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The purpose of the present work was to evaluate the use of resampling statistical methods for analysis of visual grading data—implemented in the software VGC Analyzer—by comparing the reanalyzed results from previously performed visual grading studies with the results calculated by gold standard receiver operating characteristic (ROC) methodology, Obuchowski-Rockette (OR)-Dorfman–Berbaum–Metz (DBM) multiple-readers and multiple-case (MRMC) and by analysis of simulated visual grading data where the true distribution was presumed to be known. The reanalysis was performed on two multiple-reader studies with non-paired data and paired data, respectively. The simulation study was performed by simulating a large number of visual grading characteristics (VGC) studies and by analyzing the statistical distribution of null hypothesis (H0) rejection rate. The comparison with OR-DBM MRMC showed good agreement when analyzing non-paired data for both fixed-reader and random-reader settings for the calculated area under the curve values and the confidence intervals (CIs). For paired data analysis, VGC Analyzer showed significantly lower CIs compared with the ROC software. This effect was also illustrated by the simulation study, where the VGC Analyzer, in general, showed good accuracy for simulated studies with stable statistical basis. For simulated studies with unstable statistics, the accuracy in the H0 rejection rate decreased. The present study has shown that resampling methodology can be used to accurately perform the statistical analysis of a VGC study, although the resampling technique used makes the method sensitive to small data sets.

Objectives To estimate the frequency, clinical approaches and risk factors of hypoadrenocorticism in dogs under UK primary veterinary care. Materials and methods Dogs diagnosed with hypoadrenocorticism were identified from the UK VetCompass™ programme by searching anonymised electronic patient records. Pre-existing and newly diagnosed cases of disease during 2016 were included. Cases were further sub-categorised as having a laboratory-confirmed or presumed diagnosis of hypoadrenocorticism based on the information recorded in the electronic patient records. Descriptive data were manually extracted. Multivariable logistic regression methods were used to identify demographic risk factors. Results There were 177 hypoadrenocorticism cases identified from 905,543 dogs in 2016; 72 laboratory-confirmed and 105 presumed. The 1-year period prevalence for hypoadrenocorticism in all dogs was 0.06% (95% confidence interval: 0.05-0.07%). The most common presenting clinical signs in laboratory-confirmed dogs were lethargy (51/66, 77.3%), anorexia (48/66, 66.7%) and vomiting (48/66, 66.7%). Hyperkalaemia was reported in 47 of 53 (88.7%), hyponatraemia in 46 of 53 (86.8%). Median sodium: potassium ratio was 19.00 (interquartile range: 16.20-20.60). Breed, age, neuter status and insurance status were associated with a laboratory-confirmed diagnosis of hypoadrenocorticism. No sex association with hypoadrenocorticism was observed in the multivariable model. The standard poodle had 51.38 times the odds (95% CI: 14.49-182.18) of hypoadrenocorticism compared with crossbreeds. The labradoodle and West Highland white terrier also had increased odds. Clinical significance This is the first epidemiological study to report on hypoadrenocorticism in dogs within the UK primary-care population. These results provide benchmark data of current veterinary activity relating to hypoadrenocorticism in primary-care practices.

Made available in DSpace on 2020-12-10T20:03:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Study Design. Cross-sectional study. Objective. To investigate the equivalence of electronic and paper version of self-report questionnaires for the assessment of disability, pain, fear of movement, depression, and physical activity of patients with chronic low back pain (LBP). Summary of Background Data. Paper and electronic versions of self-report questionnaires are commonly used for assessment of patients with LBP. However, the equivalence of self-report questionnaires commonly used for assessment of patients with chronic LBP remains unclear. Methods. Seventy-nine individuals with chronic LBP seeking physiotherapy care were recruited. Participants attended the clinic twice with an interval of 1 week and completed the self-reported questionnaires in a random order. The following questionnaires were administered: Roland Morris Disability Questionnaire (RMDQ); 11-point numerical rating scale (NRS); Tampa Scale for Kinesiophobia (TSK); Center for Epidemiological Studies-Depression (CES-D), and Baecke Habitual Physical Activity Questionnaire (BPAQ). To investigate the equivalence between the two questionnaire versions, intraclass correlation coefficient with 95% confidence interval and Bland-Altman plotting was used. Results. The paper and electronic versions of the RMDQ, TSK, and CES-D showed good reliability and the showed moderate reliability. In contrast, the NRS showed poor reliability between the electronic and paper versions. Conclusion. Our findings support that the electronic version of the RMDQ, TSK, CES-D, and BPAQ can be administered in clinical and research settings for assessment of patients with chronic LBP. Nevertheless, electronic version of the NRS for assessment of pain intensity should not be used interchangeably in clinical practice in patients with chronic LBP. Univ Estadual Paulista, Dept Fisioterapia, Fac Ciencias & Tecnol, Presidente Prudente, Brazil Univ Fed Minas Gerais UFMG, Dept Phys Therapy, Belo Horizonte, MG, Brazil Univ Estadual Paulista, Dept Educ Fis, Fac Ciencias & Tecnol, Presidente Prudente, Brazil Univ Estadual Paulista, Dept Fisioterapia, Fac Ciencias & Tecnol, Presidente Prudente, Brazil Univ Estadual Paulista, Dept Educ Fis, Fac Ciencias & Tecnol, Presidente Prudente, Brazil FAPESP: 2017/21336-8 FAPESP: 2016/03826-5 FAPESP: 2017/12246-5

Background The study tests the effects of data collection modes on patient responses associated with the multi-item measures such as Patient-Reported Outcomes Measurement System (PROMIS®), and single-item measures such as Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Numerical Rating Scale (NRS) measures. Methods Adult cancer patients were recruited from five cancer centers and administered measures of anxiety, depression, fatigue, sleep disturbance, pain intensity, pain interference, ability to participate in social roles and activities, global mental and physical health, and physical function. Patients were randomized to complete the measures on paper (595), interactive voice response (IVR, 596) system, or tablet computer (589). We evaluated differential item functioning (DIF) by method of data collection using the R software package, lordif. For constructs that showed no DIF, we concluded equivalence across modes if the equivalence margin, defined as ± 0.20 × pooled SD, completely surrounds 95% confidence intervals (CI's) for difference in mean score. If the 95% CI fell totally outside the equivalence margin, we concluded systematic score difference by modes. If the 95% CI partly overlaps the equivalence margin, we concluded neither equivalence nor difference. Results For all constructs, no DIF of any kind was found for the three modes. The scores on paper and tablet were more comparable than between IVR and other modes but none of the 95% CI’s were completely outside the equivalence margins, in which we established neither equivalence nor difference. Percentages of missing values were comparable for paper and tablet modes. Percentages of missing values were higher for IVR (2.3% to 6.5% depending on measures) compared to paper and tablet modes (0.7% to 3.3% depending on measures and modes), which was attributed to random technical difficulties experienced in some centers. Conclusion Across all mode comparisons, there were some measures with CI’s not completely contained within the margin of small effect. Two visual modes agreed more than visual-auditory pairs. IVR may induce differences in scores unrelated to constructs being measured in comparison with paper and tablet. The users of the surveys should consider using IVR only when paper and computer administration is not feasible.

OBJECTIVES/HYPOTHESIS The aim of the study was to investigate the healing rates, the restoration of hearing, and the time for complete healing of paper patching versus watchful waiting for traumatic tympanic membrane perforations (TTMPs). STUDY DESIGN Systematic review with meta analysis. METHODS Publications were selected by a search on "PubMed," "Embase," and "Web of Science." A meta-analysis of risk ratios for paper patching (intervention arm) and watchful waiting (control arm) was performed. RESULTS Five studies describing 393 TTMPs were included in the quantitative meta-analysis. TTMP healing rates ranged between 84.2% and 95.2% in the intervention arm and between 76.7% and 84.8% in the control arm. The pooled risk ratio of healed TTMPs was significantly higher in the intervention arm than in the control arm (risk ratio: 1.12, 95% confidence interval: 1.04-1.21). CONCLUSIONS TTMPs have high healing potential with and without intervention. The healing rate of paper patching was superior to that of watchful waiting alone. LEVEL OF EVIDENCE NA Laryngoscope, 131:2091-2097, 2021.

