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SummaryBackgroundPsychotic experiences predict adverse health outcomes, particularly if they are persistent. However, it is unclear what distinguishes persistent from transient psychotic experiences.AimsIn a large population-based cohort, we aimed to (a) describe the course of hallucinatory experiences from childhood to adolescence, (b) compare characteristics of youth with persistent and remittent hallucinatory experiences, and (c) examine prediction models for persistence.MethodYouth were assessed longitudinally for hallucinatory experiences at mean ages of 10 and 14 years (n = 3473). Multi-informant-rated mental health problems, stressful life events, self-esteem, non-verbal IQ and parental psychopathology were examined in relation to absent, persistent, remittent and incident hallucinatory experiences. We evaluated two prediction models for persistence with logistic regression and assessed discrimination using the area under the curve (AUC).ResultsThe persistence rate of hallucinatory experiences was 20.5%. Adolescents with persistent hallucinatory experiences had higher baseline levels of hallucinatory experiences, emotional and behavioural problems, as well as lower self-esteem and non-verbal IQ scores than youth with remittent hallucinatory experiences. Although the prediction model for persistence versus absence of hallucinatory experiences demonstrated excellent discriminatory power (AUC-corrected = 0.80), the prediction model for persistence versus remittance demonstrated poor accuracy (AUC-corrected = 0.61).ConclusionsThis study provides support for the dynamic expression of childhood hallucinatory experiences and suggests increased neurodevelopmental vulnerability in youth with persistent hallucinatory experiences. Despite the inclusion of a wide array of psychosocial parameters, a prediction model discriminated poorly between youth with persistent versus remittent hallucinatory experiences, confirming that persistent hallucinatory experiences are a complex multifactorial trait.

BackgroundRecovery in schizophrenia is a complex process, involving clinical, societal and personal recovery. Until now, studies analysed these domains separately, without examining their mutual relations and changes over time.AimsThis study aimed to examine different states of recovery and transition rates between states.MethodThe Pharmacotherapy Monitoring and Outcome Survey (2006–2017) yearly assesses patients with schizophrenia in the Northern Netherlands. Data from 2327 patients with one up to 11 yearly measurements on clinical, societal and personal recovery were jointly analysed with a mixture latent Markov model (MLMM).ResultsThe selected MLMM had four states that differed in degree and pattern of recovery outcomes. Patients in state 1 were least recovered on any domain (16% of measurements), and partly recovered in states 2 (25%; featured by negative symptoms) and 3 (21%; featured by positive symptoms). Patients in state 4 (38%) were most recovered, except for work, study and housekeeping. At the subsequent measurement, the probability of remaining in the same state was 77–89%, transitioning to a better state was 4–12% and transitioning to a worse state was 4–6%; no transitions occurred between states 1 and 4. Female gender, shorter illness duration and less schizophrenia were more prevalent in better states.ConclusionsQuite a high recovery rate was present among a substantial part of the measurements (38%, state 4), with a high probability (89%) of remaining in this state. Transition rates in the other states might increase to a more favourable state by focusing on adequate treatment of negative and positive symptoms and societal problems.

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.

Objective Patients with cancer are at high risk of depression. However, the risk of major depressive disorder (MDD) after cancer diagnosis has not been studied in a population setting in Japan. This cohort study used a Japanese medical claims database to examine time to MDD in cancer patients and the risk of MDD (hazard ratio; HR) compared with matched cancer‐free controls. Methods Primary endpoint was time to MDD (starting 6 months before cancer diagnosis) in adult (18–74 years) cancer patients; secondary endpoint was time to MDD (6 months before to 12 months after cancer diagnosis) in a matched cohort of cancer patients and cancer‐free controls. Multivariate analyses were performed to determine HRs for all cancers and for each cancer site. Results Of 35 008 cancer patients (mean age, 53.3 years), 2201 (6.3%) were diagnosed with MDD within 66 months. Matched cancer patients (n = 30 372) had an elevated risk of MDD compared with cancer‐free controls (n = 303 720; HR [95% confidence interval] 2.96 [2.77–3.16]). MDD risk was highest in patients with multiple cancers, pancreatic cancer, and brain cancer. Compared with middle‐aged patients, risk was higher in patients

The highly contagious nature of SARS-CoV-2 has led to several studies on the transmission of the virus. A little studied potential fomite of great concern in the community is currency, which has been shown to harbor microbial pathogens in several studies. Since the onset of the COVID-19 pandemic, many businesses in the United States have limited the use of banknotes in favor of credit cards. However, SARS-CoV-2 has shown greater stability on plastic in several studies. Herein, the stability of SARS-CoV-2 at room temperature on banknotes, money cards and coins was investigated. In vitro studies with live virus suggested SARS-CoV-2 was highly unstable on banknotes, showing an initial rapid reduction in viable virus and no viral detection by 24 hours. In contrast, SARS-CoV-2 displayed increased stability on money cards with live virus detected after 48 hours. Environmental swabbing of currency and money cards on and near the campus of Brigham Young University supported these results, with no detection of SARS-CoV-2 RNA on banknotes, and a low level on money cards. However, no viable virus was detected on either. These preliminary results suggest that the use of money cards over banknotes in order to slow the spread of this virus may be ill-advised. These findings should be investigated further through larger environmental studies involving more locations.

BackgroundClozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia.AimsTo investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK.MethodUsing information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use.ResultsOf 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2.62, 95% CI 1.73–3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14–2.72).ConclusionsThese findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.

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

Objectives To explore epidemiological features of demodicosis relevant to UK veterinary general practitioners. Breed risk factors were proposed as distinct between juvenile‐onset and adult‐onset disease. Materials and Methods The study used anonymised clinical data on dogs under primary veterinary care at practices enrolled in the UK VetCompass Programme. Case inclusion required recording of a final demodicosis diagnosis for a dermatological condition that was present during the 2013 study period. Risk factor analysis used multivariable logistic regression modelling. Results In dogs aged 4 years (adult‐onset), the 1‐year period prevalence was 0.05% (95% confidence interval: 0.0.04 to 0.06). Six breeds showed increased odds of demodicosis compared with crossbred dogs: Chinese shar‐pei, shih‐tzu, West Highland white terrier, pug, boxer and Border terrier. Clinical Significance Juvenile‐onset demodicosis is much more common (about 10 times higher) than the adult‐onset form. Knowledge of the predisposed breeds for these two presentations can assist with diagnosis and support the concept of distinct aetiopathogenetic phenotypes.

One of the most common usages of radiation in current medical diagnosis is computed tomography (CT) using X-rays. The potential health risk of CT scans has been discussed in various studies to determine whether low-dose radiation from CT could enhance the chromosome aberration yields in pediatric patients and increase their risk of carcinogenesis. For this reason, it is of great interest to study the effects of low-dose radiation. The induction of DNA damage by a CT scan examination has been demonstrated in several reports by the γ-H2AX assay, the micronuclei assay and dicentrics measurements. However, the results of most studies showed limitations. On the other hand, epidemiological studies give contradictory results for post-natal radiation exposure in the low-dose range, so it is still difficult to draw conclusions about the effects of CT examinations and risk of carcinogenesis. This article provides an overview of previously published data and summarizes the current state of knowledge.

