Chris Stinton

Mental Health Problems in Adults With Williams Syndrome

Although many researchers have investigated emotional and behavioral difficulties in individuals with Williams syndrome, few have used standardized diagnostic assessments. We examined mental health problems in 92 adults with Williams syndrome using the Psychiatric Assessment Schedule for Adults with Developmental Disabilities-PAS-ADD (Moss, Goldberg, et al., 1996). Factors potentially associated with mental health problems were also explored. The PAS-ADD identified mental health problems in 24% of the sample. The most common were anxiety (16.5%) and specific phobias (12%). Other diagnoses included depression, agoraphobia, and social phobia. No association was found between the presence of mental health problems and either individual (e.g., age, IQ, language level) or external (life events) variables.

Health and social outcomes in adults with Williams syndrome: findings from cross-sectional and longitudinal cohorts

Previous studies have investigated trajectories of cognitive, language and adaptive functioning in Williams syndrome (WS) but little is known about how other aspects of the Williams syndrome behavioural phenotype change across the life-span. Therefore, the present study examined age associated changes in a number of different domains of functioning in adults with WS. Semi-structured interviews and standardized assessments of physical health, educational and occupational levels, self-care and independence, social interactions, and behavioural difficulties were conducted with adults with WS and their parents/carers. Ninety-two individuals with genetic confirmation of WS (50 males, 42 females) participated in a cross-sectional study (age range 19-55 years; mean 32 years) and 43 individuals (21 males, 22 females) were involved in a longitudinal study as they had taken part in a previous study of adults with WS. Not all individuals in the longitudinal cohort had genetically confirmed WS. Cross-sectional analyses revealed no age related differences in the areas of functioning investigated. However, in the longitudinal sample, significant improvements were reported in physical health, self-care and occupational skills. Social skills and adaptive behaviours had generally improved while behavioural difficulties had declined. In both cross-sectional and longitudinal cohorts there were significant correlations between adaptive functioning and IQ. These findings are consistent in indicating no age related decline in social or adaptive functioning in adults with WS, at least up to the age of 50-55 years.

Mental Rotation in Williams Syndrome: An Impaired Ability

Typically developing young children and individuals with intellectual disabilities often perform poorly on mental rotation tasks when the stimulus they are rotating lacks a salient component. However, performance can be improved when salience is increased. The present study investigated the effect of salience on mental rotation performance by individuals with Williams syndrome. Individuals with Williams syndrome and matched controls were presented with two versions of a mental rotation task: a no salient component condition and a salient component condition. The results showed that component salience did not benefit individuals with Williams syndrome in the same manner as it did controls.

Adverse events in women and children who have received intrapartum antibiotic prophylaxis treatment : a systematic review.

BackgroundAdverse events from intrapartum antibiotic prophylaxis (IAP) are poorly documented yet essential to inform clinical practice for neonatal group B Streptococcus (GBS) disease prevention. In this systematic review, we appraised and synthesised the evidence on the adverse events of IAP in the mother and/or her child.MethodsWe searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane, and Science Citation Index from date of inception until October 16th 2016. Reference lists of included studies and relevant systematic reviews were hand-searched. We included primary studies in English that reported any adverse events from intrapartum antibiotics for any prophylactic purpose compared to controls. The search was not restricted to prophylaxis for GBS but excluded women with symptoms of infection or undergoing caesarean section. Two reviewers assessed the methodological quality of studies, using the Cochrane Risk of Bias tool, and the Risk of Bias Assessment Tool for Nonrandomised Studies. Results were synthesised narratively and displayed in text and tables.ResultsFrom 2364 unique records, 30 studies were included. Despite a wide range of adverse events reported in 17 observational studies and 13 randomised controlled trials (RCTs), the evidence was inconsistent and at high risk of bias. Only one RCT investigated the long-term effects of IAP reporting potentially serious outcomes such as cerebral palsy; however, it had limited applicability and unclear biological plausibility. Seven observational studies showed that IAP for maternal GBS colonisation alters the infant microbiome. However, study populations were not followed through to clinical outcomes, therefore clinical significance is unknown. There was also observational evidence for increased antimicrobial resistance, however studies were at high or unclear risk of bias.ConclusionsThe evidence base to determine the frequency of adverse events from intrapartum antibiotic prophylaxis for neonatal GBS disease prevention is limited. As RCTs may not be possible, large, better quality, and longitudinal observational studies across countries with widespread IAP could fill this gap.Trial registrationCRD42016037195.

