Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

BACKGROUND: Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. METHODS: We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. RESULTS: Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038). CONCLUSIONS: In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility

The At Home/Chez Soi trial protocol: a pragmatic, multi-site, randomised controlled trial of a Housing First intervention for homeless individuals with mental illness in five Canadian cities

This article was published in BMJ Open following peer review and can also be viewed on the journal’s website at http://bmjopen.bmj.comIntroduction: Housing First is a complex housing and support intervention for homeless individuals with mental health problems. It has a sufficient knowledge base and interest to warrant a test of wide-scale implementation in various settings. This protocol describes the quantitative design of a Canadian five city, $110 million demonstration project and provides the rationale for key scientific decisions. Methods: A pragmatic, mixed methods, multi-site field trial of the effectiveness of Housing First in Vancouver, Winnipeg, Toronto, Montreal and Moncton, is randomising approximately 2500 participants, stratified by high and moderate need levels, into intervention and treatment as usual groups. Quantitative outcome measures are being collected over a 2-year period and a qualitative process evaluation is being completed. Primary outcomes are housing stability, social functioning and, for the economic analyses, quality of life. Hierarchical linear modelling is the primary data analytic strategy. Ethics and dissemination: Research ethics board approval has been obtained from 11 institutions and a safety and adverse events committee is in place. The results of the multi-site analyses of outcomes at 12 months and 2 years will be reported in a series of core scientific journal papers. Extensive knowledge exchange activities with non-academic audiences will occur throughout the duration of the project.This work was supported by a contract from Health Canada administrated by the Mental Health Commission of Canada

Factor structure and construct validity of the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer)

Background: The ASCOT-Carer is a self-report instrument designed to measure social care-related quality of life (SCRQoL). This article presents the psychometric testing and validation of the ASCOT-Carer four response-level interview (INT4) in a sample of unpaid carers of adults who receive publicly-funded social care services in England. Methods: Unpaid carers were identified through a survey of users of publicly-funded social care services in England. 387 carers completed a face-to-face or telephone interview. Data on variables hypothesised to be related to SCRQoL (for example, characteristics of the carer, cared-for person and care situation) and measures of carer experience, strain, health-related quality of life and overall QoL were collected. Relationships between these variables and overall SCRQoL score were evaluated through correlation, ANOVA and regression analysis to test the construct validity of the scale. Internal reliability was assessed using Cronbach’s alpha and feasibility by the number of missing responses. Results: The construct validity was supported by statistically significant relationships between SCRQoL and scores on instruments of related constructs, as well as with characteristics of the carer and care recipient in univariate and multivariate analyses. A Cronbach’s alpha of 0.87 (7 items) indicates that the internal reliability of the instrument is satisfactory and a low number of missing responses (<1%) indicates a high level of acceptance. Conclusions: The results provide evidence to support the construct validity, factor structure, internal reliability and feasibility of the ASCOT-Carer INT4 as an instrument for measuring social care-related quality of life of unpaid carers who care for adults with a variety of long-term conditions, disability or problems related to old age

Prevalence and definition of drooling in Parkinson’s disease: a systematic review

Drooling (saliva loss) is a frequently reported symptom in patients with Parkinson’s disease (PD), but an accurate estimate of the prevalence of drooling is lacking. The aim of this study was to systematically review the prevalence of drooling in published research papers. A systematic PubMed and CINAHL search was done, including studies published until January 2009. Eight studies were found, presenting prevalence rates of drooling based on responses of PD patients to questionnaires. The statistical heterogeneity was highly significant (P < 0.0001), with prevalence rates ranging from 32 to 74%. The pooled prevalence estimate with random effect analysis was of 56% (95% CI 44–67) for PD patients and 14% (95% CI 3–25) for healthy controls; the pooled relative risk (RR) with random effect analysis was 5.5 (95% CI 2.1–14.4). All studies reported data of community dwelling idiopathic PD patients, with a mean age around 65 years and mild PD in 50–60% of the cases. Heterogeneity was mainly caused by differences in definition or frequency of drooling. The highest prevalence rates included nocturnal drooling where others noted only diurnal drooling. Analysis of the data of two studies showed that drooling is reported frequently by 22–26% of the patients. Prevalence rates were lower in milder PD patients. The summarized findings demonstrate that drooling can be present in half of all PD patients. In about a quarter of PD patients, drooling appears to be a frequently occurring problem. We recommend to report drooling in future studies with more detailed consideration of severity, frequency and nocturnal versus diurnal complaints

