The safety of early pharmacological venous thromboembolism prophylaxis in patients with traumatic intracranial haemorrhage: a systematic review and meta-analysis.

INTRODUCTION: In patients with traumatic intracranial haemorrhage (tICH) there is significant risk of both venous thromboembolism (VTE) and haemorrhage progression. There is a paucity of literature to inform the timing of pharmacological thromboprophylaxis (PTP) initiation. AIM: This meta-analysis aims to summarise the current literature on the timing of PTP initiation in tICH. METHODS: This meta-analysis followed the Methodological Expectations of Cochrane Intervention Reviews checklist and the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Following the literature search, studies were matched against the criteria for inclusion. Data from included studies was pooled, analysed using random-effect analysis and presented as forest plots of risk ratios, except one result reported as difference of means. The ROBINS-I tool was used to assess the risk of bias in the studies. The GRADE approach was taken to assess the quality of included studies. Heterogeneity of studies was assessed using Tau∧2. Funnel plots were generated and used in conjunction with Harbord's test and Rucker's arcsine to assess for small-study effect including publication bias. RESULTS: A total of 9927 ICH patients who received PTP were included from 15 retrospective observational cohort studies, 4807 patients received early PTP, the remaining 5120 received late PTP. The definition of early was dependent on the study but no more than 72-hours after admission. The mean age of the included cohort was 45.3 (std dev ±9.5) years, and the proportion of males was 71%. Meta-analysis indicated that there was a significant difference between early and late groups for the rate of VTE (RR, 0.544; p = 0.000), pulmonary embolus (RR, 0.538; p = 0.004), deep vein thrombosis (RR, 0.484; p = 0.000) and the intensive care unit length of stay (difference of means, -2.021; 95% CI, -2.250, -1.792; p = 0.000; Tau∧2 = 0.000), favouring the early group. However, the meta-analysis showed no significant difference between the groups for the rate of mortality (RR, 1.008; p = 0.936), tICH progression (RR, 0.853; p = 0.157), and neurosurgical intervention (RR, 0.870; p = 0.480). CONCLUSION: These findings indicated that early PTP appears to be safe and effective in patients with tICH.

Midterm Clinical Outcomes of Reimplantation Versus Remodeling Valve-Sparing Aortic Root Replacement in Patients With Connective Tissue Disorders: A Meta-Analysis.

This meta-analysis aimed to compare the midterm clinical outcomes of reimplantation versus remodeling techniques for valve-sparing aortic root replacement (VSARR) in patients with connective tissue disorders (CTDs). Studies were screened and identified after the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines from the PubMed, Web of Science, and Embase databases. Forest plots were produced using Review Manager 5.3 (Cochrane, UK). Studies comparing early and midterm clinical outcomes of reimplantation versus remodeling VSARR in patients with CTD with a mean age ≥18 years were included. The sensitivity analysis excluded studies and subgroups of patients that received ring or suture annuloplasty in addition to remodeling surgery. The study selection identified 9 eligible studies. After analysis of the study period and location for patient crossover, 7 retrospective studies consisting of 597 patients (301 reimplantation and 296 remodeling) were pooled. The pooling revealed no significant difference in postoperative mortality (estimated mean follow-up of 10.5 years) (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.30 to 1.48, I2 = 30%, p = 0.32), reoperation (OR 0.35, CI 0.04 to 3.30, I2 = 81%, p = 0.36), or occurrence of postoperative aortic regurgitation of ≥2 (OR 0.56, CI 0.31 to 1.02, I2 = 47%, p = 0.06). The sensitivity analysis excluding annuloplasty demonstrated improved mortality (OR 0.19, CI 0.06 to 0.64, I2 = 0%, p = 0.007) and decreased aortic regurgitation of ≥2 (OR 0.23, CI 0.10 to 0.53, I2 = 47%, p = 0.0005) in reimplantation VSARR. The rates of reoperation remained insignificant in the sensitivity analysis (OR 0.43, CI 0.05 to 3.53, I2 = 71%, p = 0.43). In conclusion, this meta-analysis has demonstrated no significant difference in the midterm clinical outcomes of reimplantation versus remodeling techniques of VSARR. The sensitivity analysis excluding studies and patient subgroups that received remodeling and annuloplasty suggests remodeling alone to be inferior to reimplantation in patients with CTDs. Further research is required to assess remodeling and annuloplasty against reimplantation in patients of this demographic because the current body of knowledge does not allow sufficient analysis.

Transcatheter aortic valve implantation versus surgical aortic valve replacement in dialysis-dependent patients: a meta-analysis.

OBJECTIVES: This meta-analysis aims to compare the clinical outcomes of transcatheter aortic valve implantation (TAVI) versus aortic valve replacement (AVR) for aortic stenosis in dialysis-dependent patients. METHODS: Literature searches employed PubMed, Web of Science, Google Scholar and Embase to identify relevant studies. Bias-treated data were prioritized, isolated and pooled for analysis; raw data were utilized where bias-treated data were unavailable. Outcomes were analysed to assess for study data crossover. RESULTS: Literature search identified 10 retrospective studies; following data source analysis, five studies were included. Upon pooling of bias-treated data, TAVI was significantly favoured in early mortality [odds ratio (OR), 0.42; 95% confidence interval (95% CI), 0.19-0.92; I2  = 92%; P  = 0.03], 1-year mortality (OR, 0.88; 95% CI 0.80-0.97; I2  = 0%; P  = 0.01), rates of stroke/cerebrovascular events (OR, 0.71; 95% CI 0.55-0.93; I2  = 0%; P  = 0.01) and blood transfusions (OR, 0.36; 95% CI 0.21-0.62; I2  = 86%; P  = 0.0002). Pooling demonstrated fewer new pacemaker implantations in the AVR group (OR, 3.33; 95% CI 1.94-5.73; I2  = 74%; P  ≤ 0.0001) and no difference in the rate of vascular complications (OR, 2.27; 95% CI 0.60-8.59; I2  = 83%; P  = 0.23). Analysis including raw data revealed the length of hospital stay to favour TAVI with a mean difference of -9.20 days (95% CI -15.58 to -2.82; I2  = 97%; P  = 0.005). CONCLUSION: Bias-treated meta-analysis comparing surgical AVR and TAVI favoured TAVI in early mortality, 1-year mortality, rates of stroke/cerebrovascular events and blood transfusions. There was no difference in the rates of vascular complications; however, TAVI required more pacemaker implantations. Data pooling including raw data revealed that the length of hospital admission favours TAVI.

Hypertension alters the function and expression profile of the peptide cotransporters PEPT1 and PEPT2 in the rodent renal proximal tubule.

Hypertension is a major risk factor for kidney and cardiovascular disease. The treatment of hypertensive individuals by selected ACE inhibitors and certain di-and tripeptides halts the progression of renal deterioration and extends life-span. Renal reabsorption of these low molecular weight substrates are mediated by the PEPT1 and PEPT2 cotransporters. This study aims to investigate whether hypertension and ageing affects renal PEPT cotransporters at gene, protein expression and distribution as well as function in the superficial cortex and the outer medulla of the kidney. Membrane vesicles from the brush border (BBMV) and outer medulla (OMMV) were isolated from the kidneys of young Wistar Kyoto (Y-WKY), young spontaneously hypertensive (Y-SHR), and middle aged SHR (M-SHR) rats. Transport activity was measured using the substrate, ß-Ala-Lys (AMCA). Gene expression levels of PEPT genes were assessed with qRT-PCR while renal localisation of PEPT cotransporters was examined by immunohistochemistry with Western Blot validation. The Km and Vmax of renal PEPT1 were decreased significantly in SHR compared to WKY BBMV, whilst the Vmax of PEPT2 showed differences between SHR and WKY. By contrast to the reported cortical distribution of PEPT1, PEPT1-staining was detected in the outer medulla, whilst PEPT2 was expressed primarily in the cortex of all SHR; PEPT1 was significantly upregulated in the cortex of Y-SHR. These outcomes are indicative of a redistribution of PEPT1 and PEPT2 in the kidney proximal tubule under hypertensive conditions that has potential repercussions for nutrient handling and the therapeutic use of ACE inhibitors in hypertensive individuals.