BackgroundMental health policy makers require evidence-based information to optimise effective care provision based on local need, but tools are unavailable.AimsTo develop and validate a population-level prediction model for need for early intervention in psychosis (EIP) care for first-episode psychosis (FEP) in England up to 2025, based on epidemiological evidence and demographic projections.MethodWe used Bayesian Poisson regression to model small-area-level variation in FEP incidence for people aged 16–64 years. We compared six candidate models, validated against observed National Health Service FEP data in 2017. Our best-fitting model predicted annual incidence case-loads for EIP services in England up to 2025, for probable FEP, treatment in EIP services, initial assessment by EIP services and referral to EIP services for ‘suspected psychosis’. Forecasts were stratified by gender, age and ethnicity, at national and Clinical Commissioning Group levels.ResultsA model with age, gender, ethnicity, small-area-level deprivation, social fragmentation and regional cannabis use provided best fit to observed new FEP cases at national and Clinical Commissioning Group levels in 2017 (predicted 8112, 95% CI 7623–8597; observed 8038, difference of 74 [0.92%]). By 2025, the model forecasted 11 067 new treated cases per annum (95% CI 10 383–11 740). For every 10 new treated cases, 21 and 23 people would be assessed by and referred to EIP services for suspected psychosis, respectively.ConclusionsOur evidence-based methodology provides an accurate, validated tool to inform clinical provision of EIP services about future population need for care, based on local variation of major social determinants of psychosis.

Diagnostic Exome Sequencing in 100 Consecutive Patients With Both Epilepsy and Intellectual Disability Snoeijen-Schouwenaars FM, van Ool JS, Verhoeven JS, et al. Epilepsia. 2019;60(1):155-164. doi:10.1111/epi.14618. Epub December 7, 2018. PMID: 30525188.Objective:Epilepsy is highly prevalent among patients with intellectual disability (ID), and seizure control is often difficult. Identification of the underlying etiology in this patient group is important for daily clinical care. We assessed the diagnostic yield of whole-exome sequencing (WES). In addition, we evaluated which clinical characteristics influence the likelihood of identifying a genetic cause and we assessed the potential impact of the genetic diagnosis on (antiepileptic) treatment strategy.Methods:One hundred patients with both unexplained epilepsy and (borderline) ID (intelligence quotient ≤85) were included. All patients were evaluated by a clinical geneticist, a (pediatric) neurologist, and/or a specialist ID physician. Whole-exome sequencing analysis was performed in 2 steps. In step 1, analysis was restricted to the latest versions of ID and/or epilepsy gene panels. In step 2, exome analysis was extended to all genes (so-called full exome analysis). The results were classified according to the American College of Medical Genetics and Genomics guidelines. Results: In 58 patients, the diagnostic WES analysis reported one or more variant(s). In 25 of the 100 patients, these were classified as (likely) pathogenic, in 24 patients as variants of uncertain significance, and in the remaining patients the variant was most likely not related to the phenotype. In 10 (40%) of 25 patients with a (likely) pathogenic variant, the genetic diagnosis might have an impact on the treatment strategy in the future.Significance:This study illustrates the clinical diagnostic relevance of WES for patients with both epilepsy and ID. It also demonstrates that implementing WES diagnostics might have impact on the (antiepileptic) treatment strategy in this population. Confirmation of variants of uncertain significance in (candidate) genes may further increase the yield. Diagnostic Yield of Genetic Tests in Epilepsy: A Meta-Analysis and Cost-Effectiveness Study Sánchez Fernández I, Loddenkemper T, Gaínza-Lein M, Sheidley BR, Poduri A. Neurology. 2019. Epub ahead of print. pii: 10.1212/WNL.0000000000006850. doi:10.1212/WNL.0000000000006850. PMID: 30610098 Objective:To compare the cost-effectiveness of genetic testing strategies in patients with epilepsy of unknown etiology.Methods:This meta-analysis and cost-effectiveness study compared strategies involving 3 genetic tests: chromosomal microarray (CMA), epilepsy panel (EP) with deletion/duplication testing, and whole-exome sequencing (WES) in a cost-effectiveness model, using “no genetic testing”“ as a point of comparison.Results:Twenty studies provided information on the diagnostic yield of CMA (8 studies), EP (9 studies), and WES (6 studies). The diagnostic yield was highest for WES: 0.45 (95% confidence interval [CI]: 0.33-0.57; 0.32 [95% CI: 0.22-0.44] adjusting for potential publication bias), followed by EP: 0.23 (95% CI: 0.18-0.29) and CMA: 0.08 (95% CI: 0.06-0.12). The most cost-effective test was WES with an incremental cost-effectiveness ratio (ICER) of US$15 000/diagnosis. However, after adjusting for potential publication bias, the most cost-effective test was EP (ICER: US$15 848/diagnosis) followed by WES (ICER: US$34 500/diagnosis). Among combination strategies, the most cost-effective strategy was WES, then if nondiagnostic, EP, then if nondiagnostic, CMA (ICER: US$15 336/diagnosis); although adjusting for potential publication bias, the most cost-effective strategy was EP ± CMA ± WES (ICER: US$18 385/diagnosis). Although the cost-effectiveness of individual tests and testing strategies overlapped, CMA was consistently less cost-effective than WES and EP.Conclusion:Whole-exome sequencing and EP are the most cost-effective genetic tests for epilepsy. Our analyses support for a broad population of patients with unexplained epilepsy, starting with these tests. Although less expensive, CMA has lower yield, and its use as the first-tier test is thus not supported from a cost-effectiveness perspective.

BackgroundGeneralised anxiety disorder and symptoms are associated with poor physical, emotional and social functioning and frequent primary and acute care visits. We investigated recent temporal trends in anxiety and related mental illness in UK general practice.AimsThe aims of this analysis are to examine temporal changes in recording of generalised anxiety in primary care and initial pharmacologic treatments.MethodAnnual incidence rates of generalised anxiety diagnoses and symptoms were calculated from 795 UK general practices contributing to The Health Improvement Network (THIN) database between 1998 and 2018. Poisson mixed regression was used to account for age, gender and general practitioner practice. Subsequent pharmacologic treatment was examined.ResultsGeneralised anxiety recording rates increased in both genders aged 18–24 between 2014 and 2018. For women, the increase was from 17.06 to 23.33/1000 person years at risk (PYAR); for men, 8.59 to 11.65/1000 PYAR. Increases persisted for a composite of anxiety and depression (49.74 to 57.81/1000 PYAR for women; 25.41 to 31.45/1000 PYAR for men). Smaller increases in anxiety were seen in both genders age 25–34 and 35–44. Anxiety rates among older patients remained stable, although a composite of anxiety and depression decreased for older women. About half of drug-naïve patients were prescribed anxiety drugs within 1 year following diagnosis. The most common choice was a selective serotonin reuptake inhibitor. Benzodiazepine prescription rate has fallen steadily.ConclusionsWe observed a substantial increase in general practitioner consulting for generalised anxiety and depression recently, concentrated within younger people and in particular women.

