WOMAN-2 Pilot Study Data

Data and supporting material produced as part of a pilot study to test outcome questions for the WOMAN-2 trial of tranexamic acid for the prevention of postpartum haemorrhage. This pilot study was conducted in one hospital which will also be conducting the WOMAN-2 Trial in Pakistan. The pilot study population included participants similar to those to be included in the WOMAN-2 Trial: women who are anaemic, and having given birth. Participants took part in an interview which included answering questions from the draft participant reported outcomes questionnaire. A small subset of participants enrolled in this pilot study also took part in a cognitive interview directly following the questionnaire to learn how they understood the questions. Each row of the dataset table represents data for an individual participant

Long-term athletic training does not alter age-associated reductions of left-ventricular mid-diastolic lengthening or expansion at rest

Purpose: The interaction of ageing and exercise training status on left-ventricular (LV) peak strain is unclear. Additionally, strain analysis across the entire cardiac cycle facilitates a more detailed assessment of deformation, yet this has not been implemented to characterize the ageing LV and in association with training status. This study investigated healthy ageing and training status on LV systolic and diastolic strain utilizing novel echocardiographic applications. Methods: Forty healthy males were included and allocated into four groups; young recreationally active (YRA,n = 9; 28 ± 5 years), old recreationally active (ORA, n = 10; 68 ± 6), young trained (YT,n = 10; 27 ± 6 years), and old trained (OT, n = 11, 64 ± 4 years) groups. Two-dimensional speckle-tracking echocardiography was performed to ascertain peak LV longitudinal and circumferential strain (base and apex) strain within each myocardial layer and at 5% increments across the cardiac cycle. Results: Older groups had lower diastolic longitudinal lengthening and circumferential expansion between 40–85% mid-diastole, regardless of training status (P 0.05). Longitudinal and circumferential (base and apex) peak and layer-specific strain did not differ between groups (P > 0.05). Conclusion: Novel applications of diastolic strain revealed lower age-associated LV longitudinal lengthening and circumferential expansion in older age. Yet, diastolic strain profiles did not differ based on chronic habits of exercise training and, thus, older trained men did not demonstrate an attenuation of age-associated differences in mid-diastolic LV strain. © 2020, The Author(s)

Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT

Background: Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation and death. We assessed the effects of tranexamic acid in traumatic brain injury patients.Objective: To assess the effects of tranexamic acid on death, disability and vascular occlusive events in traumatic brain injury patients. We also assessed cost-effectiveness.Design: Randomised trial and economic evaluation. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers and those assessing outcomes were masked to allocation. All analyses were by intention to treat. We assessed the cost-effectiveness of tranexamic acid versus no treatment from a UK NHS perspective using the trial results and a Markov model.Setting: 175 hospitals in 29 countries.Participants: Adults with traumatic brain injury within 3 hours of injury with a Glasgow Coma Scale score of ≤ 12 or any intracranial bleeding on computerised tomography scan, and no major extracranial bleeding, were eligible.Intervention: Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo.Main outcome measures: Head injury death in hospital within 28 days of injury in patients treated within 3 hours of injury. Secondary outcomes were early head injury deaths, all-cause and cause-specific mortality, disability, vascular occlusive events, seizures, complications and adverse events.Results: Among patients treated within 3 hours of injury (n = 9127), the risk of head injury death was 18.5% in the tranexamic acid group versus 19.8% in the placebo group (855/4613 vs. 892/4514; risk ratio 0.94, 95% confidence interval 0.86 to 1.02). In a prespecified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the tranexamic acid group versus 14.0% in the placebo group (485/3880 vs. 525/3757; risk ratio 0.89, 95% confidence interval 0.80 to 1.00). There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury (166/2846 vs. 207/2769; risk ratio 0.78, 95% confidence interval 0.64 to 0.95), but in those with severe head injury (689/1739 vs. 685/1710; risk ratio 0.99, 95% confidence interval 0.91 to 1.07) there was no apparent reduction (p-value for heterogeneity = 0.030). Early treatment was more effective in mild and moderate head injury (p = 0.005), but there was no obvious impact of time to treatment in cases of severe head injury (p = 0.73). The risk of disability, vascular occlusive events and seizures was similar in both groups. Tranexamic acid is highly cost-effective for mild and moderate traumatic brain injury (base case of £4288 per quality-adjusted life-year gained).Conclusion: Early tranexamic acid treatment reduces head injury deaths. Treatment is cost-effective for patients with mild or moderate traumatic brain injury, or those with both pupils reactive.Future work: Further trials should examine early tranexamic acid treatment in mild head injury. Research on alternative routes of administration is needed.Limitations: Time to treatment may have been underestimated.Trial registration: Current Controlled Trials ISRCTN15088122, ClinicalTrials.gov NCT01402882, EudraCT 2011-003669-14, Pan African Clinical Trial Registry PACTR20121000441277.Funding: The project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 26. See the NIHR Journals Library website for further project information. In addition, funding was provided by JP Moulton Charitable Trust, Joint Global Health Trials (Medical Research Council, Department for International Development and the Wellcome Trust). This project was funded by the NIHR Global Health Trials programme

