Genetic diversity is a predictor of mortality in humans

BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased geneti

Genetic diversity is a predictor of mortality in humans

BackgroundIt has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease.ResultsWe performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person’s risk of death by 1.57%.ConclusionsThis effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-014-0159-7) contains supplementary material, which is available to authorized users

Patient factors associated with dermatology outpatient non-attendance : an analysis of racial and ethnic diversity

Non-attendance to dermatology outpatient appointments is a risk factor for poorer patient outcomes. The culturally and linguistically diverse (CALD) communities in Australia have been identified as at risk of poorer health outcomes, but there is a paucity of data assessing patient factors that may increase outpatient non-attendance. To investigate this, we performed a retrospective cross-sectional study of dermatology appointments from patients attending a tertiary, referral public hospital located in one of Australia's most racially and ethnically diverse communities. Patients within the 18-45 years age bracket were 61% more likely not to attend when compared with older age groups. Those born in Oceania, Middle East Asia, and surprisingly Australia were more likely to miss an appointment, whilst those born in East and Southeast Asia were more likely to attend. Those who spoke Arabic at home were more likely not to attend, whilst those who spoke Vietnamese at home were more likely to attend. This study sheds further light on health disparities in non-attendance and emphasizes the importance of not collectively amalgamating all groups of the CALD community

An Internet-Based Intervention for Cardiovascular Disease Management Integrated With Primary Care Electronic Health Records: Mixed Methods Evaluation of Implementation Fidelity and User Engagement

Background: Growing evidence supports the benefits of eHealth interventions to increase patient engagement and improve outcomes for a range of conditions. However, ineffective program delivery and usage attrition limit exposure to these interventions and may reduce their effectiveness.Objective: This study aims to evaluate the delivery fidelity of an eHealth intervention, describe use patterns, compare outcomes between low and high users, and identify mediating factors on intervention delivery and receipt.Methods: This is a mixed methods study of an internet-based intervention being evaluated for effectiveness in a randomized controlled trial (RCT). The intervention comprised medication and cardiovascular disease (CVD) risk data uploaded from the primary care electronic health record (EHR); interactive, personalized CVD risk score estimation; goal setting and self-monitoring; an interactive social forum; and optional receipt of heart health messages. Fidelity was assessed over 12 months. Trial outcomes were compared between low and high users. Data sources included program delivery records, web log data, trial data, and thematic analysis of communication records.Results: Most participants in the intervention group (451/486, 93%) had an initial training session conducted by telephone (413/447, 92.4% of participants trained), with a mean duration of 44 minutes (range 10-90 minutes). Staff conducted 98.45% (1776/1804) of the expected follow-ups, mostly by telephone or email. Of the 451 participants who commenced log-ins, 46.8% (211) were categorized as low users (defined as at least one log-in in 3 or fewer months of follow-up), 40.4% (182) were categorized as high users (at least one log-in in more than 3 months of follow-up), and 12.8% (58) were nonadopters (no log-ins after their training session). The mean log-in frequency was 3-4 per month in ongoing users. There was no significant difference between the groups in the primary trial outcome of adherence to guideline-recommended medications (P=.44). In unadjusted analyses, high users had significantly greater eHealth literacy scores (P=.003) and were more likely to meet recommended weekly targets for fruit (P=.03) and fish (P=.004) servings; however, the adjusted findings were not significant. Interactive screen use was highest for goal tracking and lowest for the chat forum. Screens with EHR-derived data held only an early interest for most users. Fidelity measures (reach, content, dose delivered, and dose received) were influenced by the facilitation strategies used by staff, invisible qualities of staff-participant communication, and participants’ responsiveness to intervention attributes.Conclusions: A multifeature internet-based intervention was delivered with high fidelity to the RCT protocol and was regularly used by 40.4% (182/451) of users over 12 months. Higher log-in frequency as an indicator of greater intervention exposure was not associated with statistically significant improvements in eHealth literacy scores, lifestyle changes, or clinical outcomes. Attributes of the intervention and individualized support influenced initial and ongoing use

TASCS

Low Dose Corticosteroids and Theophylline in the Treatment of Chronic Obstructive Pulmonary Disease – the TASCS Study (Theophylline and Steroids in COPD Study

Effect of extended hours dialysis on markers of chronic kidney disease-mineral and bone disorder in the ACTIVE Dialysis study

Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups.The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression.Phosphate binder use was reduced with extended hours (- 0.83 tablets per day [95% CI -1.61, - 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (- 0.219 mmol/L [- 0.314, - 0.124; P

The β-Blocker to lower cardiovascular dialysis events (BLOCADE) feasibility study: a randomized controlled trial

Background β-Blocking agents reduce cardiovascular mortality in patients with heart disease, but their potential benefit in dialysis patients is unclear. We aimed to determine the feasibility of a randomized controlled trial (RCT). Study Design Pilot RCT. Setting & Participants Patients who received dialysis for 3 or more months and were 50 years or older (or ≥18 years with diabetes or cardiovascular disease) were recruited from 11 sites in Australia and New Zealand. We aimed to recruit 150 participants. Intervention After a 6-week run-in with the β-blocker carvedilol, we randomly assigned participants to treatment with carvedilol or placebo for 12 months. Outcomes & Measurements The prespecified primary outcome was the proportion of participants who tolerated carvedilol, 6.25 mg, twice daily during the run-in period. After randomization, we report participant withdrawal and the incidence of intradialytic hypotension (IDH). Results Of 1,443 patients screened, 354 were eligible, 91 consented, and 72 entered the run-in stage. 49 of 72 run-in participants (68%; 95% CI, 57%-79%) achieved the primary outcome. 5 of the 23 withdrawals from run-in were attributable to bradycardia or hypotension. After randomization, 10 of 26 allocated to carvedilol and 4 of 23 allocated to placebo withdrew. 4 participants randomly assigned to carvedilol withdrew because of bradycardia or hypotension. Overall, there were 4 IDH events per 100 hemodialysis sessions; in participants allocated to carvedilol versus placebo, respectively, there were 7 versus 2 IDH events per 100 hemodialysis sessions (P = 0.1) in the 2 weeks immediately following a dose increase and 4 versus 3 IDH events per 100 hemodialysis sessions after no dose increase (P = 0.7). Limitations Unable to recruit planned sample size. Conclusions Recruiting patients receiving dialysis to an RCT of β-blocker versus placebo will prove challenging. Possible solutions include international collaboration and exploring novel trial designs such as a registry-based RCT

The Effect of Exit-Site Antibacterial Honey Versus Nasal Mupirocin Prophylaxis on the Microbiology and Outcomes of Peritoneal Dialysis-Associated Peritonitis and Exit-Site Infections: A Sub-Study of the Honeypot Trial.

♦ Background: The HONEYPOT study recently reported that daily exit-site application of antibacterial honey was not superior to nasal mupirocin prophylaxis for preventing overall peritoneal dialysis (PD)-related infection. This paper reports a secondary outcome analysis of the HONEYPOT study with respect to exit-site infection (ESI) and peritonitis microbiology, infectious hospitalization and technique failure.♦ Methods: A total of 371 PD patients were randomized to daily exit-site application of antibacterial honey plus usual exit-site care (N = 186) or intranasal mupirocin prophylaxis (in nasal Staphylococcus aureus carriers only) plus usual exit-site care (control, N = 185). Groups were compared on rates of organism-specific ESI and peritonitis, peritonitis- and infection-associated hospitalization, and technique failure (PD withdrawal).♦ Results: The mean peritonitis rates in the honey and control groups were 0.41 (95% confidence interval [CI] 0.32 – 0.50) and 0.41 (95% CI 0.33 – 0.49) episodes per patient-year, respectively (incidence rate ratio [IRR] 1.01, 95% CI 0.75 – 1.35). When specific causative organisms were examined, no differences were observed between the groups for gram-positive (IRR 0.99, 95% CI 0.66 – 1.49), gram-negative (IRR 0.71, 95% CI 0.39 – 1.29), culture-negative (IRR 2.01, 95% CI 0.91 – 4.42), or polymicrobial peritonitis (IRR 1.08, 95% CI 0.36 – 3.20). Exit-site infection rates were 0.37 (95% CI 0.28 – 0.45) and 0.33 (95% CI 0.26 – 0.40) episodes per patient-year for the honey and control groups, respectively (IRR 1.12, 95% CI 0.81 – 1.53). No significant differences were observed between the groups for gram-positive (IRR 1.10, 95% CI 0.70 – 1.72), gram-negative (IRR: 0.85, 95% CI 0.46 – 1.58), culture-negative (IRR 1.88, 95% CI 0.67 – 5.29), or polymicrobial ESI (IRR 1.00, 95% CI 0.40 – 2.54). Times to first peritonitis-associated and first infection-associated hospitalization were similar in the honey and control groups. The rates of technique failure (PD withdrawal) due to PD-related infection were not significantly different between the groups.♦ Conclusion: Compared with standard nasal mupirocin prophylaxis, daily topical exit-site application of antibacterial honey resulted in comparable rates of organism-specific peritonitis and ESI, infection-associated hospitalization, and infection-associated technique failure in PD patients