586 research outputs found
Issues in the development of advance directives in mental health care
No full text<i>Background</i>: Interest in advance directives in mental health care is growing internationally. There is no clear universal agreement as to what such an advance directive is or how it should function. <i>Aim</i>: To describe the range of issues embodied in the development of advance directives in mental health care. <i>Method</i>: The literature on advance directives is examined to highlight the pros and cons of different versions of advance directive. <i>Results</i>: Themes emerged around issues of terminology, competency and consent, the legal status of advance directives independent or collaborative directives and their content. Opinions vary between a unilateral legally enforceable instrument to a care plan agreed between patient and clinician. <i>Conclusion</i>: There is immediate appeal in a liberal democracy that values individual freedom and autonomy in giving weight to advance directives in mental health care. They do not, however, solve all the problems of enforced treatment and early access to treatment. They also raise new issues and highlight persistent problems. <i>Declaration</i> <i>of</i> <i>interest</i>: The research was funded by the Nuffield Foundation grant number
MNH/00015G
Identification and Management of Statin-Associated Symptoms in Clinical Practice: Extension of a Clinician Survey to 12 Further Countries
No full textStatins are the first-choice pharmacological treatment for patients with hypercholesterolemia and at risk for cardiovascular disease; however, a minority of patients experience statin-associated symptoms (SAS) and are considered to have reduced statin tolerance. The objective of this study was to establish how patients with SAS are identified and managed in clinical practice in Austria, Belgium, Colombia, Croatia, the Czech Republic, Denmark, Portugal, Switzerland, Russia, Saudi Arabia, Turkey, and the United Arab Emirates. A cross-sectional survey was conducted (2015-2016) among clinicians (n = 60 per country; Croatia: n = 30) who are specialized/experienced in the treatment of hypercholesterolemia. Participants were asked about their experience of patients presenting with potential SAS and how such patients were identified and treated. Muscle-related symptoms were the most common presentation of potential SAS (average: 51%; range across countries [RAC] 17-74%); other signs/symptoms included persistent elevation in transaminases. To establish whether symptoms are due to statins, clinicians required rechallenge after discontinuation of statin treatment (average: 77%; RAC 40-90%); other requirements included trying at least one alternative statin. Clinicians reported that half of high-risk patients with confirmed SAS receive a lower-dose statin (average: 53%; RAC 43-72%), and that most receive another non-statin lipid-lowering therapy with or without a concomitant statin (average: 65%; RAC 52-83%). The specialists and GPs surveyed use stringent criteria to establish causality between statin use and signs or symptoms, and persevere with statin treatment where possibl
Efficacy and Safety of Alternate-Day Versus Daily Dosing of Statins : a Systematic Review and Meta-Analysis
No full textWe conducted a meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs to synthesize evidence about the efficacy and safety of alternate-day vs daily dosing of statins.
We searched selected databases through January 2, 2017 to identify relevant RCTs and quasi-RCTs. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), while secondary outcomes included adverse events and adherence.
Twelve RCTs and 1 quasi-RCT (n = 1023 patients) were included in the analysis. Pooled analysis revealed no statistically significant difference between alternate-day and daily regimens of atorvastatin and rosuvastatin in terms of change in LDL-C (mean difference [MD] 6.79 mg/dL, 95% confidence interval [CI] -1.59, 15.17, p = 0.11, and 10.51 mg/dL, 95%CI -0.23, 21.26, p = 0.06, respectively) and TG (p > 0.05). Daily regimens of atorvastatin and rosuvastatin were superior to alternate-day regimes in term of change in TC (MD 12.45 mg/L, 95%CI 8.14, 16.76, p 0.05). Both regimens of statins were generally well tolerated with good adherence.
Alternate-day dosing of individual statins (especially atorvastatin and rosuvastatin) is as efficacious as daily dosing on LDL-C and TG
Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates a novel isoform of APOB
No full textBackground: Apolipoprotein B (APOB) is an integral part of the LDL, VLDL, IDL, Lp(a) and chylomicron lipoprotein particles. The APOB pre-mRNA consists of 29 constitutively-spliced exons. APOB exists as two natural isoforms: the full-length APOB100 isoform, assembled into LDL, VLDL, IDL and Lp(a) and secreted by the liver in humans; and the C-terminally truncated APOB48, assembled into chylomicrons and secreted by the intestine in humans. Down-regulation of APOB100 is a potential therapy to lower circulating LDL and cholesterol levels.Results: We investigated the ability of 2' O-methyl RNA antisense oligonucleotides (ASOs) to induce the skipping of exon 27 in endogenous APOB mRNA in HepG2 cells. These ASOs are directed towards the 5' and 3' splice-sites of exon 27, the branch-point sequence (BPS) of intron 26-27 and several predicted exonic splicing enhancers within exon 27. ASOs targeting either the 5' or 3' splice-site, in combination with the BPS, are the most effective. The splicing of other alternatively spliced genes are not influenced by these ASOs, suggesting that the effects seen are not due to non-specific changes in alternative splicing. The skip 27 mRNA is translated into a truncated isoform, APOB87(SKIP27).Conclusion: The induction of APOB87(SKIP27) expression in vivo should lead to decreased LDL and cholesterol levels, by analogy to patients with hypobetalipoproteinemia. As intestinal APOB mRNA editing and APOB48 expression rely on sequences within exon 26, exon 27 skipping should not affect APOB48 expression unlike other methods of down-regulating APOB100 expression which also down-regulate APOB48
Colesevelam improved lipoprotein particle subclasses in patients with prediabetes and primary hyperlipidaemia
No full textBackground: A randomised, double-blind, placebo-controlled study evaluated lipid- and glucose-lowering effects of colesevelam in patients with prediabetes and primary hyperlipidaemia. We report the effect of colesevelam on lipoprotein particle concentration and particle size (determined by nuclear magnetic resonance spectroscopy) in these patients. Methods: Adults with prediabetes (World Health Organization criteria), low-density lipoprotein cholesterol(LDL-C) ? 100 mg/dL (?2.6 mmol/L) and triglycerides less than 500 mg/dL ( less than 5.6 mmol/L) were randomised to colesevelam 3.75 g/day or placebo for 16 weeks. The intent-to-treat population comprised 103 colesevelam and 106 placebo recipients. Results: At the end of the study, mean reduction from baseline in total LDL particle concentration was significantly greater with colesevelam versus placebo (mean treatment difference: ?113 nmol/L; p = 0.02). Increases in total very low-density lipoprotein particle concentration (VLDL-P) and high-density lipoprotein particle concentration (HDL-P) did not differ significantly between the groups; however, with colesevelam versus placebo, there were significantly (p less than 0.05) greater increases in large and medium VLDL-P and large HDL-P and reductions in small VLDL-P. Mean size increases were significantly greater with colesevelam for VLDL (mean treatment difference: 5.3 nm; p less than 0.0001) and HDL (0.1 nm; p = 0.002). Conclusions: Colesevelam improved the overall atherogenic lipoprotein profile in adults with prediabetes and primary hyperlipidaemia, despite potentially less favourable changes in VLDL particles. © The Author(s) 2012
Use of ‘Dear Colleague’ Letters in the US House of Representatives: A Study of Internal Communications
No full textDear colleague letters — formal, written, Member-to-Member correspondence — provide a
unique window into internal communications in the House of Representatives. In general, studies
of congressional political communications tend to focus on external messaging by Members
(candidates) to their constituents (voters) through a focus on electoral or constituent
communication. Yet, these studies may or may not tell us why Members choose to engage in
internal communication. To address this gap, this paper draws on the literature and presents new
hypotheses about factors that increase a Member’s likelihood of using dear colleague letters.
Using House dear colleague letter data from the first session of the 111th Congress (2009), a
negative binomial regression tests the importance of seniority, electoral vulnerability, leadership
status, and majority party status for dear colleague letter senders. The analysis demonstrates that
being a rank-n-file majority party members who are electorally “safe” are more likely to use the
dear colleague system.This article reflects the views of the author and does not necessarily reflect the views of the Congressional Research Service or the Library of Congress. The author would like to thank Jessica Gerrity, Beth Rosenson, Susan Smelcer, Shannon Bow, Colleen Shogan, Eric Uslaner and Roger Davidson for their comments on earlier drafts. A previous version of this paper was presented at the 2009 Midwest Political Science Association Annual Meeting.https://www.tandfonline.com/doi/full/10.1080/13572334.2013.73715
Physicians’ interpretation of “class effects” A need for thoughtful re-evaluation
No full textAbstractThe concept of pharmacologic “class effects” exists across a broad range of medical products and is particularly pervasive with regard to cardiovascular agents. Evolution of the concept over the past two decades has shown the influence of physicians’ practice patterns, pharmaceutical companies, health maintenance organizations and the Food and Drug Administration (FDA). Understanding the evolution of health care, social and economic policies, acknowledging the correction of medical misconceptions and inaccurate understanding and appreciating the emergence of new medical knowledge over the past decade should modify the clinician’s viewpoint of “class effects.” These revelations should signal caution in extrapolating the outcome efficacy or safety of one agent to another within a pharmacologic class. The authors urge clinicians, pharmaceutical companies, health maintenance organizations and the FDA to re-examine their concept of “class effects.” An appeal is made for physicians to prescribe those pharmaceutical agents with definitive evidence of mortality and morbidity efficacy and safety established by appropriately scaled randomized clinical trials
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