Effect of Electronic Prescribing Compared to Paper-Based (Handwritten) Prescribing on Primary Medication Adherence in an Outpatient Setting: A Systematic Review.

BACKGROUND: Electronic prescriptions are often created and delivered electronically to the pharmacy while paper-based/handwritten prescriptions may be delivered to the pharmacy by the patients. These differences in the mode of creation and transmission of the two types of prescription could influence the rate at which outpatients fill new prescriptions of previously untried medications. OBJECTIVES: This study aimed to evaluate literatures to determine the impact of electronic prescribing compared with paper-based/handwritten prescribing on primary medication adherence in an outpatient setting. METHODS: The keywords and phrases "outpatients," "e-prescriptions," "paper-based prescriptions," and "primary medication adherence" were combined with their relevant synonyms and medical subject headings. A comprehensive literature search was conducted on EMBASE, CINAHL, and MEDLINE databases, and Google Scholar. The results of the search were screened and selected using predefined inclusion and exclusion criteria. The Critical Appraisal Skills Program (CASP) was used for quality appraisal of included studies. Data relevant to the objective of the review were extracted and analyzed through narrative synthesis. RESULTS: A total of 10 original studies were included in the final review, including 1 prospective randomized study and 9 observational studies. Nine of the 10 studies were performed in the United States. Four of the studies indicated that electronic prescribing significantly increases initial medication adherence, while four of the studies suggested the opposite. The remaining two studies found no significant difference in primary medication adherence between the two methods of prescribing. The variations in the studies did not allow the homogeneity required for meta-analysis to be achieved. CONCLUSION: The conflicting findings relating to the efficacy of primary medication adherence across both systems demonstrate the need for a standardized measure of medication adherence. This would help further determine the respective benefits of both approaches. Future research should also be conducted in different countries to give a more accurate representation of adherence.

HTK versus multidose cardioplegias for myocardial protection in adult cardiac surgery: A meta-analysis.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) cardioplegia for myocardial protection obviates the need for maintenance cardioplegia doses, and thus allows for greater focus on procedure accuracy. The aim of this meta-analysis is to evaluate the safety and efficacy of HTK versus multidose cardioplegias during cardiac surgery in an adult population. METHODS: Electronic searches were performed using PubMed, Science Direct, and Google Scholar databases. The key search terms included HTK cardioplegia AND cardiac surgery AND adult. This was followed by a meta-analysis investigating cardiopulmonary bypass (CPB) duration, cross-clamp duration, spontaneous defibrillation, inotropic support, mortality, atrial fibrillation, creatine kinase muscle brain band (CK-MB) and troponin I (TnI). RESULTS: Seven randomized controlled trials (n = 804) were analyzed. Spontaneous defibrillation following aortic cross-clamp removal significantly favored HTK (odds ratio [OR], 2.809; 95% confidence interval [CI], 1.574 to 5.012; I2 = 0%; p < .01). There were no other notable significant differences between HTK and multidose cardioplegia in any of the parameters measured. In particular, the OR for mortality was 1.237 (95% CI, 0.385 to 3.978; I2 = 0%; p = .721) and the mean difference for CPB duration overall was 2.072 min (95% CI, -2.405 to 6.548; I2 = 74%; p = .364). CONCLUSION: HTK is safe and effective during adult cardiac surgery when compared with multidose cardioplegias for myocardial protection during surgical correction of acquired pathology in the adult population. HTK may, therefore, be suitable for complex cases or those of extensive duration, without the prospect of increased postoperative morbidity or mortality.

Effect of ageing and hypertension on the expression and activity of PEPT2 in normal and hypertrophic hearts.

