We conducted a nested case–control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA‐DR and ‐DQ ...incompatibility at the eplet level. Cases (n = 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n = 104) with a similar follow‐up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios OR of 2.84 95% confidence interval (CI): 1.03, 7.84 and 4.62 95% CI: 1.51, 14.14) in the presence of 27–43 and >43 HLA‐DR + DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA‐DR + DQ eplet mismatches. Our study suggests that minimization of HLA‐DR + DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study.
In this nested case‐control study from a Canadian cohort of adult kidney transplant recipients, the number of HLA‐DR and HLA‐DQ related eplet mismatches is independently associated with the development of transplant glomerulopathy.
Consumer-wearable activity trackers are small electronic devices that record fitness and health-related measures.
The purpose of this systematic review was to examine the validity and reliability of ...commercial wearables in measuring step count, heart rate, and energy expenditure.
We identified devices to be included in the review. Database searches were conducted in PubMed, Embase, and SPORTDiscus, and only articles published in the English language up to May 2019 were considered. Studies were excluded if they did not identify the device used and if they did not examine the validity or reliability of the device. Studies involving the general population and all special populations were included. We operationalized validity as criterion validity (as compared with other measures) and construct validity (degree to which the device is measuring what it claims). Reliability measures focused on intradevice and interdevice reliability.
We included 158 publications examining nine different commercial wearable device brands. Fitbit was by far the most studied brand. In laboratory-based settings, Fitbit, Apple Watch, and Samsung appeared to measure steps accurately. Heart rate measurement was more variable, with Apple Watch and Garmin being the most accurate and Fitbit tending toward underestimation. For energy expenditure, no brand was accurate. We also examined validity between devices within a specific brand.
Commercial wearable devices are accurate for measuring steps and heart rate in laboratory-based settings, but this varies by the manufacturer and device type. Devices are constantly being upgraded and redesigned to new models, suggesting the need for more current reviews and research.
This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory ...hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.
Objective
To compare pregnancy outcomes, accounting for allocated group, between methyldopa‐treated and labetalol‐treated women in the CHIPS Trial (ISRCTN 71416914) of ‘less tight’ versus ‘tight’ ...control of pregnancy hypertension.
Design
Secondary analysis of CHIPS Trial cohort.
Setting
International randomised controlled trial (94 sites, 15 countries).
Population or sample
Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation.
Methods
Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors.
Main outcome measures
CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre‐eclampsia and delivery at <34 or <37 weeks.
Results
Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post‐randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile adjusted odds ratio (aOR) 0.48; 95% CI 0.20–0.87. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40–1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.32–0.92), severe hypertension (aOR 0.51; 95% CI 0.31–0.83), pre‐eclampsia (aOR 0.55; 95% CI 0.36–0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29–0.96) or <37 weeks (aOR 0.55; 95% CI 0.35–0.85).
Conclusion
These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre‐existing hypertension, may have had better outcomes.
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There was no evidence that women treated with methyldopa versus labetalol had worse outcomes.
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There was no evidence that women treated with methyldopa versus labetalol had worse outcomes.
Objective
To examine the association between pre‐eclampsia definition and pregnancy outcome.
Design
Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data.
Setting
...International multicentre randomised controlled trial (RCT).
Population
In all, 987 women with non‐severe non‐proteinuric pregnancy hypertension.
Methods
We evaluated the association between pre‐eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control.
Main outcome measures
Main CHIPS trial outcomes: primary (perinatal loss or high‐level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth.
Results
Of 979/987 women with informative data, 280 (28.6%) progressed to pre‐eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre‐eclampsia defined broadly as proteinuria or one/more maternal symptoms, signs or abnormal laboratory tests. The broad (versus restrictive) definition had significantly higher sensitivities (range 62–79% versus 36–50%), lower specificities (range 53–65% versus 72–82%), and similar or higher diagnostic odds ratios and ‘true‐positive’ to ‘false‐positive’ ratios. Stratified analyses showed similar results. Addition of available fetoplacental manifestations (stillbirth or birthweight <10th centile) to the broad pre‐eclampsia definition improved sensitivity (74–87%).
Conclusions
A broad (versus restrictive) pre‐eclampsia definition better identifies women who develop adverse pregnancy outcomes. These findings should be replicated in a prospective study within routine healthcare to ensure that the anticipated increase in surveillance and intervention in a larger number of women with pre‐eclampsia is associated with improved outcomes, reasonable costs and congruence with women's values.
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A broad (versus restrictive) pre‐eclampsia definition better identifies the risk of adverse pregnancy outcomes.
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A broad (versus restrictive) pre‐eclampsia definition better identifies the risk of adverse pregnancy outcomes.
This article includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights16602
Molecular fossils of biological lipids are preserved in 2700-million-year-old shales from the Pilbara Craton, Australia. Sequential extraction of adjacent samples shows that these hydrocarbon ...biomarkers are indigenous and syngenetic to the Archean shales, greatly extending the known geological range of such molecules. The presence of abundant 2α-methylhopanes, which are characteristic of cyanobacteria, indicates that oxygenic photosynthesis evolved well before the atmosphere became oxidizing. The presence of steranes, particularly cholestane and its 28- to 30-carbon analogs, provides persuasive evidence for the existence of eukaryotes 500 million to 1 billion years before the extant fossil record indicates that the lineage arose.
Competing events (or risks) preclude the observation of an event of interest or alter the probability of the event's occurrence and are commonly encountered in transplant outcomes research. ...Transplantation, for example, is a competing event for death on the waiting list because receiving a transplant may significantly decrease the risk of long‐term mortality. In a typical analysis of time‐to‐event data, competing events may be censored or incorporated into composite end points; however, the presence of competing events violates the assumption of “independent censoring,” which is the basis of standard survival analysis techniques. The use of composite end points disregards the possibility that competing events may be related to the exposure in a way that is different from the other components of the composite. Using data from the Scientific Registry of Transplant Recipients, this paper reviews the principles of competing risks analysis; outlines approaches for analyzing data with competing events (cause‐specific and subdistribution hazards models); compares the estimates obtained from standard survival analysis, which handle competing events as censoring events; discusses the appropriate settings in which each of the two approaches could be used; and contrasts their interpretation.
The authors review the principles of competing risk analysis, provide a summary of the transplant literature where competing risk methods have been applied, and use data from the Scientific Registry of Transplant Recipients to compare the risk of mortality in sensitized waitlisted kidney transplant candidates using standard survival analysis models versus subdistribution hazards models.
Continuous positive airway pressure (CPAP) improves cardiac function in patients with congestive heart failure (CHF) who also have Cheyne-Stokes respiration and central sleep apnea (CSR-CSA). ...However, the effects of CPAP in CHF patients without CSR-CSA have not been tested, and the long-term effects of this treatment on clinical cardiovascular outcomes are unknown.
We conducted a randomized, controlled trial in which 66 patients with CHF (29 with and 37 without CSR-CSA) were randomized to either a group that received CPAP nightly or to a control group. Change in left ventricular ejection fraction (LVEF) from baseline to 3 months and the combined mortality-cardiac transplantation rate over the median 2.2-year follow-up period were compared between the CPAP-treated and control groups. For the entire group of patients, CPAP had no significant effect on LVEF, but it was associated with a 60% relative risk reduction (95% confidence interval, 2% to 64%) in mortality-cardiac transplantation rate in patients who complied with CPAP therapy. Stratified analysis of patients with and without CSR-CSA revealed that those with CSR-CSA experienced both a significant improvement in LVEF at 3 months and a relative risk reduction of 81% (95% confidence interval, 26% to 95%) in the mortality-cardiac transplantation rate of those who used CPAP. CPAP had no significant effect on either of these outcomes in patients without CSR-CSA.
CPAP improves cardiac function in CHF patients with CSR-CSA but not in those without it. Although not definitive, our findings also suggest that CPAP can reduce the combined mortality-cardiac transplantation rate in those CHF patients with CSR-CSA who comply with therapy.
Objectives Human subjects and Old World primates have high levels of antibody to galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (α-Gal). Commercially available bioprosthetic heart valves of ...porcine and bovine origin retain the Gal antigen despite current processing techniques. Gal-deficient pigs eliminate this xenoantigen. This study tests whether binding of human anti-Gal antibody effects calcification of wild-type and Gal-deficient glutaraldehyde-fixed porcine pericardium by using a standard subcutaneous implant model. Methods Expression of α-Gal was characterized by lectin Griffonia simplicifolia –IB4 staining. Glutaraldehyde-fixed pericardial disks from Gal-positive and Gal-deficient pigs were implanted into 12-day-old Wistar rats and 1.5-kg rabbits with and without prelabeling with affinity-purified human anti-Gal antibody. Calcification of the implants was determined after 3 weeks by using inductively coupled plasma spectroscopy. Results The α-Gal antigen was detected in wild-type but not Gal-deficient porcine pericardium. Wild-type disks prelabeled with human anti-Gal antibody exhibited significantly greater calcification compared with that seen in antibody-free wild-type samples (mean ± standard error of the mean: 111 ± 8.4 and 74 ± 9.6 mg/g, respectively; P = .01). In the presence of anti-Gal antibody, a significantly greater level of calcification was detected in wild-type compared with GTKO porcine pericardium (111 ± 8.4 and 55 ± 11.8 mg/g, respectively; P = .005). Calcification of Gal-deficient pericardium was not affected by the presence of anti-Gal antibody (51 ± 9.1 and 55 ± 11.8 mg/g). Conclusions In this model anti-Gal antibody accelerates calcification of wild-type but not Gal-deficient glutaraldehyde-fixed pericardium. This study suggests that preformed anti-Gal antibody present in all patients might contribute to calcification of currently used bioprosthetic heart valves. Gal-deficient pigs might become the preferred source for new, potentially calcium-resistant bioprosthetic heart valves.
Abundant, micrometer-scale, spherical aggregates of 2- to 5-nanometer-diameter sphalerite (ZnS) particles formed within natural biofilms dominated by relatively aerotolerant sulfate-reducing bacteria ...of the family Desulfobacteriaceae. The biofilm zinc concentration is about 106times that of associated groundwater (0.09 to 1.1 parts per million zinc). Sphalerite also concentrates arsenic (0.01 weight %) and selenium (0.004 weight %). The almost monomineralic product results from buffering of sulfide concentrations at low values by sphalerite precipitation. These results show how microbes control metal concentrations in groundwater- and wetland-based remediation systems and suggest biological routes for formation of some low-temperature ZnS deposits.
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