Purpose To study respiratory effects of exposure to soft paper dust exposure, a relationship that is rarely studied. Methods Soft tissue paper mill workers at a Swedish paper mill were investigated using a questionnaire and lung function and atopy screening. Spirometry without bronchodilation was performed with a dry wedge spirometer, and forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were obtained and expressed as percent predicted. Exposure to soft paper dust was assessed from historical stationary and personal measurements of total dust, in addition to historical information about the work, department, and production. The impact of high exposure to soft paper dust (> 5 mg/m3) vs. lower exposure ≤ 5 mg/m3, as well as cumulative exposure, was analyzed using multiple linear regression models. Multivariate models were adjusted for smoking, atopy, gender, and body mass index. Results One hundred ninety-eight current workers (124 male and 74 female) were included. There were significant associations between both cumulative exposure and years of high exposure to soft paper dust and impaired lung function. Each year of high exposure to soft paper dust was associated with a 0.87% decrease in FEV1 [95% confidence interval (CI) − 1.39 to − 0.35] and decreased FVC (− 0.54%, 95% CI − 1.00 to − 0.08) compared to the lower exposed workers. Conclusions The present study shows that occupational exposure to soft paper dust (years exceeding 5 mg/m3 total dust) is associated with lung function impairment and increased prevalence of obstructive lung function impairment.

Since our previous publication of organ dose for the pediatric CT cohort in the UK, there have been questions about the magnitude of uncertainty in our dose estimates. We therefore quantified shared and unshared uncertainties in empirical CT parameters extracted from 1073 CT films (1978–2008) from 36 hospitals in the study and propagated these uncertainties into organ doses using Monte Carlo random sampling and NCICT organ dose calculator. The average of 500 median brain and marrow doses for the full cohort was 35 (95% confidence interval: 30–40) mGy and 6 (5–7) mGy, respectively. We estimated that shared uncertainty contributed ~99% of coefficient of variation of median brain doses in brain scans compared to unshared uncertainty (1% contribution). We found that the previous brain doses were slightly underestimated for 1990 compared to the results in the current study due to the revised CTDI models based on CT films.

OBJECTIVE We hypothesized that a paper documentation and discharge bundle can expedite patient care during an influenza-related surge. METHODS Retrospective cohort study of low-acuity patients younger than 21 years surging into a pediatric emergency department between January and March 2018 with influenza-like illness. Patient visits documented using a paper bundle were compared with those documented in the electronic medical record on the same date of visit. The primary outcome of interest was time from physician evaluation to discharge for patient visits documented using the paper bundle compared with those documented in the electronic medical record. Secondary outcome was difference in return visits within 72 hours. We identified patient and visit level factors associated with emergency department length of stay. RESULTS A total of 1591 patient visits were included, 1187 documented in the electronic health record and 404 documented using the paper bundle. Patient visits documented using the paper bundle had a 21% shortened median time from physician evaluation to discharge (41 minutes; interquartile range, 27-62.8 minutes) as compared with patient visits documented in the electronic health record (52 minutes; interquartile range, 35-61 minutes; P < 0.001). There was no difference in return visits (odds ratio, 0.7; 95% confidence interval, 0.2, 2.2). CONCLUSIONS Implementation of paper charting during an influenza-related surge was associated with shorter physician to discharge times when compared with patient visits documented in the electronic health record. A paper bundle may improve patient throughput and decrease emergency department overcrowding during influenza or coronavirus disease-related surge.

Objective. To develop an automated system to classify the severity of hypoxic-ischaemic encephalopathy injury (HIE) in neonates from the background electroencephalogram (EEG). Approach. By combining a quadratic time–frequency distribution (TFD) with a convolutional neural network, we develop a system that classifies 4 EEG grades of HIE. The network learns directly from the two-dimensional TFD through 3 independent layers with convolution in the time, frequency, and time–frequency directions. Computationally efficient algorithms make it feasible to transform each 5 min epoch to the time–frequency domain by controlling for oversampling to reduce both computation and computer memory. The system is developed on EEG recordings from 54 neonates. Then the system is validated on a large unseen dataset of 338 h of EEG recordings from 91 neonates obtained across multiple international centres. Main results. The proposed EEG HIE-grading system achieves a leave-one-subject-out testing accuracy of 88.9% and kappa of 0.84 on the development dataset. Accuracy for the large unseen test dataset is 69.5% (95% confidence interval, CI: 65.3%–73.6%) and kappa of 0.54, which is a significant ( P < 0.001 ) improvement over a state-of-the-art feature-based method with an accuracy of 56.8% (95% CI: 51.4%–61.7%) and kappa of 0.39. Performance of the proposed system was unaffected when the number of channels in testing was reduced from 8 to 2—accuracy for the large validation dataset remained at 69.5% (95% CI: 65.5%–74.0%). Significance. The proposed system outperforms the state-of-the-art machine learning algorithms for EEG grade classification on a large multi-centre unseen dataset, indicating the potential to assist clinical decision making for neonates with HIE.

Purpose: In vivo optical imaging technologies like high-resolution microendoscopy (HRME) can image nuclei of the oral epithelium. In principle, automated algorithms can then calculate nuclear features to distinguish neoplastic from benign tissue. However, images frequently contain regions without visible nuclei, due to biological and technical factors, decreasing the data available to and accuracy of image analysis algorithms. Approach: We developed the nuclear density-confidence interval (ND-CI) algorithm to determine if an HRME image contains sufficient nuclei for classification, or if a better image is required. The algorithm uses a convolutional neural network to exclude image regions without visible nuclei. Then the remaining regions are used to estimate a confidence interval (CI) for the number of abnormal nuclei per mm 2 , a feature used by a previously developed algorithm (called the ND algorithm), to classify images as benign or neoplastic. The range of the CI determines whether the ND-CI algorithm can classify an image with confidence, and if so, the predicted category. The ND and ND-CI algorithm were compared by calculating their positive predictive value (PPV) and negative predictive value (NPV) on 82 oral biopsies with histopathologically confirmed diagnoses. Results: After excluding the images that could not be classified with confidence, the ND-CI algorithm had higher PPV (65% versus 59%) and NPV (78% versus 75%) than the ND algorithm. Conclusions: The ND-CI algorithm could improve the real-time classification of HRME images of the oral epithelium by informing the user if an improved image is required for diagnosis.

Objectives Evaluation of a computerised electrocardiogram algorithm compared to the interpretation of a team of board-certified veterinary cardiologists. Materials and methods This was a cross-sectional retrospective cohort study. A total of 399 electronic canine electrocardiogram recordings screened from 1391 electrocardiograms were enrolled in the study. A panel of seven cardiologists, masked to patient information, evaluated electrocardiograms for the following: P-wave amplitude and duration; PR-interval; R-wave amplitude; QRS duration; heart rate; mean electrical axis; and final overall diagnosis for the detection of arrhythmia and any abnormal electrocardiogram anomaly. Results The sensitivity of the electrocardiogram algorithm for detecting arrhythmias was 99.7% (95% confidence intervals, CI: 98.5 to 99.9) and the specificity was 99.5% (95% CI: 98.0 to 99.9) compared to the consensus result created by panel of cardiologists. The sensitivity of the algorithm for the detection of any electrocardiogram anomaly, including abnormal measurements, was 71.3% (95% CI: 65.5 to 76.7) and the specificity was 35.1% (95% CI: 27.0 to 43.8) compared to the panel of cardiologists. Clinical significance The electrocardiogram algorithm was shown to have high sensitivity for the detection of arrhythmias, but not all electrocardiogram anomalies. The results support the use of this algorithm as a tool to aid in the triage of the electrocardiogram workflow.

We propose a pipeline to acquire a scalar tapering measurement from the carina to the most distal point of an individual airway visible on computed tomography (CT). We show the applicability of using tapering measurements on clinically acquired data by quantifying the reproducibility of the tapering measure. We generate a spline from the centerline of an airway to measure the area and arclength at contiguous intervals. The tapering measurement is the gradient of the linear regression between area in log space and arclength. The reproducibility of the measure was assessed by analyzing different radiation doses, voxel sizes, and reconstruction kernel on single timepoint and longitudinal CT scans and by evaluating the effect of airway bifurcations. Using 74 airways from 10 CT scans, we show a statistical difference, p = 3.4 × 10 − 4, in tapering between healthy airways ( n = 35) and those affected by bronchiectasis ( n = 39). The difference between the mean of the two populations is 0.011 mm − 1, and the difference between the medians of the two populations was 0.006 mm − 1. The tapering measurement retained a 95% confidence interval of ±0.005 mm − 1 in a simulated 25 mAs scan and retained a 95% confidence of ±0.005 mm − 1 on simulated CTs up to 1.5 times the original voxel size. We have established an estimate of the precision of the tapering measurement and estimated the effect on precision of the simulated voxel size and CT scan dose. We recommend that the scanner calibration be undertaken with the phantoms as described, on the specific CT scanner, radiation dose, and reconstruction algorithm that are to be used in any quantitative studies.