Some dipeptides have been implicated in myocardial protection, but little is known about their membrane transporter PEPT2. The aim of this study was to determine whether the expression and activity of the cardiac-type PEPT2 cotransporter could be affected by ageing and/or hypertension. Sarcolemmal vesicles (SV) were isolated from the hearts of all rat groups using a standard procedure to investigate the transport activity and protein abundance by fluorescence spectroscopy and Western blot, respectively. SLC15A2 "PEPT2" gene expression was relatively quantified by RT-qPCR. In the Wistar rat groups, the protein and gene expression of PEPT2 were upregulated with ageing. These changes were accompanied by corresponding increases in the competitive inhibition and the transport rate (Vmax) of ß-Ala-Lys (AMCA) into SV isolated from middle-aged hearts. Although, the transport rate of ß-Ala-Lys (AMCA) into SV isolated from old hearts was significantly the lowest compared to middle-aged and young adult hearts, the inhibition percentage of ß-Ala-Lys (AMCA) transport by Gly-Gln was the highest. In the WKY and SHR rat groups, Y-SHR hypertrophied hearts showed an increase in PEPT2 gene expression accompanied by a significant decrease in protein expression and activity. With advanced age, however, M-SHR hypertrophied hearts revealed significantly lower gene expression, but higher protein expression and activity than Y-SHR hearts. These findings suggest that increased expression of PEPT2 cotransporter in all types of middle-aged hearts could be exploited to facilitate di-and tripeptide transport by PEPT2 in these hearts, which subsequently could result in improved myocardial protection in these populations.

Effect of methionine feeding on oxidative stress, intracellular calcium and contractility in cardiomyocytes isolated from male and female rats.

Homocysteine (Hcy) is a breakdown product of methionine metabolism. The risk of cardiovascular disease (CVD) correlates with an increase in plasma Hcy levels. The aim of this study was to investigate whether 1% methionine supplementation of adult rats altered intracellular reactive oxygen species (ROS) generation, intracellular Ca2+ content, and contractile activity in freshly isolated cardiomyocytes. This was measured under normal conditions and during oxidative stress in freshly isolated cardiomyocytes. Single rat cardiomyocytes from both sexes were isolated by enzymatic and mechanical dispersion techniques. Fluorescence microscopy was used to measure ROS production and intracellular Ca2+ concentration. Cell contraction was measured using a video camera. During exposure to 200 µM, H2O2 female cardiomyocytes produced significantly fewer ROS and had a higher intracellular Ca2+ concentration compared to male cardiomyocytes in control and methionine-fed conditions. The contractility of cardiomyocytes isolated from male rats was insignificantly decreased after methionine feeding compared to control, while the contractility of cardiomyocytes from female rats insignificantly reduced after methionine feeding and acute exposure to oxidative stress. These findings provide evidence that during exposure to 200 µM H2O2, cardiomyocytes from female rats produce less ROS and have higher intracellular Ca2+ levels. There were no significant effects on contractility in cardiomyocytes from either gender and under any of the different conditions.

Microplegia in cardiac surgery: Systematic review and meta-analysis.