El CAV-AEP publica anualmente el calendario de vacunaciones que estima idóneo para los niños residentes en España, teniendo en cuenta la evidencia científica disponible. Se mantiene el esquema 2 + 1 (2, 4 y 11 meses) con vacunas hexavalentes (DTPa-VPI-Hib-HB) y con antineumocócica conjugada 13-valente. Se aconseja un refuerzo a los 6 años, preferentemente con DTPa (si está disponible), junto a una dosis de polio para aquellos que recibieron esquemas 2 + 1, así como vacunación con Tdpa en adolescentes y en cada embarazo, preferentemente entre las 27 y las 32 semanas. La vacuna del rotavirus debería ser sistemática para todos los lactantes. Se sigue proponiendo la incorporación en el calendario de la vacuna antimeningocócica B, con esquema 2 + 1 en lactantes. Además de la inclusión de la vacuna antimeningocócica conjugada tetravalente (MenACWY) a los 12 años con rescate hasta los 18 años, inclusive, el CAV recomienda que esta vacuna sea introducida también a los 12 meses de edad, sustituyendo a MenC. Igualmente, se recomienda en los mayores de 6 semanas de edad con factores de riesgo o que viajen a países de elevada incidencia de estos serogrupos. Se emplearán esquemas de 2 dosis para triple vírica (12 meses y 3-4 años) y varicela (15 meses y 3-4 años). La segunda dosis se podría aplicar como vacuna tetravírica. Se recomienda la vacunación sistemática universal frente al VPH, tanto a chicas como a chicos, preferentemente a los 12 años, debiendo realizar un mayor esfuerzo para mejorar las coberturas. La de 9 genotipos amplía la cobertura para ambos sexos, The CAV-AEP annually publishes the immunisation schedule considered optimal for all children resident in Spain, taking into account the available evidence. The 2 + 1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa- VPI-Hib-HB) and with 13-valent pneumococcal conjugate. A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2 + 1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks. Rotavirus vaccine should be systematic for all infants. Meningococcal B vaccine, with a 2+1 schedule, should be included in routine calendar. In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups. Two-dose schedules for MMR (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine. Universal systematic vaccination against HPV is recommended, both for girls and boys, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders

The Fukushima Health Management Survey (FHMS) was implemented in the wake of the 2011 Fukushima Daiichi Nuclear Power Plant accident. The primary purpose of this survey was to monitor the long-term health of residents, promote their future well-being and confirm whether long-term low-dose radiation exposure affects health. The FHMS results indicated very low-radiation exposure doses among residents and that no discernible increased incidence of radiation-related health effects could be expected. However, psychological distress was found to be far greater among people in Fukushima than those in other areas affected by the accident’s preceding Great East Japan Earthquake and the resultant tsunami. Additionally, prevalence of lifestyle-related health problems such as being overweight, hypertension, diabetes mellitus, dyslipidaemia and liver dysfunction increased among evacuees. Thyroid examinations of asymptomatic individuals, using ultrasound techniques, also contributed to public concern and fear about the health effects of radiation. The FHMS ultimately revealed that ethical considerations are important in the design and implementation of health surveillance and epidemiological studies.

Background Being a current psychiatric in-patient is one of the strongest statistical risk factors for suicide. It is usually assumed that this strong association is not causal but is a result of the combination of the selection of high-risk patients for admission and the imperfect protection from suicide afforded by psychiatric wards. Logically, a third factor, which is causal, might play a role in the association. It has recently been suggested that adverse experiences in psychiatric units such as trauma, stigma and loss of social role might precipitate some in-patient suicides. Aims To consider whether there is a causal association between psychiatric hospitalisation and suicide. Method We used the framework of Austin Bradford Hill’s criteria for assessing causality in epidemiology to consider the possibility that psychiatric hospitalisation might causally contribute to the extent and variation in in-patient suicide rates. Results The association between psychiatric hospitalisation and suicide clearly meets five of the nine Hill’s criteria (strength of association, consistency, plausibility, coherence and analogy) and partially meets three of the remaining four criteria (gradient of exposure, temporality and experimental evidence). Conclusions Admission to hospital itself might play a causal role in a proportion of in-patient suicides. The safety of being in hospital with respect to suicide could be examined with a large-scale randomised controlled trial (RCT). In the absence of an RCT, the possibility of a causal role provides further impetus to calls to make care in the community more available and psychiatric hospitals more acceptable to patients. Declaration of interest M.M.L. and C.J.R. have provided expert testimony in legal proceedings following in-patient suicide. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Background Previous research has found that a “web-push” approach to data collection, which involves contacting people by mail to request an Internet survey response while withholding a paper response option until later in the contact process, consistently achieves lower response rates than a “paper-only” approach, whereby all respondents are contacted and requested to respond by mail. Method An experiment was designed, as part of the Millennium Cohort Family Study, to compare response rates, sample representativeness, and cost between a web-push and a paper-only approach; each approach comprised 3 stages of mail contacts. The invited sample (n = 4,935) consisted of spouses married to U.S. Service members, who had been serving in the military between 2 and 5 years as of October, 2011. Results The web-push methodology produced a significantly higher response rate, 32.8% compared to 27.8%. Each of the 3 stages of postal contact significantly contributed to response for both treatments with 87.1% of the web-push responses received over the Internet. The per-respondent cost of the paper-only treatment was almost 40% higher than the web-push treatment group. Analyses revealed no meaningfully significant differences between treatment groups in representation. Conclusion These results provide evidence that a web-push methodology is more effective and less expensive than a paper-only approach among young military spouses, perhaps due to their heavy reliance on the internet, and we suggest that this approach may be more effective with the general population as they become more uniformly internet savvy.

Recognized for conducting cutting-edge science in the field of radiation health effects research, the Department of Energy's (DOE) Russian Health Studies Program has continued to generate excitement and enthusiasm throughout its 23-year mission to assess worker and public health risks from radiation exposure resulting from nuclear weapons production activities in the former Soviet Union. The three goals of the Program are to: (1) clarify the relationship between health effects and chronic, low-to-medium dose radiation exposure; (2) estimate the cancer risks from exposure to gamma, neutron, and alpha radiation; and (3) provide information to the national and international organizations that determine radiation protection standards and practices. Research sponsored by DOE's Russian Health Studies Program is conducted under the authority of the Joint Coordinating Committee for Radiation Effects Research (JCCRER), a bi-national committee representing Federal agencies in the United States and the Russian Federation. Signed in 1994, the JCCRER Agreement established the legal basis for the collaborative research between USA and Russian scientists to determine the risks associated with working at or living near Russian former nuclear weapons production sites. The products of the Program are peer-reviewed publications on cancer risk estimates from worker and community exposure to ionizing radiation following the production of nuclear weapons in Russia. The scientific return on investment has been substantial. Through 31 December 2015, JCCRER researchers have published 299 peer-reviewed publications. To date, the research has focused on the Mayak Production Association (Mayak) in Ozersk, Russia, which is the site of the first Soviet nuclear weapons production facility, and people in surrounding communities along the Techa River. There are five current projects in the Russian Health Studies Program: two radiation epidemiology studies; two historical dose reconstruction studies and a worker biorepository. National and international standard-setting organizations use cancer risk estimates computed from epidemiological and historical dose reconstruction studies to validate or revise radiation protection standards. An overview of the most important research results will be presented.

Background The domestic rabbit is a common pet species, but limited research exists on the health of pet rabbits. This study aimed to characterise common disorders of pet rabbits and reasons for mortality as recorded by veterinary practices in England. Methods This cross-sectional study covered anonymised clinical records of 6349 rabbits attending 107 primary veterinary care clinics. Results The median age was 3.2 years (interquartile range (IQR) 1.6–5.1), and the median adult bodyweight was 2.1 kg (IQR 1.7–2.6). The most common breed types were domestic (n=2022, 31.9 per cent), lop (1675, 26.4 per cent) and Netherland dwarf (672, 10.6 per cent). For those rabbits that died during the study period, the median age at death was 4.3 years (IQR 2.1–7.0). The most common causes of death were recorded as myiasis (prevalence 10.9 per cent, 95 per cent confidence interval (CI): 7.4 to 15.2), anorexia (4.9 per cent, 95 per cent CI: 4.0 to 10.4), recumbency/collapse (4.9 per cent, 95 per cent CI: 4.0 to 10.4) and ileus (4.3 per cent, 95 per cent CI: 3.5 to 9.5). The most prevalent specific disorders recorded were overgrown claw/nails (16.0 per cent, 95 per cent CI: 14.5 to 17.5), overgrown molar(s) (7.6 per cent, 95 per cent CI: 6.6 to 8.7), perineal soiling (4.5 per cent, 95 per cent CI: 3.7 to 5.4), overgrown incisor(s) (4.3 per cent, 95 per cent CI: 3.5 to 5.2) and ileus (4.2 per cent, 95 per cent CI: 3.4 to 5.0). Conclusions This study augments the limited evidence base on rabbit health and can assist veterinarians to better advise owners on optimal animal husbandry priorities.

Infective endocarditis is a severe disease with high mortality. Despite a global trend towards an increase in staphylococcal aetiologies, in older patients and a decrease in viridans streptococci, we have observed in recent studies great epidemiologic disparities between countries. In order to evaluate these differences among Mediterranean countries, we performed a PubMed search of infective endocarditis case series for each country. Data were available for 13 of the 18 Mediterranean countries. Despite great differences in diagnostic strategies, we could classify countries into three groups. In northern countries, patients are older (>50 years old), have a high rate of prosthetic valves or cardiac electronic implantable devices and the main causative agent is Staphylococcus aureus. In southern countries, patients are younger (

This paper revisits and reiterates the needs, purposes and requirements of biodosimetric assays for long-term dose and health risk assessments. While the most crucial need for biodosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure assessment. Hence, the needs for retrospective dose estimation are likely to be greater in the future. The value of biodosimetry can be considerably enhanced with the development of new or improved methods, particularly with suitability for application at long periods of time after exposure.

Cinnamaldehyde (CNMA), an organic compound that gives cinnamon its flavor and odor, was investigated for its virucidal activity on norovirus surrogates, murine norovirus (MNV) and feline calicivirus (FCV), and hepatitis A virus (HAV). Initially, different concentrations of CNMA (0.1, 0.5 and 1 %) were individually mixed with each virus at titers of ca. 6–7 log10 TCID50/ml and incubated 2 h at 4 and 37 °C. CNMA was effective in reducing the titers of norovirus surrogates in a dose-dependent manner after 2 h at 37 °C, while HAV titers were reduced by 1 log10 after treatment with 1 % of CNMA. When incubation time was extended, HAV titers were reduced by 3.4 and 2.7 log10 after overnight incubation at 37 °C with 1 and 0.5 % of CNMA, respectively. Moreover, this paper analyzed, for the first time, the antiviral activity of adding an active electrospun interlayer based on zein and CNMA to a polyhydroxybutyrate packaging material (PHB) in a multilayer form. Biodegradable multilayer systems prepared with 2.60 mg/cm2 (~9.7 %) of CNMA completely inactivated FCV according to ISO 22196:2011, while MNV titers were reduced by 2.75 log10. When the developed multilayer films were evaluated after one month of preparation or at 25 °C, the antiviral activity was reduced as compared to freshly prepared multilayer films evaluated at 37 °C. The results show the excellent potential of this system for food contact applications as well as for active packaging technologies in order to maintain or extend food quality and safety., This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (RYC-2012-09950, AGL2015-63855-C2-1 and INIA Grant RTA2014-00024-C04-03). GS was supported by the “Ramón y Cajal” Young Investigator and MJF was recipient of a Juan de la Cierva contract from the MINECO. JLC-M was supported by the Departamento Administrativo de Ciencia, Tecnología e Innovación (Colciencias) of Colombian Government and WR by the “Student Mobility for Placement e SMP” Grant of the EU Life Learning Program.

Power-frequency magnetic field exposure science as it relates to men and couples have not been explored despite the advantage of this information in the design and interpretation of reproductive health epidemiology studies. This analysis examined the distribution and temporal variability of exposures in men, and the correlation of exposures within couples using data from a longitudinal study of 25 men and their female partners recruited from an infertility clinic. The average and 90th percentile demonstrated fair to good reproducibility, whereas the maximum showed poor reproducibility over repeated sampling days, each separated by a median of 4.6 weeks. Average magnetic field exposures were also strongly correlated within couples, suggesting that one partner's data could be used as a surrogate in the absence of data from the other for this metric. Environment was also an important effect modifier in these explored matters. These issues should be considered in future relevant epidemiology studies.

Stranded California sea lions considered unable to survive in the wild are often placed in public display facilities. Exposure to the biotoxin domoic acid (DA) is a common cause of stranding, and chronic effects are observed long after initial exposure. Medical records for 171 sea lions placed in US institutions between 2000 and 2016 were reviewed, including results from clinical examinations, histopathology, behavioural testing and advanced imaging. There was a statistically significant increase in neurological disease detected in neonates (24%) compared with other age classes (11%). Sixty per cent of all neurological cases died during the study period. In the 11 neurological neonate cases, six died (55%) and five are still alive with three of five developing epilepsy during placement. Of the six neurological neonate cases that died, one was attributed to DA toxicosis, one to seizures and four to acute unexplained neurological disease. This survey suggests delayed neurological disease can develop in sea lions after stranding as neonates. These data coupled with stranding records and epidemiological data on DA-producing algal blooms suggest further research into effects of neonatal exposure to DA on risk of neurological disease in later life is warranted. California sea lions offer a natural model of DA exposure to study such effects.

Introduction Hantaviruses are maintained by mammalian hosts, such as rodents, and are shed in their excretions. Clinical disease can occur in humans from spillover infection. Brown rats (Rattus norvegicus) are the globally distributed reservoir host of Seoul virus (SEOV). Human cases of SEOV-associated haemorrhagic fever with renal syndrome (SEOV-HFRS)have been reported in Great Britain (GB) since 1977. Methods Brown rats (n=68) were trapped from a variety of peridomestic locations, with a focus on pig farms. Kidney and lung tissues were tested for viral RNA using a pan-hantavirus RT-PCR assay followed by Sanger sequencing and analysis. Results SEOV RNA was detected in 19 per cent (13/68, 95% CI 11 to 30) of rats and all sequences fell within SEOV lineage 9. Twelve sequences were highly similar to each other and to the previously reported GB Humber strain of SEOV (98 per cent). One rat SEOV sequence was more distant. The SEOV prevalence in rats from pig farms was significantly greater (p=0.047) than other sites sampled. No significant sex or age differences were observed among positive and negative rats. Discussion The results from this study suggest that SEOV could be widespread in wild rats in GB and therefore pose a potential risk to public health.

Extending on earlier work, trends in bovine tuberculosis (bTB) from 2003 to 2015 are described for the countries of the UK and the Republic of Ireland using standardised definitions and measures. Based on measures of animal and herd incidence, there remains a stable situation of extremely low prevalence in Scotland and the Low Risk Area of England, and a higher but ongoing reduction in prevalence in the Republic of Ireland. In Northern Ireland, there has been a rising bTB trend during 2010-2015, although not to levels experienced during 2002-2004. In the High Risk Area and Edge Area of England during 2010-2015, the rising bTB trends have continued but with some recent evidence of stabilisation. In Wales, prevalence has fallen subsequent to a peak in 2008. The paper considers country-level differences in the light of key policy changes, which are presented in detail. This work is unique, and will assist policymakers when critically evaluating policy options for effective control and eradication. Ongoing updates of this analysis would be useful, providing an evidence base for country-level comparison of bTB trends into the future. The use of multivariable analytical methods should be considered, but will rely on substantial sharing of raw data across the five countries.

BackgroundRelevance of diminished mental capacity in anorexia nervosa (AN) to course of disorder is unknown.AimsTo examine prognostic relevance of diminished mental capacity in AN.MethodA longitudinal study was conducted in 70 adult female patients with severe AN. At baseline, mental capacity was assessed by psychiatrists, and clinical and neuropsychological data (decision-making) were collected. After 1 and 2 years, clinical and neuropsychological assessments were repeated, and remission and admission rates were calculated.ResultsPeople with AN with diminished mental capacity had a less favourable outcome with regard to remission and were admitted more frequently. Their appreciation of illness remained hampered. Decision-making did not improve, in contrast to people with full mental capacity.ConclusionsPeople with AN with diminished mental capacity seem to do less well in treatment and display decision-making deficiencies that do not ameliorate with weight improvement.

We investigated whether dried cerebrospinal fluid (CSF) conserved on filter paper can be used as a substrate for accurate PCR diagnosis of important causes of bacterial meningitis in the Lao PDR. Using mock CSF, we investigated and optimized filter paper varieties, paper punch sizes, elution volumes and quantities of DNA template to achieve sensitive and reliable detection of bacterial DNA from filter paper specimens. FTA Elute Micro Card™ (Whatman, Maidstone, UK) was the most sensitive, consistent and practical variety of filter paper. Following optimization, the lower limit of detection for Streptococcus pneumoniae from dried mock CSF spots was 14 genomic equivalents (GE)/μL (interquartile range 5.5 GE/μL) or 230 (IQR 65) colony forming units/mL. A prospective clinical evaluation for S. pneumoniae, S. suis and Neisseria meningitidis was performed. Culture and PCR performed on fresh liquid CSF from patients admitted with a clinical diagnosis of meningitis (n = 73) were compared with results derived from dried CSF spots. Four of five fresh PCR-positive CSF samples also tested PCR positive from dried CSF spots, with one patient under the limit of detection. In a retrospective study of S. pneumoniae samples (n = 20), the median (IQR; range) CSF S. pneumoniae bacterial load was 1.1 × 104 GE/μL (1.2 × 105; 1 to 6.1 × 106 DNA GE/μL). Utilizing the optimized methodology, we estimate an extrapolated sensitivity of 90%, based on the range of CSF genome counts found in Laos. Dried CSF filter paper spots could potentially help us to better understand the epidemiology of bacterial meningitis in resource-poor settings and guide empirical treatments and vaccination policies. © 2013 The Authors. Clinical Microbiology and Infection published by John Wiley and Sons Ltd on behalf of the European Society of Clinical Microbiology and Infectious Disease.

Prescription veterinary medicine (PVM) use in the United Kingdom is an area of increasing focus for the veterinary profession. While many studies measure antimicrobial use on dairy farms, none report the quantity of antimicrobials stored on farms, nor the ways in which they are stored. The majority of PVM treatments occur in the absence of the prescribing veterinarian, yet there is an identifiable knowledge gap surrounding PVM use and farmer decision making. To provide an evidence base for future work on PVM use, data were collected from 27 dairy farms in England and Wales in Autumn 2016. The number of different PVM stored on farms ranged from 9-35, with antimicrobials being the most common therapeutic group stored. Injectable antimicrobials comprised the greatest weight of active ingredient found while intramammary antimicrobials were the most frequent unit of medicine stored. Antimicrobials classed by the European Medicines Agency as critically-important to human health were present on most farms, and the presence of expired medicines and medicines not licensed for use in dairy cattle was also common. The medicine resources available to farmers are likely to influence their treatment decisions, therefore evidence of the PVM stored on farms can help inform understanding of medicine use.

The aim of this work was to identify the key mechanisms governing transport of organic chemical substances from consumer articles to cotton wipes. The results were used to establish a mechanistic model to improve assessment of dermal contact exposure. Four types of PVC flooring, 10 types of textiles and one type of inkjet printed paper were used to establish the mechanisms and model. Kinetic extraction studies in methanol demonstrated existence of matrix diffusion and indicated the presence of a substance surface layer on some articles. Consequently, the proposed substance transfer model considers mechanical transport from a surface film and matrix diffusion in an article with a known initial total substance concentration. The estimated chemical substance transfer values to cotton wipes were comparable to the literature data (relative transfer ∼2%), whereas relative transfer efficiencies from spiked substrates were high (∼50%). For consumer articles, high correlation (r 2 =0.92) was observed between predicted and measured transfer efficiencies, but concentrations were overpredicted by a factor of 10. Adjusting the relative transfer from about 50% used in the model to about 2.5% removed overprediction. Further studies are required to confirm the model for generic use. © 2016 Nature America, Inc. All rights reserved.

Objectives To describe the epidemiology of end stage renal disease (ESRD). Design Mixed-methods systematic review. Setting The countries of the Gulf Cooperation Council (GCC) which consist of Saudi Arabia, the United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman. Participants Defined to have ESRD or patients on regular dialysis for a minimum dialysis period of at least three months. Since many outcomes were reviewed, studies that estimated the incidence and prevalence of ESRD as outcomes should not have defined the study population as ESRD population or patients on regular dialysis. Studies where the study population mainly comprised children or pregnant woman were excluded. Main outcome measures The trends of the incidence, prevalence, and mortality rate of ESRD; also, causes of mortality, primary causes and co-morbid conditions associated with ESRD. Results 44 studies included in this review show that the incidence of ESRD has increased while the prevalence and mortality rate of ESRD in the GCC has not been reported sufficiently. The leading primary causes of ESRD recorded in the countries of the GCC is diabetes with the most prevalent co-morbid conditions being Hypertension and Hepatitis C Virus infection; the most common cause of death was cardiovascular disease and sepsis. Conclusions This review highlights that the lack of national renal registries data is a critical issue in the countries of the GCC. The available data also do not provide an accurate and updated estimate for relevant outcomes. Additionally, considering the increasing burden of chronic kidney disease (CKD), these results stressed the needs and the importance of preventative strategies for leading causes of ESRD. Furthermore, more studies are needed to describe the epidemiology of ESRD and for assessing the overall quality of renal care.

