Exercise-based cardiac rehabilitation for adults with stable angina (review)

This is the final version of the article. Available from Cochrane Collaboration via the DOI in this record.BACKGROUND: A previous Cochrane review has shown that exercise-based cardiac rehabilitation (CR) can benefit myocardial infarction and post-revascularisation patients. However, the impact on stable angina remains unclear and guidance is inconsistent. Whilst recommended in the guidelines of American College of Cardiology/American Heart Association and the European Society of Cardiology, in the UK the National Institute for Health and Care Excellence (NICE) states that there is "no evidence to suggest that CR is clinically or cost-effective for managing stable angina". OBJECTIVES: To assess the effects of exercise-based CR compared to usual care for adults with stable angina. SEARCH METHODS: We updated searches from the previous Cochrane review 'Exercise-based cardiac rehabilitation for patients with coronary heart disease' by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, DARE, CINAHL and Web of Science on 2 October 2017. We searched two trials registers, and performed reference checking and forward-citation searching of all primary studies and review articles, to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a follow-up period of at least six months, which compared structured exercise-based CR with usual care for people with stable angina. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data according to the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors also independently assessed the quality of the evidence using GRADE principles and we presented this information in a 'Summary of findings' table. MAIN RESULTS: Seven studies (581 participants) met our inclusion criteria. Trials had an intervention length of 6 weeks to 12 months and follow-up length of 6 to 12 months. The comparison group in all trials was usual care (without any form of structured exercise training or advice) or a no-exercise comparator. The mean age of participants within the trials ranged from 50 to 66 years, the majority of participants being male (range: 74% to 100%). In terms of risk of bias, the majority of studies were unclear about their generation of the randomisation sequence and concealment processes. One study was at high risk of detection bias as it did not blind its participants or outcome assessors, and two studies had a high risk of attrition bias due to the numbers of participants lost to follow-up. Two trials were at high risk of outcome reporting bias. Given the high risk of bias, small number of trials and participants, and concerns about applicability, we downgraded our assessments of the quality of the evidence using the GRADE tool.Due to the very low-quality of the evidence base, we are uncertain about the effect of exercise-based CR on all-cause mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.18 to 5.67; 195 participants; 3 studies; very low-quality evidence), acute myocardial infarction (RR 0.33, 95% CI 0.07 to 1.63; 254 participants; 3 studies; very low-quality evidence) and cardiovascular-related hospital admissions (RR 0.14, 95% CI 0.02 to 1.1; 101 participants; 1 study; very low-quality evidence). We found low-quality evidence that exercise-based CR may result in a small improvement in exercise capacity compared to control (standardised mean difference (SMD) 0.45, 95% CI 0.20 to 0.70; 267 participants; 5 studies, low-quality evidence). We were unable to draw conclusions about the impact of exercise-based CR on quality of life (angina frequency and emotional health-related quality-of-life score) and CR-related adverse events (e.g. skeletomuscular injury, cardiac arrhythmia), due to the very low quality of evidence. No data were reported on return to work. AUTHORS' CONCLUSIONS: Due to the small number of trials and their small size, potential risk of bias and concerns about imprecision and lack of applicability, we are uncertain of the effects of exercise-based CR compared to control on mortality, morbidity, cardiovascular hospital admissions, adverse events, return to work and health-related quality of life in people with stable angina. Low-quality evidence indicates that exercise-based CR may result in a small increase in exercise capacity compared to usual care. High-quality, well-reported randomised trials are needed to assess the benefits and harms of exercise-based CR for adults with stable angina. Such trials need to collect patient-relevant outcomes, including clinical events and health-related quality of life. They should also assess cost-effectiveness, and recruit participants that are reflective of the real-world population of people with angina.University of Exeter Medical School, UK. The Cochrane Heart Group US Satellite is supported by intramural support from the Northwestern University Feinberg School of Medicine and the Northwestern University Clinical and Translational Science (NUCATS) Institute (UL1TR000150)., USA. This project was supported by the National Institute for Health Research, via Cochrane Incentive funding to the Heart Group

