Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

A Peace of My Mind: Catriona Martin

Catriona Martin (left) is a coordinator for the “100 Days of Peacemaking Campaign,” and a volunteer that serves through Oasis Global currently in London, England. Born in the United Kingdom, she has traveled widely all over the world serving, teaching, and volunteering for the non-profit organization, Oasis Global. Catriona has volunteered for Oasis for nine years, serving in London, England, Pasadena, California, and Harare, Zimbabwe. From the website: “Our vision is for a community, a place where everyone is included, making a contribution and reaching their God-given potential” in a way that is “inclusive, integrated, empowering, and comprehensive so all people experience wholeness and fullness of life.” Interviewed by Kristina Grossman May 201

Disponibilité de misoprostol dans la communauté : Est-il sans danger?

This paper evaluates the safety and acceptability of long-term community-based use of misoprostol for management of postpartum hemorrhage (PPH) in home-births, by comparing deliveries with and without misoprostol use in communities of Kigoma, Tanzania. We administered a standardized survey instrument to women who delivered between August 2004 and May 2007. 940 women completed questionnaires, corresponding to 950 deliveries. Findings showed that the majority of TBAs administered misoprostol at the correct time (76%). Receipt of three or five tablets was most commonly reported (47% and 43% respectively). Misoprostol users were significantly more likely to experience shivering, high temperature, nausea, and vomiting after delivery; adjustment for gynecological history and delivery characteristics revealed no significant differences in experience of symptoms. Misoprostol was highly acceptable to all women surveyed. Misoprostol at the community level is a safe intervention (Afr J Reprod Health 2009; 13[2]:117-128).Cet article évalue la sauveté et l’acceptabilité de l’emploi à long terme de misoprostol dans la communauté pour le traitement de l’hémorragie du post partum (HPP) dans les naissances à domicile, en comparant les accouchements avec et sans l’utilisation de misoprostol dans les communautés de Kigoma, Tanzamie. Nous avons administré un instrument d’enquête standardisé aux femmes qui ont accouché entre le mois d’août 2004 et mai 2007. 940 femmes ont rempli des questionnaires, ce qui correspondait à 950 accouchements. Les résultats ont montré que la majorité des sages-femmes traditionnelles (SFTs) ont administre misoprostol comme il faut (76%). Elles ont indiqué en général avoir reçu trois ou cinq comprimés (47% et 43% respectivement). Les utilisateurs de misoprostol avaient la possibilité de subir le frissonnement, la haute température, la nausée et le vomissement après l’accouchement ; l’ajustement pour l’histoire gynécologique et les caractéristiques de l’accouchement n’ont pas révélé des différences significatives quant aux symptômes. Misoprostol a été bien acceptable à toutes les femmes enquêtées. Misoprostol au niveau de la communauté est une intervention sans danger (Afr J Reprod Health 2009; 13[2]:117-128)

The urban land use in the COSMO-CLM model: a comparison of three parameterizations for Berlin

The regional non-hydrostatic climate model COSMO-CLM is increasingly being used on fine spatial scales of 1–5 km. Such applications require a detailed differentiation between the parameterization for natural and urban land uses. Since 2010, three parameterizations for urban land use have been incorporated into COSMO-CLM. These parameterizations vary in their complexity, required city parameters and their computational cost. We perform model simulations with the COSMO-CLM coupled to these three parameterizations for urban land in the same model domain of Berlin on a 1-km grid and compare results with available temperature observations. While all models capture the urban heat island, they differ in spatial detail, magnitude and the diurnal variation.status: publishe

The urban land use in the COSMO-CLM model: a comparison of three parameterizations for Berlin

The regional non-hydrostatic climate model COSMO-CLM is increasingly being used on fine spatial scales of 1–5 km. Such applications require a detailed differentiation between the parameterization for natural and urban land uses. Since 2010, three parameterizations for urban land use have been incorporated into COSMO-CLM. These parameterizations vary in their complexity, required city parameters and their computational cost. We perform model simulations with the COSMO-CLM coupled to these three parameterizations for urban land in the same model domain of Berlin on a 1-km grid and compare results with available temperature observations. While all models capture the urban heat island, they differ in spatial detail, magnitude and the diurnal variation

Standardizing abortion research outcomes (STAR): a protocol for developing, disseminating and implementing a core outcome set for medical and surgical abortion.

Background Abortion is one of the most common events in women’s healthcare worldwide. Currently there is no standardization for the selection and reporting of outcomes in abortion clinical trials. This heterogeneity in clinical trials can make it difficult to draw meaningful conclusions across studies. Objective We aim to develop, disseminate, and implement a core outcome set (COS) for medical and surgical abortion trials. Materials and Methods To guide this project, we have assembled a local study management team and an international advisory group including abortion providers, researchers, methodologists, and abortion clients. A preliminary list of potential outcomes will be developed by undertaking a systematic review of abortion trials. A qualitative review will determine outcomes that are meaningful to women with experience of abortion. The modified Delphi method will use iterative group consensus to reduce the long list of outcomes. Participants in the modified Delphi method will include service-providers, researchers, clients, client advocates, and leaders of relevant medical journals and professional societies. Consensus on the COS will be reached via Delphi and a consensus meeting. Outcome measurements will be designated for each core outcome. Dissemination will be widespread including journals and professional societies. Discussion Results of this project will guide the development of future trials, advise trial reporting in collaborating journals, improve the strength of literature reviews and subsequent guidelines, and promote work in the field of COS development. Development and adoption of a COS in abortion would assist researchers in planning future trials, performing reviews, and creating guidelines or recommendations.</p

Mail-Order Pharmacy Dispensing of Mifepristone for Medication Abortion After In-Person Screening

ImportanceBefore 2021, the US Food and Drug Administration required mifepristone to be dispensed in person, limiting access to medication abortion.ObjectiveTo estimate the effectiveness, acceptability, and feasibility of dispensing mifepristone for medication abortion using a mail-order pharmacy.Design, setting, and participantsThis prospective cohort study was conducted from January 2020 to May 2022 and included 11 clinics in 7 states (5 abortion clinics and 6 primary care sites, 4 of which were new to abortion provision). Eligible participants were seeking medication abortion at 63 or fewer days' gestation, spoke English or Spanish, were age 15 years or older, and were willing to take misoprostol buccally. After assessing eligibility for medication abortion through an in-person screening, mifepristone and misoprostol were prescribed using a mail-order pharmacy. Patients had standard follow-up care with the clinic. Clinical information was collected from medical records. Consenting participants completed online surveys about their experiences 3 and 14 days after enrolling. A total of 540 participants were enrolled; 10 withdrew or did not take medication. Data were analyzed from August 2022 to December 2023.InterventionMifepristone, 200 mg, and misoprostol, 800 µg, prescribed to a mail-order pharmacy and mailed to participants instead of dispensed in person.Main outcomes and measuresProportion of patients with a complete abortion with medications only, reporting satisfaction with the medication abortion, and reporting timely delivery of medications.ResultsClinical outcome information was obtained and analyzed for 510 abortions (96.2%) among 506 participants (median [IQR] age, 27 [23-31] years; 506 [100%] female; 194 [38.3%] Black, 88 [17.4%] Hispanic, 141 [27.9%] White, and 45 [8.9%] multiracial/other individuals). Of these, 436 participants (85.5%; 95% CI, 82.2%-88.4%) received medications within 3 days. Complete abortion occurred after medication use in 499 cases (97.8%; 95% CI, 96.2%-98.9%). There were 24 adverse events (4.7%) for which care was sought for medication abortion symptoms; 3 patients (0.6%; 95% CI, 0.1%-1.7%) experienced serious adverse events requiring hospitalization (1 with blood transfusion); however, no adverse events were associated with mail-order dispensing. Of 477 participants, 431 (90.4%; 95% CI, 87.3%-92.9%) indicated that they would use mail-order dispensing again for abortion care, and 435 participants (91.2%; 95% CI, 88.3%-93.6%) reported satisfaction with the medication abortion. Findings were similar to those of other published studies of medication abortion with in-person dispensing.Conclusions and relevanceThe findings of this cohort study indicate that mail-order pharmacy dispensing of mifepristone for medication abortion was effective, acceptable to patients, and feasible, with a low prevalence of serious adverse events. This care model should be expanded to improve access to medication abortion services

Standardizing abortion research outcomes (STAR): Results from an international consensus development study.

ObjectiveTo develop a minimum data set, known as a core outcome set, for future abortion randomized controlled trials.Study designWe extracted outcomes from quantitative and qualitative systematic reviews of abortion studies to assess using a modified Delphi method. Via email, we invited researchers, clinicians, patients, and healthcare organization representatives with expertise in abortion to rate the importance of the outcomes on a 9-point Likert scale. After 2 rounds, we used descriptive analyses to determine which outcomes met the predefined consensus criteria. We finalized the core outcome set during a series of consensus development meetings.ResultsWe entered 42 outcomes, organized in 15 domains, into the Delphi survey. Two-hundred eighteen of 251 invitees (87%) provided responses (203 complete responses) for round 1 and 118 of 218 (42%) completed round2. Sixteen experts participated in the development meetings. The final outcome set includes 15 outcomes: 10 outcomes apply to all abortion trials (successful abortion, ongoing pregnancy, death, hemorrhage, uterine infection, hospitalization, surgical intervention, pain, gastrointestinal symptoms, and patients' experience of abortion); 2 outcomes apply to only surgical abortion trials (uterine perforation and cervical injury), one applies only to medical abortion trials (uterine rupture); and 2 apply to trials evaluating abortions with anesthesia (over-sedation/respiratory depression and local anesthetic systemic toxicity).ConclusionUsing robust consensus science methods we have developed a core outcome set for future abortion research.ImplicationsStandardized outcomes in abortion research could decrease heterogeneity among trials and improve the quality of systematic reviews and clinical guidelines. Researchers should select, collect, and report these core outcomes in future abortion trials. Journal editors should advocate for core outcome set reporting