Republished: Antiplatelet therapy for secondary prevention of coronary artery disease

The choice and duration of antiplatelet therapy for secondary prevention of coronary artery disease (CAD) is determined by the clinical context and treatment strategy. Oral antiplatelet agents for secondary prevention include the cyclo-oxygenase-1 inhibitor aspirin, and the ADP dependent P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor. Aspirin constitutes the cornerstone in secondary prevention of CAD and is complemented by clopidogrel in patients with stable CAD undergoing percutaneous coronary intervention. Among patients with acute coronary syndrome, prasugrel and ticagrelor improve net clinical outcome by reducing ischaemic adverse events at the expense of an increased risk of bleeding as compared with clopidogrel. Prasugrel appears particularly effective among patients with ST elevation myocardial infarction to reduce the risk of stent thrombosis compared with clopidogrel, and offered a greater net clinical benefit among patients with diabetes compared with patients without diabetes. Ticagrelor is associated with reduced mortality without increasing the rate of coronary artery bypass graft (CABG)-related bleeding as compared with clopidogrel. Dual antiplatelet therapy should be continued for a minimum of 1 year among patients with acute coronary syndrome irrespective of stent type; among patients with stable CAD treated with new generation drug-eluting stents, available data suggest no benefit to prolong antiplatelet treatment beyond 6 months.

Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.

Prevention of Rebleeding From Esophageal Varices in Patients With Cirrhosis Receiving Small-Diameter Stents Versus Hemodynamically Controlled Medical Therapy

BACKGROUND & AIMS Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis. METHODS We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form-36 health survey) were secondary outcome measures. RESULTS A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups. CONCLUSIONS Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.

Prevention of ischemic complications during aneurysm surgery

Ischemic complications during aneurysm surgery are a frequent cause of postoperative infarctions and new neurological deficits. In this article, we discuss imaging and neurophysiological tools that may help the surgeon to detect intraoperative ischemia. The strength of intraoperative digital subtraction angiography (DSA) is the full view of the arterial and venous vessel. DSA is the gold standard in complex and giant aneurysms, but due to certain disadvantages, it cannot be considered standard of care. Microvascular Doppler sonography is probably the fastest diagnostic tool and can quickly aid diagnosis of large vessel occlusions. Intraoperative indocyanine green videoangiography is the best tool to assess flow in perforating and larger arteries, as well as occlusion of the aneurysm sac. Intraoperative neurophysiological monitoring with somatosensory and motor evoked potentials indirectly measures blood flow by recording neuronal function. It covers all causes of intraoperative ischemia, provided that ischemia occurs in the brain areas under surveillance. However, every method has advantages and disadvantages. No single method is superior to the others in every aspect. Therefore, it is very important for the neurosurgeon to know the strengths and weaknesses of each tool in order to have them available, to know how to use them for each individual situation, and to be ready to apply them within the time window for reversible cerebral ischemia.

Clinical Practice Recommendations For The Management And Prevention Of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

Currently no pharmacogenomics-based criteria exist to guide clinicians in identifying individuals who are at risk of hearing loss from cisplatin-based chemotherapy. This review summarizes findings from pharmacogenomic studies that report genetic polymorphisms associated with cisplatin-induced hearing loss and aims to (1) provide up-to-date information on new developments in the field; (2) provide recommendations for the use of pharmacogenetic testing in the prevention, assessment and management of cisplatin-induced hearing loss in children and adults; and (3) identify knowledge gaps to direct and prioritize future research. These practice recommendations for pharmacogenetic testing in the context of cisplatin-induced hearing loss reflect a review and evaluation of recent literature and are designed to assist clinicians in providing optimal clinical care for patients receiving cisplatin based chemotherapy.

[Prevention of Postthrombotic Syndrom]

Post-thrombotic syndrome (PTS) is a complication which occurs after deep vein thrombosis in spite of optimal anticoagulation. The term ’post-thrombotic syndrome’ summarizes all clinical symptoms and skin lesions developing in the aftermath of deep vein thrombosis. In order to prevent PTS various therapeutic options exist, the choice is depending on the time lapse since the event of thrombosis. At the acute phase of pelvic vein thrombosis catheter-directed lysis has proved to be an efficient therapy. Starting from the acute phase up to the chronic phase compression therapy should be administered. In the chronic phase clinically relevant improvement of PTS can be achieved by recanalisation of the venous outflow tract in the pelvic axis by endovascular stenting. Surgery or endovenous thermal ablation of the insufficient superficial venous system are further and supplementary sensible treatment options.

Comparative cost-effectiveness of Option B+ for prevention of mother-to-child transmission of HIV in Malawi.

OBJECTIVE To estimate the cost-effectiveness of prevention of mother-to-child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared with ART during pregnancy or breastfeeding only unless clinically indicated ('Option B'). DESIGN Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme. METHODS Individual-based simulation model. We simulated cohorts of 10 000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterized the model with data from the literature and by analysing programmatic data. We compared total costs of antenatal and postnatal care, and lifetime costs and disability-adjusted life-years of the infected infants between Option B+ and Option B. RESULTS During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared with 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted. CONCLUSION Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.

Prevention of cement leakage into the hip joint by a standard cement plug during PFN-A cement augmentation: a technical note.

Medial penetration of the helical blade into the hip joint after fixation of trochanteric fractures using the proximal femur nail antirotation (PFN-A) is a potential failure mode. In low demand patients a blade exchange with cement augmentation may be an option if conversion to total hip arthroplasty is unfeasible to salvage the cut-through. This article describes a technique to avoid intraarticular cement leakage using a cement plug to close the defect in the femoral head caused by the cut-through.

Diseases in neonatal foals. Part 1: the 30 day incidence of disease and the effect of prophylactic antimicrobial drug treatment during the first three days post partum

REASONS FOR PERFORMING STUDY: Neonatal diseases have been grouped and analysed but up-to-date statistically significant information about the incidence and prevalence of diseases in foals is limited. Since the 1950s it has been a common management practice to administer a 3 day course of antimicrobial drugs to neonatal foals. This was shown to significantly reduce the incidence of infections (Platt 1977). Since then management practices have improved and it is widely believed that prophylactic antimicrobial drugs are no longer necessary in foal rearing. OBJECTIVES: To determine the 30 day incidences or prevalences (depending on case definition) of various diseases and conditions in the neonatal foal and ascertain the influence of a prophylactic 3 day treatment on the frequency of infections. METHODS: The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). Depending on the stud farm's practice in the use of prophylactic antimicrobial drugs, 2 groups of newborn foals (treated and untreated) were identified and followed for 30 days. RESULTS: The 30 day incidences of infectious diseases under study were between 0.2% (osteomyelitis) and 5.85% (systemic disease with diarrhoea). The overall incidence for 'total infectious diseases' was 8.27%. The most commonly observed noninfectious condition was limb deformities (12.11% of all foals). There was no significant difference in the incidence of infectious diseases between the 2 groups. CONCLUSION: Infectious diseases are still an important problem in neonatal foals requiring further investigation as to which factors other than antimicrobial prophylaxis are relevant for disease prevention. POTENTIAL RELEVANCE: The results provide an up-to-date overview about the frequencies of various neonatal foal diseases. They do not support the traditional prophylactic use of antimicrobials to prevent infectious diseases in healthy newborn foals. However, it should be noted that this study was not a randomised controlled trial and therefore does not provide the strongest possible evidence for this conclusion.

Report from the National Institute of Allergy and Infectious Diseases workshop on drug allergy

Allergic reactions to drugs are a serious public health concern. In 2013, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop on drug allergy. International experts in the field of drug allergy with backgrounds in allergy, immunology, infectious diseases, dermatology, clinical pharmacology, and pharmacogenomics discussed the current state of drug allergy research. These experts were joined by representatives from several National Institutes of Health institutes and the US Food and Drug Administration. The participants identified important advances that make new research directions feasible and made suggestions for research priorities and for development of infrastructure to advance our knowledge of the mechanisms, diagnosis, management, and prevention of drug allergy. The workshop summary and recommendations are presented herein.

Tackling of unhealthy diets, physical inactivity, and obesity: health effects and cost-effectiveness

The obesity epidemic is spreading to low-income and middle-income countries as a result of new dietary habits and sedentary ways of life, fuelling chronic diseases and premature mortality. In this report we present an assessment of public health strategies designed to tackle behavioural risk factors for chronic diseases that are closely linked with obesity, including aspects of diet and physical inactivity, in Brazil, China, India, Mexico, Russia, and South Africa. England was included for comparative purposes. Several population-based prevention policies can be expected to generate substantial health gains while entirely or largely paying for themselves through future reductions of health-care expenditures. These strategies include health information and communication strategies that improve population awareness about the benefits of healthy eating and physical activity; fiscal measures that increase the price of unhealthy food content or reduce the cost of healthy foods rich in fibre; and regulatory measures that improve nutritional information or restrict the marketing of unhealthy foods to children. A package of measures for the prevention of chronic diseases would deliver substantial health gains, with a very favourable cost-effectiveness profile.

Mood and nonmood components of perceived stress and exacerbation of Crohnʼs disease

BACKGROUND: Diverse psychological factors are involved in the pathophysiology of stress. In order to devise effective intervention strategies, it is important to elucidate which factors play the most important role in the association between psychological stress and exacerbation of Crohn's disease (CD). We hypothesized that the association between perceived stress and exacerbation of CD would remain after removal of mood and anxiety components, which are largely involved in stress perception. METHODS: In all, 468 adults with CD were recruited and followed in different hospitals and private practices of Switzerland for 18 months. At inclusion, patients completed the Perceived Stress Questionnaire and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. During the follow-up, gastroenterologists assessed whether patients presented with a CD exacerbation. By means of binary logistic regression analysis, we estimated the factor by which one standard deviation of perceived stress would increase the odds of exacerbation of CD with and without controlling for anxiety and depression. RESULTS: The odds of exacerbation of CD increased by 1.85 times (95% confidence interval 1.43-2.40, P < 0.001) for 1 standard deviation of perceived stress. After removing the anxiety and depression components, the residuals of perceived stress were no longer associated with exacerbation of CD. CONCLUSIONS: The association between perceived stress and exacerbation of CD was fully attributable to the mood components, specifically anxiety and depression. Future interventional studies should evaluate the treatment of anxiety and depression as a strategy for potential prevention of CD exacerbations. (Inflamm Bowel Dis 2011;).

Secondary prevention through cardiac rehabilitation: from knowledge to implementation. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation

Increasing awareness of the importance of cardiovascular prevention is not yet matched by the resources and actions within health care systems. Recent publication of the European Commission's European Heart Health Charter in 2008 prompts a review of the role of cardiac rehabilitation (CR) to cardiovascular health outcomes. Secondary prevention through exercise-based CR is the intervention with the best scientific evidence to contribute to decrease morbidity and mortality in coronary artery disease, in particular after myocardial infarction but also incorporating cardiac interventions and chronic stable heart failure. The present position paper aims to provide the practical recommendations on the core components and goals of CR intervention in different cardiovascular conditions, to assist in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of CR. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, national or individual centre level, need to consider where and how structured programmes of CR can be delivered to all patients eligible. Thus a novel, disease-oriented document has been generated, where all components of CR for cardiovascular conditions have been revised, presenting both well-established and controversial aspects. A general table applicable to all cardiovascular conditions and specific tables for each clinical disease have been created and commented.

Advances in the prevention, management and treatment of community-acquired pneumonia

Despite the availability of powerful antibiotics, community-acquired pneumonia (CAP) remains one of the leading reasons for morbidity and mortality worldwide, and despite the availability of powerful antibiotics, there has been only little improvement in case fatality rates for many years. Consequently, it cannot be expected that novel antibiotics will substantially improve outcomes in CAP. Therefore, this review focuses on novel approaches that may reduce CAP-related mortality: the impact of immunomodulation by macrolides and fluoroquinolones and the prevention of CAP by pneumococcal vaccines.