Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance.

PURPOSE: Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers. MATERIALS AND METHODS: Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort. RESULTS: PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001). CONCLUSIONS: Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.

Increased targeted HIV testing and reduced undiagnosed HIV infections among gay and bisexual men.

OBJECTIVES: To evaluate the impact of government HIV strategies that aimed to increase HIV testing uptake and frequency among gay and bisexual men (GBM) in New South Wales (NSW), Australia. DESIGN: We analysed HIV testing data from existing passive and sentinel surveillance systems between 2010 and 2018. METHODS: Six indicators were measured: (1) state-wide total HIV laboratory tests; (2) number of GBM attending publicly-funded clinics; (3) 12-monthly testing uptake; (4) annual testing frequency; (5) HIV testing with a STI diagnosis; and (6) HIV positivity. Mathematical modelling was used to estimate (7) the proportion of men with undiagnosed HIV. Indicators were stratified by Australian vs. overseas-born. RESULTS: Overall, 43,560 GBM attended participating clinics (22,662 Australian-born, 20,834 overseas-born) from 2010-2018. Attendees increased from 5,186 in 2010 to 16,507 in 2018. There were increasing trends (p<0.001 for all) in testing uptake (83.9% to 95.1%); testing with a STI diagnosis (68.7% to 94.0%); annual HIV testing frequency (1.4 to 2.7); and a decreasing trend (p<0.01) in HIV positivity (1.7% to 0.9%).Increases in testing were similar in Australian-born and overseas-born GBM. However, there were decreasing trends in the estimated undiagnosed HIV proportion overall (9.5% to 7.7%) and in Australian-born GBM (7.1% to 2.8%), but an increasing trend in overseas-born GBM (15.3% to 16.9%) (p<0.001 for all).

Proficiency panel testing--a reliable tool in external quality assessment of sputum smear microscopy services in Gujarat, India.

OBJECTIVE: To assess the proficiency of Senior TB Laboratory Supervisors (STLSs) and district level Laboratory Technicians (LTs) in sputum smear microscopy. METHOD: Intermediate Reference Laboratory (IRL), Ahmedabad had manufactured and validated Proficiency Panel Testing slides from sputum samples, made On Site Evaluation (OSE) visits of District TB Centres (DTCs) in two rounds, and conducted Proficiency Panel Testing of STLSs & DTC-LTs from January 2005 to June 2009. RESULTS: High level of concordance in Z-N smear grading was found between Microbiologist and district laboratory staff. DTC readers reported overall consistency level of more than 98% in Z-N grade agreement during both the IRL, EQA, OSE visits. The tendency to over-grade the panel slides was much higher (more than 22%) as compared to under-grade (less than 2%) them in "correct slides". High False Positive (HFP) error was not observed in the present study. CONCLUSION: Laboratory supervisor's proficiency can be quickly assessed by Proficiency Panel Testing, under multi-level quality assurance network system of sputum smear microscopy in public health programmes like the RNTCP. Proficiency Panel Testing is highly replicable and reproducible tool for quick and reliable assessment of proficiency of the staff and it can be made more effective by raising the proportion of lower grade positive slides in panel set of each reader. DTC readers' overall agreement level of more than 98% in Z-N grade suggests high level of precision and excellent consistency during both the IRL, EQA, OSE rounds. It is concluded that even for a large network of sputum smear microscopy centres under public health programmes like the RNTCP in order to take corrective action, Proficiency Panel Testing can be effectively used for quick identification of suboptimal- technical performance of the supervisory staff.

Prevalence of speech and language disorders in 5-year-old kindergarten children in the Ottawa-Carleton region.

A representative sample of 5-year-old kindergarten children was assessed for speech and/or language disorder. Of the 1,655 children tested, 180 were identified as having speech or language impairment. It is estimated that within the total reference population, between 16.2% and 21.8% would show some impairment; for the boys, the rate would be 15.5% to 20.7% and for the girls, between 19.1% and 25.1%. Most of these children would show some language impairment as opposed to speech problems only. Approximately 36% of the identified boys and 30% of the girls would have speech problems only, the remainder having speech and language problems or language problems only. Followup studies of these children are needed to ascertain their outcome and language status in middle childhood.