Hepatic artery aneurysm repair: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hepatic artery aneurysms remain a clinically significant entity. Their incidence continues to rise slowly and mortality from spontaneous rupture is high. Repair is recommended in those aneurysms greater than 2 cm in diameter. It is not surprising that vascular comorbidities, such as ischaemic heart disease, are common in surgical patients, particularly those with arterial aneurysms such as these. The decision of when to operate on patients who require urgent surgery despite having recently suffered an acute coronary syndrome remains somewhat of a grey and controversial area. We discuss the role of delayed surgery and postoperative followup of this vascular problem.</p> <p>Case presentation</p> <p>A 58-year-old man was admitted with a 5.5 cm hepatic artery aneurysm. The aneurysm was asymptomatic and was an incidental finding as a result of an abdominal computed tomography scan to investigate an episode of haemoptysis (Figure <figr fid="F1">1</figr>). Three weeks prior to admission, the patient had suffered a large inferior myocardial infarction and was treated by thrombolysis and primary coronary angioplasty. Angiographic assessment revealed a large aneurysm of the common hepatic artery involving the origins of the hepatic, gastroduodenal, left and right gastric arteries and the splenic artery (Figures <figr fid="F2">2</figr> and <figr fid="F3">3</figr>). Endovascular treatment was not considered feasible and immediate surgery was too high-risk in the early post-infarction period. Therefore, surgery was delayed for 3 months when aneurysm repair with reconstruction of the hepatic artery was successfully performed. Graft patency was confirmed with the aid of an abdominal arterial duplex. Plasma levels of conventional liver function enzymes and of alpha-glutathione-<it>S</it>-transferase were within normal limits. This was used to assess the extent of any hepatocellular damage perioperatively. The patient made a good recovery and was well at his routine outpatient check-ups.</p> <p>Conclusion</p> <p>There is no significant difference in cardiac risk in patients who have undergone vascular surgery within 6 months of a myocardial infarction compared with those who have had the operation in the 6 to12 month time frame. Use of alpha-glutathione-<it>S</it>-transferase gives an indication of the immediate state of hepatic function and should be used in addition to traditional liver function tests to monitor hepatic function postoperatively.</p

Restoring Vision through “Project Prakash”: The Opportunities for Merging Science and Service

“So how does this help society?” is a question we are often asked as scientists. The lack of immediate and tangible results cannot be held against a scientific project but statements of future promise in broad and inchoate terms can sometimes pass the benefit-buck indefinitely. There is no incentive against over-stating the benefits, especially when they are hypothetical and lie in the distant future. Few scientists will say their science is not designed to serve society. Yet the proliferation of “potential benefits” in grant proposals and the Discussion sections of research papers, in the absence of tangible translations, can make the service element of science seem like a cliched ritual. Its repetition hollows out its meaning, breeding cynicism about the idea that basic science can be of service

Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma.

Background: Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses. Spontaneous pneumothoraces as a result of response to anti-cancer therapy are rare in oncology but have been documented in a number of tumour types including lung cancer. This includes cytotoxic chemotherapy as well as molecular targeted agents such as gefitinib and Bevacizumab. These often require chest drain insertion or surgical intervention with associated morbidity and mortality. They have also been associated with response to treatment. This is the first report we are aware of documenting pneumothorax as response to crizotinib therapy.Case presentation: A 48-year-old Caucasian male presented with a Stage IV, TTF1 positive, EGFR wild-type adenocarcinoma of the lung. He received first line chemotherapy with three cycles of cisplatin-pemetrexed chemotherapy with a differential response, and then second-line erlotinib for two months before further radiological evidence of disease progression. Further analysis of his diagnostic specimen identified an ALK rearrangement by fluorescence in situ hybridization (FISH). He was commenced on crizotinib therapy 250 mg orally twice daily. At his 4-week assessment he had a chest radiograph that identified a large left-sided pneumothorax with disease response evident on the right. Chest CT confirmed a 50% left-sided pneumothorax on a background of overall disease response. A chest tube was inserted with complete resolution of the pneumothorax that did not recur following its removal.Conclusion: Our case demonstrates this potential complication of crizotinib therapy and we therefore recommend that pneumothorax be considered in patients on crizotinib presenting with high lung metastatic burden and with worsening dyspnoea. © 2013 Gennatas et al.; licensee BioMed Central Ltd

Potential health impacts of heavy metals on HIV-infected population in USA.

