What differentiates primary care physicians who predominantly prescribe diuretics for treating mild to moderate hypertension from those who do not? A comparative qualitative study

<p>Abstract</p> <p>Background</p> <p>Thiazide diuretics are cost-effective for the treatment of mild to moderate hypertension, but physicians often opt for more expensive treatment options such as angiotensin II receptor blockers or angiotensin converting enzyme inhibitors. With escalating health care costs, there is a need to elucidate the factors influencing physicians' treatment choices for this highly prevalent chronic condition. The purpose of this study was to describe the characteristics of physicians' decision-making process regarding hypertension treatment choices.</p> <p>Methods</p> <p>A comparative qualitative study was conducted in 2009 in the Canadian province of Quebec. Overall, 29 primary care physicians--who are also participating in an electronic health record research program--participated in a semi-structured interview about their prescribing decisions. Physicians were categorized into two groups based on their patterns of prescribing antihypertensive drugs: physicians who predominantly prescribe diuretics, and physicians who predominantly prescribe drug classes other than diuretics. Cases of hypertension that were newly started on antihypertensive therapy were purposely selected from each physician's electronic health record database. Chart stimulated recall interview, a technique utilizing patient charts to probe recall and provide context to physician decision-making during clinical encounters, was used to elucidate reasons for treatment choices. Interview transcripts were synthesized using content analysis techniques, and factors influencing physicians' decision making were inductively generated from the data.</p> <p>Results</p> <p>We identified three themes that differentiated physicians who predominantly prescribe diuretics from those who predominantly prescribe other drug classes for the initial treatment of mild to moderate hypertension: a) perceptions about the efficacy of diuretics, b) preferred approach to hypertension management and, c) perceptions about hypertension guidelines. Specifically, physicians had differences in beliefs about the efficacy, safety and tolerability of diuretics, the most effective approach for managing mild to moderate hypertension, and in aggressiveness to achieve treatment targets. Marketing strategies employed by the pharmaceutical industry and practice experience appear to contribute to these differences in management approach.</p> <p>Conclusions</p> <p>Physicians preferring more expensive treatment options appear to have several misperceptions about the efficacy, safety and tolerability of diuretics. Efforts to increase physicians' prescribing of diuretics may need to be directed at overcoming these misperceptions.</p

Homotypic endothelial nanotubes induced by wheat germ agglutinin and thrombin

Endothelial barrier formation is maintained by intercellular communication through junctional proteins. The mechanisms involved in maintaining endothelial communication subsequent to barrier disruption remain unclear. It is known that low numbers of endothelial cells can be interconnected by homotypic actin-driven tunneling nanotubes (TNTs) which could be important for intercellular transfer of information in vascular physiology. Here we sought insight into the triggers for TNT formation. Wheat germ agglutinin, a C-type lectin and known label for TNTs, unexpectedly caused striking induction of TNTs. A succinylated derivative was by contrast inactive, suggesting mediation by a sialylated protein. Through siRNA-mediated knockdown we identified that this protein was likely to be CD31, an important sialylated membrane protein normally at endothelial cell junctions. We subsequently considered thrombin as a physiological inducer of endothelial TNTs because it reduces junctional contact. Thrombin reduced junctional contact, redistributed CD31 and induced TNTs, but its effect on TNTs was CD31-independent. Thrombin-induced TNTs nevertheless required PKCα, a known mediator of thrombin-dependent junctional remodelling, suggesting a necessity for junctional proteins in TNT formation. Indeed, TNT-inducing effects of wheat germ agglutinin and thrombin were both correlated with cortical actin rearrangement and similarly Ca2+-dependent, suggesting common underlying mechanisms. Once formed, Ca2+ signalling along TNTs was observed