OBJECTIVE To explore differences in baseline King-Devick Test (KD) completion time between 2 testing modalities: (1) spiral-bound paper cards (cards) and (2) iPad application (iPad). DESIGN Cross-sectional cohort analysis. SETTING National Collegiate Athlete Association (NCAA) institutions. PARTICIPANTS Student athletes from 13 women's and 11 men's collegiate sports who completed KD baseline testing as part of their first year in the Concussion Assessment, Research and Education (CARE) Consortium from 2014 to 2016 (n = 2003, 52.2% male). INDEPENDENT VARIABLES King-Devick Test modalities; cards or iPad. MAIN OUTCOME MEASURE Baseline KD completion time (seconds). RESULTS Mean baseline KD completion time of the iPad modality group [42.8 seconds, 95% confidence interval (CI), 42.1-43.3] was 2.8 seconds (95% CI, 2.1-3.4) greater than the cards group (40.0 seconds, 95% CI, 39.7-40.3) (t(1, 1010.7) = -8.0, P < 0.001, Cohen's d = 0.41). CONCLUSIONS Baseline KD performance is slower when tested on an iPad than when tested on spiral-bound paper cards. The 2 KD modalities should not be used interchangeably in concussion assessments because differences in the modalities can lead to time differences similar in magnitude to those used to indicate concussion. From a research perspective, modality may influence interpretation and/or synthesis of findings across studies.

Objective: The objective of the study is to investigate the relation between pretreatment depressive symptoms (DS) and the course of DS during the first year after cancer diagnosis, and overall survival among people with head and neck cancer (HNC). Methods: Data from the Head and Neck 5000 prospective clinical cohort study were used. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) pretreatment, at 4 and 12-month follow-up. Also, socio-demographic, clinical, lifestyle, and mortality data were collected. The association between before start of treatment DS (HADS-depression > 7) and course (never DS, recovered from DS, or persistent/recurrent/late DS at 12-month follow-up) and survival was investigated using Cox regression. Unadjusted and adjusted analyses were performed. Results: In total, 384 of the 2144 persons (18%) reported pretreatment DS. Regarding DS course, 63% never had DS, 16% recovered, and 20% had persistent/recurrent/late DS. People with pretreatment DS had a higher risk of earlier death than people without DS (hazard ratio (HR) = 1.65; 95% confidence interval (CI) 1.33-2.05), but this decreased after correcting for socio-demographic, clinical, and lifestyle-related factors (HR = 1.21; 95% CI 0.97-1.52). Regarding the course of DS, people with persistent/recurrent/late DS had a higher risk of earlier death (HR = 2.04; 95% CI 1.36-3.05), while people who recovered had a comparable risk (HR = 1.12; 95% CI 0.66-1.90) as the reference group who never experienced DS. After correcting for socio-demographic and clinical factors, people with persistent/recurrent/late DS still had a higher risk of earlier death (HR = 1.66; 95% CI 1.09-2.53). Conclusions: Pretreatment DS and persistent/recurrent/late DS were associated with worse survival among people with HNC.

Objectives To estimate the internal consistency, test–retest reliability and comparability of paper and computer versions of the Finnish version of the Tampa Scale of Kinesiophobia (TSK-FIN) among patients with chronic pain. In addition, patients’ personal experiences of completing both versions of the TSK-FIN and preferences between these two methods of data collection were studied. Design Test–retest reliability study. Paper and computer versions of the TSK-FIN were completed twice on two consecutive days. Participants The sample comprised 94 consecutive patients with chronic musculoskeletal pain participating in a pain management or individual rehabilitation programme. The group rehabilitation design consisted of physical and functional exercises, evaluation of the social situation, psychological assessment of pain-related stress factors, and personal pain management training in order to regain overall function and mitigate the inconvenience of pain and fear-avoidance behaviour. Results The mean TSK-FIN score was 37.1 [standard deviation (SD) 8.1] for the computer version and 35.3 (SD 7.9) for the paper version. The mean difference between the two versions was 1.9 (95% confidence interval 0.8 to 2.9). Test–retest reliability was 0.89 for the paper version and 0.88 for the computer version. Internal consistency was considered to be good for both versions. The intraclass correlation coefficient for comparability was 0.77 (95% confidence interval 0.66 to 0.85), indicating substantial reliability between the two methods. Conclusion Both versions of the TSK-FIN demonstrated substantial intertest reliability, good test–retest reliability, good internal consistency and acceptable limits of agreement, suggesting their suitability for clinical use. However, subjects tended to score higher when using the computer version. As such, in an ideal situation, data should be collected in a similar manner throughout the course of rehabilitation or clinical research.

Objectives To assess the measurement equivalence of the original paper version of an adapted tablet version of the EuroQol five-dimensional questionnaire (EQ-5D). Methods A randomly selected sample of 509 individuals aged 18 to 64 years from the general population responded to the EQ-5D at two time points separated by a minimum interval of 24 hours and were allocated to one of the following groups: test-retest group (tablet-tablet) or crossover group (paper-tablet and tablet-paper). Agreement between methods was determined using the intraclass correlation coefficient (ICC) and the κ coefficient. Results In the crossover group, the following ICC values were obtained: 0.76 (confidence interval [CI] 0.58–0.89) for EQ-5D scores and 0.77 (CI 0.68–0.84) for visual analogue scale in subjects responding first to the tablet version; 0.83 (CI 0.75–0.89) for EQ-5D scores and 0.75 (CI 0.67–0.85) for visual analogue scale in subjects responding first to the paper version. In the test-retest group, the ICC was 0.85 (CI 0.73–0.91) for EQ-5D scores and 0.79 (CI 0.66–0.87) for visual analogue scale. The κ values were higher than 0.69 in this group. The internal consistencies of the paper and tablet methods were similar. Conclusions The paper and tablet versions of the EQ-5D are equivalent. Test-retest and crossover agreement was high and the acceptability of the methods was similar among individuals. Objetivos Avaliar a equivalência de medidas da versão original em papel de uma versão adaptada para tablet do questionário de cinco dimensões EuroQol (EQ-5D). Métodos Uma amostra selecionada aleatoriamente de 509 indivíduos com idade entre 18 e 64 anos da população geral respondeu ao EQ-5D em dois momentos separados por um intervalo mínimo de 24 horas e foram alocados em um dos seguintes grupos: grupo teste-reteste (tablet -tablet) ou grupo crossover (papel-tablet e tablet-papel). A concordância entre os métodos foi determinada por meio do coeficiente de correlação intraclasse (ICC) e do coeficiente κ. Resultados No grupo crossover, os seguintes valores de ICC foram obtidos: 0,76 (intervalo de confiança [IC] 0,58–0,89) para escores EQ-5D e 0,77 (IC 0,68–0,84) para escala visual analógica em indivíduos que responderam primeiro à versão tablet; 0,83 (IC 0,75–0,89) para pontuações EQ-5D e 0,75 (IC 0,67–0,85) para escala visual analógica em indivíduos que responderam primeiro à versão em papel. No grupo teste-reteste, o ICC foi de 0,85 (IC 0,73–0,91) para os escores do EQ-5D e 0,79 (IC 0,66–0,87) para a escala visual analógica. Os valores de κ foram superiores a 0,69 neste grupo. As consistências internas dos métodos de papel e tablet foram semelhantes. Conclusões As versões em papel e tablet do EQ-5D são equivalentes. A concordância teste-reteste e crossover foi alta e a aceitabilidade dos métodos foi semelhante entre os indivíduos.

BackgroundThere is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood.AimsTo determine the association between gestational vitamin D status and ASD.MethodBased on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases).ResultsIndividuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only.ConclusionsMid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.

The Social Difficulties Inventory (SDI-21) assesses everyday problems experienced by cancer patients, including difficulties with self-care, work and relationships. Early development and psychometric evaluation studies have validated the SDI-21 for computer administration. However, several recent studies have administered the SDI-21 on paper. We sought to test the score equivalence of electronic and paper versions of the SDI-21. A randomised two-arm crossover trial in a sample of cancer patients with varied diagnoses. Patients completed electronic (via the internet) and paper versions of the SDI-21, with half randomly assigned to complete the electronic version first (n = 51) and half the paper version first (n = 60). Patients were asked to complete both versions at home, within 2 weeks. Analyses were performed for the SDI-21 summary score and three subscales. Score distributions and internal reliabilities for the paper and electronic versions were highly similar. There were no significant differences between mean summary or subscale scores for the two administration modes. All mean score differences (all

Background and aim: To update our 1996 review on the incidence of subarachnoid haemorrhage (SAH) and assess the relation of incidence with region, age, gender and time period.Methods: We searched for studies on the incidence of SAH published until October 2005. The overall incidences with corresponding 95% confidence intervals were calculated. We determined the relationship between the incidence of SAH and determinants by means of univariate Poisson regression.Results: We included 51 studies (33 new), describing 58 study populations in 21 countries, observing 45 821 896 person-years. Incidences per 100 000 person-years were 22.7 (95% CI 21.9 to 23.5) in Japan, 19.7 (18.1 to 21.3) in Finland, 4.2 (3.1 to 5.7) in South and Central America, and 9.1 (8.8 to 9.5) in the other regions. With age category 45-55 years as the reference, incidence ratios increased from 0.10 (0.08 to 0.14) for age groups younger than 25 years to 1.61 (1.24 to 2.07) for age groups older than 85 years. The incidence in women was 1.24 (1.09 to 1.42) times higher than in men; this gender difference started at age 55 years and increased thereafter. Between 1950 and 2005, the incidence decreased by 0.6% (1.3% decrease to 0.1% increase) per year.Conclusions: The overall incidence of SAH is approximately 9 per 100 000 person-years. Rates are higher in Japan and Finland and increase with age. The preponderance of women starts only in the sixth decade. The decline in incidence of SAH over the past 45 years is relatively moderate compared with that for stroke in general.