INTRODUCTION: Human serofrequency of antibodies against Taenia solium antigens was determined and risk factors for cysticercosis transmission were identified. METHODS: Individuals (n=878) from periurban and rural locations of Lages, SC, were interviewed to gather demographic, sanitary and health information. Interviews and blood sample collections by finger prick on Whatman filter paper were performed from August 2004 to May 2005. Observation determined that 850 samples were suitable for analysis and were tested by ELISA using vesicular fluid of Taenia crassiceps heterologous antigen. To ensure the reliability of the results, 77 samples of the dried blood were matched with sera. The reactive samples were submitted to a serum confirmatory immunoblot (IB) test using purified Taenia crassiceps glycoproteins. RESULTS: The ELISA results for the dried blood and serum samples were statistically consistent. ELISA was positive in 186 (21.9%) out of 850 individuals. A group of 213 individuals were asked to collect vein blood for IB (186 with positive result in ELISA and 27 with inappropriate whole blood samples) and 130 attended the request. The IB was positive in 29 (3.4%) out of 850 individuals. A significant correlation (p = 0.0364) was determined among individuals who tested positive in the IB assay who practiced both pig rearing and kitchen gardening. CONCLUSIONS: ELISA with dried blood eluted from filter paper was suitable for cysticercosis population surveys. In Lages, human infection was associated with pig rearing and kitchen gardening. The prevalence index was compatible with other Latin American endemic areas. INTRODUÇÃO: O primeiro levantamento sobre cisticercose humana e identificação dos fatores de risco associados à transmissão, foram realizados em Lages, SC. MÉTODOS: Oitocentos e setenta e sete voluntários de regiões periurbana e rural foram entrevistados e forneceram informações demográficas e condições sanitárias e de saúde. Amostras de sangue foram coletadas por meio de punção digital em papel filtro entre agosto 2004 e maio 2005. Verificou-se que 850 amostras estavam adequadas para análise. No ELISA, utilizou-se o antígeno heterólogo liquido vesicular de Taenia crassiceps. Para assegurar a confiabilidade dos resultados de ELISA, foram pareadas 77 amostras de soro e sangue eluido do papel filtro. A confirmação do diagnóstico sorológico foi feita por immunoblot (IB) com glicoproteínas purificadas de Taenia crassiceps. RESULTADOS: A reatividade de IgG eluída de sangue em papel filtro mostrou-se compatível com a dos soros correspondentes. A triagem por ELISA de 850 indivíduos revelou 186 (21,9%) positivos. De 213 pessoas convidadas a colher soro para IB (186 ELISA positivo e 27 com amostras de sangue total inadequadas), compareceram 130. O IB foi positivo em 29 (3,4%) de 850 amostras. Houve correlação significativa entre IB positivo e a prática de criação de suínos e de horta caseira (p = 0,0364). CONCLUSÕES: ELISA com sangue total em papel filtro mostrou-se adequado para inquéritos populacionais para cisticercose. A transmissão da cisticercose humana na área estudada mostrou correlação com criação suína domestica e horta caseira. A prevalência obtida foi semelhante à relatada em áreas endêmicas da América Latina.

Before organizing mixed-mode data collection for the self-administered questionnaire of the Belgian Health Interview Survey, measurement effects between the paper-and-pencil and the web-based questionnaire were evaluated. A two-period cross-over study was organized with a sample of 149 employees of two Belgian research institutes (age range 22-62 years, 72% female). Measurement agreement was assessed for a diverse range of health indicators related to general health, mental and psychosocial health, health behaviors and prevention with kappa coefficients and intraclass correlation (ICC). The quality of the data collected by both modes was evaluated by quantifying the missing, 'don't know' and inconsistent values and data entry mistakes. Good to very good agreement was found for all categorical indicators with kappa coefficients superior to 0.60, except for two mental and psychosocial health indicators namely the presence of a sleeping disorder and of a depressive disorder (kappa≥0.50). For the continuous indicators high to acceptable agreement was observed with ICC superior to 0.70. Inconsistent answers and data-entry mistakes were only occurring in the paper-and-pencil mode. There were no less missing values in the web-based mode compared to the paper-and-pencil mode. The study supports the idea that web-based modes provide, in general, equal responses to paper-and-pencil modes. However, health indicators based upon factual and objective items tend to have higher measurement agreement than indicators requiring an assessment of personal subjective feelings. A web-based mode greatly facilitates the data-entry process and guides the completing of a questionnaire. However, item non-response was not positively affected. ispartof: PLOS ONE vol:13 issue:5 ispartof: location:United States status: published

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. First recognised by Bouillard in 1823 and later described by Trousseau in 1844, multiple studies have since provided considerable evidence for a clinical association between VTE and cancer. Across all cancers, the risk for VTE is elevated 7-fold; in certain malignancies, the risk for VTE may be increased up to 28-fold. Venous thromboembolism is the second leading cause of death in patients with cancer; among survivors, complications commonly include recurrent VTE and post-thrombotic syndrome, and (more rarely) chronic thromboembolic pulmonary hypertension, which are costly, and have a profound impact on the patient's quality of life. Tumour cells can activate blood coagulation through multiple mechanisms, including production of procoagulant, fibrinolytic, and proaggregating activities, release of proinflammatory and proangiogenic cytokines, and interacting directly with host vascular and blood cells (e.g., endothelial cells, leukocytes, and platelets) through adhesion molecules. Increasing evidence suggests that elements of the haemostatic system also have a direct role in eliciting or enhancing angiogenesis, cell survival, and metastasis. Despite the problem posed by VTE in the setting of cancer, it is evident that a significant number of oncologists do not recognise the link between cancer, its treatment, and thrombogenesis. On 22 May 2009, a group of UK-based physicians met in London, UK, to evaluate recent data on cancer thrombosis. This article (1 of 4) briefly reviews key data on the epidemiology and pathophysiology of VTE as a context for a discussion and consensus statement developed by meeting attendees, on the implications of this information for UK clinical practice.

Self-collection of buccal cells provides a noninvasive method for obtaining biologic samples for genetic analyses in pediatric studies. Nevertheless, low yields, microbial contamination, and degradation of buccal samples present challenges for epidemiologic studies incorporating genetic investigations. The aims of this study were to compare the quality and yield of DNA extracted from buccal specimens with BuccalAmp swabs (Epicenter BioTechnologies, Madison, Wisconsin) or FTA cards (Whatman, Inc., Clifton, New Jersey) and to investigate the use of whole-genome amplification (WGA) for increasing DNA yields for single nucleotide polymorphism analyses. Buccal specimens were collected from 55 children with acute lymphoblastic leukemia and 52 control children without acute lymphoblastic leukemia in New South Wales, Australia, in 2003-2004. Real-time polymerase chain reaction was used to evaluate polymorphisms in the genes encoding the cytochrome p450 enzyme CYP3A4 (CYP3A4 A392G, also known as CYP3A4*1B) and the steroid xenobiotic receptor (SXR C25385T). Results showed that DNA could be isolated from buccal specimens collected by use of both methods and that yields could be substantially improved with WGA without introducing genotyping error. However, DNA quality was poorer in samples collected by BuccalAmp swabs, and the presence of polymerase chain reaction inhibitors in these samples reduced the sensitivity of quantitative real-time PCR analysis. These findings show that different methods for collecting buccal samples impact on the downstream success of genetic investigations and influence DNA quality after WGA.

