Comparing the mapping between EQ-5D-5L, EQ-5D-3L and the EORTC-QLQ-C30 in non-small cell lung cancer patients.

BACKGROUND: Several mapping algorithms have been published with the EORTC-QLQ-C30 for estimating EQ-5D-3L utilities. However, none are available with EQ-5D-5L. Moreover, a comparison between mapping algorithms in the same set of patients has not been performed for these two instruments simultaneously. In this prospective data set of 100 non-small cell lung cancer (NSCLC) patients, we investigate three mapping algorithms using the EQ-5D-3L and EQ-5D-5L and compare their performance. METHODS: A prospective non-interventional cohort of 100 NSCLC patients were followed up for 12 months. EQ-5D-3L, EQ-5D-5L and EORTC-QLQ-C30 were assessed monthly. EQ-5D-5L was completed at least 1 week after EQ-5D-3L. A random effects linear regression model, a beta-binomial (BB) and a Limited Variable Dependent Mixture (LVDM) model were used to determine a mapping algorithm between EQ-5D-3L, EQ-5D-5L and QLQ-C30. Simulation and cross validation and other statistical measures were used to compare the performances of the algorithms. RESULTS: Mapping from the EQ-5D-5L was better: lower AIC, RMSE, MAE and higher R(2) were reported with the EQ-5D-5L than with EQ-5D-3L regardless of the functional form of the algorithm. The BB model proved to be more useful for both instruments: for the EQ-5D-5L, AIC was -485, R(2) of 75 %, MAE of 0.075 and RMSE was 0.092. This was -385, 69 %, 0.099 and 0.113 for EQ-5D-3L respectively. The mean observed vs. predicted utilities were 0.572 vs. 0.577 and 0.515 vs. 0.523 for EQ-5D-5L and EQ-5D-3L respectively, for OLS; for BB, these were 0.572 vs. 0.575 and 0.515 vs. 0.518 respectively and for LVDMM 0.532 vs 0.515 and 0.569 vs 0.572 respectively. Less over-prediction at poorer health states was observed with EQ-5D-5L. CONCLUSIONS: The BB mapping algorithm is confirmed to offer a better fit for both EQ-5D-3L and EQ-5D-5L. The results confirm previous and more recent results on the use of BB type modelling approaches for mapping. It is recommended that in studies where EQ-5D utilities have not been collected, an EQ-5D-5L mapping algorithm is used.

A Single-Center Randomized Trial of Intraoperative Zero-Balanced Ultrafiltration During Cardiopulmonary Bypass for Patients With Impaired Kidney Function Undergoing Cardiac Surgery.

OBJECTIVES: The authors investigated whether zero-balance ultrafiltration (Z-BUF) during bypass significantly improves clinical and cost outcomes or biomarkers of kidney injury for patients with preoperative kidney impairment (estimated glomerular filtration rate [eGFR]<60 mL/minute) undergoing cardiac surgery. DESIGN: A single-center randomized controlled trial recruited, patients between 2010 and 2013, with a 12-months follow-up. SETTING: Hospital. PARTICIPANTS: One hundred ninety-nine patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: Patients were assigned randomly to receive zero-balance ultrafiltration (Z-BUF) or not, with stratification for degree of kidney dysfunction and diabetes. MEASUREMENTS AND MAIN RESULTS: The authors assessed clinical efficacy and kidney function biomarkers. Cumulative probability of discharge from the intensive care unit (ICU) was assessed by Kaplan-Meier plots and was found not to be significantly different between the two trial arms (p = 0.61). After adjusting for EuroSCORE, diabetes, eGFR, cardioplegia types and type of surgery in a Cox proportional hazard model, hazard ratios (HR) for ICU length of stay between the Z-BUF and no-Z-BUF groups was not significantly different: HR (95% CI): 0.89 (0.66, 1.20; p = 0.44). In contrast, significant reductions in postoperative chest infections and the composite of clinical endpoints (death, strokes, and myocardial infarctions) in the Z-BUF group were observed. In addition, Z-BUF significantly abrogated the rise in the kidney damage markers urinary NGAL/creatinine ratio, urea, creatinine and eGFR during CPB and adverse events risks. CONCLUSIONS: Z-BUF during bypass surgery is associated with significant reductions in morbidity and biomarkers of CPB-induced acute kidney injury soon after CPB, which are indicative of clearance of inflammatory/immune mediators from the circulation.

Gender differences in the expression of genes involved during cardiac development in offspring from dams on high fat diet.

Previously we have demonstrated that maternal high fat diet (HF) during pregnancy increase cardiovascular risk in the offspring, and pharmacological intervention using statins in late pregnancy reduced these risk factors. However the effects of maternal HF-feeding and statin treatment during pregnancy on development of heart remain unknown. Hence we measured expression of genes involved in cell cycle progression (cyclin G1), ventricular remodelling brain natriuretic peptide (BNP), and environmental stress response small proline-rich protein 1A (SPRR 1A) in the offspring left ventricle (LV) from dams on HF with or without statin treatment. Female C57 mice were fed a HF diet (45% kcal fat) 4 weeks prior to conception, during pregnancy and lactation. From the second half of the pregnancy and throughout lactation, half of the pregnant females on HF diet were given a water-soluble statin (Pravastatin) in their drinking water (HF + S). At weaning offspring were fed HF diet to adulthood (generating dam/offspring dietary groups HF/HF and HF + S/HF). These groups were compared with offspring from dams fed standard chow (C 21% kcal fat) and fed C diet from weaning (C/C). LV mRNA levels for cyclin G1, BNP and SPRR 1A were measured by RT-PCR. Heart weights and BP in HF/HF offspring were higher versus C/C group. Maternal Pravastatin treatment reduced BP and heart weights in HF + S/HF female offspring to levels found in C/C group. LV cyclin G1 mRNA levels were lower in HF/HF versus both C/C and HF + S/HF offspring. BNP mRNA levels were elevated in HF/HF females but lower in males versus C/C. BNP gene expression in HF + S/HF offspring was similar to HF/HF. SPRR 1A mRNA levels were similar in all treatment groups. Statins given to HF-fed pregnant dams reduced cardiovascular risk in adult offspring, and this is accompanied by changes in expression of genes involved in adaptive remodelling in the offspring LV and that there is a gender difference.

Using Behavior Change Interventions in Cardiac and Pulmonary Rehabilitation: Perspectives from Healthcare Professionals in the United Kingdom.

This study explores healthcare professionals' experiences of using behavior change interventions in clinical practice. Semi-structured qualitative interviews were conducted with 11 healthcare professionals working in a cardiac and pulmonary rehabilitation National Health Service Trust in the United Kingdom. Interviews were transcribed and analyzed using inductive thematic analysis. Four overarching themes representing healthcare practitioners' perceptions of using behavior change interventions were identified: (1) reliance on experiential learning, (2) knowledge transition, (3) existing professional development programs, and (4) barriers and facilitators for continued professional development. The results are discussed in relation to the implications they may have for behavior change training in clinical healthcare practice. Healthcare professionals require bespoke and formalized training to optimize their delivery of behavior change interventions in cardiac and pulmonary rehabilitation. Doing so will enhance intervention fidelity and implementation that can potentially ameliorate patient rehabilitation outcomes.

Tumor necrosis factor alpha -308 gene locus promoter polymorphism: an analysis of association with health and disease.

Tumor necrosis factor-alpha (TNF-alpha) is a potent immunomediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of its gene within major histocompatibility complex and biological activities has raised the possibility that polymorphisms within this locus may contribute to the pathogenesis of wide range of autoimmune and infectious diseases. For example, a bi-allelic single nucleotide substitution of G (TNFA1 allele) with A (TNFA2 allele) polymorphism at -308 nucleotides upstream from the transcription initiation site in the TNF-alpha promoter is associated with elevated TNF-alpha levels and disease susceptibilities. However, it is still unclear whether TNF-alpha -308 polymorphism plays a part in the disease process, in particular whether it could affect transcription factor binding and in turn influence TNF-alpha transcription and synthesis. Several studies have suggested that TNFA2 allele is significantly linked with the high TNF-alpha-producing autoimmune MHC haplotype HLA-A1, B8, DR3, with elevated serum TNF-alpha levels and a more severe outcome in diseases. This review discusses the genetics of the TNF-alpha -308 polymorphism in selected major diseases and evaluates its common role in health and disease.

Impact of community-based chronic obstructive pulmonary disease service, a multidisciplinary intervention in an area of high deprivation: a longitudinal matched controlled study.

OBJECTIVE: To examine the effects of a consultant-led, community-based chronic obstructive pulmonary disease (COPD) service, based in a highly deprived area on emergency hospital admissions. DESIGN: A longitudinal matched controlled study using difference-in-differences analysis to compare the change in outcomes in the intervention population to a matched comparison population, 5 years before and after implementation. SETTING: A deprived district in the North West of England between 2005 and 2016. INTERVENTION: A community-based, consultant-led COPD service providing diagnostics, treatment and rehabilitation from 2011 to 2016. MAIN OUTCOME MEASURES: Emergency hospital admissions, length of stay per emergency admission and emergency readmissions for COPD. RESULTS: The intervention was associated with 24 fewer emergency COPD admissions per 100 000 population per year (95% CI -10.6 to 58.8, p=0.17) in the postintervention period, relative to the control group. There were significantly fewer emergency admissions in populations with medium levels of deprivation (64 per 100 000 per year; 95% CI 1.8 to 126.9) and among men (60 per 100 000 per year; 95% CI 12.3 to 107.3). CONCLUSION: We found limited evidence that the service reduced emergency hospital admissions, after an initial decline the effect was not sustained. The service, however, may have been more effective in some subgroups.

Impact of a community-based cardiovascular disease service intervention in a highly deprived area.

OBJECTIVE: To examine the effects on emergency hospital admissions, length of stay and emergency re-admissions of providing a consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service, based in a highly deprived area in the North West of England. METHODS: A longitudinal matched controlled study using difference-in-differences analysis compared the change in outcomes in the intervention population, to the change in outcomes in a matched comparison population that had not received the intervention, 5 years before and after implementation. The outcomes were emergency hospitalisations, length of inpatient stay and re-admission rates for cardiovascular disease (CVD). RESULTS: Findings show that the intervention was associated with 66 fewer emergency CVD admissions per 100 000 population per year (95% CI 22.13 to 108.98) in the post-intervention period, relative to the control group. No significant measurable effects on length of stay or emergency re-admission rates were observed. CONCLUSION: This consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service was associated with a lower rate of emergency hospital admissions in a highly disadvantaged population. Similar approaches could be an effective component of strategies to reduce unplanned hospital admissions.

In Situ Oxidative Stress and Atrial Cell Deaths in Patients with Valve Disease.

BACKGROUND: Left ventricular hypertrophy and myocardial remodeling occur with aortic valve disease and may lead to heart failure. Although increased oxidative stress and inflammatory factors have been implicated in heart failure, their role in the progression of valve disease remains unclear. OBJECTIVES: We investigated the role of oxidative stress and inflammatory factors in valve disease whether this relates to cell death. METHODS: Blood samples were taken from 24 patients with valve disease before surgery and the results were compared with those from blood samples from 30 control healthy subjects. Myocardial biopsies from patients with valve disease were also collected before cannulation of the right atrial appendage. NF-κB activities in atrial and mononuclear cells nuclear extracts were determined by electrophoretic mobility shift assay. RESULTS: Nuclear factor kappaB activities were significantly greater in mononuclear cells from AVD patients compared with healthy controls and the antigens were detectable in atrial tissues valve disease patients. Plasma C-reactive protein, B-natriuretic peptides, plasma tumor necrosis factor alpha and soluble tumor necrosis factor receptor 1 and 3-nitrotyrosine levels were significantly higher in valve disease patients. Inducible nitric oxide and 3-nitrotyrosine antigens and cells expressing CD45 antigens were detected within atrial tissues obtained from valve disease patients suggesting oxidative stress originated from in situ leukocytes. CONCLUSION: The findings suggest that oxidative stress originating from in situ leukocytes within the atrial myocardium may be the potential trigger for excessive transcriptional activities and apoptotic cell death within the atrial myocardium of valve disease patients. This represents a potential therapeutic target.

NO-cGMP and TNF-alpha counter regulatory system in blood: understanding the mechanisms leading to myocardial dysfunction and failure.

One of the major conceptual advances in the understanding of the pathogenesis of heart failure has been the insight that myocardial dysfunction and heart failure may progress as the result of the sustained over-expression of nitric oxide (NO) metabolites locally and in blood modulated by inducible nitric oxide synthase (iNOS). This by virtue of their deleterious effects is sufficient to contribute to disease progression by provoking left ventricular (LV) remodeling, hypertrophy and progressive LV dysfunction. Recently, tumor necrosis factor-alpha (TNF-alpha) has also been identified in this setting of heart failure. Analogous to the situation with NO, the over-expression of TNF-alpha is sufficient to contribute to disease progression in heart failure phenotype. Although important interactions between TNF-alpha and the NO have been recognized in the cardiovascular system for over a decade, the nature and importance of the interactions between these biologically active molecules in cardiac hypertrophy has become apparent only in the recent times. Therefore, we focused on the prevailing updated evidence which suggests that there is a functionally significant cross-regulation between NO and TNF-alpha signaling in blood thus playing a part in cardiac hypertrophy and failure. The discussions presented here will have a bearing on the therapeutic potential via inhibitors of these pathways in reducing cardiomyocyte hypertrophy and the LV dysfunction.

Functional adaptation to oxidative stress by memory T cells: an analysis of the role in the cardiovascular disease process.

T cells participate in combating infection and critically determine the outcomes in any given disease process. Impaired immune response occurs in a number disease processes such as in cancer and atherosclerosis although the underlying mechanisms are still not fully understood. This article gives an up-to-date review of T cells development and functional adaptation to pathophysiological stimuli and participation in the cardiovascular disease process. In addition, we have discussed the signaling pathways controlled by the microenvironment that determine T cells function and resultant type of immune response. We have also discussed in detail how oxidative stress is a key component of the micro environmental interaction.

Tracing the origins of postoperative atrial fibrillation: the concept of oxidative stress-mediated myocardial injury phenomenon.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia associated with coronary artery surgery and is an important factor contributing to postoperative morbidity and mortality. Recently, there is growing evidence that dysregulation of the oxidant-antioxidant balance, inflammatory factors and discordant alteration of energy metabolites may play a significant role in its pathogenesis. DESIGN: We evaluated the link between postoperative atrial fibrillation with inflammatory factors and oxidative stress. METHODS: We searched all databases in Medline, Pubmed, ISI, the Cochrane database, and Embase. We identified more than 100 trials, multiple metaanalyses, and three sets of practice guidelines for the prevention of PAF in cardiac surgery. RESULTS: Mechanisms of postoperative AF are likely to be multifactorial and are influenced by preoperative, intraoperative and postoperative factors including a genetic basis. Electrical remodelling is thought to be related to the generation of reactive oxidant species and inflammatory factors during the ischemia-reperfusion phase of cardiac surgery. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was found to be the primary source of superoxide within the human atrial myocardium (in patients in sinus rhythm and in those with AF) and linked with paroxysmal and chronic AF. Reactive oxidant species cause lipid peroxidation, breakdown of cell membrane, decreased mitochondrial function, calcium overload and apoptosis. This affect was shown to be reversed by exogenous nitric oxide/donors (sodium nitroprusside). Inflammatory factors such as the rise in white blood cell count, C-reactive proteins were implicated in the pathogenesis of AF. In contrast, new evidence identifies statins as having both antioxidant and anti-inflammatory properties and that their use reduces the incidence of postoperative AF (57% in the control vs. 35% in the atorvastatin group). Other antiinflammatory strategies include steroids with one study showing postoperative AF occurred in 21% in the steroid group compared with 51% in the placebo group although their use resulted in an increase in other complications. The mainstay of therapy however, remains to be beta-blockers alone which impart a modest influence on overall rates of AF with a reduction from 33.7 to 16.9% (OR: 0.37, 95% CI: 0.29-0.48). Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers has been shown in one study to reduce the risk of developing new-onset AF by nearly 50%, although this has not been adequately evaluated in cardiac surgery. CONCLUSION: Inflammatory factors and oxidative stress play a major role in the pathogenesis of postoperative AF. This review provides an analysis of current evidence in support of efforts directed at antiinflammatory and antioxidant agents as interventions.

Ethnicity and adverse operative outcomes among Australian patients undergoing first-time isolated coronary artery bypass graft surgery.

The study compared cardiovascular risks factors, morbidity and in-hospital mortality following coronary artery bypass graft (CABG) surgery in Australian patients of different ethnic backgrounds including Aboriginal (AB), Italian (IT), Indian (IA), British Caucasians (BC), and Chinese (CH). These groups AB (n = 20), CH (n = 12), IT (n = 104), BC (n = 493), and IA (n = 16) all had first-time isolated CABG surgery at St. Vincent's Hospital, Melbourne from March 2001 to March 2007. AB patients were current or past smokers with the highest prevalence of preoperative diabetes (P = 0.001) and mostly had nonelective CABG surgery (P = 0.018). AB patients had higher incidences of postoperative respiratory failure (P = 0.001) compared with the other groups. In contrast, past history of MI (P = 0.012) was associated with IA patients. Both IA and AB groups had significantly higher acute renal failure rates requiring temporary dialysis (P = 0.025), longer ICU (P = 0.003) and hospital stays (P = 0.03) compared to BC, IT and CH groups. All groups had similar 30-day (P = 0.59) in-hospital mortality. The higher incidences of in-hospital morbidity observed in IA and AB compared to BC, IT, and CH groups suggests that ethnic lifestyle may be a strong risk factor. Larger confirmatory studies are required to verify incidents and elucidate reasons why ethnic-associated perioperative complications exist.

A variant of position -308 of the Tumour necrosis factor alpha gene promoter and the risk of coronary heart disease.

PURPOSE: The aim of this study was to investigate whether the variability between individuals with coronary heart disease (CHD) is related to the prevalence of TNF-alpha gene promoter -308 variant in un-matched British Caucasian population from East Midlands. PROCEDURES: Genotypes and allele frequencies were determined using restriction fragment length polymorphism analysis of polymerase chain reaction (PCR) products. Genomic DNA prepared from peripheral blood leukocytes of patients (n=97) and healthy controls (n=95) demonstrated two alleles TNF*1 (G) and TNF*2 (A). FINDINGS: The genotype distribution in patients was GG, n=59; GA, n=36; and AA, n=2 and in controls was GG, n=41; GA, n=40; and AA, n=14 (P=0.014). The association analysis demonstrated that TNF*1 allele in patients appears to be associated with greater incidences of CHD (OR 2.15; CI, 1.36-3.39; P=0.001). CONCLUSIONS: Our results suggest that TNF*1 allele (TNF-alpha -308 GG or GA) has a high prevalence among British Caucasian population that correlates with an increased CHD risk.

An intervention for pulmonary rehabilitators to develop a social identity for patients attending exercise rehabilitation: a feasibility and pilot randomised control trial protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a degenerative condition that can impair health-related quality of life (HRQoL). A number of self-management interventions, employing a variety of behavioural change techniques (BCTs), have been adopted to improve HRQoL for COPD patients. However, a lack of attention has been given to group management interventions with an emphasis on incorporating BCTs into rehabilitators' practice. This study aims to pilot and feasibly explore a social identity group management intervention, delivered by COPD rehabilitation staff to patients attending exercise pulmonary rehabilitation. Doing so will help inform the plausibility of the intervention before conducting a full trial to evaluate its effectiveness to improve HRQoL. METHODS: This is a two-centre, randomised cross-over controlled trial. Two pulmonary rehabilitation centres based in the UK will be randomly allocated to two treatment arms (standard care and intervention). Outcome measurements relating to HRQoL and social identity will be completed pre- and post-exercise rehabilitation. Focus group interviews will be conducted at the end of exercise rehabilitation to capture participants' contextualised experiences of the intervention. COPD rehabilitators will undertake semi-structured interviews at the end of the trial to garner their holistic perspectives of intervention fidelity and implementation. DISCUSSION: This is the first study to adopt a social identity approach to develop a rehabilitator-led, group management intervention for COPD patients attending exercise pulmonary rehabilitation. The results of this study will provide evidence for the feasibility and sample size requirements to inform a larger study, which can ascertain the intervention's effectiveness for improving HRQoL for COPD patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02288039. Date 31 October 2014.

Proportional weight loss in six months as a risk factor for mortality in stage IV non-small cell lung cancer.

OBJECTIVE: To evaluate different weight loss (WL) cut-off points as prognostic markers of 3-month survival after diagnosis of stage IV non-small cell lung cancer (NSCLC). METHODS: This was a prospective study involving 104 patients with metastatic (stage IV) NSCLC who were admitted to a cancer treatment center in southern Brazil between January of 2014 and November of 2016. We evaluated total WL and WL per month, as well as WL and WL per month in the 6 months preceding the diagnosis. The patients were followed for 3 months after diagnosis. A Cox proportional hazards regression model and Kaplan-Meier curves were used in order to evaluate 3-month survival. RESULTS: The median WL in the 6 months preceding the diagnosis was 6% (interquartile range, 0.0-12.9%). Patients with WL ≥ 5% had a median survival of 78 days, compared with 85 days for those with WL < 5% (p = 0.047). Survival at 3 months was 72% for the patients with WL ≥ 5% (p = 0.047), 61% for those with WL ≥ 10% (p < 0.001), and 45% for those with WL ≥ 15% (p < 0.001). In the multivariate analysis, the hazard ratio for risk of death was 4.51 (95% CI: 1.32-15.39) for the patients with WL ≥ 5%, 6.34 (95% CI: 2.31-17.40) for those with WL ≥ 10%, and 14.17 (95% CI: 5.06-39.65) for those with WL ≥ 15%. CONCLUSIONS: WL in the 6 months preceding the diagnosis of NSCLC is a relevant prognostic factor and appears to be directly proportional to the rate of survival at 3 months.

Nitric oxide in blood. The nitrosative-oxidative disequilibrium hypothesis on the pathogenesis of cardiovascular disease.

There is growing evidence that altered production and/or spatio-temporal distribution of reactive oxidant species and reactive nitrosative species in blood creates oxidative and/or nitrosative stresses in the failing myocardium and endothelium. This contributes to the abnormal cardiac and vascular phenotypes that characterize cardiovascular disease. These derangements at the system level can now be interpreted at the integrated cellular and molecular levels in terms of effects on signaling elements in the heart and vasculature. The end results of nitric oxide/redox disequilibrium have implications for cardiac and vascular homeostasis and may result in the development of atherosclerosis, myocardial tissue remodelling and hypertrophy. Reactive oxygen species/reactive nitrogen species generation is also attributed to the transit from hypertrophic to apoptotic phenotypes, a possible mechanism of myocardial failure. In this review, we highlight the possible roles of altered production and/or spatio-temporal distribution of reactive oxidant species and reactive nitrosative species in blood on the pathogenesis of the failing cardiovascular system.

Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium.

OBJECTIVES: We have shown previously that human diabetic myocardium cannot be preconditioned. Here, we have investigated the basis of this cardioprotective deficit. METHODS: Right atrial sections from four patient groups-non-diabetic, insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) receiving glibenclamide, and NIDDM receiving metformin-were subjected to one of the following protocols: aerobic control, simulated ischemia/reoxygenation, ischemic preconditioning before ischemia, and pharmacological preconditioning with alpha 1 agonist phenylephrine, adenosine, the mito-K(ATP) channel opener diazoxide, the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA), or the p38 mitogen-activated protein kinase (p38MAPK) activator anisomycin. Cellular damage was assessed using creatine kinase leakage and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction. In mitochondrial preparations from non-diabetic and diabetic myocardium, mitochondrial membrane potential (Psi(m)) was assessed using JC-1 dye, and production of reactive oxygen species was determined. RESULTS: Preconditioning with ischemia, phenylephrine, adenosine, or diazoxide failed to protect diabetic myocardium. However, activation of PKC or p38MAPK was still protective. In isolated non-diabetic mitochondria, diazoxide partially depolarized Psi(m), an effect not seen in diabetic mitochondria. Furthermore, diazoxide increased superoxide production in non-diabetic but not in diabetic mitochondria. CONCLUSIONS: Our results show that the cardioprotective deficit in diabetic myocardium arises upstream of PKC and p38MAPK. We suggest that mitochondrial dysfunction in diabetic myocardium, possibly dysfunctional mito-K(ATP) channels, leads to impaired depolarization and superoxide production, and that this causes the inability to respond to preconditioning.