Noninfectious comorbidities such as cardiovascular diseases have become increasingly prevalent and occur earlier in life in persons with HIV infection. Despite the emerging body of literature linking environmental exposures to chronic disease outcomes in the general population, the impacts of environmental exposures have received little attention in HIV-infected population. The aim of this study is to investigate whether individuals living with HIV have elevated prevalence of heavy metals compared to non-HIV infected individuals in United States. We used the National Health and Nutrition Examination Survey (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead, and total mercury in HIV infected and non-HIV infected subjects. In this cross-sectional study, we found that HIV-infected individuals had higher concentrations of all heavy metals than the non-HIV infected group. In a multivariate linear regression model, HIV status was significantly associated with increased blood cadmium (p=0.03) after adjusting for age, sex, race, education, poverty income ratio, and smoking. However, HIV status was not statistically associated with lead or mercury levels after adjusting for the same covariates. Our findings suggest that HIV-infected patients might be significantly more exposed to cadmium compared to non-HIV infected individuals which could contribute to higher prevalence of chronic diseases among HIV-infected subjects. Further research is warranted to identify sources of exposure and to understand more about specific health outcomes

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Self-reported medication side effects in an older cohort living independently in the community - the Melbourne Longitudinal Study on Health Ageing (MELSHA) : cross-sectional analysis of prevalence and risk factors

Background Medication side effects are an important cause of morbidity, mortality and costs in older people. The aim of our study was to examine prevalence and risk factors for self-reported medication side effects in an older cohort living independently in the community.Methods The Melbourne Longitudinal Study on Healthy Ageing (MELSHA), collected information on those aged 65 years or older living independently in the community and commenced in 1994. Data on medication side effects was collected from the baseline cohort (n = 1000) in face-to-face baseline interviews in 1994 and analysed as cross-sectional data. Risk factors examined were: socio-demographics, health status and medical conditions; medication use and health service factors. Analysis included univariate logistic regression to estimate unadjusted risk and multivariate logistic regression analysis to assess confounding and estimate adjusted risk.Results Self-reported medication side effects were reported by approximately 6.7% (67/1000) of the entire baseline MELSHA cohort, and by 8.5% (65/761) of those on medication. Identified risk factors were increased education level, co-morbidities and health service factors including recency of visiting the pharmacist, attending younger doctors, and their doctor\u27s awareness of their medications. The greatest increase in risk for medication side effects was associated with liver problems and their doctor\u27s awareness of their medications. Aging and gender were not risk factors.Conclusion Prevalence of self-reported medication side effects was comparable with that reported in adults attending General Practices in a primary care setting in Australia. The prevalence and identified risk factors provide further insight and opportunity to develop strategies to address the problem of medication side effects in older people living independently in the community setting. <br /

Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains

Background: The degree of heterotypic immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is a major determinant of the spread of emerging variants and the success of vaccination campaigns, but remains incompletely understood. Methods: We examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the United Kingdom and spread globally. We determined titres of spike glycoprotein-binding antibodies and authentic virus neutralising antibodies induced by B.1.1.7 infection to infer homotypic and heterotypic immunity. Results: Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant. The drop in cross-reactivity was significantly more pronounced following B.1.1.7 than parental strain infection. Conclusions: The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric

Expression of APOBEC3G/3F and G-to-A Hypermutation Levels in HIV-1-Infected Children with Different Profiles of Disease Progression

OBJECTIVE: Increasing evidence has accumulated showing the role of APOBEC3G (A3G) and 3F (A3F) in the control of HIV-1 replication and disease progression in humans. However, very few studies have been conducted in HIV-infected children. Here, we analyzed the levels of A3G and A3F expression and induced G-to-A hypermutation in a group of children with distinct profiles of disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Perinatally HIV-infected children were classified as progressors or long-term non-progressors according to criteria based on HIV viral load and CD4 T-cell counts over time. A group of uninfected control children were also enrolled in the study. PBMC proviral DNA was assessed for G-to-A hypermutation, whereas A3G and A3F mRNA were isolated and quantified through TaqMan® real-time PCR. No correlation was observed between disease progression and A3G/A3F expression or hypermutation levels. Although all children analyzed showed higher expression levels of A3G compared to A3F (an average fold of 5 times), a surprisingly high A3F-related hypermutation rate was evidenced in the cohort, irrespective of the child's disease progression profile. CONCLUSION: Our results contribute to the current controversy as to whether HIV disease progression is related to A3G/A3F enzymatic activity. To our knowledge, this is the first study analyzing A3G/F expression in HIV-infected children, and it may pave the way to a better understanding of the host factors governing HIV disease in the pediatric setting