Aim: The clinical and epidemiological characteristics of chronic inflammatory demyelinating polyneuropathy (CIDP) in an Italian population were assessed. Subjects and methods: All subjects with a diagnosis of demyelinating neuropathy after 1990 in Piemonte and Valle d’Aosta (4 334 225 inhabitants) were considered. The diagnosis of CIDP was based on the research criteria of the American Academy of Neurology. 165 of 294 patients met the diagnostic criteria. Results: The crude prevalence rate was 3.58/100 000 population (95% CI 3.02 to 4.20). At the prevalence day, 76 (49.0%) cases had definite, 67 (43.2%) probable and 12 (7.7%) possible CIDP; disability was mild in 105 (67.7%) cases, moderate in 32 (20.6%) and severe in 18 (11.6%). The course was remitting–relapsing in 40 cases (25.8%), chronic progressive in 96 (61.9%) and monophasic in 19 (12.3%). Considering the 95 patients whose disorder presented in the period 1995–2001, the mean annual crude incidence rate was 0.36/100 000 population (95% CI 0.29 to 0.44), with a male to female ratio of 2.3:1. 14 cases were affected by diabetes mellitus. In multivariate analysis, factors related to severe disability at the prevalence day were: age>60 years; failure of immunomodulating therapies at the time of diagnosis; worse disability at nadir; and chronic course. Conclusion: Incidence and prevalence rates of CIDP in Italy were higher than those observed in most previous studies. At the prevalence day, more than 80% of cases had a mild or moderate disability, indicating either a good response to immunomodulating therapy or a tendency of CIDP to have a mild course in most cases.

OBJECTIVES: Cigarette price increases reduce smoking prevalence but as a tobacco control policy are undermined by the availability of lower cost alternatives such as hand-rolling tobacco. The aim of this descriptive study is to explore time trends in the price of manufactured cigarettes and hand-rolling tobacco, and in the numbers of people who smoke these products, over recent years in the UK. SETTINGS AND PARTICIPANTS: UK. OUTCOME MEASURES: Trends in the most popular price category (MPPC) data for cigarettes and hand-rolling tobacco from 1983 to 2012 adjusted for inflation using the Retail Price Index, and trends in smoking prevalence and the proportion of smokers using hand-rolling tobacco from 1974 to 2010. RESULTS: After adjustment for inflation, there was an increase in prices of manufactured cigarettes and hand-rolling tobacco between 1983 and 2012. Between 1974 and 2010, the prevalence of smoking fell from 45% to 20%, and the estimated total number of smokers from 25.3 to 12.4 million. However the number of people smoking hand-rolling tobacco increased from 1.4 to 3.2 million, and MPPC cigarette price was strongly correlated with number of people smoking hand-rolling tobacco. CONCLUSIONS: Although the ecological study design precludes conclusions on causality, the association between increases in manufactured cigarette price and the number of people smoking hand-rolling tobacco suggests that the lower cost of smoking hand-rolling tobacco encourages downtrading when cigarette prices rise. The magnitude of this association indicates that the lower cost of hand-rolling tobacco seriously undermines the use of price as a tobacco control measure.

Diagnostic reference levels (DRLs) for medical x-ray procedures are being implemented currently in the Netherlands. By order of the Dutch Healthcare Inspectorate, a survey has been conducted among 20 Dutch hospitals to investigate the level of implementation of the Dutch DRLs in current radiological practice. It turns out that hospitals are either well underway in implementing the DRLs or have already done so. However, the DRLs have usually not yet been incorporated in the QAsystem of the department nor in the treatment protocols. It was shown that the amount of radiation used, as far as it was indicated by the hospitals, usually remains below the DRLs. A procedure for comparing dose levels to the DRLs has been prescribed but is not Always followed in practice. This is especially difficult in the case of children, as most general hospitals receive few children. Health Phys. 108(4):462–464; 2015

Objectives: The objective of the present study was to investigate the risk of death from non-malignant diseases in female pulp and paper workers in Norway. Methods: A total of 3143 women first employed between 1920–93 were included in the study cohort. Information about each cohort member was obtained from personnel record files in the mills in order to identify employment periods and job categories. Data on cause and date of death were added by linkage to the Cause of Death Register using unique personal identification numbers. The follow up period was 1951–2000. Standardised mortality ratios (SMRs) with 95% confidence intervals (95% CIs) were calculated using the national female mortality rates as reference. Poisson regression analysis was used to examine internal relations between the duration of employment in paper departments and the risk of death from selected causes. Relative risks (RRs) and 95% CIs were calculated. Results: The study showed a significantly increased risk for total non-malignant mortality (SMR = 1.14, 95% CI 1.05 to 1.24), mainly due to increased mortality from ischaemic heart disease (SMR = 1.22, 95% CI 1.03 to 1.43) and cerebrovascular diseases (SMR = 1.16, 95% CI 0.94 to 1.42). Analysis by department showed the highest risk of death in paper department workers with short term employment. Internal analyses showed a 5% and 9% increase in risk of dying from ischaemic heart disease and respiratory diseases, respectively, among paper department workers exposed to paper dust. The risk decreased with increasing duration of employment. Conclusion: The increased risk of ischaemic heart diseases and respiratory diseases seen among employees of paper departments may be related to exposure to paper dust.

Drug-associated interstitial lung disease (ILD) is not uncommon, with diverse patterns ranging from benign infiltrates to the potentially fatal acute respiratory distress syndrome. As acute respiratory failure due to drug-associated ILD has an unpredictable onset and rapid time course, establishing a diagnosis is often difficult. An accurate diagnosis is based on clinical, radiological (including high-resolution computed tomography) and histological manifestations, although is often only possible by exclusion. Cancer chemotherapy is commonly associated with acute disease that, on pathology, is often diffuse alveolar damage. Furthermore, a combination of drugs with or without radiotherapy can increase the risk of ILD. This article reviews treatments for non-small-cell lung cancer (NSCLC) that are associated with the development of ILD and how systematic evaluation of the possible role of these drugs in ILD is warranted. A difference between Japan and the rest of the world in reporting rates of ILD when gefitinib (‘Iressa’) has been used in advanced NSCLC is also discussed. However, the difference remains unexplained, leaving important epidemiological and mechanistic questions.

