Effects of shared medical appointments on quality of life and cost-effectiveness for patients with a chronic neuromuscular disease. Study protocol of a randomized controlled trial

Contains fulltext : 96862.pdf (publisher's version ) (Open Access)BACKGROUND: Shared medical appointments are a series of one-to-one doctor-patient contacts, in presence of a group of 6-10 fellow patients. This group visits substitute the annual control visits of patients with the neurologist. The same items attended to in a one-to-one appointment are addressed. The possible advantages of a shared medical appointment could be an added value to the present management of neuromuscular patients. The currently problem-focused one-to-one out-patient visits often leave little time for the patient's psychosocial needs, patient education, and patient empowerment. METHODS/DESIGN: A randomized, prospective controlled study (RCT) with a follow up of 6 months will be conducted to evaluate the clinical and cost-effectiveness of shared medical appointments compared to usual care for 300 neuromuscular patients and their partners at the Radboud University Nijmegen Medical Center. Every included patient will be randomly allocated to one of the two study arms. This study has been reviewed and approved by the medical ethics committee of the region Arnhem-Nijmegen, The Netherlands. The primary outcome measure is quality of life as measured by the EQ-5D, SF-36 and the Individualized neuromuscular Quality of Life Questionnaire. The primary analysis will be an intention-to-treat analysis on the area under the curve of the quality of life scores. A linear mixed model will be used with random factor group and fixed factors treatment, baseline score and type of neuromuscular disease. For the economic evaluation an incremental cost-effectiveness analysis will be conducted from a societal perspective, relating differences in costs to difference in health outcome. Results are expected in 2012. DISCUSSION: This study will be the first randomized controlled trial which evaluates the effect of shared medical appointments versus usual care for neuromuscular patients. This will enable to determine if there is additional value of shared medical appointments to the current therapeutical spectrum. When this study shows that group visits produce the alleged benefits, this may help to increase the acceptance of this innovative and creative way of using one of the most precious resources in health care more efficiently: time. TRIAL REGISTRATION: DutchTrial Register http://www.trialregister.nlNTR1412

Linear-in-the-parameters oblique least squares (LOLS) provides more accurate estimates of density-dependent survival

Survival is a fundamental demographic component and the importance of its accurate estimation goes beyond the traditional estimation of life expectancy. The evolutionary stability of isomorphic biphasic life-cycles and the occurrence of its different ploidy phases at uneven abundances are hypothesized to be driven by differences in survival rates between haploids and diploids. We monitored Gracilaria chilensis, a commercially exploited red alga with an isomorphic biphasic life-cycle, having found density-dependent survival with competition and Allee effects. While estimating the linear-in-the-parameters survival function, all model I regression methods (i.e, vertical least squares) provided biased line-fits rendering them inappropriate for studies about ecology, evolution or population management. Hence, we developed an iterative two-step non-linear model II regression (i.e, oblique least squares), which provided improved line-fits and estimates of survival function parameters, while robust to the data aspects that usually turn the regression methods numerically unstable

Routinely collected data for randomized trials: promises, barriers, and implications

This work was supported by Stiftung Institut für klinische Epidemiologie. The Meta-Research Innovation Center at Stanford University is funded by a grant from the Laura and John Arnold Foundation. The funders had no role in design and conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript or its submission for publication.Peer reviewedPublisher PD

Continued misuse of orphan drug legislation: a life-threatening risk for mexiletine.

Contains fulltext : 218857.pdf (Publisher’s version ) (Closed access

Profile of subjective quality of life and its correlates in a nation-wide sample of high school students in an Arab setting using the WHOQOL-Bref

<p>Abstract</p> <p>Background</p> <p>The upsurge of interest in the quality of life (QOL) of children is in line with the 1989 Convention on the Rights of the Child, which stressed the child's right to adequate circumstances for physical, mental, and social development. The study's objectives were to: (i) highlight how satisfied Kuwaiti high school students were with life circumstances as in the WHOQOL-Bref; (ii) assess the prevalence of at risk status for impaired QOL and establish the QOL domain normative values; and (iii) examine the relationship of QOL with personal, parental, and socio-environmental factors.</p> <p>Method</p> <p>A nation-wide sample of students in senior classes in government high schools (N = 4467, 48.6% boys; aged 14-23 years) completed questionnaires that included the WHOQOL-Bref.</p> <p>Results</p> <p>Using Cummins' norm of 70% - 80%, we found that, as a group, they barely achieved the well-being threshold score for physical health (70%), social relations (72.8%), environment (70.8%) and general facet (70.2%), but not for psychological health (61.9%). These scores were lower than those reported from other countries. Using the recommended cut-off of <1<it>SD </it>of population mean, the prevalence of at risk status for impaired QOL was 12.9% - 18.8% (population age-adjusted: 15.9% - 21.1%). In all domains, boys had significantly higher QOL than girls, mediated by anxiety/depression; while the younger ones had significantly higher QOL (<it>p </it>< 0.001), mediated by difficulty with studies and social relations. Although poorer QOL was significantly associated with parental divorce and father's low socio-economic status, the most important predictors of poorer QOL were perception of poor emotional relationship between the parents, poor self-esteem and difficulty with studies.</p> <p>Conclusion</p> <p>Poorer QOL seemed to reflect a circumstance of social disadvantage and poor psychosocial well-being in which girls fared worse than boys. The findings indicate that programs that address parental harmony and school programs that promote study-friendly atmospheres could help to improve psychosocial well-being. The application of QOL as a school population health measure may facilitate risk assessment and the tracking of health status.</p

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe

2D-DIGE proteomic analysis of vastus lateralis from COPD patients with low and normal fat free mass index and healthy controls

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with several extra-pulmonary effects of which skeletal muscle wasting is one of the most common and contributes to reduced quality of life, increased morbidity and mortality. The molecular mechanisms leading to muscle wasting are not fully understood. Proteomic analysis of human skeletal muscle is a useful approach for gaining insight into the molecular basis for normal and pathophysiological conditions. Methods To identify proteins involved in the process of muscle wasting in COPD, we searched differentially expressed proteins in the vastus lateralis of COPD patients with low fat free mass index (FFMI), as a surrogate of muscle mass (COPDL, n = 10) (FEV1 33 ± 4.3% predicted, FFMI 15 ± 0.2 Kg.m−2), in comparison to patients with COPD and normal FFMI (COPDN, n = 8) and a group of age, smoking history, and sex matched healthy controls (C, n = 9) using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) technology, combined with mass spectrometry (MS). The effect of silencing DOT1L protein expression on markers of cell arrest was analyzed in skeletal muscle satellite cells (HSkMSCs) in vitro and assessed by qPCR and Western blotting. Results A subset of 7 proteins was differentially expressed in COPDL compared to both COPDN and C. We found an increased expression of proteins associated with muscle homeostasis and protection against oxidative stress, and a decreased expression of structural muscle proteins and proteins involved in myofibrillogenesis, cell proliferation, cell cycle arrest and energy production. Among these was a decreased expression of the histone methyltransferase DOT1L. In addition, silencing of the DOT1L gene in human skeletal muscle satellite cells in vitro was significantly related to up regulation of p21 WAF1/Cip1/CDKN1A, a marker of cell arrest and ageing. Conclusions 2D-DIGE coupled with MS identified differences in the expression of several proteins in the wasted vastus lateralis that are relevant to the disease process. Down regulation of DOT1L in the vastus lateralis of COPDL patients may mediate the muscle wasting process through up regulation of markers of cell arrest and senescence