The influence of age and exercise training status on left ventricular systolic twist mechanics in healthy males—an exploratory study

Age-related differences in twist may be mitigated with exercise training, although this remains inconclusive. Moreover, temporal left ventricular (LV) systolic twist mechanics, including early-systolic (twistearly), and beyond peak twist (twistpeak) alone, have not been considered. Therefore, further insights are required to ascertain the influence of age and training status on twist mechanics across systole. Forty males were included and allocated into 1 of 4 groups based on age and training status: young recreationally active (YRA, n = 9; 28 ± 5 years), old recreationally active (ORA, n = 10; 68 ± 6 years), young trained (YT, n = 10; 27 ± 6 years), and old trained (OT, n = 11, 64 ± 4 years) groups. Two-dimensional speckle-tracking echocardiography was performed to determine LV twist mechanics, including twistearly, twistpeak, and total twist (twisttotal), by considering the nadir on the twist time-curve during early systole. Twisttotal was calculated by subtracting twistearly from their peak values. LV twistpeak was higher in older than younger men (p = 0.036), while twistpeak was lower in the trained than recreationally-active (p = 0.004). Twistpeak is underestimated compared with twisttotal (p < 0.001), and when early-systolic mechanics were considered, to calculate twisttotal, the age effect (p = 0.186) was dampened. LV twist was higher in older than younger age, with lower twist in exercise-trained than recreationally-active males. Twistpeak is underestimated when twistearly is not considered, with novel observations demonstrating that the age effect was dampened when considering twistearly. These findings elucidated a smaller age effect when early phases of systole are considered, while lower LV systolic mechanics were observed in older aged trained than recreationally-active males

Development and Validation of a Socioeconomic Kidney Transplant Derailers Index

Background: Socioeconomic barriers can prevent successful kidney transplant (KT) but are difficult to measure efficiently in clinical settings. We created and validated an individual-level, single score Kidney Transplant Derailers Index (KTDI) and assessed its association with waitlisting and living donor KT (LDKT) rates. Methods: The dataset included 733 patients presenting for KT evaluation in a transplant center in California. Exploratory factor analysis was used to identify socioeconomic barriers to KT (derailers) to include in the index. Potential KT derailers included health insurance, employment, financial insecurity, educational attainment, perception of neighborhood safety, access to a vehicle, having a washer/dryer, and quality of social support. Validity was tested with associations between KTDI scores and the following: (1) the Area Deprivation Index (ADI) and (2) time to KT waitlisting and LDKT. Results: Nine derailers were retained, omitting only social support level from the original set. The KTDI was scored by summing the number of derailers endorsed (mean: 3.0; range: 0–9). Black patients had higher estimated KTDI scores than other patient groups (versus White patients, 3.8 versus 2.1; P \u3c 0.001, effect size = 0.81). In addition, the KTDI was associated with the ADI (γ = 0.70, SE = 0.07; P \u3c 0.001). Finally, in comparison to the lower tertile, patients in the upper and middle KTDI tertiles had lower hazard of waitlisting (upper tertile hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.25-0.45; middle tertile HR: 0.54, 95% CI: 0.40-0.72) and receiving an LDKT (upper tertile HR: 0.15, 95% CI: 0.08-0.30; middle tertile HR: 0.35, 95% CI: 0.20-0.62). These associations remained significant when adjusting for the ADI and other patient characteristics. Conclusions: The KTDI is a valid indicator of socioeconomic barriers to KT for individual patients that can be used to identify patients at risk for not receiving a KT

Giardia duodenalis and Cryptosporidium occurrence in Australian sea lions (Neophoca cinerea) exposed to varied levels of human interaction

AbstractGiardia and Cryptosporidium are amongst the most common protozoan parasites identified as causing enteric disease in pinnipeds. A number of Giardia assemblages and Cryptosporidium species and genotypes are common in humans and terrestrial mammals and have also been identified in marine mammals. To investigate the occurrence of these parasites in an endangered marine mammal, the Australian sea lion (Neophoca cinerea), genomic DNA was extracted from faecal samples collected from wild populations (n = 271) in Southern and Western Australia and three Australian captive populations (n = 19). These were screened using PCR targeting the 18S rRNA of Giardia and Cryptosporidium. Giardia duodenalis was detected in 28 wild sea lions and in seven captive individuals. Successful sequencing of the 18S rRNA gene assigned 27 Giardia isolates to assemblage B and one to assemblage A, both assemblages commonly found in humans. Subsequent screening at the gdh and β-giardin loci resulted in amplification of only one of the 35 18S rRNA positive samples at the β-giardin locus. Sequencing at the β-giardin locus assigned the assemblage B 18S rRNA confirmed isolate to assemblage AI. The geographic distribution of sea lion populations sampled in relation to human settlements indicated that Giardia presence in sea lions was highest in populations less than 25 km from humans. Cryptosporidium was not detected by PCR screening in either wild colonies or captive sea lion populations. These data suggest that the presence of G. duodenalis in the endangered Australian sea lion is likely the result of dispersal from human sources. Multilocus molecular analyses are essential for the determination of G. duodenalis assemblages and subsequent inferences on transmission routes to endangered marine mammal populations