Background: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. Methods: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population-based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. Results: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months-58 years), which was younger than in the reference population (difference between means 8 years, 95% confidence interval (CI) 3-13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex and mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13-30 years), which suggests clinical anticipation. Conclusions: Few patients with familial BAVMs have been described. These patients were diagnosed at younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

Background: The mismatch between perfusion and diffusion lesions on magnetic resonance perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) may help identify patients for thrombolysis. Evidence underlying this hypothesis was assessed. Methods: All papers describing magnetic resonance PWI/DWI findings in patients with acute ischaemic stroke, and their functional and/or radiological outcome at 1 month, with or without thrombolysis were systematically reviewed. Results: 11 papers fulfilled the inclusion criteria. Among these, there were 5 different mismatch definitions and at least 7 different PWI methods. Only 3 papers including 61 patients with and 18 without mismatch provided data on mismatch, outcome and influence of thrombolysis. Mismatch ( v no mismatch) without thrombolysis was associated with a non-significant twofold increase in the odds of infarct expansion (odds ratio (OR) 2.2, 95% confidence interval (CI) 0.34 to 14.1), which did not change with thrombolysis (OR 2.0, 95% CI 0.37 to 10.9). Half of the patients without mismatch also had infarct growth (with or without thrombolysis). No data were available on functional outcome. Conclusions: Standardised definitions of mismatch and perfusion are needed. Infarct growth may occur even in the absence of mismatch. Currently, data available on mismatch are too limited to guide thrombolysis in routine practice. More data are needed from studies including patients with and without mismatch, and randomised treatment allocation, to determine the role of mismatch.

Background: Severe head injury (SHI) is one of the most important health, social and economic problems in industrialised countries. Unfortunately, none of the neuroprotection trials for traumatic brain injury have shown efficacy. One of the reasons for this failure could be the inclusion of patients with high probability of early death. A population-based, retrospective study was conducted to develop a prognostic model for identification of these patients. Methods: Between January 1987 and August 1999, a total of 895 patients (⩾15 years of age) with non-missile SHI were studied, in whom a computed tomography scan was carried out within the first 6 h of injury. The association between early death (first 48 h after injury) and independent prognostic factors was determined by logistic regression analysis. A scoring system was also constructed. Results: The early-death rate was 20%. Independent predictors of early mortality after SHI were non-evacuated mass (odds ratio (OR) 65, 95% confidence interval (CI) 11 to 379), diffuse injury IV (OR 25, 95% CI 5 to 112), diffuse injury III (OR 8, 95% CI 3 to 22), flaccidity (OR 7, 95% CI 3 to 15), non-reactive bilaterally mydriasis (OR 6, 95% CI 3 to 12), evacuated mass (OR 4, 95% CI 1 to 11), age ⩾65 years (OR 4, 95% CI 1 to 9), decerebration (OR 3, 95% CI 2 to 7) and shock (OR 3, 95% CI 2 to 6). The prognostic model correctly identified 93% of the patients. Conclusions: This prognostic model is based on simple clinical and radiological data readily available during the first 6 h after injury and is useful for identification of early death after SHI.

Background: While the incidence of amyotrophic lateral sclerosis (ALS) is similar across the world (range, 1.0 to 2.5/100 000), a latitude gradient from north to south has been observed. Objective: To determine the incidence of ALS in Puglia, a region of south eastern Italy, and to test the latitude gradient hypothesis comparing the present study with findings in studies conducted with the same design in a northern latitude. Methods: Puglia (4 086 613 residents in 2001) is the site of a multicentre-multisource prospective population based registry established in 1997. All incident ALS cases during the period 1998–99 were enrolled and followed up. Cases were classified using the first and the revised El Escorial criteria. Results: During the study period 130 cases were enrolled. The annual crude incidence for ALS in Puglia for the two year period 1998–99 was 1.6/100 000 (95% confidence interval, 1.3 to 1.9). The incidence was higher for men (incidence rate (IR) = 2.1 (1.7 to 2.7) than for women (IR = 1.2 (0.9 to 1.5)) in all age groups, with a male to female ratio of 1.6. For both men and women, the incidence increased through age 75 and declined rapidly afterwards. The mean annual incidence adjusted by age and sex to the 2001 Italian population was 1.7/100 000 (1.4 to 2.0). Conclusions: ALS incidence is within a narrow range across countries, with a peak between 65 and 75 years and a higher incidence in men . A north to south latitude gradient of ALS incidence is not supported by the results of cohort studies.

To determine potential predictors of good outcome in primary medium to large intracerebral haemorrhages (ICH) which could be useful for selecting patients for surgical procedures.Subjects were 138 patients with spontaneous hemispheric ICH20 ml. They were non-surgically treated and were admitted consecutively to 15 hospitals within the first 12 hours of symptom onset (mean (SD), 5.8 (3.1) hours). Haematoma volume was measured on computed tomography (CT) at admission. Stroke severity was assessed by the Canadian stroke scale (CSS). Good outcome was defined as modified Rankin scoreor =2 at three months.At the end of the follow up period, 45 patients (32.6%) had good outcome. Baseline stroke severity, systolic and diastolic blood pressure, body temperature, and acute phase reaction biochemical markers (ESR, C-reactive protein, fibrinogen, neutrophil count) were significantly associated with good outcome in bivariate analyses. Of the initial CT scan variables, intraventricular contamination, deep location, mass effect, and greater ICH volume were related to poor outcome. On multiple logistic regression analysis, cortical location of bleeding (odds ratio 3.79 (95% confidence interval 1.2 to 12.01); p = 0.023), high CSS score (OR 2.3 (1.6 to 3.1); p0.0001), and low fibrinogen concentrations (OR 0.92 (0.87 to 0.97); p = 0.001) were independent predictors of good outcome. These three factors correctly classified 85% of patients.Good outcome in medium to large ICH can be predicted on admission by three readily assessable factors (CSS score, ICH location, and fibrinogen levels). These predictors may be helpful in selecting patients for surgical treatment.

Objective: To study whether lower arterial oxygen saturation (SaO2) and chronic obstructive pulmonary disease (COPD) are associated with cerebral white matter lesions and lacunar infarcts. Methods: We measured SaO2 twice with a pulse oximeter, assessed the presence of COPD, and performed MRI in 1077 non-demented people from a general population (aged 60–90 years). We rated periventricular white matter lesions (on a scale of 0–9) and approximated a total subcortical white matter lesion volume (range 0–29.5 ml). All analyses were adjusted for age and sex and additionally for hypertension, diabetes, body mass index, pack years smoked, cholesterol, haemoglobin, myocardial infarction, and left ventricular hypertrophy. Results: Lower SaO2 was independent of potential confounders associated with more severe periventricular white matter lesions (score increased by 0.12 per 1% decrease in SaO2 (95% confidence interval 0.01 to 0.23)). Participants with COPD had more severe periventricular white matter lesions than those without (adjusted mean difference in score 0.70 (95% confidence interval 0.23 to 1.16)). Lower SaO2 and COPD were not associated with subcortical white matter lesions or lacunar infarcts. Conclusion: Lower SaO2 and COPD are associated with more severe periventricular white matter lesions.

