechanism underlying th

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Urge Incontinence: Quality of Life and Patients' Valuation of Symptom Reduction

Objective: Previous studies have demonstrated the effect of incontinence, and urge incontinence in particular, on patients' quality of life. This study assessed the effects of urge incontinence on quality of life and measured the value of a reduction in symptoms. Design: A self-administered questionnaire was mailed to 591 patients with urge or mixed incontinence. 495 (83.8%) surveys were returned with complete quality of life and symptom data. Of the total sample, 411 patients received the willingness-to-pay (WTP) survey, from which 257 (62.53%) returns were judged complete and reliable. Information was collected about the number of micturitions and urinary leakages. Health-related quality of life (HR-QOL) was measured using the Short Form 36 (SF-36) Health Survey. Socioeconomic characteristics were also recorded. Value was assessed with a binary WTP question. Main outcome measures and results: Quality of life among the sample population was significantly lower in 5 of 8 dimensions compared with the general US population, and was significantly related to the severity of the symptoms in 6 of 8 dimensions. The median (mean) willingness to pay was $US27.24 ($US87.74) per month for a 25% reduction in micturitions and leakages, and $US75.92 ($US244.54) per month for a 50% reduction in micturitions and leakages. As expected, the willingness to pay was significantly related to the size of the reduction in micturitions and leakages, and household income. Conclusions: Patients with incontinence perceive substantial benefits from a reduction in the number of micturitions and leakages.Pharmacoeconomics, Quality-of-life, Urge-incontinence, Willingness-to-pay