Accreditation in general practice in Denmark:study protocol for a cluster-randomized controlled trial

BACKGROUND: Accreditation is used increasingly in health systems worldwide. However, there is a lack of evidence on the effects of accreditation, particularly in general practice. In 2016 a mandatory accreditation scheme was initiated in Denmark, and during a 3-year period all practices, as default, should undergo accreditation according to the Danish Healthcare Quality Program. The aim of this study is primarily to evaluate the effects of a mandatory accreditation scheme. METHODS/DESIGN: The study is conducted as a cluster-randomized controlled trial among 1252 practices (clusters) with 2211 general practitioners in Denmark. Practices allocated to accreditation in 2016 serve as the intervention group, and practices allocated to accreditation in 2018 serve as controls. The selected outcomes should meet the following criteria: (1) a high degree of clinical relevance; (2) the possibility to assess changes due to accreditation; (3) availability of data from registers with no self-reporting data. The primary outcome is the number of prescribed drugs in patients older than 65 years. Secondary outcomes are changes in outcomes related to other perspectives of safe medication, good clinical practice and mortality. All outcomes relate to quality indicators included in the Danish Healthcare Quality Program, which is based on general principles for accreditation. DISCUSSION: The consequences of accreditation and standard-setting processes are generally under-researched, particularly in general practice. This is the largest study in general practice with a randomized implementation approach to evaluate the clinical effects of a nation-wide mandatory accreditation scheme in general practice. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02762240. Registered on 24 May 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-017-1818-6) contains supplementary material, which is available to authorized users

ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model

<p>Abstract</p> <p>Background</p> <p>We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE^-/-) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.</p> <p>Methods</p> <p>Thickening of the aortic valve leaflets in apoE^-/-mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.</p> <p>Results</p> <p>Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).</p> <p>Conclusion</p> <p>Moderate uremia causes thickening of the aortic valves in apoE^-/-mice, which can be attenuated by ACE inhibition. The nephrectomized apoE^-/-mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.</p

Lipoprotein(a) accelerates atherosclerosis in uremic mice

Uremic patients have increased plasma lipoprotein(a) [Lp(a)] levels and elevated risk of cardiovascular disease. Lp(a) is a subfraction of LDL, where apolipoprotein(a) [apo(a)] is disulfide bound to apolipoprotein B-100 (apoB). Lp(a) binds oxidized phospholipids (OxPL), and uremia increases lipoprotein-associated OxPL. Thus, Lp(a) may be particularly atherogenic in a uremic setting. We therefore investigated whether transgenic (Tg) expression of human Lp(a) increases atherosclerosis in uremic mice. Moderate uremia was induced by 5/6 nephrectomy (NX) in Tg mice with expression of human apo(a) (n = 19), human apoB-100 (n = 20), or human apo(a) + human apoB [Lp(a)] (n = 15), and in wild-type (WT) controls (n = 21). The uremic mice received a high-fat diet, and aortic atherosclerosis was examined 35 weeks later. LDL-cholesterol was increased in apoB-Tg and Lp(a)-Tg mice, but it was normal in apo(a)-Tg and WT mice. Uremia did not result in increased plasma apo(a) or Lp(a). Mean atherosclerotic plaque area in the aortic root was increased 1.8-fold in apo(a)-Tg (P = 0.025) and 3.3-fold (P = 0.0001) in Lp(a)-Tg mice compared with WT mice. Plasma OxPL, as detected with the E06 antibody, was associated with both apo(a) and Lp(a). In conclusion, expression of apo(a) or Lp(a) increased uremia-induced atherosclerosis. Binding of OxPL on apo(a) and Lp(a) may contribute to the atherogenicity of Lp(a) in uremia