Background: Existing evidence suggests that some patients who sustain a head injury suffer cognitive decline many years later, and that head injury and possession of the APOE e4 allele are each risk factors for Alzheimer's disease. Objective: To determine whether late cognitive decline after head injury is more prevalent among carriers of APOE e4. Methods: A database of head injured patients was used. Initial assessment was at the time of their injury, between 1968 and 1985, and outcome data at six months were available. Their ages at the time of injury ranged between 2 and 70 years. A cohort of 396 subjects was reassessed at a mean of 18 years later, with determination of APOE genotype and detailed neuropyschological testing. Results: Judging by the Glasgow outcome scale, twice as many patients had deteriorated as improved between six months after injury and the late assessment; 22.2% of APOE e4 carriers had a good late outcome compared with 30.5% of non-carriers (95% confidence interval for the difference, -0.7% to 17.2%; p = 0.084). There were no clear differences between e4 carriers and non-carriers in detailed neuropsychological assessments. Conclusions: Although this study provides additional evidence that a late decline may occur after head injury, there was no clear relation to APOE genotype. Despite the follow up interval of 15 to 25 years, the cohort is still too young (mean age 42.1 years) to assess the risk of Alzheimer's disease.

Objective: To investigate the incidence and prevalence of multiple sclerosis in Vasterbotten County in northern Sweden. Methods: Multiple sources were used in the case identification process. Follow up interviews with clinical examinations were undertaken and, when indicated, additional paraclinical investigations were done. In this way case ascertainment was assured and supplemental clinical data were collected. The incidence rate was based on symptom onset. Onset adjusted prevalence was applied. Results: The crude incidence rate of multiple sclerosis in 1988–97 in Vasterbotten County was 5.2/105 (95% confidence interval, 4.4 to 6.2): 6.7/105 (6.0 to 8.3) in women and 3.7/105 (2.7 to 4.9) in men. The onset adjusted prevalence for 31 December 1997 was 154/105 (139 to 170): 202/105 (179 to 228) in women and 105/105 (89 to 125) in men. When compared with a previous estimate of prevalence, a yearly 2.6% increase in prevalence between 1990 and 1997 was found, mainly attributable to a higher incidence than mortality. Conclusions: The present incidence rate and prevalence confirms earlier findings that Vasterbotten is a high risk area for multiple sclerosis. The adjusted incidence was twice as high as the incidence from 1974–88 in the only previous Swedish population based study from Goteborg, but comparable with other recent Fennoscandian multiple sclerosis incidence rates.

Objectives: To determine if cardiovascular disease may be a risk factor in the development of chronic idiopathic axonal polyneuropathy (CIAP). Methods: In this incidence case-control study, the prevalence of cardiovascular disease and risk factors in 97 patients with CIAP (mean age 67.5 (SD 7.9) years) and the prevalence of neuropathic features in 97 patients with peripheral arterial disease (PAD) (mean age 67.1 (SD 7.3) years) were investigated. The results were compared with those for 96 age and sex matched controls without diagnosed PAD or polyneuropathy (mean age 67.5 (SD 9.1) years). In a randomly chosen subgroup of 23 patients with CIAP, 42 patients with PAD, and 48 controls, an electrodiagnostic investigation was performed. Results: Patients with CIAP more often had manifest cardiovascular disease and cardiovascular risk factors than controls (stroke 18% v 6% of patients, odds ratio (OR) 3.2 (95% confidence interval (CI) 1.8 to 5.9); heart disease 29% v 15%, OR 2.4 (95% CI 1.2 to 4.9); family history of cardiovascular disease 42% v 21%, OR 2.8 (95% CI (1.5 to 5.2); hypertension 56% v 39%, OR 2.0 (95% CI 1.1 to 3.6); hypercholesterolaemia 46% v 21%, OR 3.3 (95% CI 1.5 to 7.3); current smoking 38% v 23%, OR 2.1 (95% CI 1.1 to 3.9)). The prevalence of cardiovascular disease and cardiovascular risk factors was lower than in patients with PAD. Patients with PAD more often had polyneuropathy than controls (15% v 5%, OR 3.3 (95% CI 1.1 to 10.0)). There was a trend towards lower nerve conduction velocities and lower amplitudes on electrodiagnostic investigation compared with controls. Conclusion: This study shows that cardiovascular disease and CIAP often coexist, and therefore cardiovascular disease may be a cofactor in the development of CIAP.

The aim of this study was to determine the airway exposure of sugar and papermaking factory workers to aflatoxin B1 (AFB1) and to explore the potential association between AFB1 airway exposure and the risk of hepatocellular carcinoma (HCC) in a case-control study. Dust samples were collected from the sugarcane bagasse warehouse, and presser and paper production workshops. Blood samples were collected from 181 workshop employees and 203 controls who worked outside the workshop. AFB1 albumin adducts were detected using a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). To explore the association between AFB1 airway exposure and the risk of HCC, the medical records of 68 HCC patients who worked in a sugar and papermaking factory between January 1994 and December 2013 were analyzed. A questionnaire was used to collect information from 150 healthy controls who worked for the same company and lived near the factory. AFB1 was detected in the dust samples, but could not be detected in any of the rice samples. An analysis of serum samples revealed serum AFB1 albumin adducts in 102 (56.35 %) of the study participants. However, in the control group, only 12 (5.9 %) individuals had detectable levels of AFB1 albumin adducts. Those with airway exposure to Aspergillus flavus-contaminated dust had an elevated risk of HCC compared to those without exposure (odds ratio, 5.24; 95 % confidence interval, 2.77–9.88; P = 0.00). The findings of this study indicate that occupational AFB1 airway exposure might be associated with the risk of AFB1-related HCC among the population that was used in this study. Intervention programs aimed at reducing exposure to inhalational AFB1 are needed urgently. Additional suitably designed, multicenter, prospective studies using large samples are needed to further confirm the results.

Background: Electronic patient-reported outcomes (PRO) provide quick and usually reliable assessments of patients’ health-related quality of life (HRQL). Objective: An electronic version of the Patient-Reported Outcomes Quality of Life-human immunodeficiency virus (PROQOL-HIV) questionnaire was developed, and its face validity and reliability were assessed using standard psychometric methods. Methods: A sample of 80 French outpatients (66% male, 52/79; mean age 46.7 years, SD 10.9) were recruited. Paper-based and electronic questionnaires were completed in a randomized crossover design (2-7 day interval). Biomedical data were collected. Questionnaire version and order effects were tested on full-scale scores in a 2-way ANOVA with patients as random effects. Test-retest reliability was evaluated using Pearson and intraclass correlation coefficients (ICC, with 95% confidence interval) for each dimension. Usability testing was carried out from patients’ survey reports, specifically, general satisfaction, ease of completion, quality and clarity of user interface, and motivation to participate in follow-up PROQOL-HIV electronic assessments. Results: Questionnaire version and administration order effects (N=59 complete cases) were not significant at the 5% level, and no interaction was found between these 2 factors ( P =.94). Reliability indexes were acceptable, with Pearson correlations greater than .7 and ICCs ranging from .708 to .939; scores were not statistically different between the two versions. A total of 63 (79%) complete patients’ survey reports were available, and 55% of patients (30/55) reported being satisfied and interested in electronic assessment of their HRQL in clinical follow-up. Individual ratings of PROQOL-HIV user interface (85%-100% of positive responses) confirmed user interface clarity and usability. Conclusions: The electronic PROQOL-HIV introduces minor modifications to the original paper-based version, following International Society for Pharmacoeconomics and Outcomes Research (ISPOR) ePRO Task Force guidelines, and shows good reliability and face validity. Patients can complete the computerized PROQOL-HIV questionnaire and the scores from the paper or electronic versions share comparable accuracy and interpretation. [J Med Internet Res 2014;16(4):e115]

P Garnerin, quality manager and F Clergue, department head and professor J-F Sicard, anaesthetist and F Bonnet, department head and professor Background—Reporting systems in anaesthesia have generally focused on critical events (including death) to trigger investigations of latent and active errors. The decrease in the rate of these critical events calls for a broader definition of significant anaesthetic events, such as hypotension and bradycardia, to monitor anaesthetic care. The association between merely undesirable events and critical events has not been established and needs to be investigated by voluntary reporting systems. Objectives—To establish whether undesirable anaesthetic events are correlated with critical events in anaesthetic voluntary reporting systems. Methods—As part of a quality improvement project, a systematic reporting system was implemented for monitoring 32 events during elective surgery in our hospital in 1996. The events were classified according to severity (critical/undesirable) and nature (process/outcome) and control charts and logistic regression were used to analyse the data. Results—During a period of 30 months 22% of the 6439 procedures were associated with anaesthetic events, 15% of which were critical and 31% process related. A strong association was found between critical outcome events and critical process events (OR 11.5 (95% confidence interval (CI) 4.4 to 27.8)), undesirable outcome events (OR 4.8 (95% CI 2.0 to 11.8)), and undesirable process events (OR 4.8 (95% CI 1.3 to 13.4)). For other classes of events, risk factors were related to the course of anaesthesia (duration, occurrence of other events) and included factors determined during the pre-anaesthetic visit (risk of haemorrhage, difficult intubation or allergic reaction). Conclusion—Undesirable events are associated with more severe events and with pre-anaesthetic risk factors. The way in which information on significant events can be used is discussed, including better use of preoperative information, reduction in the collection of redundant information, and more structured reporting. (Quality in Health Care 2000;9:203–209) Key Words: reporting system; correlation analysis; quality assessment; adverse events; anaesthesia

