An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

sj-docx-1-hej-10.1177_00178969241228945 – Supplemental material for Engage, educate, escape: The New Jersey Department of Health Project Firstline Escape Room

Supplemental material, sj-docx-1-hej-10.1177_00178969241228945 for Engage, educate, escape: The New Jersey Department of Health Project Firstline Escape Room by Kelly McLaughlin, Jasmine Davis, Miriam Gonzales, Celina Koh, Laura Taylor and Tara L Crowell in Health Education Journal</p

Discovery of PSR J0523-7125 as a Circularly Polarized Variable Radio Source in the Large Magellanic Cloud

We report the discovery of a highly circularly polarized, variable, steep-spectrum pulsar in the Australian Square Kilometre Array Pathfinder (ASKAP) Variables and Slow Transients (VAST) survey. The pulsar is located about $1^\circ$ from the center of the Large Magellanic Cloud, and has a significant fractional circular polarization of $\sim$20%. We discovered pulsations with a period of 322.5 ms, dispersion measure (DM) of 157.5 pc cm$^{-3}$, and rotation measure (RM) of $+456$ rad m$^{-2}$ using observations from the MeerKAT and the Parkes telescopes. This DM firmly places the source, PSR J0523$-$7125, in the Large Magellanic Cloud (LMC). This RM is extreme compared to other pulsars in the LMC (more than twice that of the largest previously reported one). The average flux density of $\sim$1 mJy at 1400 MHz and $\sim$25 mJy at 400 MHz places it among the most luminous radio pulsars known. It likely evaded previous discovery because of its very steep radio spectrum (spectral index $\alpha \approx -3$, where $S_\nu \propto \nu^\alpha$) and broad pulse profile (duty cycle $\gtrsim35$%). We discuss implications for searches for unusual radio sources in continuum images, as well as extragalactic pulsars in the Magellanic Clouds and beyond. Our result highlighted the possibility of identifying pulsars, especially extreme pulsars, from radio continuum images. Future large-scale radio surveys will give us an unprecedented opportunity to discover more pulsars and potentially the most distant pulsars beyond the Magellanic Clouds.Comment: 17 pages, 7 figures; accepted by Ap