Visit-to-Visit HbA1c Variability Is Associated With Cardiovascular Disease and Microvascular Complications in Patients With Newly Diagnosed Type 2 Diabetes.

OBJECTIVE: To investigate the association between visit-to-visit HbA1c variability and cardiovascular events and microvascular complications in patients with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: This retrospective cohort study analyzed patients from Tayside and Fife in the Scottish Care Information-Diabetes Collaboration (SCI-DC) who were observable from the diagnosis of diabetes and had at least five HbA1c measurements before the outcomes were evaluated. We used the previously reported HbA1c variability score (HVS), calculated as the percentage of the number of changes in HbA1c >0.5% (5.5 mmol/mol) among all HbA1c measurements within an individual. The association between HVS and 10 outcomes was assessed using Cox proportional hazards models. RESULTS: We included 13,111-19,883 patients in the analyses of each outcome. The patients with HVS >60% were associated with elevated risks of all outcomes compared with the lowest quintile (for example, HVS >80 to ≤100 vs. HVS ≥0 to ≤20, hazard ratio 2.38 [95% CI 1.61-3.53] for major adverse cardiovascular events, 2.4 [1.72-3.33] for all-cause mortality, 2.4 [1.13-5.11] for atherosclerotic cardiovascular death, 2.63 [1.81-3.84] for coronary artery disease, 2.04 [1.12-3.73] for ischemic stroke, 3.23 [1.76-5.93] for heart failure, 7.4 [3.84-14.27] for diabetic retinopathy, 3.07 [2.23-4.22] for diabetic peripheral neuropathy, 5.24 [2.61-10.49] for diabetic foot ulcer, and 3.49 [2.47-4.95] for new-onset chronic kidney disease). Four sensitivity analyses, including adjustment for time-weighted average HbA1c, confirmed the robustness of the results. CONCLUSIONS: Our study shows that higher HbA1c variability is associated with increased risks of all-cause mortality, cardiovascular events, and microvascular complications of diabetes independently of high HbA1c.

A Dietary Intervention of Bioactive Enriched Foods Aimed at Adults at Risk of Metabolic Syndrome: Protocol and Results from PATHWAY-27 Pilot Study.

Around a quarter of the global adult population have metabolic syndrome (MetS) and therefore increased risk of cardiovascular mortality and diabetes. Docosahexaenoic acid, oat beta-glucan and grape anthocyanins have been shown to be effective in reducing MetS risk factors when administered as isolated compounds, but their effect when administered as bioactive-enriched foods has not been evaluated. OBJECTIVE: The overall aim of the PATHWAY-27 project was to evaluate the effectiveness of bioactive-enriched food consumption on improving risk factors of MetS. A pilot study was conducted to assess which of five bioactive combinations provided within three different food matrices (bakery, dairy or egg) were the most effective in adult volunteers. The trial also evaluated the feasibility of production, consumer acceptability and gastrointestinal tolerance of the bioactive-enriched food. METHOD: The study included three monocentric, parallel-arm, double-blind, randomised, dietary intervention trials without a placebo. Each recruiting centre tested the five bioactive combinations within a single food matrix. RESULTS: The study was completed by 167 participants (74 male, 93 female). The results indicated that specific bioactive/matrix combinations have effects on serum triglyceride or HDL-cholesterol level without adverse effects. CONCLUSION: The study evidenced that bioactive-enriched food offers a promising food-based strategy for MetS prevention, and highlighted the importance of conducting pilot studies.

Endoscopic sphincterotoMy for delayIng choLecystectomy in mild acute biliarY pancreatitis (EMILY study): protocol of a multicentre randomised clinical trial.