Long-Term Aerobic Exercise Improves Vascular Function in Old Age: A Systematic Review, Meta-Analysis and Meta Regression of Observational and Interventional Studies

There is an emerging body of literature relating to the effectiveness of frequent aerobic exercise as a prophylactic for age-associated dysfunction of large arteries, yet systematic evaluation and precise estimate of this effect is unknown. We conducted a systematic review and meta-analysis of controlled studies examining flow mediated dilatation (FMD) of athletic older persons and otherwise healthy sedentary counterparts to (i) compare FMD as a determinant of endothelial function between athletes and sedentary (ii) summarise the effect of exercise training on FMD in studies of sedentary ageing persons. Studies were identified from systematic search of major electronic databases from inception to January 2018. Study quality was assessed before conducting a random effects meta-analysis to calculate a pooled ES (mean difference) with 95% CI’s. Thirteen studies [10 cross-sectional (n=485); 4 intervention (n=125] with age ranges from 62-75 years underwent quantitative pooling of data. Older athletes had more favourable FMD compared with sedentary controls (2.1%; CI: 1.4%, 2.8%; P<0.001). There was no significant improvement in the vascular function of sedentary cohorts following a period of exercise training (0.7%; CI: -0.675%, 2.09%; P=0.316). However, there was a significant increase in baseline diameter from pre to post intervention (0.098%; CI: 0.066%, 0.130%; P<0.001). In addition, there was no significant difference in endothelial independent vasodilation between the trained and sedentary older adults (1.57%; CI: -0.13%, 3.27%; P=0.07) or from pre to post exercise intervention (1.48%; CI: -1.34%, 4.3%; P=0.3). In conclusion, long-term aerobic exercise appears to attenuate the decline in endothelial vascular function, a benefit which is maintained during chronological ageing. However, currently there is not enough evidence to suggest that exercise interventions improve vascular function in previously sedentary healthy older adults

Improved physical health in middle-older aged golf caddies following 24-weeks of high-volume physical activity

Background: The physical demands of golf caddying, including walking while carrying a golf bag, may potentially affect body composition, and markers of metabolic, cardiovascular, and musculoskeletal health. Therefore, this study examined the impact of 24 weeks of caddying on physical health in middle-older aged males. Methods: Eleven full-time experienced male caddies (age: 59 [8] y; caddying experience: 14 [12] y) were recruited from a local golf course. The following were assessed at preseason and after 24 weeks of caddying (March–September 2022): body composition, heart rate, blood pressure, blood lipids, and performance tests (static and dynamic balance, strength, and submaximal fitness). Physical activity (PA) levels were assessed at preseason and at the mid-point of the caddying season. Across the caddying season, participants completed a monthly average of 24.0 (3.8) rounds. Results: Following the caddying season, improvements in static balance (Δ = 13.5 s), dynamic balance (Δ = −1.8 s), and lower back absolute strength (Δ = 112.8 N), and muscle quality (Δ = 2.0 N·kg−1) were observed (all P &lt; .05). Additionally, blood lipids, including total cholesterol (Δ = −0.6 mmol·L−1), high-density lipoprotein cholesterol (Δ = 0.1 mmol·L−1), low-density lipoprotein cholesterol (Δ = −0.6 mmol·L−1) (all P &lt; .05), and body composition, including body mass (Δ = −2.7 kg), fat mass (Δ = −1.9 kg), fat percentage (Δ = −1.4%), fat-to-muscle ratio (Δ = −0.03), and body mass index (Δ = −0.9 kg·m−2) (all P &lt; .05) improved. Caddying did not offer beneficial changes to cardiovascular variables or cardiorespiratory fitness (P &gt; .05), while coronary heart disease risk score decreased (Δ = −3.3%) (P &lt; .05). In relation to PA, light- (Δ = 145 min) and moderate-intensity (Δ = 71 min) PA, moderate to vigorous PA (Δ = 73 min), and total PA (Δ = 218 min) between preseason and the mid-point of the caddying season increased, while sedentary time (Δ = −172 min) decreased (all P &lt; .05). Conclusion: Golf caddying can provide several physical health benefits such as improvements in various markers of cardiometabolic health, lower back absolute strength, and static and dynamic balance. The physical health improvements that caddying offers is likely contributed to by increased PA volume and intensity through walking on the golf course. Therefore, caddying may represent a feasible model for increasing PA volume and intensity and achieve physical health–related benefits