Newborn screening for Tyrosinemia type 1 using succinylacetone – a systematic review of test accuracy

BackgroundTyrosinemia type 1 is an autosomal recessive disorder of amino acid metabolism. Without treatment, death in childhood is common. Treatment with nitisinone and dietary restrictions are associated with improved outcomes; some studies suggest better outcomes when treatment begins at an asymptomatic stage. Newborn screening allows for earlier identification, but there is uncertainty regarding the test accuracy of the current method: succinylacetone measurement in dried blood spots using tandem mass spectrometry.MethodsWe conducted a systematic review of literature published up to January 2016. Two reviewers independently assessed titles, abstracts, full texts, and conducted quality appraisals. A single reviewer extracted data, which was checked by a second reviewer.ResultsTen studies provided test accuracy data: five studies reporting screening experiences and five case–control studies. Sensitivity (29 cases in total) and specificity (34,403 controls in total) were 100% in the case–control studies, but could not be calculated in the studies reporting screening experiences due to a lack of follow-up of screen-negative babies. Positive predictive values in the screening experience studies ranged from 66.7% (2 true positive cases, 1 false positive case from ~500,000 people screened) to 100% (8 true positive cases from 856,671 people screened); negative predictive values could not be calculated. Positive and negative predictive values cannot be calculated from case–control studies.ConclusionsScreening for Tyrosinemia type 1 using tandem mass spectrometry measurement of succinylacetone from dried blood spots appears to be promising. Confirmation of test accuracy data should be obtained from studies that include a two-year follow-up of individuals who screen negative.

Association between use of systematic reviews and national policy recommendations on screening newborn babies for rare diseases: systematic review and meta-analysis

Abstract Objective To understand whether international differences in recommendations of whether to screen for rare diseases using the newborn blood spot test might in part be explained by use of systematic review methods. Design Systematic review and meta-analysis. Data sources Website searches of 26 national screening organisations. Eligibility criteria for study selection Journal articles, papers, legal documents, presentations, conference abstracts, or reports relating to a national recommendation on whether to screen for any condition using the newborn blood spot test, with no restrictions on date or language. Data extraction Two reviewers independently assessed whether the recommendation for or against screening included systematic reviews, and data on test accuracy, benefits of early detection, and potential harms of overdiagnosis. Analysis The odds of recommending screening according to the use of systematic review methods was estimated across conditions using meta-analysis. Results 93 reports were included that assessed 104 conditions across 14 countries, totalling 276 recommendations (units of analysis). Screening was favoured in 159 (58%) recommendations, not favoured in 98 (36%), and not recommended either way in 19 (7%). Only 60 (22%) of the recommendations included a systematic review. Use of a systematic review was associated with a reduced probability of screening being recommended (23/60 (38%) v 136/216 (63%), odds ratio 0.17, 95% confidence interval 0.07 to 0.43). Of the recommendations, evidence for test accuracy, benefits of early detection, and overdiagnosis was not considered in 115 (42%), 83 (30%), and 211 (76%), respectively. Conclusions Using systematic review methods is associated with a reduced probability of screening being recommended. Many national policy reviews of screening for rare conditions using the newborn blood spot test do not assess the evidence on the key benefits and harms of screening.

Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model

Background:The faecal immunochemical test (FIT) is replacing the guaiac faecal occult blood test in colorectal cancer screening. Increased uptake and FIT positivity will challenge colonoscopy services. We developed a risk prediction model combining routine screening data with FIT concentration to improve the accuracy of screening referrals.Methods:Multivariate analysis used complete cases of those with a positive FIT (⩾20 μg g−1) and diagnostic outcome (n=1810; 549 cancers and advanced adenomas). Logistic regression was used to develop a risk prediction model using the FIT result and screening data: age, sex and previous screening history. The model was developed further using a feedforward neural network. Model performance was assessed by discrimination and calibration, and test accuracy was investigated using clinical sensitivity, specificity and receiver operating characteristic curves.Results:Discrimination improved from 0.628 with just FIT to 0.659 with the risk-adjusted model (P=0.01). Calibration using the Hosmer–Lemeshow test was 0.90 for the risk-adjusted model. The sensitivity improved from 30.78% to 33.15% at similar specificity (FIT threshold of 160 μg g−1). The neural network further improved model performance and test accuracy.Conclusions:Combining routinely available risk predictors with the FIT improves the clinical sensitivity of the FIT with an increase in the diagnostic yield of high-risk adenomas.