INTRODUCTION: According to the literature, early cholecystectomy is necessary to avoid complications related to gallstones after an initial episode of acute biliary pancreatitis (ABP). A randomised, controlled multicentre trial (the PONCHO trial) revealed that in the case of gallstone-induced pancreatitis, early cholecystectomy was safe in patients with mild gallstone pancreatitis and reduced the risk of recurrent gallstone-related complications, as compared with interval cholecystectomy. We hypothesise that carrying out a sphincterotomy (ES) allows us to delay cholecystectomy, thus making it logistically easier to perform and potentially increasing the efficacy and safety of the procedure. METHODS/DESIGN: EMILY is a prospective, randomised, controlled multicentre trial. All patients with mild ABP, who underwent ES during the index admission or in the medical history will be informed to take part in EMILY study. The patients will be randomised into two groups: (1) early cholecystectomy (within 6 days after discharge) and (2) patients with delayed (interval) cholecystectomy (between 45 and 60 days after discharge). During a 12-month period, 93 patients will be enrolled from participating clinics. The primary endpoint is a composite endpoint of mortality and recurrent acute biliary events (that is, recurrent ABP, acute cholecystitis, uncomplicated biliary colic and cholangitis). The secondary endpoints are organ failure, biliary leakage, technical difficulty of the cholecystectomy, surgical and other complications. ETHICS AND DISSEMINATION: The trial has been registered internationally ISRCTN 10667869, and approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (EKU/2018/12176-5). TRIAL REGISTRATION NUMBER: ISCRTN 10667869; Pre-results.

Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE). METHODS: Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence. RESULTS: We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence. CONCLUSIONS: This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke. TRIAL REGISTRATION: PROSPERO; CRD42017073904.

Real-life evaluation of COPD treatment in a Bulgarian population: a 1-year prospective, observational, noninterventional study.

Introduction: This was the first study designed to prospectively evaluate treatment patterns in chronic obstructive pulmonary disease (COPD) and the degree of adherence with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy recommendations in routine clinical practice in Bulgaria. Methods: The study was conducted in an outpatient setting and enrolled patients of both genders, aged >40 years, who were diagnosed with COPD (as per GOLD 2013). Evaluations were performed at baseline and at 6- and 12-month visits. Results: Of the 811 enrolled patients, 719 were assessed and completed the 12-month observation period. Overall, a substantial number of patients experienced moderate airflow limitation (~49% patients, GOLD 2 as per GOLD 2013; mean postbronchodilator forced expiratory volume in 1 second value was ~50% of the predicted value), belonged to GOLD group D (~51% patients), and had COPD assessment test score ≥10 or modified Medical Research Council score ≥2 (~79% patients), and ≤1 exacerbation in the past 1 year (~80% patients). Short-acting ß2-agonists (~63% patients), inhaled corticosteroids/long-acting ß2-agonist fixed-dose combination (~62% patients), and long-acting muscarinic antagonists (~59% patients) were the most frequently used medications at all visits, regardless of severity. High levels of deviation from GOLD recommendations were observed in GOLD groups A and B patients. The deviation comprised high use of inhaled corticosteroid-containing regimens in ~45% and 63% of patients in GOLD groups A and B, respectively. Only 25 (3%) of the 796 patients reported at least one adverse event. Conclusion: The routine clinical practice for COPD in Bulgaria deviates from the GOLD recommendations largely in patients at a low risk (GOLD groups A and B), while the deviation was lesser in those at a higher risk (GOLD groups C and D).

A Pilot Randomized Controlled Trial of a Guided Self-Help Intervention to Manage Chronic Orofacial Pain.

AIMS: To conduct a pilot trial to test the feasibility of a guided self-help intervention for chronic orofacial pain. METHODS: A pilot randomized controlled trial was conducted to compare the intervention with usual treatment. A total of 37 patients with chronic orofacial pain were randomized into either the intervention group (n = 19) or the usual treatment (control) group (n = 18). Validated outcome measures were used to measure the potential effectiveness of the intervention over a number of domains: physical and mental functioning (Short Form 36 [SF-36]); anxiety and depression (Hospital Anxiety and Depression Scale [HADS]); pain intensity and interference with life (Brief Pain Inventory [BPI]); disability (Manchester Orofacial Pain Disability Scale [MOPDS]); and illness behavior (Revised Illness Perceptions Questionnaire [IPQr]). Bootstrap confidence intervals were computed for the treatment effect (ES) posttreatment and at 3 months follow-up and adjusted for baseline values of the outcome measure by using analysis of covariance. RESULTS: At posttreatment and the 3-month follow-up, 11 participants in the intervention group and 7 in the control group failed to complete outcome measures. The intervention was acceptable and could be feasibly delivered face to face or over the telephone. Although the pilot trial was not powered to draw conclusions about the effectiveness, it showed significant (P < .05) effects of the intervention on physical and mental functioning and treatment control. CONCLUSION: The self-help intervention was acceptable to patients and allowed them to better understand and self-manage chronic orofacial pain. It showed potential effectiveness on outcome domains related to functioning and illness perception. Further research is needed to understand the cost effectiveness of the intervention for chronic orofacial pain.