The authors assessed the health effects of emission reduction of malodorous sulfur compounds in a prospective cohort study with a controlled natural experiment. A total of 810 subjects (83%) participated in the follow up: 316 from the severely polluted, 306 from the moderately polluted, and 188 from the nonpolluted communities. In the severely polluted community, the annual ambient air concentration of total reduced sulfur compounds decreased from 11 microg/m3 to 6 microg/m3. Compared with the nonpolluted community, the relative decrease in acute respiratory infections, adjusted for a change in smoking habits, was 0.53 episodes/person-year (95% confidence interval = 0.22, 0.83) in the severely polluted community and 0.36 episodes/person-year (95% confidence interval = 0.06, 0.66) in the moderately polluted community. In addition, the frequency of nasal symptoms (p = .004) and cough (p = .037) decreased significantly. The results are consistent with the hypothesis that exposure to malodorous sulfur compounds increases the risk of acute respiratory infections and symptoms of the respiratory tract.

Background: Studies on the prevalence of multiple sclerosis have been carried out worldwide, showing a heterogeneous distribution between countries and even between the different regions of the same country. Methods: We estimated the regional and national prevalence of multiple sclerosis in France on 1 January 2003, based on the computerised database of the national farmer health insurance system (“Mutualite Sociale Agricole”). Results: There were 2667 cases of multiple sclerosis registered on the prevalence date, out of 4 098 477 affiliates. After standardisation on age, estimates for the national prevalence of multiple sclerosis in French farmers were 65.0 per 100 000 inhabitants (95% confidence interval 62.5 to 67.5), 41.9 per 100 000 in men (39.1 to 44.7) and 96.3 per 100 000 in women (92.0 to 100.6). The prevalence of multiple sclerosis was significantly higher in the north eastern regions (approximately 100 per 100 000 inhabitants) compared with the south western regions (around 50 per 100 000 inhabitants). Conclusion: Our study is the first to evaluate the overall prevalence of multiple sclerosis in France and its 22 regions using the same methodology. Our results may be generalised to the whole French population as there is no convincing evidence of an increased or decreased susceptibility to multiple sclerosis among farmers or persons living in the countryside. This places France among the countries of medium to high prevalence. Confirming the uneven distribution of multiple sclerosis that correlates with latitude, raises once more the question of the role of genetic and environmental factors in the susceptibility to multiple sclerosis.

The authors studied a cohort of 30,157 male pulp and paper workers in British Columbia, Canada. Of these, 20,373 worked in kraft mills only, 5,249 in sulfite mills only, and 4,535 in both kraft and sulfite mills. All workers with at least 1 year of employment on January 1, 1950, or thereafter until December 31, 1992, were studied. Standardized mortality ratios (SMRs) were used to compare the mortality rates of the cohort with those of the Canadian male population. Ninety percent confidence intervals (CIs) for the SMRs were obtained. Cancer risks significantly associated with work duration and time from first employment of 15 years or more were observed: 1) total cohort: pleura (SMR = 3.61, 90% CI 1.42-7.58); kidney (SMR = 1.69, 90% CI 1.13-2.43); brain (SMR = 1.51, 90% CI 1.03-2.16); 2) workers in kraft mills only: kidney (SMR = 1.92, 90% CI 1.04-3.26); 3) workers in sulfite mills only: Hodgkin's disease (SMR = 4.79, 90% CI 1.29-12.37); 4) workers ever employed in both kraft and sulfite mills: esophagus (SMR = 1.91, 90% CI 1.00-3.33). These malignancies have been associated with the following known or suspected carcinogens to which pulp and paper workers may have been exposed: asbestos (pleura), biocides (kidney), formaldehyde (kidney, brain, Hodgkin's disease), hypochlorite (esophagus). A nested case-control study with detailed exposure assessment is under way to help determine whether excess risks for specific cancers reflect exposure among subsets of workers.

BACKGROUND: Occupational exposure to irritants is associated with chronic bronchitis. The aim of this study was to elucidate whether repeated peak exposures with respiratory symptoms, gassings, to sulphur dioxide (SO2) and other irritant gases could increase the risk of chronic bronchitis. METHODS: The study population comprised 3,060 Swedish pulp mill workers (84% males) from a cohort study, who completed a comprehensive questionnaire with items on chronic bronchitis symptoms, smoking habit, occupational history, and specific exposures, including gassings. 2,037 have worked in sulphite mills. Incidence rates and hazard ratios (HRs) for the observation period, 1970-2000, in relation to exposure and the frequency of repeated gassings to SO2 and other irritant gases were calculated. RESULTS: The incidence rate for chronic bronchitis among workers with repeated gassings was 3.5/1,000 person-years compared with 1.5/1,000 person-years among unexposed workers (HR 2.1, 95% confidence interval (CI) 1.4-3.1). The risk was even higher in the subgroup with frequent gassings (HR 3.2, 95% CI 2.0-5.2), particularly among never-smokers (HR 8.7, 95% CI 3.5-22). CONCLUSIONS: Repeated gassings to irritant gases increased the incidence of chronic bronchitis in our study population during and after work in pulp mills, supporting the hypothesis that occupational exposures to irritants negatively affect the airways. These results underscore the importance of preventive actions in this work environment.

BackgroundWeb-based questionnaires have become increasingly popular in health research. However, reported response rates vary and response bias may be introduced. ObjectiveThe aim of this study was to evaluate whether sending a mixed invitation (paper-based together with Web-based questionnaire) rather than a Web-only invitation (Web-based questionnaire only) results in higher response and participation rates for female childhood cancer survivors filling out a questionnaire on fertility issues. In addition, differences in type of response and characteristics of the responders and nonresponders were investigated. Moreover, factors influencing preferences for either the Web- or paper-based version of the questionnaire were examined. MethodsThis study is part of a nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female childhood cancer survivors. The Web-based version of the questionnaire was available for participants through the Internet by means of a personalized user name and password. Participants were randomly selected to receive either a mixed invitation (paper-based questionnaire together with log-in details for Web-based questionnaire, n = 137) or a Web-only invitation (log-in details only, n = 140). Furthermore, the latter group could request a paper-based version of the questionnaire by filling out a form. ResultsOverall response rates were comparable in both randomization groups (83% mixed invitation group vs 89% in Web-only invitation group, P = .20). In addition, participation rates appeared not to differ (66% or 90/137, mixed invitation group vs 59% or 83/140, Web-only invitation group, P =.27). However, in the mixed invitation group, significantly more respondents filled out the paper-based questionnaire compared with the Web-only invitation group (83% or 75/90 and 65% or 54/83, respectively, P = .01). The 44 women who filled out the Web-based version of the questionnaire had a higher educational level than the 129 women who filled out the paper-based version (P = .01). Furthermore, the probability of filling out the Web-based questionnaire appeared to be greater for women who were allocated to the Web-only invitation group (OR = 2.85, 95% CI 1.31 - 6.21), were older (OR = 1.08, 95% CI 1.02 - 1.15), had a higher educational level (OR high vs low = 0.06, 95% CI 0.01 - 0.52), or were students (OR employed vs student = 3.25, 95% CI 1.00 - 10.56). ConclusionsAlthough overall response as well as participation rates to both types of invitations were similar, adding a paper version of a questionnaire to a Web-only invitation resulted in more respondents filling out the paper-based version. In addition, women who were older, had a higher level of education, or were students, were more likely to have filled out the Web-based version of the questionnaire. Given the many advantages of Web-based over paper-based questionnaires, researchers should strongly consider using Web-based questionnaires, although possible response bias when using these types of questionnaires should be taken into account. Trial RegistrationNederlands Trial Register NTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922 (Archived by WebCite at http://www.webcitation.org/5zRRdMrDv)

A physician's alert prompted us to investigate workers' cancer risk at a paperboard printing manufacturer. We conducted a retrospective cohort mortality study of all 2,050 persons who had worked at the facility for more than 1 day, calculated standardized incidence ratios (SIRs) for bladder and renal cell cancer, and conducted a nested case-control study for renal cell cancer. Standardized mortality ratios (SMRs) from all causes [SMR = 1.0, 95% confidence interval (CI) = 0.9-1.2] and all cancers (SMR = 0.6, 95% CI = 0.3-1.0) were not greater than expected. One bladder cancer and one renal cell cancer were included in the mortality analysis. Six incident renal cell cancers were observed, however, compared with less than two renal cell cancers expected (SIR = 3.7, 95% CI = 1.4-8.1). Based on a nested case-control analysis, the risk of renal cell cancer was associated with overall length of employment but was not limited to any single department or work process. Although pigments containing congeners of dichlorobenzidine and o-toluidine had been used at the plant, environmental sampling could not confirm any current exposure. Several limitations and a potential selection bias limit the inferences that can be drawn.

Objectives: Visual analog scales are frequently used as a means of allowing participants to rate symptoms during clinical trials. The accuracy and reproducibility of these scales play an important role in determining the experimental value of the data they provide. This study was initiated to compare the data collected using paper- and computer-based (Tablet PC) analog scales to better understand the variability in data provided by a visual analog scale. Methods: Thirty participants rated ocular comfort, redness, and clarity of vision (right and left eyes) on a nondemarcated horizontal line on both paper and a Tablet PC. Measurements were taken in the morning between the hours of 8:30 and 10:30 am and again the same day between 2:30 and 4:30 pm. Results: The mean difference between the measures recorded in the morning for the 2 media was 2.6 ± 0.9 (confidence intervals, 2 standard errors of the differences) units on a 100 unit scale, with the Tablet PC having the higher mean measure. The limits of agreement (2 standard deviations of the differences) was 9.4 units. Comparing the difference of the differences (1.0 ± 1.3) between the 2 methods of measure (morning vs. afternoon) the visual analog scales on the Tablet PC seemed to have good reproducibility of agreement in comparison with the paper version. Conclusions: Discrepancy analysis yielded no significant difference and slight bias between paper- and computer-based analog scales. Repeatability of measures using the Tablet PC was also demonstrated. These results suggest that the choice of medium does not significantly influence the outcome for subjective analog scales.

Objective To investigate the effect of font size and paper thickness on the response to, and completion of, a self-completion postal questionnaire among older people with joint pain. Study Design and Setting Randomized trial. People aged 50 years and older with joint pain who consulted a general practitioner at one of five general practices in Central Cheshire were sent a postal questionnaire. Questionnaire format (large or small font size, thick or thin paper) was randomly allocated using a 2 × 2 factorial design. Results Questionnaires were received from 502 out of 650 participants (crude response 77%). Response was significantly higher for participants receiving questionnaires with a larger font size (79.3% vs. 75.2%; hazard ratio 1.26, 95% confidence interval: 1.02, 1.56). Paper thickness had no significant effect on response. Completion (measure by assessing double-page turnover error) was increased in participants receiving questionnaires printed on thicker paper (3.2% vs. 7.1%; P = 0.049) but was not affected by font size. Conclusion This study demonstrates that questionnaires in larger font and on thicker paper may produce higher and more complete responses than surveys using standard size font and standard thickness paper, and should therefore be considered in studies among older people.

Background: In clinical and research settings, the Mini-Mental State Examination (MMSE) is commonly used to measure cognitive change over time. The interpretation of changes in MMSE is often difficult. They do not necessarily result from true clinical change. Their interpretation requires comparison with normative data for change. However, MMSE change norms are lacking for long intervals. Objective: To examine what is a reliable change in MMSE for long follow-up periods commonly used in clinic. To provide normative data for change. Methods: A sample of 119 cognitively normal individuals, aged 75 years and over, who participated in the Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants were tested six times at 1.5 year intervals with the MMSE over a mean period of 7.1 years. Reliable change indices were computed for a common confidence interval (90%). Results: In repeated assessments with 1.5 year intervals, a change in MMSE of at least 2–4 points indicated a reliable change at the 90% confidence level. Conclusion: Small changes in MMSE can be interpreted only with great uncertainty. They have a reasonable probability of being caused by measurement error, regression to the mean or practice.

We evaluated the use of capillary blood samples stored on filter papers for diagnosis of dengue virus infection. Venous and capillary blood samples were collected from 130 patients suspected of having dengue fever. We compared the performances of standard reference methods using capillary blood samples absorbed onto filter papers versus venous blood samples. The resulting sensitivity, specificity, and positive predictive value of tests performed on filter paper compared to those performed on venous blood samples were 81.6% (62/76; 95% confidence interval [CI], 74.9% to 88.3%), 90.7% (49/54; 95% CI, 85.7% to 95.7%), and 92.5% (62/67; 95% CI, 86.2% to 98.8%), respectively. During the acute phase of dengue virus infection (day 1 to day 4), the tests performed on capillary blood samples had a sensitivity of 88.5% (95% CI, 82.0% to 95.0%) and a specificity of 93.8% (95% CI, 88.9% to 98.7%). During the convalescent phase of infection, this method allowed the viral serotype to be determined for 4 of 15 (27%) dengue virus-infected patients for whom virological diagnosis using venous samples was negative. Capillary blood samples could therefore be a good alternative for the diagnosis of dengue virus infection in tropical areas. Indeed, these samples are convenient for storage and transport without the need for a cold chain and simplify the collection of samples from children. Moreover, our results suggest that viral particles persist longer in capillary blood than in peripheral blood. Analysis of the viability of viral particles under these conditions may give new insights into the physiopathology of dengue virus infection and the transmission of dengue virus during outbreaks.

The objective of this study was to evaluate cancer mortality in pulp and paper industry workers exposed to chlorinated organic compounds. We assembled a multinational cohort of workers employed between 1920 and 1996 in 11 countries. Exposure to both volatile and nonvolatile organochlorine compounds was estimated at the department level using an exposure matrix. We conducted a standardized mortality ratio (SMR) analysis based on age and calendar-period-specific national mortality rates and a Poisson regression analysis. The study population consisted of 60,468 workers. Workers exposed to volatile organochlorines experienced a deficit of all-cause [SMR = 0.91; 95% confidence interval (CI), 0.89-0.93] and all-cancer (SMR = 0.93; 95% CI, 0.89-0.97) mortality, with no evidence of increased risks for any cancer of a priori interest. There was a weak, but statistically significant, trend of increasing risk of all-cancer mortality with increasing weighted cumulative exposure. A similar deficit in all-cause (SMR = 0.94; 95% CI, 0.91-0.96) and all-cancer (SMR = 0.94; 95% CI, 0.89-1.00) mortality was observed in those exposed to nonvolatile organochlorines. No excess risk was observed in cancers of a priori interest, although mortality from Hodgkin disease was elevated (SMR = 1.76; 95% CI, 1.02-2.82) . In this study we found little evidence that exposure to organochlorines at the levels experienced in the pulp and paper industry is associated with an increased risk of cancer, apart from a weak but significant association between all-cancer mortality and weighted cumulative volatile organochlorine exposure.

Assessment of smell function in clinical routine is often limited due to a lack of time and/or costs of the personnel administering the test. The aim of the present study was to validate a procedure allowing for self-administered olfactory testing in a clinical setting. Seventy-four healthy subjects (13 male, 61 female) from 18 to 30 years of age (mean 20.3 years) were tested on 2 days (interval 7-21 days, mean 8.7 days) with 16 odors of the "Sniffin' Sticks" identification test kit. On one occasion, the test was administered by an examiner. On another occasion, subjects administered the test to themselves, with the odors being identified after they had been "painted" on a sheet of paper. No significant differences were obtained between the results from both test procedures. With a maximum score of 16, assisted testing yielded a mean score of 13.7 [standard deviation (SD) 1.3] while the self-administered procedure yielded an average score of 13.8 (SD = 1.5) (P = 0.72). The mean difference between the assisted and the self-administered smell test procedures was 0.05 (SD = 1.28). The 95% confidence interval of differences ranged from -2.51 to 2.61. These results suggest that odor identification with the Sniffin' Sticks can also be administered by the subjects themselves.

OBJECTIVE: To determine whether evidence from observational studies supports the widely held belief that hypertension is more commonly a risk factor for deep than for lobar supratentorial intracerebral haemorrhage.METHODS: Studies comparing the frequency of hypertension as a risk factor for deep versus lobar supratentorial intracerebral haemorrhage, excluding haemorrhages with identified secondary causes, were identified and subjected to a meta-analysis. The effects of predefined methodological quality criteria on the results were assessed and other sources of bias were considered.RESULTS: The pooled result from all 28 included studies (about 4000 patients) found hypertension to be about twice as common in patients with deep as in those with lobar haemorrhage (odds ratio (OR) 2.10, 95% confidence interval (95% CI) 1.82 to 2.42), but there was significant heterogeneity between studies. The pooled OR was less extreme for studies that used a pre-stroke definition of hypertension, were population based or included first-ever strokes only. In the three studies meeting all criteria (601 patients), deep haemorrhage was associated with a smaller, statistically significant excess of hypertension (OR 1.50, 95% CI 1.09 to 2.07). The OR for studies confined to younger patients seemed to be more extreme (12.32, 95% CI 6.13 to 24.77), but none of these studies fulfilled our methodological quality criteria. Additional, unquantified sources of bias included uncertainty about whether those doctors reporting brain scans were blind to hypertension status, uncertain reliability of the classification of haemorrhage location and variable rates of investigation for secondary causes.CONCLUSIONS: An excess of hypertension was found in patients with deep versus lobar intracerebral haemorrhages without an identified secondary cause, but this may be due to residual, unquantified methodological biases.