Double Reading in Breast Cancer Screening: Cohort Evaluation in the CO-OPS Trial

Purpose To investigate the effect of double readings by a second radiologist on recall rates, cancer detection, and characteristics of cancers detected in the National Health Service Breast Screening Program in England. Materials and Methods In this retrospective analysis, 805 206 women were evaluated through screening and diagnostic test results by extracting 1 year of routine data from 33 English breast screening centers. Centers used double reading of digital mammograms, with arbitration if there were discrepant interpretations. Information on reader decisions, with results of follow-up tests, were used to explore the effect of the second reader. The statistical tests used were the test for equality of proportions, the χ2 test for independence, and the t test. Results The first reader recalled 4.76% of women (38 295 of 805 206 women; 95% confidence interval [CI]: 4.71%, 4.80%). Two readers recalled 6.19% of women in total (49 857 of 805 206 women; 95% CI: 6.14%, 6.24%), but arbitration of discordant readings reduced the recall rate to 4.08% (32 863 of 805 206 women; 95% CI: 4.04%, 4.12%; P < .001). A total of 7055 cancers were detected, of which 627 (8.89%; 95% CI: 8.22%, 9.55%; P < .001) were detected by the second reader only. These additional cancers were more likely to be ductal carcinoma in situ (30.5% [183 of 600] vs 22.0% [1344 of 6114]; P < .001), and additional invasive cancers were smaller (mean size, 14.2 vs 16.7 mm; P < .001), had fewer involved nodes, and were likely to be lower grade. Conclusion Double reading with arbitration reduces recall and increases cancer detection compared with single reading. Cancers detected only by the second reader were smaller, of lower grade, and had less nodal involvement.

Bacterial load and molecular markers associated with early-onset Group B Streptococcus

Background: The natural history of neonatal group B Streptococcus (GBS) is poorly understood. Little is known about the bacterial factors influencing the transmission of GBS from mother to neonate, or the development of invasive early-onset GBS disease (EOGBS) in colonized neonates. We reviewed whether bacterial load and molecular markers are associated with GBS vertical transmission and progression to EOGBS. Methods: We searched Medline, Embase, Cochrane and Web of Science from inception to October 10, 2016, for observational studies in English. We also hand-searched reference lists of relevant publications and experts cross-checked included studies. Two reviewers independently screened studies, extracted data and appraised the quality of included studies using the Quality in Prognosis Studies tool. We conducted random-effects meta-analyses where possible and narratively synthesized the evidence in text and tables. Results: Seventeen studies were included from 1107 records retrieved from electronic databases and publication references. Meta-analyses of 3 studies showed that neonates colonized by serotype III had a higher risk of developing EOGBS than serotype Ia (pooled risk ratio: 1.51, 95% confidence interval: 1.12–2.03) and serotype II (risk ratio: 1.95, 95% confidence interval: 1.10–3.45). Eleven studies showed that in heavily colonized mothers, 2–3 times more neonates were colonized, and in heavily colonized neonates, up to 15 times more neonates had EOGBS, compared with light colonization. Most evidence was published before 2000 and was at risk of bias. Conclusions: Acknowledging the difficulty of natural history studies, well-controlled studies are needed to assess the predictive value of pathogen subtype and heavy load; they may be useful for better-targeted prevention.

Changing behavior and accuracy with time on task in mammography screening

Background: The vigilance decrement and prevalence effect both describe changes to speed and accuracy with time on task. Whilst there is much laboratory based research on these effects, little is known about whether they occur in real world mammography practice. Methods: The Changing Case Order to Optimise Patterns of Performance in Screening (CO-OPS) trial randomised 37,724 batches containing 1.2 million women attending breast screening to intervention or control (222,208 from the Midlands of England). In the control arm the batch was examined in the same order by both readers, in the intervention arm it was examined in a different order by both readers. Time taken, recall decision by both readers, and cancers detected were recorded for each case, and used to examine patterns of performance with time on task. Results: 49,575 women were recalled and 10,484 had cancer detected. Median time taken to examine each case was 35 seconds (out of cases where time taken was 10 minutes or less). The intervention did not affect overall cancer detection rates or recall rates. A more detailed analysis of the Midlands data indicates cancer detection rate did not change when reading up to 60 cases in a batch, but recall rate reduced. Time taken per case reduced with time on task, from a median 41 seconds when examining the second case in the batch to 28.5 seconds examining the 60th case. Conclusion: Reader behavior and performance systematically changes with time on task in breast screening.