BACKGROUND: Consensus on the optimum choice of cardioplegia remains elusive. One possibility that has been suggested to have beneficial properties is microplegia, a cardioplegia of reduced crystalloid volume. The aim of this meta-analysis is to comprehensively investigate microplegia against a range of clinical outcomes. METHODS: To identify potential studies, systematic searches were carried out in four databases (eg, Pubmed, EMBASE). The search strategy included the key concepts of "microplegia" OR "mini-cardioplegia" OR "miniplegia" AND "cardiac surgery." This was followed by a meta-analysis investigating: mortality, crystalloid volume; cardiopulmonary bypass time; cross-clamp time; intra-aortic balloon pump use; spontaneous heartbeat recovery; inotropic support; low cardiac output syndrome; myocardial infarction; acute renal failure; atrial fibrillation, reoperation for bleeding; creatine kinase myocardial band (CK-MB); intensive care unit (ICU) time and hospital stay. RESULTS: Eleven studies comprising 5798 participants were analyzed. Microplegia used a lower volume of crystalloids and led to a higher spontaneous return of heartbeat, odds ratio (OR) 4.271 (95% confidence intervals [CIs]: 1.935, 9.423; I2 = 76.57%; P < .001) and a lower requirement for inotropic support, OR: 0.665 (95% CI: 0.47, 0.941; I2 = 3.53%; P = .021). Microplegia was also associated with a lower CK-MB release, mean difference (MD) -6.448 ng/mL (95% CI: -9.386, -3.511; I2 = 0%; P < .001) and a shorter ICU stay, MD: -0.411 days (95% CI: -0.812, -0.009; I2 = 17.65%; P = .045). All other comparisons were nonsignificant. CONCLUSIONS: Microplegia has similar effects to other types of cardioplegia and is beneficial with regard to spontaneous return of heartbeat, inotropic support, ICU stay, and CK-MB release.

Effect of Age on Clinical Outcomes Following On-/Off-Pump Coronary Artery Bypass: Meta-Analysis and Meta-Regression.

OBJECTIVE: There is currently much debate about which patients would benefit more after on- or off-pump coronary artery bypass grafting (CABG). The aim of this meta-analysis and meta-regression is to investigate the effect of age on short-term clinical outcomes after these approaches. METHODS: To identify potential studies, systematic searches were carried out in the Excerpta Medica dataBASE (EMBASE), PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL). The search strategy included the key concepts of "cardiopulmonary bypass" AND "coronary artery bypass grafting" AND "off pump" OR "on pump". This was followed by a meta-analysis and meta-regression investigating the effect of age on the incidences of stroke, myocardial infarction (MI), and mortality. RESULTS: Thirty-seven studies including 15,324 participants were analysed. Overall, there was a significant odds reduction for patients receiving off-pump CABG suffering a stroke (odds ratio [OR] 0.770, 95% confidence intervals [CI] 0.594, 0.998, P=0.048); however, when patients were subdivided according to different age bands, this difference disappeared. There were also no significant differences in the odds of mortality (OR 0.876, 95% CI 0.703, 1.093, P=0.241) or MI (OR 0.937, 95% CI 0.795, 1.105, P=0.439). Meta-regression analysis revealed no significant relationship between age and stroke (P=0.652), age and mortality (P=548), and age and MI (P=0.464). CONCLUSION: Patients undergoing CABG are becoming older and may suffer from multiple comorbidities increasing their risk profile. However, with respect to short-term clinical outcomes, the patient's age does not help in determining whether off- or on-pump is superior.

Effect of age on clinical outcomes following on-/off-pump coronary artery bypass: meta-analysis and meta-regression

Abstract Objective: There is currently much debate about which patients would benefit more after on- or off-pump coronary artery bypass grafting (CABG). The aim of this meta-analysis and meta-regression is to investigate the effect of age on short-term clinical outcomes after these approaches. Methods: To identify potential studies, systematic searches were carried out in the Excerpta Medica dataBASE (EMBASE), PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL). The search strategy included the key concepts of "cardiopulmonary bypass" AND "coronary artery bypass grafting" AND "off pump" OR "on pump". This was followed by a meta-analysis and meta-regression investigating the effect of age on the incidences of stroke, myocardial infarction (MI), and mortality. Results: Thirty-seven studies including 15,324 participants were analysed. Overall, there was a significant odds reduction for patients receiving off-pump CABG suffering a stroke (odds ratio [OR] 0.770, 95% confidence intervals [CI] 0.594, 0.998, P=0.048); however, when patients were subdivided according to different age bands, this difference disappeared. There were also no significant differences in the odds of mortality (OR 0.876, 95% CI 0.703, 1.093, P=0.241) or MI (OR 0.937, 95% CI 0.795, 1.105, P=0.439). Meta-regression analysis revealed no significant relationship between age and stroke (P=0.652), age and mortality (P=548), and age and MI (P=0.464). Conclusion: Patients undergoing CABG are becoming older and may suffer from multiple comorbidities increasing their risk profile. However, with respect to short-term clinical outcomes, the patient's age does not help in determining whether off- or on-pump is superior.

Effect of vitamin D supplementation on endothelial function - An updated systematic review with meta-analysis and meta-regression.

BACKGROUND AND AIMS: Atherogenesis and endothelial dysfunction contribute to cardiovascular risk and vitamin D has been implemented in endothelial repair. This systematic review, meta-analysis and meta-regression aims to establish the effect of vitamin D supplementation on endothelial function. METHODS AND RESULTS: To conduct the systematic review we searched the Cochrane Library of Controlled Trials, PubMed, ProQuest and EMBASE for randomized controlled trials that investigated the effects of vitamin D supplementation on flow-mediated dilation (FMD%), pulse wave velocity (PWV), and central augmentation index (AIx). Meta-analysis was based on a random effects model and inverse-variance methods to calculate either mean difference (MD) or standardized mean difference (SMD) as effects sizes. This was followed by meta-regression investigating the effect of baseline vitamin D concentrations, vitamin D dosing and study duration. Risk of bias was assessed using the JADAD scale and funnel plots. We identified 1056 studies of which 26 studies met inclusion criteria for quantitative analysis. Forty-two percent of the 2808 participants had either deficient or insufficient levels of vitamin D. FMD% (MD 1.17% (95% CI -0.20, 2.54), p = 0.095), PWV (SMD -0.09 m/s (95% CI -0.24, 0.07), p = 0.275) and AIx (SMD 0.05% (95% CI -0.1, 0.19), p = 0.52) showed no improvement with vitamin D supplementation. Sub-analysis and meta-regression revealed a tendency for AIx and FMD% to increase as weekly vitamin doses increased; no other significant relationships were identified. CONCLUSIONS: Vitamin D supplementation showed no improvement in endothelial function. More evidence is required before recommendations for management of endothelial dysfunction can be made.

Molecular changes to the rat renal cotransporters PEPT1 and PEPT2 due to ageing.

Renal PEPT1 and PEPT2 cotransporters play an important role in the balance of circulating body oligopeptides and selected peptidomimetic drugs. We aim to comprehensively characterise age-related changes of the renal PEPT cotransporters at the gene, protein, and functional level. Brush border membrane vesicles (BBMV) and outer medulla membrane vesicles (OMMV) were isolated from the kidneys of young, middle-aged and old rats. The protein expression of PEPT1 was not only increased in BBMV from old rats, but PEPT1 also appeared in OMMV from middle-aged and old rats. SLC15A1 gene expression in the renal cortex increased in middle-aged group. PEPT2 protein expression was not only increased with ageing, but PEPT2 also was found in BBMV from middle-aged and old groups. SLC15A2 gene expression in the renal outer medulla increased in the old group. These changes in the expressions and localisations of PEPT1 and PEPT2 could explain the changes to transport activity in BBMV and OMMV. These findings provide novel insights that would be useful for maintaining protein nutrition and optimising the delivery of some peptidomimetic drugs in elderly individuals.

Hybrid coronary revascularization versus conventional coronary artery bypass grafting: Systematic review and meta-analysis.

BACKGROUND: Hybrid coronary revascularization (HCR) combining minimally invasive grafting of the left internal mammary artery to the left anterior descending artery with percutaneous coronary intervention has become a viable option for treating coronary artery disease. The aim of this meta-analysis was to compare HCR with conventional coronary artery bypass grafting (CABG) in a range of clinical outcomes and hospital costs. METHODS: To identify potential studies, systematic searches were carried out in various databases. The key search terms included "hybrid revascularization" AND "coronary artery bypass grafting" OR "HCR" OR "CABG." This was followed by a meta-analysis investigating the need for blood transfusion, hospital costs, ventilation time, hospital stay, cerebrovascular accident, myocardial infarction, mortality, postoperative atrial fibrillation, renal failure, operation duration, and ICU stay. RESULTS: The requirement for blood transfusion was significantly lower for HCR: odds ratio 0.38 (95% confidence intervals [CIs] 0.31-0.46, P < .00001) as was the hospital stay: mean difference (MD) -1.48 days (95% CI, -2.61 to -0.36, P = 0.01) and the ventilation time: MD -8.99 hours (95% CI, -15.85 to -2.13, P = .01). On the contrary, hospital costs were more expensive for HCR: MD $3970 (95% CI, 2570-5370, P < .00001). All other comparisons were insignificant. CONCLUSIONS: In the short-term, HCR is as safe as conventional CABG and may offer certain benefits such as a lower requirement for blood transfusion and shorter hospital stays. However, HCR is more expensive than conventional CABG.

Effect of exercise therapy on established and emerging circulating biomarkers in patients with heart failure: a systematic review and meta-analysis.

Background: Biomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). The established biomarkers of myocardial stretch, brain natriuretic peptide (BNP) and amino (N) portion of BNP (NT-proBNP) have been extensively studied, and early analyses have demonstrated response to exercise training. Several other biomarkers have been identified over the last decade and may provide valuable and complementary information which may guide treatment strategies, including exercise therapy. Methods: A systematic search of PubMed, EMBASE and Cochrane Trials Register to 31 October 2017 was conducted for exercise-based rehabilitation trials in HF. Randomised and controlled trials that reported biomarkers, BNP, NT-proBNP, soluble ST2, galectin-3, mid-regional atrial natriuretic peptide, mid-regional adrenomedullin and copeptin, were included. Results: Forty-three studies were included in the systematic review, with 27 studies suitable for meta-analyses. Data pooling was only possible for NT-proBNP and BNP. Meta-analyses of conventional training studies demonstrated a statistically significant improvement in NT-proBNP (pmol/L); mean difference (MD) -32.80 (95% CI -56.19 to -9.42), p=0.006 and in BNP (pmol/L); MD -17.17 (95% CI -29.56 to -4.78), p=0.007. Pooled data of non-conventional training failed to demonstrate any statistically significant improvements. Conclusion: Pooled data indicated a favourable effect of conventional exercise therapy on the established biomarkers, NT-proBNP and BNP; however, this was in contrast to a number of studies that could not be pooled. Limited evidence exists as to the effect of exercise training on emerging biomarkers.

Hiding in Plain Sight? It's Time to Investigate Other Possible Transmission Routes for Hepatitis E Virus (HEV) in Developed Countries.

Historically in developed countries, reported hepatitis E cases were typically travellers returning from countries where hepatitis E virus (HEV) is endemic, but now there are increasing numbers of non-travel-related ("autochthonous") cases being reported. Data for HEV in New Zealand remain limited and the transmission routes unproven. We critically reviewed the scientific evidence supporting HEV transmission routes in other developed countries to inform how people in New Zealand may be exposed to this virus. A substantial body of indirect evidence shows domesticated pigs are a source of zoonotic human HEV infection, but there is an information bias towards this established reservoir. The increasing range of animals in which HEV has been detected makes it important to consider other possible animal reservoirs of HEV genotypes that can or could infect humans. Foodborne transmission of HEV from swine and deer products has been proven, and a large body of indirect evidence (e.g. food surveys, epidemiological studies and phylogenetic analyses) support pig products as vehicles of HEV infection. Scarce data from other foods suggest we are neglecting other potential sources of foodborne HEV infection. Moreover, other transmission routes are scarcely investigated in developed countries; the role of infected food handlers, person-to-person transmission via the faecal-oral route, and waterborne transmission from recreational contact or drinking untreated or inadequately treated water. People have become symptomatic after receiving transfusions of HEV-contaminated blood, but it is unclear how important this is in the overall hepatitis E disease burden. There is need for broader research efforts to support establishing risk-based controls.