Effects of maternal high-fat diet and statin treatment on bone marrow endothelial progenitor cells and cardiovascular risk factors in female mice offspring fed a similar diet.

OBJECTIVES: The aim of this study was to prove that one possible statin-related protective mechanism in dams and offspring fed a high-fat diet (HFD) is the reduction in cardiovascular risk and impairment of the vasculogenic element of endothelial regeneration. METHODS: To explore this, virgin C57 BL/6 mice (n = 8/group) were fed an HFD (fat: 45% kcal) or standard chow (C; fat: 21% kcal) from weaning and throughout their pregnancy and lactation. Half of the HFD group also was given the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin (S) through their drinking water (5 mg/kg body weight per day) to create HF+S dam group (n = 8/group). Offspring from each group were fed HFD or C diet from weaning to adulthood, generating respective dam/offspring dietary groups (C/C, HF/HF, HF+S/HF; n = 8/group). Body weight, blood pressure, and serum lipid profile were measured in female offspring at age 24 wk, and bone marrow endothelial progenitor cells (EPCs) were cultured. RESULTS: The results indicated that in the female offspring, the statin-fed (HF+S/HF) cohort had lower total and low-density lipoprotein cholesterol concentrations, were less obese and hypertensive, and had reduced C-reactive proteins (CRPs) compared with the HF/HF phenotype. The results also showed an increased bone marrow EPCs expressing colony numbers (P < 0.001) compared with the HF/HF phenotype. CONCLUSIONS: Results from the present study demonstrated that statin administration in early life to dams fed on a HFD had a significant effect on their female offspring in terms of reduction in cardiovascular risk factors. Additionally, statin administration to female offspring on an HFD during early life was associated with reduction in circulating CRPs and an increased bone marrow EPC numbers and colony-forming characteristics.

A Review of Interventions to Improve Enrolment and Adherence to Cardiac Rehabilitation Among Patients Aged 65 Years or Above.

PURPOSE: This review provides an overview and quality assessment of existing interventions, assessing the intervention types that are most effective at increasing enrolment and adherence to cardiac rehabilitation in older patients aged ≥65 years Methods: The review of the literature was performed using electronic databases to search for randomised controlled trials that aimed to increase enrolment and/or adherence to cardiac rehabilitation in older patients aged ≥65 years. The main key words were cardiac rehabilitation, enrolment, adherence and older patients. Studies were included if; (1) the intervention targeted improving enrolment and/or adherence to at least one of the following components of the cardiac rehabilitation programme: exercise, education or maintaining lifestyle changes; (2) assess the effectiveness of an intervention on increasing enrolment and/or adherence to a cardiac rehabilitation programme or any of its components; (3) include measures for assessing enrolment and/or adherence to a cardiac rehabilitation programme or any of its components; (4) the study included patients with a mean age of ≥65 years who were deemed eligible to participate in a cardiac rehabilitation programme. Included studies could be published in any language and there were no date restrictions for included studies. Studies focusing on pharmaceutical adherence were not included for the purpose of this review. RESULTS: Seven studies were included, with four investigating enrolment (1944 participants) and three assessing adherence to intervention programmes (410 participants). Three studies (1919 participants) reported higher enrolment to cardiac rehabilitation in the intervention group. Two studies that reported increases in enrolment to cardiac rehabilitation were deemed to have an unclear or high risk of bias. All three studies (410 participants) reported better adherence to cardiac rehabilitation in the intervention group when compared to the control group. Two studies that reported better completion of cardiac rehabilitation were deemed to have an unclear or high risk of bias. No formal meta-analysis was conducted due to the observed multiple heterogeneity among outcome measures, the low number of included studies and variability in study designs. CONCLUSION: This review found only weak evidence to suggest that interventions can increase enrolment or adherence to cardiac rehabilitation programmes for patients aged ≥65 years, therefore no practice recommendations could be made and further high-quality research is needed in this population group.