Hybrid proteins CFP10 and ESAT6. A path from developing a molecule to population screening for TB infection

AbstractEffective population screening for glaucoma would enable earlier diagnosis and prevention of irreversible vision loss. The UK National Screening Committee (NSC) recently published a review that examined the viability, effectiveness and appropriateness of a population-based screening programme for primary open-angle glaucoma (POAG). In our article, we summarise the results of the review and discuss some future directions that may enable effective population screening for glaucoma in the future. Two key questions were addressed by the UK NSC review; is there a valid, accurate screening test for POAG, and does evidence exist that screening reduces morbidity from POAG compared with standard care. Six new studies were identified since the previous 2015 review. The review concluded that screening for glaucoma in adults is not recommended because there is no clear evidence for a sufficiently accurate screening test or for better outcomes with screening compared to current care. The next UK NSC review is due to be conducted in 2023. One challenge for POAG screening is that the relatively low disease prevalence results in too many false-positive referrals, even with an accurate test. In the future, targeted screening of a population subset with a higher prevalence of glaucoma may be effective. Recent developments in POAG polygenic risk prediction and deep learning image analysis offer potential avenues to identifying glaucoma-enriched sub-populations. Until such time, opportunistic case finding through General Ophthalmic Services remains the primary route for identification of glaucoma in the UK and greater public awareness of the service would be of benefit.

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Quantitative Checklist for Autism in Toddlers (Q-CHAT). A population screening study with follow-up: the case for multiple time-point screening for autism

BMJ Paediatrics Open ◽

10.1136/bmjpo-2020-000700 ◽

2021 ◽

Vol 5 (1) ◽

pp. e000700

Author(s):

Carrie Allison ◽

Fiona E Matthews ◽

Liliana Ruta ◽

Greg Pasco ◽

Renee Soufer ◽

...

Keyword(s):

Phase 1 ◽

Autism Spectrum ◽

Population Screening ◽

Diagnostic Assessment ◽

Test Accuracy ◽

Multiple Time ◽

Phase 2 ◽

Time Points ◽

Screening Study

ObjectiveThis is a prospective population screening study for autism in toddlers aged 18–30 months old using the Quantitative Checklist for Autism in Toddlers (Q-CHAT), with follow-up at age 4.DesignObservational study.SettingLuton, Bedfordshire and Cambridgeshire in the UK.Participants13 070 toddlers registered on the Child Health Surveillance Database between March 2008 and April 2009, with follow-up at age 4; 3770 (29%) were screened for autism at 18–30 months using the Q-CHAT and the Childhood Autism Spectrum Test (CAST) at follow-up at age 4.InterventionsA stratified sample across the Q-CHAT score distribution was invited for diagnostic assessment (phase 1). The 4-year follow-up included the CAST and the Checklist for Referral (CFR). All with CAST ≥15, phase 1 diagnostic assessment or with developmental concerns on the CFR were invited for diagnostic assessment (phase 2). Standardised diagnostic assessment at both time-points was conducted to establish the test accuracy of the Q-CHAT.Main outcome measuresConsensus diagnostic outcome at phase 1 and phase 2.ResultsAt phase 1, 3770 Q-CHATs were returned (29% response) and 121 undertook diagnostic assessment, of whom 11 met the criteria for autism. All 11 screened positive on the Q-CHAT. The positive predictive value (PPV) at a cut-point of 39 was 17% (95% CI 8% to 31%). At phase 2, 2005 of 3472 CASTs and CFRs were returned (58% response). 159 underwent diagnostic assessment, including 82 assessed in phase 1. All children meeting the criteria for autism identified via the Q-CHAT at phase 1 also met the criteria at phase 2. The PPV was 28% (95% CI 15% to 46%) after phase 1 and phase 2.ConclusionsThe Q-CHAT can be used at 18–30 months to identify autism and enable accelerated referral for diagnostic assessment. The low PPV suggests that for every true positive there would, however, be ~4–5 false positives. At follow-up, new cases were identified, illustrating the need for continued surveillance and rescreening at multiple time-points using developmentally sensitive instruments. Not all children who later receive a diagnosis of autism are detectable during the toddler period.

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