Hip disability and osteoarthritis outcome score (HOOS) – validity and responsiveness in total hip replacement

BACKGROUND: The aim of the study was to evaluate if physical functions usually associated with a younger population were of importance for an older population, and to construct an outcome measure for hip osteoarthritis with improved responsiveness compared to the Western Ontario McMaster osteoarthritis score (WOMAC LK 3.0). METHODS: A 40 item questionnaire (hip disability and osteoarthritis outcome score, HOOS) was constructed to assess patient-relevant outcomes in five separate subscales (pain, symptoms, activity of daily living, sport and recreation function and hip related quality of life). The HOOS contains all WOMAC LK 3.0 questions in unchanged form. The HOOS was distributed to 90 patients with primary hip osteoarthritis (mean age 71.5, range 49–85, 41 females) assigned for total hip replacement for osteoarthritis preoperatively and at six months follow-up. RESULTS: The HOOS met set criteria of validity and responsiveness. It was more responsive than WOMAC regarding the subscales pain (SRM 2.11 vs. 1.83) and other symptoms (SRM 1.83 vs. 1.28). The responsiveness (SRM) for the two added subscales sport and recreation and quality of life were 1.29 and 1.65, respectively. Patients ≤ 66 years of age (range 49–66) reported higher responsiveness in all five subscales than patients >66 years of age (range 67–85) (Pain SRM 2.60 vs. 1.97, other symptoms SRM 3.0 vs. 1.60, activity of daily living SRM 2.51 vs. 1.52, sport and recreation function SRM 1.53 vs. 1.21 and hip related quality of life SRM 1.95 vs. 1.57). CONCLUSION: The HOOS 2.0 appears to be useful for the evaluation of patient-relevant outcome after THR and is more responsive than the WOMAC LK 3.0. The added subscales sport and recreation function and hip related quality of life were highly responsive for this group of patients, with the responsiveness being highest for those younger than 66

A prosodically controlled word and nonword repetition task for 2- to 4- year-olds: Evidence from typically developing children

An association has been found between nonword repetition and language skills in school-aged children with both typical and atypical language development (Dollaghan & Campbell, 1998; Ellis Weismer et al., 2000; Gathercole & Baddeley, 1990; Montgomery, 2002). This raises the possibility that younger children’s repetition performance may be predictive of later language deficits. In order to investigate this possibility, it is important to establish that elicited repetition with very young children is both feasible and informative. To this end, a repetition task was designed and carried out with 66 children aged 2-4. The task consisted of 18 words and 18 matched nonwords that were systematically manipulated for length and prosodic structure. In addition, an assessment of receptive vocabulary was administered. The repetition task elicited high levels of response. Total scores as well as word and nonword scores were sensitive to age. Lexical status and item length affected performance regardless of age: words were repeated more accurately than nonwords, and one-syllable items were repeated more accurately than two-syllable items, which were in turn repeated more accurately than three-syllable items. The effect of prosodic structure was also significant. Whole syllable errors were almost exclusive to unstressed syllables, with those preceding stress being most vulnerable. Performance on the repetition task was significantly correlated with performance on the receptive vocabulary test. Since this repetition task was effective in eliciting responses from most of the 2 to 4-year-old participants, tapped developmental change in their repetition skills, and revealed patterns in their performance, it has the potential to identify deficits in very early repetition skills that may be indicative of wider language difficulties

The Norwich Patellar Instability Score:validity, internal consistency and responsiveness for people conservatively-managed following first-time patellar dislocation

Background: This paper assessed the validity, internal consistency, responsiveness and floor-ceiling effects of the Norwich Patellar Instability (NPI) Score for a cohort of conservatively managed people following first-time patellar dislocation (FTPD).  Methods: Fifty patients were recruited, providing 130 completed datasets over 12 months. The NPI Score, Lysholm Knee Score, Tegner Level of Activity Score and isometric knee extension strength were assessed at baseline, six weeks, six and 12 months post-injury.  Results: There was high convergent validity with a statistically significant correlation between the NPI Score and the Lysholm Knee Score (p < 0.001), Tegner Level of Activity Score (p < 0.001) and isometric knee extension strength (p < 0.002). Principal component analysis revealed that the NPI Score demonstrated good concurrent validity with four components account for 70.4% of the variability. Whilst the NPI Score demonstrated a flooring-effect for 13 of the 19 items, no ceiling effect was reported. There was high internal consistency with a Cronbach Alpha value of 0.93 (95% CI: 0.91 to 0.93). The NPI Score was responsive to change over the 12 months period with an effect size of 1.04 from baseline to 12 months post-injury.  Conclusions: The NPI Score is a valid tool to assess patellar instability symptoms in people conservatively managed following FTPD.  Level of evidence: Level I

Construct-level predictive validity of educational attainment and intellectual aptitude tests in medical student selection: meta-regression of six UK longitudinal studies

Background: Measures used for medical student selection should predict future performance during training. A problem for any selection study is that predictor-outcome correlations are known only in those who have been selected, whereas selectors need to know how measures would predict in the entire pool of applicants. That problem of interpretation can be solved by calculating construct-level predictive validity, an estimate of true predictor-outcome correlation across the range of applicant abilities. Methods: Construct-level predictive validities were calculated in six cohort studies of medical student selection and training (student entry, 1972 to 2009) for a range of predictors, including A-levels, General Certificates of Secondary Education (GCSEs)/O-levels, and aptitude tests (AH5 and UK Clinical Aptitude Test (UKCAT)). Outcomes included undergraduate basic medical science and finals assessments, as well as postgraduate measures of Membership of the Royal Colleges of Physicians of the United Kingdom (MRCP(UK)) performance and entry in the Specialist Register. Construct-level predictive validity was calculated with the method of Hunter, Schmidt and Le (2006), adapted to correct for right-censorship of examination results due to grade inflation. Results: Meta-regression analyzed 57 separate predictor-outcome correlations (POCs) and construct-level predictive validities (CLPVs). Mean CLPVs are substantially higher (.450) than mean POCs (.171). Mean CLPVs for first-year examinations, were high for A-levels (.809; CI: .501 to .935), and lower for GCSEs/O-levels (.332; CI: .024 to .583) and UKCAT (mean = .245; CI: .207 to .276). A-levels had higher CLPVs for all undergraduate and postgraduate assessments than did GCSEs/O-levels and intellectual aptitude tests. CLPVs of educational attainment measures decline somewhat during training, but continue to predict postgraduate performance. Intellectual aptitude tests have lower CLPVs than A-levels or GCSEs/O-levels. Conclusions: Educational attainment has strong CLPVs for undergraduate and postgraduate performance, accounting for perhaps 65% of true variance in first year performance. Such CLPVs justify the use of educational attainment measure in selection, but also raise a key theoretical question concerning the remaining 35% of variance (and measurement error, range restriction and right-censorship have been taken into account). Just as in astrophysics, ‘dark matter’ and ‘dark energy’ are posited to balance various theoretical equations, so medical student selection must also have its ‘dark variance’, whose nature is not yet properly characterized, but explains a third of the variation in performance during training. Some variance probably relates to factors which are unpredictable at selection, such as illness or other life events, but some is probably also associated with factors such as personality, motivation or study skills

A comparison of the measurement properties of the Juvenile Arthritis Functional Assessment Scale with the childhood health assessment questionnaire in daily practice

We compared the measurement properties of a performance test (Juvenile Arthritis Functional Assessment Scale; JAFAS) with a questionnaire-based instrument (Childhood Health Assessment Questionnaire; CHAQ) to measure functional ability in patients with juvenile idiopathic arthritis on the level of individual items. In 28 consecutive children visiting an outpatient paediatrics clinic, the JAFAS (range 0–20) and CHAQ (range 0–3) were applied, and measures of disease activity and joint range of motion (ROM) were determined. Twenty-eight children with a median age of 10 years and median disease duration of 3.2 years were included. The median JAFAS score was 0, and the median CHAQ score was 0.125. Cronbach’s alpha was 0.92 for the JAFAS and 0.96 for the CHAQ. The Spearman correlation coefficient between the JAFAS and the CHAQ was 0.55 (P < 0.01). With six out of ten items, the JAFAS classified the child as less disabled than with corresponding CHAQ activities. Overall, associations with measures of disease activity and ROM were higher for the CHAQ than for the JAFAS. A performance test (JAFAS) does not appear to have an added benefit over the questionnaire-based assessment (CHAQ) of physical function in a cross-sectional study