The nature and frequency of genital injuries sustained by female rape victims in Johannesburg

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Science in Emergency Medicine. MScMed (Emergency Medicine) Johannesburg, November 2013Background: Little research has addressed the types and meaning of genital injury in South African rape victims. In South Africa, rape victims in private practice are examined using gross visualisation and a light source only. Research has shown that the use of toluidine blue and/ or a colposcope increases the number of injuries seen. Objective: To determine rape victim demographics and describe the genital injuries and other associated injuries reported during medico-legal examination of female rape victims older than 15 in four private Johannesburg hospitals between 1 January 2008 and 31 December 2009, as well as to determine any associations between these variables and the race or age of the victim. Method: A retrospective chart review of 310 sexual assault victims seen at these hospitals. Results: Black victims made up 62% of the study. One genital injury was recorded for 27% of the victims, while 21% had between 2 and 8 of a possible 11 injuries. The most commonly injured sites were the posterior fourchette, the hymen and the fossa navicularis. Bruising was the most common associated injury. Alcohol was reported in just fewer than 10% of cases. Conclusion: The incidence of positive genital injury documented is comparable to other research. Genital injuries are not inevitable consequences of sexual assault

Patient perceptions and expectations regarding imaging for metastatic disease in early stage breast cancer

Abstract Purpose The probability of detecting radiologically evident metastatic disease in asymptomatic women with newly diagnosed operable breast cancer is low. Despite the recommendations of most practice guidelines imaging is still frequently performed. Relatively little is known about what patients believe is important when it comes to radiologic staging. Methods Patients with early stage breast cancer who had completed their definitive breast surgery were surveyed about their personal experiences, perceptions, and expectations on the issue of perioperative imaging for distant metastatic disease. Results Over a 3 month period, 245 women with primary operable breast cancer completed the questionnaire (87.0% response rate) and 80.8% indicated having had at least one imaging test for distant metastatic disease. These were either of the thorax (72.2%), abdomen (55.9%) or skeleton (65.3%) with a total of 701 imaging tests (average of 3.5 tests per patient imaged) performed. Overall, 57.1% indicated that they would want imaging done if the chance of detecting metastases was ≤10%. Although 80.0% of patients indicated that, “doing whatever their doctor recommended” was important to them, 70.4% also noted that they would be uncomfortable if their physician did not order imaging, even if this was in keeping with practice guidelines. Conclusions Most patients with early stage breast cancer recall having imaging tests for distant metastases. Given the choice, most would prefer having imaging performed, even if this is not in line with current guidelines. If patient expectations are, in part, driving excessive imaging, new strategies addressing this are required

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Clinical practice guidelines and consensus statements in oncology--an assessment of their methodological quality.

Consensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine's standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine's standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.Thirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored consistently lower than the others over both domains. No journals adhered to all the items related to the transparency of document development. One journal's consensus statements endorsed a product made by the sponsoring pharmaceutical company in 64% of cases.Guidance documents are an essential part of oncology care and should be subjected to a rigorous and validated development process. Consensus statements had lower methodological quality than clinical practice guidelines using AGREE II. At a minimum, journals should ensure that that all consensus statements and clinical practice guidelines adhere to AGREE II criteria. Journals should consider explicitly requiring guidelines to declare pharmaceutical company sponsorship and to identify the sponsor's product to enhance transparency

Range and 95% confidence intervals for Rigour of development scores.

<p>CO = Current Oncology. EJC = European Journal of Cancer<b>.</b> CS = Consensus statements. JCO = Journal of Clinical Oncology<b>.</b> CPG = Clinical practice guidelines.</p

Range and 95% confidence intervals for Editorial independence scores.

<p>CO = Current Oncology. EJC = European Journal of Cancer. CS = Consensus statements. JCO = Journal of Clinical Oncology. CPG = Clinical practice guidelines.</p