Background: The number of elderly patients being admitted with aneurysmal subarachnoid haemorrhage (SAH) has been increasing. Treatment of the aneurysm may be offset by the higher rate of surgical or endovascular complications. Aim: To study the clinical condition at onset, complications during clinical course, treatment and outcome in a consecutive series of elderly patients. Methods: Patients who were ⩾75 years at the onset of SAH were selected from the databases of two hospitals. Data on clinical condition at onset (poor condition defined as World Federation of Neurological Surgeons (WFNS) Scale IV and V), clinical course, treatment and outcome were extracted. Univariate and multivariate regression analyses were carried out to identify predictors for in-hospital death and poor outcome, defined as death or dependency. Results: The data of 170 patients were retrieved, of whom 25 (15%) patients were independent at discharge; none of these patients had been admitted in a poor condition. Poor clinical condition on admission (odds ratio (OR) 7.9; 95% confidence interval (CI) 3.7 to 17) and recurrent haemorrhage (OR 7.5; 95% CI 2.5 to 23) were the strongest predictors for in-hospital death. Recurrent haemorrhage was the strongest predictor for poor outcome in the subset of patients who were admitted in good clinical condition. In all, 10 of 47 (21%) patients were independent at discharge after neurosurgical clipping (n = 34) or endovascular coiling (n = 13). Conclusion: Elderly patients with SAH have a poor prognosis. The effect of the initial haemorrhage is the most common reason for poor outcome. For patients who are admitted in good clinical condition, the most important complication leading to poor outcome is recurrent haemorrhage. Treatment of the aneurysm in patients ⩾75 years is feasible, may improve the outcome and should be strongly considered in patients who are admitted in a good condition.

The aim of the present study was to investigate whether repeated peak exposure (gassings) to sulphur dioxide (SO2) and other irritant gases increases the risk of new-onset asthma. A questionnaire was sent to 4,112 sulphite workers, of whom 1,919 completed the questionnaire and 396 completed the short-form questionnaire, which was sent out as a last reminder. A sample of 130 nonrespondents completed a telephone interview using the short-form questionnaire. The incidence of adult-onset, physician-diagnosed asthma during employment duration was analysed in relation to exposure to SO2 and gassings giving rise to respiratory symptoms. Incidence rates, as well as incidence rate ratios with 95% confidence interval (CI), were calculated. Further Cox regression models were used allowing assessment of hazard ratios (HR) stratified for sex and adjusted for atopy, smoking habits and age. The incidence rate for asthma among sulphite mill workers reporting gassings of SO2 was 6.2 out of 1,000 person-yrs, compared with 1.9 out of 1,000 person-yrs among subjects unexposed to SO2 and any gassings (HR (95% CI) 4.0 (2.1-7.7)). Among males reporting gassings to SO2, the HR (95% CI) for asthma was 5.8 (2.6-13) compared with unexposed males. In conclusion, repeated peak exposure to sulphur dioxide increased the incidence of asthma during work in sulphite pulp mills, which supports the hypothesis of irritant-induced asthma.

Background: The possibility that head injury may influence the development of multiple sclerosis (MS) has been studied inconclusively in the past. Objective: To determine whether head injury is associated with an increased risk of MS. Method: Analysis of database of linked hospital and death records, comparing the occurrence of MS in a cohort of people admitted to hospital with head injury and a reference cohort. Results: The rate ratio for MS after head injury, compared with the reference cohort, was 1.1 (95% confidence interval, 0.88 to 1.36). There was no significant increase in the risk of MS at either short or long time periods after head injury. Using length of hospital stay as a proxy for severity of injury, there was no significant increase in the rate ratio for MS after head injuries with hospital stays of less than two days (rate ratio = 1.1 (0.71 to 1.57)), two or more days (rate ratio = 1.0 (0.68 to 1.45)), or seven or more days (rate ratio = 1.3 (0.64 to 2.34)). Conclusions: The method used, record linkage, ensures that patients’ recollection of injury, or any tendency to attribute MS to injury, cannot have influenced the results. Injuries to the head were not associated with either the aetiological initiation or the clinical precipitation of onset of multiple sclerosis.

Background and objectives: Whether the association between mild hyperhomocysteinaemia and ischaemic stroke is the consequence of a predisposing genetic background or is due to the confounding influence of established predisposing factors remains to be determined. Methods: Plasma total homocysteine (tHcy) concentration and the distribution of the C 677 T genotypes of the methylenetetrahydrofolate reductase gene ( MTHFR ) were compared in 174 consecutive patients with stroke aged Results: tHcy concentrations were markedly higher in patients with ischaemic stroke (median 11.9 μmol/l, range 2.0–94.0) than in controls (median 9.8 μmol/l, range 4.7–49.6). An increased risk was also associated with the TT 677 genotype (odds ratio (OR) 1.98; 95% confidence interval (CI) 1.04 to 3.78) and with the T allele (1.40; 95% 1.03 to 1.92) of the MTHFR gene. A differential effect of Hcy levels on risk of stroke was observed according to the distribution of environmental–behavioural risk factors, with a stronger influence in the subcategory of people with hypertension and smokers (OR 24.8; 95% CI 3.15 to 196). A comparable environmental-dependent TT 677 MTHFR genotype–stroke association was observed in the genotype-disease analysis. Conclusions: A consistency of phenotype-disease analysis and genotype-disease analysis is indicated by analysing specific subcategories of patients, defined by the distribution of established risk factors. The assumption that the Hcy–stroke relationship is unlikely due to a reverse-causality bias is indirectly supported by our data.

Neurodevelopmental treatment (NDT) is a rehabilitation approach increasingly used in the care of stroke patients, although no evidence has been provided for its efficacy.To investigate the effects of NDT on the functional status and quality of life (QoL) of patients with stroke during one year after stroke onset.324 consecutive patients with stroke from 12 Dutch hospitals were included in a prospective, non-randomised, parallel group study. In the experimental group (n = 223), nurses and physiotherapists from six neurological wards used the NDT approach, while conventional treatment was used in six control wards (n = 101). Functional status was assessed by the Barthel index. Primary outcome was "poor outcome", defined as Barthel index12 or death after one year. QoL was assessed with the 30 item version of the sickness impact profile (SA-SIP30) and the visual analogue scale.At 12 months, 59 patients (27%) in the NDT group and 24 (24%) in the non-NDT group had poor outcome (corresponding adjusted odds ratio = 1.7 (95% confidence interval, 0.8 to 3.5)). At discharge the adjusted odds ratio was 0.8 (0.4 to 1.5) and after six months it was 1.6 (0.8 to 3.2). Adjusted mean differences in the two QoL measures showed no significant differences between the study groups at six or 12 months after stroke onset.The NDT approach was not found effective in the care of stroke patients in the hospital setting. Health care professionals need to reconsider the use of this approach.

Objective: To estimate the mortality of progressive supranuclear palsy (PSP) and to assess the quality of death certification in patients with PSP who died in England and Wales. Methods: An analysis was conducted of ICD-9 (International Classification of Diseases, version 9) coded deaths obtained through the Office of National Statistics over an eight year period. Results: The crude annual mortality rate was 1.77 (95% confidence interval, 1.64 to 1.90) cases per million, using the mid-1996 population estimate for England and Wales. Annual mortality increased over time, possibly as a result of increased incidence or increased awareness of the disorder. Forty nine death certificates from deceased patients previously diagnosed clinically showed that the commonest proximate cause of death was pneumonia, occurring in 45% of cases (22/49). The underlying cause of death was cited as pneumonia in 14% of cases (7/49). PSP was mentioned in only 65% of death certificates (32/49). Eight of the 49 cases (16%) underwent necropsy and results were available for five of these cases. PSP was confirmed pathologically in four; the remaining case was diagnosed as Parkinson's disease. Conclusions: Further research is needed to establish the reasons for the observed increase in mortality. Determining the population mortality rate for PSP using the ICD-9 coding system is problematic but is likely to improve following the introduction of ICD-10 updated codes and coding rules.