Primary non-gonococcal urethritis

A study of the aetiology and diagnosis in males based on a series of 118 cases.There are two types of non -gonococcal urethritis, namely, primary and secondary.Primary non-gonococcal urethritis may be described as a urethritis arising independently of any gonococcal infection.Synonymous terms are primary non -gonorrhoeal urethritis, primary non -specific urethritis, urethritis simplex, idiopathic urethritis, and pseudo -gonorrhoea. The latter term is chiefly used .to describe the more acute cases of primary non - specific urethritis.Secondary non -gonococcal urethritis is a residual urethritis after the original infecting organism, the gonococcus, has apparently died out. This is a relatively frequent type as in the majority of cases of gonorrhoea, even within a few days of the appearance of the discharge, secondary organisms may be found in the purulent exudate. In 1930 the 'writer investigated a series of 155 cases of early acute gonorrhoea attending the Venereal Diseases Department of the Royal Infirmary, Edinburgh and cultured secondary organisms from the urethral pus of 130 patients (83.5 per cent). By far the commonest organism found was staphylococcus albus followed by diphtheroids, streptococci, staphylococcus aureus, and bacillus coli in that order of frequency.In the majority of cases, then, gonorrhoea is a ;mixed infection from the earliest stages of the -4- disease. A probable explanation of this phenomenon is that the organisms normally inhabiting, the anterior urethra become virulent, and as the disease spreads backwards to the posterior urethra these potential pathogens travel with it.Frequently secondary organisms gain a firm foothold in the damaged mucous membrane and may result in a continuance of the urethritis for a considerable period after the gonococci have been eliminated

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

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

Long-term monitoring of the Great Barrier Reef

H. Sweatman, S. Burgess, A. Cheal, G. Coleman, S. Delean, M. Emslie, I. Miller, K. Osborne and A. McDonald, A. Thompson.http://trove.nla.gov.au/work/3491122

Long-term monitoring of the Great Barrier Reef. 261p.

H. Sweatman, D. Abdo, S. Burgess, A. Cheal, G. Coleman, S. Delean, M. Emslie, I. Miller, K. Osborne, W. Oxley, C. Page and A. Thompsonhttp://trove.nla.gov.au/work/3491122