Boceprevir and telaprevir‐based triple therapy for chronic hepatitis C: virological efficacy and impact on kidney function and model for end‐stage liver disease score

Triple therapy using telaprevir or boceprevir [hepatitis C virus (HCV)‐NS3/NS4A protease inhibitors (PI)] in association with PEG‐IFN/ribavirin has recently become the new standard of care (SOC) for treatment of HCV genotype 1 patients. Our objective was to assess the efficacy and tolerance of triple therapy in routine clinical practice. A total of 186 consecutive HCV patients initiating triple therapy were enrolled in a single centre study. Clinical, biological and virological data were collected at baseline and during follow‐up as well as tolerance and side effect details. Among 186 HCV patients initiating triple therapy, 69% received telaprevir and 31% boceprevir. Sixty‐one per cent of patients had cirrhosis. The overall extended rapid virological response (eRVR) rate and sustained virological response (SVR) rate were 57.0% and 59.7%, respectively. IL28B CC phenotype was associated with increased probability of achieving eRVR and SVR, whereas previous non‐response was associated with low eRVR and SVR rates. The SVR rate increased from 30.8% in previously non‐responders to 59.1% in partial non‐responders and 75% in relapsers. SVR rate in naive patients was 62.5%. Glomerular filtration rate assessed by MDRD after 12 weeks of therapy was significantly reduced for both PI (P < 0.001). The model for end‐stage liver disease (MELD) score was significantly increased at W12 for telaprevir (P = 0.008) and at W24 for boceprevir (P = 0.027). PI‐based triple therapy leads to high rates of virological response even in previously non‐responder patients. Renal function after triple therapy is impaired as well as MELD score in all patients. Cautious clinical monitoring should focus not only on haematological and dermatological side effects but also on renal function.     

The Role of Exercise and Physical Activity in Weight Loss and Maintenance

This review explores the role of physical activity (PA) and exercise training (ET) in the prevention of weight gain, initial weight loss, weight maintenance, and the obesity paradox. In particular, we will focus the discussion on the expected initial weight loss from different ET programs, and explore intensity/volume relationships. Based on the present literature, unless the overall volume of aerobic ET is very high, clinically significant weight loss is unlikely to occur. Also, ET also has an important role in weight regain after initial weight loss. Overall, aerobic ET programs consistent with public health recommendations may promote up to modest weight loss (~ 2 kg), however the weight loss on an individual level is highly heterogeneous. Clinicians should educate their patients on reasonable expectations of weight loss based on their physical activity program and emphasize that numerous health benefits occur from PA programs in the absence of weight loss.     

Cardiac Rehabilitation in the United States

Coronary heart disease (CHD) is a significant cause of morbidity and mortality in the United States (US). In addition to this, many of the risk factors of CHD, such as obesity, sedentary lifestyle, diabetes mellitus, and poor nutrition, are disproportionately high in the US. Despite the many known benefits of cardiac rehabilitation (CR), referral and participation rates in these programs are paradoxically low. Over the course of this review, we will discuss some of the many benefits of CR, some of the risk factors for CHD in the US, and factors that affect referral and participation in these programs.     

Antihypertensive therapy versus alternative therapeutic options for prehypertension: an evidence-based approach

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) defines hypertension as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg. The JNC-7 defines 'prehypertension' to include systolic BP values between 120 and 139 mmHg and diastolic BP values between 80 and 89 mmHg. Individuals with blood pressure in the prehypertension range are clearly at increased risk of developing hypertension in the future and have an increased risk of cardiovascular morbidity and mortality, compared with those with normal BP. However, there is paucity of evidence to intervene in these patients. In this article we discuss an evidence-based approach to therapeutic options in patients with prehypertension.     

Physical Activity and Risk of Metabolic Phenotypes of Obesity: A Prospective Taiwanese Cohort Study in More Than 200,000 Adults

ObjectiveTo examine the association between physical activity (PA) and the risk for metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO) in Asian adults.Patients and MethodsData were obtained from 205,745 healthy individuals 18 years or older. Individuals were classified as inactive, lower or upper insufficiently active, active, and high active. Metabolically unhealthy was defined as having 1 or more of the metabolic syndrome criteria, excluding the abdominal obesity criterion.ResultsThe percentages of metabolically healthy normal-weight (MHNW), metabolically healthy overweight (MHOW), MHO, and MUO in our cohort were 30.8% (63,408 of 205,745), 5.8% (12,002 of 205,745), 4.1% (8329 of 205,745), and 20.7% (42,564 of 205,745), respectively. During a mean follow-up of 6 (range, 0.5-19) years, among 63,408 MHNW participants, 1890 (3.0%) and 1174 (1.9%) developed MUO and MHO, respectively. Among 12,002 MHOW participants, 3404 (28.4%) developed MUO and 2734 (22.8%) developed MHO. A total of 5506 of 8329 (66.1%) participants moved from MHO to MUO, and 5675 of 42,564 (13.3%) moved from MUO to MHO. Compared with being inactive, MHNW individuals who were active or high active showed lower risk for MUO. Among those with MHOW, being high active was associated with reduced risk for MUO and MHO. Although among MHO participants, PA was not associated with incident MUO, being active or high active was linked to a greater likelihood of moving from MUO to MHO.ConclusionPA may prevent the development of both MHO and MUO. PA also helps increase the transition from MUO to MHO, which may contribute to reduce the subsequent development of type 2 diabetes mellitus and major cardiovascular disease complications.     

A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO₂), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO₂ (7,319), VE/VCO₂ slope (5,044), EOV (1,617), and OUES (584). Peak VO₂, the VE/VCO₂ slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO₂ and the VE/VCO₂ slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.