As part of an International Agency for Research on Cancer (IARC) international epidemiological study of workers in the pulp and paper industry, previously unpublished exposure measurements were assembled in a database. This article summarizes the results of 3,873 measurements carried out in the production departments of paper and paperboard mills and recycling plants in 12 countries. In the paper and paperboard mills, most of the agents were measured in the pulping and refining departments and in on-machine coating and winding of paper/paperboard. Exposures to asbestos, carbon monoxide, formaldehyde, fungal spores, bacteria, nitrogen dioxide, minerals dusts, paper dust, sulphuric acid and different solvents sometimes exceeded exposure limit values. In the re-pulping and de-inking departments of recycling plants high exposures to formaldehyde, fungal spores, bacteria and paper dust were observed. High exposures to asbestos, bioaerosols, carbon monoxide and paper dust were found in many departments; ammonia, formaldehyde, mineral and paper dust and solvents were found in coating machines; and diphenyl and polychlorobiphenyls (PCBs) were found in some special circumstances. Measurements in the newsprint and uncoated paper machine departments revealed only a few elevated exposures. In nearly all departments, measurements of epichlorohydrin, PCBs, sulphur dioxide, hydrogen sulphide and mercaptans tended to be low, often even below their detection limits. In spite of some uncertainties in the measurement data, the study provides new insights into the level and variation of occupational exposures of production workers in the paper and paperboard industry. © Springer-Verlag 2004.

Objective: To describe the occurrence of myasthenia gravis in the Baltic area. Methods: Data were obtained from hospital files recorded during the period 1942 to 1996 from neurologists and the patient organisation. Survival data were checked with the Estonian Citizenship and Migration Board. Prevalence was determined on 1 January 1997. A questionnaire on the course of myasthenia gravis was sent to all the prevalent patients. Results: The size of the population surveyed was 1 462 130. The average annual incidence from 1970 to 1996 was 4.0 per million (women, 5.2; men, 2.6). The point prevalence was 99 per million (women, 133; men 59). The incidence in the younger age group (

Objective: To study the demographic characteristics of patients with carpal tunnel syndrome and changes in incidence over time. Methods: Prospective collection of neurophysiological and clinical data on all patients presenting to the subregional department of clinical neurophysiology in Canterbury, UK, from 1992 to 2001 and to the electromyography clinic in St Luke's Hospital, Huddersfield, UK, from 1991 to 1993. Results: 6245 new cases of neurophysiologically confirmed carpal tunnel syndrome were identified in Canterbury and 590 in Huddersfield. The average annual incidences (per 100 000) were 139.4 for women and 67.2 for men in East Kent, and 83.2 for women and 48.0 for men in Huddersfield. Corrected to the WHO European standard population these rates were 120.5 for women and 60.0 for men in East Kent, and 61.5 for women and 35.0 for men in Huddersfield. Between 1992 and 2001 there was an increase in the number of confirmed cases in East Kent but a decrease in their average severity. The age distributions were bimodal with a peak in the 50–54 age group and a second peak between 75 and 84 years. Over half the cases were bilateral. The disorder was consistently worse in the elderly, and more severe in men than in women in all age groups. Conclusions: The age distributions of unselected cases of carpal tunnel syndrome in both clinics differ markedly from that usually portrayed in surgical series. There was a significant increase in cases diagnosed between 1992 and 2001 in Canterbury, probably the result of increased ascertainment of milder cases. Median nerve impairment is more severe in the elderly and in men at all ages.

Background The occurrence of ataxic polyneuropathy in an endemic area in south west Nigeria has been attributed to exposure to cyanide from cassava foods. However, it has been shown that the prevalence of ataxic polyneuropathy is not high in several communities in the tropics where exposure to cyanide from cassava foods is high. Objectives To determine the incidence of ataxic polyneuropathy in an endemic community, and to compare the intake of cassava foods, exposure to cyanide, and levels of thiols in cases and controls. Methods A cohort of 3167 healthy subjects aged 10 years and over in Ososa, Nigeria, was followed for two years, screened, and examined neurologically. Ataxic polyneuropathy was diagnosed if sensory polyneuropathy and sensory gait ataxia were both present. Controls were selected randomly within 10 year age groups of subjects who screened negative. Intake of cassava foods, exposure to cyanide, concentrations of thiols (glutathione, cysteine, and γ glutamylcysteine) in plasma, and visual evoked potentials were measured. Results Person–years of follow up were 6246 for 1469 male and 1698 female subjects in the cohort. The incidence of ataxic polyneuropathy was 64 per 10 000 person–years (31 for male and 93 for female subjects). Multivariate odd ratios were 0.78 (95% CI 0.23 to 2.61) for intake of the commonest cassava food, and 1.64 (0.56 to 5.09) for concentration of thiocyanate in plasma. The concentration of thiols was less than the reference limits in two controls, but in none of the cases. The latency of P100 was prolonged in 20 cases (69%) compared with 14 controls (42%) (p

Objective: To determine, using a systematic review of case-control studies, whether head injury is a significant risk factor for Alzheimer’s disease. We sought to replicate the findings of the meta-analysis of Mortimer et al (1991). Methods: A predefined inclusion criterion specified case-control studies eligible for inclusion. A comprehensive and systematic search of various electronic databases, up to August 2001, was undertaken. Two independent reviewers screened studies for eligibility. Fifteen case-control studies were identified that met the inclusion criteria, of which seven postdated the study of Mortimer et al . Results: We partially replicated the results of Mortimer et al . The meta-analysis of the seven studies conducted since 1991 did not reach significance. However, analysis of all 15 case-control studies was significant (OR 1.58, 95% CI 1.21 to 2.06), indicating an excess history of head injury in those with Alzheimer’s disease. The finding of Mortimer et al that head injury is a risk factor for Alzheimer’s disease only in males was replicated. The excess risk of head injury in those with Alzheimer’s disease is only found in males (males: OR 2.29, 95% CI 1.47 to 2.06; females: OR 0.91, 95% CI 0.56 to 1.47). Conclusions: This study provides support for an association between a history of previous head injury and the risk of developing Alzheimer’s disease.

Objectives: To determine the prevalence of neurological involvement in Behcet’s disease in a prospective study, and to describe the clinical patterns of neurological presentation in this disease in patients attending a multidisciplinary clinic in Baghdad. Methods: All patients attending the clinic who fulfilled the international study group criteria for the diagnosis of Behcet’s disease were studied during a two year period starting in April 1999. Patients were assessed neurologically by a neuro-Behcetologist. All those with clinical neurological manifestations were sent for CSF examination, cranial magnetic resonance imaging, and magnetic resonance venography and were followed up to explore the patterns of neurological relapse. Results: 140 patients with Behcet’s disease were studied. Their mean age was 34.2 years (range 16 to 66); 105 (75%) were men and 35 (25%) were women. The mean duration of the disease was 4.2 years (range 0.4 to 26). Twenty patients (14%) had neurological involvement (neuro-Behcet’s disease); 14 of these (70%) were men and six (30%) women. The mean age at the first neurological presentation was 34.1 years. The mean duration of follow up of patients with neuro-Behcet’s disease was 20.7 months. Ten patients with neuro-Behcet’s disease (50%) presented with parenchymal CNS involvement, six (30%) with intracranial hypertension, and four (20%) with a mixed pattern of both parenchymal CNS involvement and intracranial hypertension. Conclusions: Careful neurological assessment of patients with Behcet’s disease may show a relatively high prevalence of neuro-Behcet features, and though the clinical patterns of presentation are characteristic a mixed pattern may occur.

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.