Interpretation:We found a consistent, positive relation between physicians' and patients' preventive health practices. Objectively establishing this healthy doctor-healthy patient relation should encourage preventionoriented health care systems to better support and evaluate the effects on patients of improving the physical health of medical students and physicians. AbstractResearch CMAJ
BackgroundThe efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems. This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies.MethodsIn this multicenter open-label trial, 1,360 patients recruited after hospitalization for heart failure exacerbation (38%) or from the community (62%) were randomly assigned to either disease management or usual care. Disease management, delivered by multi-disciplinary teams, included coordination of care, patient education, monitoring disease symptoms and patient adherence to medication regimen, titration of drug therapy, and home tele-monitoring of body weight, blood pressure and heart rate. Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists.The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause. Secondary endpoints included the number of all hospital admissions, health-related quality of life and depression during follow-up. Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center.ResultsDuring the follow-up, 388 (56.9%) patients assigned to disease management and 387 (57.1%) assigned to usual care had a primary endpoint event. The median (range) time elapsed until the primary endpoint event or end of study was 2.0 (0–5.0) years among patients assigned to disease management, and 1.8 (0–5.0) years among patients assigned to usual care (adjusted hazard ratio, 0.908; 95% confidence interval, 0.788 to 1.047). Hospital admissions were mostly (70%) unrelated to heart failure.Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up.ConclusionsThis comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint, but it improved health-related quality of life and depression. A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care.Clinical trial registrationClinicaltrials.gov identifier: NCT00533013. Trial registration date: 9 August 2007. Initial protocol release date: 20 September 2007.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0855-z) contains supplementary material, which is available to authorized users.
Dubin-Johnson syndrome (DJS)is an inherited disorder characterized by conjugated hyperbilirubinemia and is caused by a deficiency of the multidrug resistance protein 2 (MRP2) located in the apical membrane of hepatocytes. The aim of this study was to identify the mutations in two previously characterized clusters of patients with Dubin-Johnson syndrome among Iranian and Moroccan Jews and determine the consequence of the mutations on MRP2 expression and function by expression studies. All 32 exons and adjacent regions of the MRP2 gene were screened by polymerase chain reaction and DNA sequencing. Two novel mutations were identified in exon 25. One mutation, 3517A3 T, predicting a I1173F substitution, was found in 22 homozygous Iranian Jewish DJS patients from 13 unrelated families and a second mutation, 3449G3 A, predicting a R1150H substitution, was found in 5 homozygous Moroccan Jewish DJS patients from 4 unrelated families. Use of four intragenic dimorphisms and haplotype analyses disclosed a specific founder effect for each mutation. The mutations were introduced into an MRP2 expression vector by site-directed mutagenesis, transfected into HEK-293 cells, and analyzed by a fluorescence transport assay, immunoblot, and immunocytochemistry. Continuous measurement of probenecid-sensitive carboxyfluorescein efflux revealed that both mutations impaired the transport activity of MRP2. Immunoblot analysis and immunocytochemistry showed that MRP2 (R1150H) matured properly and localized at the plasma membrane of transfected cells. In contrast, expression of MRP2 (I1173F) was low and mislocated to the endoplasmic reticulum of the transfected cells. These findings provide an explanation for the DJS phenotype in these two patient groups. Furthermore, the close localization of the two mutations identify this region of MRP2 as important for both activity and processing of the protein. Dubin-Johnson syndrome (DJS)1 is an autosomal recessive disorder manifested by chronic conjugated hyperbilirubinemia and accumulation of a dark pigment in liver parenchymal cells (1, 2). The disorder has recently been associated with several mutations in the multidrug resistance protein 2 (MRP2) gene (3-7). MRP2, also known as the canalicular multispecific organic anion transporter, is a 190-kDa integral membrane glycoprotein expressed mainly in the canalicular (apical) membrane of liver cells. It belongs to the superfamily of ATPbinding cassette transporters, and transports endogenous and exogenous anionic conjugates from hepatocytes to the bile (8 -13). MRP2 is one of seven known MRPs that are involved in resistance of cancer cells to chemotherapeutic drugs (13-17). The MRP2 consists of 1545 amino acids, and its gene is located on chromosome 10q24 (13,14,16,18). The genomic structure of the MRP2 gene exhibits a remarkable similarity to the MRP1 gene; it contains 32 exons and spans ϳ45 kilobase pairs (6, 7).Since the original description of DJS, many cases have been described in different populations (19 -22) and a cluster of 101 patients was...
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