An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

Does classical liberalism imply an evolutionary approach to policy-making?

This paper argues that an evolutionary approach to policy-making, which emphasizes openness to change and political variety, is particularly compatible with the central tenets of classical liberalism. The chief reasons are that classical liberalism acknowledges the ubiquity of uncertainty, as well as heterogeneity in preferences and beliefs, and generally embraces gradual social and economic change that arises from accidental variation rather than deliberate, large-scale planning. In contrast, our arguments cast doubt on a different claim, namely that classical liberalism is particularly compatible with the evolutionary biological heritage of humans

Recent Innovations & Daily Problems. A new prosthesis in inguinal hernia repair:preliminary results of a pilot study.

Introduction: Elective surgery for inguinal hernia is affected by very low mortality « 1 per 10000 operation); in contrast, when surgery is carried out for complicated inguinal hernia, risks of postoperative complication are higher. TAPP is a world-wide accepted surgical practice in the treatment of elective bilateral or recurrent inguinal hernia, above all in young patients. Few exploratory studies were published on laparoscopic approach in the treatment of urgent complicated inguinal hernia. Aim of this study was to analyze feasibility (operative time, conversion rate), safety (postoperative morbidity, length of hospital stay) and quality of life (acute and chronic pain, return to work) of trans-abdominal pre-peritoneal laparoscopic hernia repair in acute incarcerated inguinal hernia. Rationale of laparoscopic trans-abdominal approach is the easier hernia reduction under vision and a better exploration of the abdominal cavity. Methods: from September 2012 to September 2013, 15 consecutive patients admitted in emergency at the Division of General Surgery of University "Sapienza", Polo Pontino, for acute incarcerated inguinal hernia were submitted to TAPP using 3 trocars (1 of 10 mm and 2 of 5mm) and polyester prosthesis fixed by fibrin glue. Exclusion criteria for laparoscopic approach were age III, previous abdominal surgery, signs of strangulated hernia. All of them were evaluated for operative time, conversion rate, postoperative morbidity, organ resection or other surgery required. All patients were scored for pain by Visual Analogic Scale (VAS) during postoperative in hospital stay at 7 days, 1,6 and 12 months after surgery. Results: median follow-up was 16 months and 12 as minimum. In all cases reduction of hernia was always possible and none conversion to open surgery was recorded, median operative time was 89 minutes (55-137 as range), omental resection was carried out in one patient (6,6%), no other organ resections needed, whereas contralateral hernia was diagnosed and repaired at the same time in 4 patients (26,6%). No major complications were observed, median blood loss was 100 ml, minor morbidity was contained to 18% represented by fever and wound infection of surgical umbilical scar. Median in hospital stay was 1,5 days with 1-5 days as range. Postoperative median acute pain, measured by visual analogic scale (VAS), was 2 (range:0-4), none patient referred any pain during follow-up. Median time of return to work was 6,5 days, ranged between 3 to 15 days. Patients' compliance to treatment and to follow-up was complete as well their satisfaction. Conclusions: In centres skilled for laparoscopy in emergency, TAPP could be considered a feasible and safe technique. In well-selected patients (especially if emolled in controlled clinical trial) TAPP could represent an alternative surgical approach for complicated incarcerated inguinal hernia to conventional open surgery even in urgency. The main advantages of laparoscopic approach are the ability to perform surgical hernia reduction under vision, a better exploration and evaluation of abdominal cavity and diagnosis and treatment of eventual contralateral defect of wall, otherwise often missed. Finally, the good control of acute and chronic pain, faster return to normal activity and work, better aesthetic results contributed to total satisfaction and compliance of the patients

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

The German Banking System and the Global Financial Crisis: Causes, Developments and Policy Responses

Germany's banking sector has been severely hit by the global financial crisis. In a German context as of February, 2009, this paper reviews briefly the structure of the banking industry, quantifies effects of the crisis on banks and surveys responses of economic policy. It is argued that policy design needs to enhance transparency and enforce the liability principle. In addition, economic policy should not eclipse principles of competition policy.Der deutsche Bankensektor ist durch die internationale Finanzkrise schwer getroffen. Auf Deutschland und die im Februar 2009 verfügbaren Informationen bezogen, werden die Struktur des Bankensektors kurz umrissen, die Effekte auf die Banken quantifiziert und wirtschaftspolitische Reaktionen aufgezeigt. Ziel der Wirtschaftspolitik ist es, die Transparenz zu erhöhen und das Haftungsprinzip durchzusetzen. Darüber hinaus sollten Grundsätze der Wettbewerbspolitik nicht in den Hintergrund geraten

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes