An inexpensive device to treat postpartum hemorrhage: a preliminary proof of concept study of health provider opinion and training in Nepal

BACKGROUND: Obstetric hemorrhage remains the leading cause of maternal mortality in resource limited areas. An inexpensive pneumatic anti-shock garment was devised of bicycle tubes and tailored cloth which can be prepared from local materials in resource-limited settings. The main purposes of this study were: 1) to determine acceptability of the device by nurses and midwives and obtain suggestions for making the device more suitable for use in their particular work environments, 2) to determine whether a three hour training course provided adequate instruction in the use of this device for the application of circumferential abdominal pelvic pressure, and 3) determine production capability and cost in a resource-limited country. METHODS: Fifty-eight nurse and midwife participants took part in three sessions over eight months in Nepal. Correct device placement was assessed on non-pregnant participants using ultrasound measurement of distal aortic flow before and after device inflation, and analyzed using confidence intervals. Participants were surveyed to determine acceptability of the device, obtain suggestions for improvement, and to collect data on clinical use. RESULTS: Device placement achieved flow decreases with a mean of 39% (95% CI 25%-53%, p < 0.001) in the first session, 28% (95% CI 21%-33%, P < 0.001) after four months and 29% (95% CI 24%-34%, p < 0.001) at 8 months. All nurses and midwives thought the device would be acceptable for use in obstetric hemorrhage and that they could make, clean, and apply it. They quickly learned to apply the device, remembered how to apply it, and were willing and able to use the device clinically. Ten providers used the device, each on one patient, to treat obstetric hemorrhage after routine measures had failed; bleeding stopped promptly in all ten, two of whom were transported to the hospital. Production of devices in Kathmandu using local tailors and supplies cost approximately $40 per device, in a limited production setting. CONCLUSIONS: Preliminary data suggest that an inexpensive, easily-made device is potentially an appropriate addition to current obstetric hemorrhage treatment in resource-limited areas and that further study is warranted

Conservation of the Illinois flora: A climate change vulnerability assessment of 73 plant species

It will be important for land managers, ecological researchers and policymakers to understand how predicted climate changes may affect the flora of Illinois. A climate change vulnerability assessment was completed in 2011 for the162 Animal Species in Greatest Need of Conservation using NatureServe’s Climate Change Vulnerability Index (CCVI) tool. Here we selected 73plant species found in Illinois and calculated their relative vulnerabilities to predicted climate changes, also using the NatureServe CCVI tool. We selected species from several groups that we felt would be broadly representative of the Illinois flora. These groups included: rare plants, invasive plants, important prairie species, important woodland/savanna species, important forest species, and plants important to society. We compiled and entered data regarding both the species’ exposures to predicted climate changes and their sensitivities to those changes. Exposures were determined by overlapping species range maps for Illinois with maps of temperature and moisture (AET:PET) predictions for the middle of this century. Species sensitivities were determined by interviewing between 4 and 12 experts for each plant species. Experts answered questions found in the CCVI tool regarding the species’ biologies, ecologies and behaviors. Results for each individual survey were averaged for each species. Results fell into one of five vulnerability categories: Extremely Vulnerable, Highly Vulnerable, Moderately Vulnerable, Not Vulnerable/Presumed Stable, and Not Vulnerable/Increase Likely. Results for these 73species in Illinois fell into all 5 vulnerability categories, with the majority (67%) falling into the Presumed Stable category. The species most vulnerable to predicted climate changes were all of conservation concern; most were federal or state listed species. Native species tended to be more vulnerable than non-natives, and plants important to prairies, savannas and forests were equally vulnerable to predicted changes. The four species were ranked as likely to increase in population size or range extent due to predicted climate changes were: Ailanthus altissima(tree of heaven), Ambrosia artemisiifolia(ragweed), Microstegium vimineum(Japanese stiltgrass) and Toxicodendron radicans(poison ivy). We advocate for 8 important next-steps to ensure adequate conservation of Illinois plants in a future with climate change, based on the findings of this report: 1) Investigate the climate change vulnerabilities of all rare plants in Illinois. Rare plants are the most vulnerable group of species in this report. 2) Prioritize research on plants’ abilities to phenologically track changes in seasonality, population genetics, species interactions, dispersal distances, thermal and hydrological tolerancesand soil preferences/tolerances. 3) Continue to monitor population trends. Increase capacity to monitor species with the most uncertain responses to climate changes, the most vulnerable species, and all rare species. 4) Monitor invasive speciesfor changes in populations and behavior. Assess all invasive species using NatureServe’s CCVI tool or another tool. 5) Increase connectivity between natural areas. Increase acreage of natural areas. 6) Managers, policymakers, researchers and the public shouldwork together to fully consider the role that assisted migration should or should not play in Illinois plant conservation. 7) Compile work done by various agencies and NGOs on the climate change vulnerabilities of Illinois species and ecosystems to detect trends, and to identify appropriate research, management and policy priorities. 8) Use adaptive management approaches to care for natural areas in Illinois in order to best achieve land management goals in an uncertain future.Illinois Natural History SurveyIllinois Department of Natural ResourcesIllinois Department of Transportationunpublishednot peer reviewedOpe

Nitric oxide-dependent bone marrow progenitor mobilization by carbon monoxide enhances endothelial repair after vascular injury

Carbon monoxide (CO) has emerged as a vascular homeostatic molecule that prevents balloon angioplasty-induced stenosis via antiproliferative effects on vascular smooth muscle cells. The effects of CO on reendothelialization have not been evaluated

Continuing the sequence?:Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland

Funding This research was made possible through access to the data and findings generated by Scotland’s four regional genetics centres at NHS Grampian, Lothian, Tayside and Greater Glasgow and Clyde. These four centres participated in Scotland’s involvement in the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health) and funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. Acknowledgements The authors would like to thank the Scottish Genomes Partnership for their support with this work. The Scottish Genomes Partnership is funded by the Chief Scientist Office of the Scottish Government Health Directorates [SGP/1] and The Medical Research Council Whole Genome Sequencing for Health and Wealth Initiative (MC/PC/15080). We are grateful for the contributions of the funding bodies; Scottish Regional Genetics centres at NHS Lothian, Tayside, Grampian and Greater Glasgow and Clyde, clinicians and healthcare teams who contributed to the provision of data as well as the analyses and interpretation of results. We also thank Morad Ansari, Christine Bell, Martin McClatchey, Nicola Williams, Austin Diamond, Jonathan Berg, Jon Warner, Alexis Duncan, Amy Rowlatt, and Tessa Coupar for their help and advice during the SGP Project, and Michael Doherty, Florence Richards and Quinn Heppe for help with costing the standard testing pathway. We thank Professor Tim Aitman for commenting on earlier drafts of the paper. We thank all participants who took part in the valuation study. The University of Aberdeen and the Chief Scientist Office of the Scottish Government Health and Social Care Directorates fund the Health Economics Research Unit (HERU). This study would not be possible without the families, patients, clinicians, nurses, research scientists, laboratory staff, and the wider Scottish Genomes Partnership team to whom we give grateful thanks.Peer reviewedPublisher PD

Patient-reported outcomes of periacetabular osteotomy from the prospective ANCHOR cohort study

BACKGROUND: Current literature describing the periacetabular osteotomy (PAO) is mostly limited to retrospective case series. Larger, prospective cohort studies are needed to provide better clinical evidence regarding this procedure. The goals of the current study were to (1) report minimum 2-year patient-reported outcomes (pain, hip function, activity, overall health, and quality of life), (2) investigate preoperative clinical and disease characteristics as predictors of clinical outcomes, and (3) report the rate of early failures and reoperations in patients undergoing contemporary PAO surgery. METHODS: A large, prospective, multicenter cohort of PAO procedures was established, and outcomes at a minimum of 2 years were analyzed. A total of 391 hips were included for analysis (79% of the patients were female, and the average patient age was 25.4 years). Patient-reported outcomes, conversion to total hip replacement, reoperations, and major complications were documented. Variables with a p value of ≤0.10 in the univariate linear regressions were included in the multivariate linear regression. The backward stepwise selection method was used to determine the final risk factors of clinical outcomes. RESULTS: Clinical outcome analysis demonstrated major clinically important improvements in pain, function, quality of life, overall health, and activity level. Increasing age and a body mass index status of overweight or obese were predictive of improved results for certain outcome metrics. Male sex and mild acetabular dysplasia were predictive of lesser improvements in certain outcome measures. Three (0.8%) of the hips underwent early conversion to total hip arthroplasty, 12 (3%) required reoperation, and 26 (7%) experienced a major complication. CONCLUSIONS: This large, prospective cohort study demonstrated the clinical success of contemporary PAO surgery for the treatment of symptomatic acetabular dysplasia. Patient and disease characteristics demonstrated predictive value that should be considered in surgical decision-making. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Genome sequencing with gene panel-based analysis for rare inherited conditions in a publicly funded healthcare system: implications for future testing

Acknowledgements This study would not be possible without the families, patients, clinicians, nurses, research scientists, laboratory staff, informaticians and the wider Scottish Genomes Partnership team to whom we give grateful thanks. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health). The Scottish Genomes Partnership was funded by the Chief Scientist Office of the Scottish Government Health Directorates (SGP/1) and The Medical Research Council Whole Genome Sequencing for Health and Wealth Initiative (MC/PC/15080). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure.Peer reviewedPublisher PD

Adaptation of HIV-1 Envelope Glycoprotein gp120 to Humoral Immunity over the Course of the Epidemic

Since 2009, a large panel of broad and potent monoclonal neutralizing antibodies (MoNAbs) against HIV-1 have been isolated. These MoNAbs can protect from lllV-1 infection and suppress established infection in animal models. Because their efficacy should be evaluated in human clinical trials, it is of importance to define the sensitivity of the most contemporary transmitted variants to these MoNAbs. We, and others previously, reported that HIV-1 has become more resistant to neutralization over the course of the epidemic (Bunnik et al., Nature Med 2010, Bouvin-Pley et al., PloS Pathog 2013). Methods: Here we extended the analyses to the most potent MoNAbs described since then, either more recently isolated or improved by structure-based gene modifications. Results: We fully confirmed the first observations showing an increasing resistance of HIV-1 clade B over time to MoNAbs targeting the major gp l20 epitopes but not to MoNAbs targeting the gp41 MPER. Despite this evolution, some MoNAbs still were able to neutralize efficiently the most recently transmitted HIV-1 variants (2006-2010). The most potent MoNAbs were the bi-specific PG9- and PG16-iMab that alone were able to neutralize an variants at less than 0.4 mg/mL. The sensitivity to iMAb remained similar over time, suggesting that the trend of increasing resistance to PG9-/PG16-iMAb may be attributed only to die antigen binding domain of PG9/PG16. NIH45-46m2 (and -m7), 10-1074 and 10E8 were also highly potent and, if combined, reached the potency of PG9-/PG16-iMAb. We also observed that 3BNC 117 was almost as potent as the modified NIH45-46 antibodies, and that the lama-derived JM4IgG2b was the most potent Ab among those that do not target the major gp 120 neutralizing epitopes. Conclusions: These data clearly suggest a continuous drift of the env gene of HIV-1 elude B over the epidemic, and that not a single epitope is concerned but the entire gp120 as a whole. The consequences of this adaptation on the envelope functionality are being explored

Expressions 1990

https://openspace.dmacc.edu/expressions/1012/thumbnail.jp

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study

Background: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. Objective: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. Design, setting, and participants: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. Outcome measurements and statistical analysis: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. Results and limitations: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). Conclusions: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. Patient summary: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer