Genotyping of European Toxoplasma gondii strains by a new high-resolution next-generation sequencing-based method.

PURPOSE: A new high-resolution next-generation sequencing (NGS)-based method was established to type closely related European type II Toxoplasma gondii strains. METHODS: T. gondii field isolates were collected from different parts of Europe and assessed by whole genome sequencing (WGS). In comparison to ME49 (a type II reference strain), highly polymorphic regions (HPRs) were identified, showing a considerable number of single nucleotide polymorphisms (SNPs). After confirmation by Sanger sequencing, 18 HPRs were used to design a primer panel for multiplex PCR to establish a multilocus Ion AmpliSeq typing method. Toxoplasma gondii isolates and T. gondii present in clinical samples were typed with the new method. The sensitivity of the method was tested with serially diluted reference DNA samples. RESULTS: Among type II specimens, the method could differentiate the same number of haplotypes as the reference standard, microsatellite (MS) typing. Passages of the same isolates and specimens originating from abortion outbreaks were identified as identical. In addition, seven different genotypes, two atypical and two recombinant specimens were clearly distinguished from each other by the method. Furthermore, almost all SNPs detected by the Ion AmpliSeq method corresponded to those expected based on WGS. By testing serially diluted DNA samples, the method exhibited a similar analytical sensitivity as MS typing. CONCLUSION: The new method can distinguish different T. gondii genotypes and detect intra-genotype variability among European type II T. gondii strains. Furthermore, with WGS data additional target regions can be added to the method to potentially increase typing resolution.

Preservation of human heart valves for replacement in children with heart valve disease: past, present and future.

Valvular heart disease affects 30% of the new-borns with congenital heart disease. Valve replacement of semilunar valves by mechanical, bioprosthetic or donor allograft valves is the main treatment approach. However, none of the replacements provides a viable valve that can grow and/or adapt with the growth of the child leading to re-operation throughout life. In this study, we review the impact of donor valve preservation on moving towards a more viable valve alternative for valve replacements in children or young adults.

The relation between the biochemical composition of knee articular cartilage and quantitative MRI: a systematic review and meta-analysis.

OBJECTIVE: Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the change in proteoglycan and collagen composition. The aim of this study is to establish the relations between quantitative magnetic resonance imaging (MRI) and biochemical concentration and organization in knee articular cartilage. METHODS: A preregistered systematic literature review was performed using the databases PubMed and Embase. Papers were included if quantitative MRI and a biochemical assay or polarized light microscopy (PLM) was performed on knee articular cartilage, and a quantified correlation was described. The extracted correlations were pooled using a random effects model. RESULTS: 21 papers were identified. The strongest pooled correlation was found for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) vs proteoglycan concentration (r = 0.59). T1ρ relaxation times are inversely correlated to proteoglycan concentration (r = -0.54). A weak correlation between T2 relaxation times and proteoglycans was found (r = -0.38). No correlation between T2 relaxation time and collagen concentration was found (r = -0.02). A heterogeneous set of correlations between T2 relaxation times and PLM were identified, including strong correlations to anisotropy. CONCLUSION: DGEMRIC measures are significantly correlated to proteoglycan concentration. The needed contrast agent is however a disadvantage; the T1ρ sequence was found as a non-invasive alternative. Remarkably, no correlation was found between T2 relaxation times and collagen concentration. T2 relaxation times is related to organization, rather than concentration of collagen fibers. PROSPERO ID: CRD42020168337.

Endometriosis and irritable bowel syndrome: similarities and differences in the spectrum of comorbidities.

STUDY QUESTION: Do the spectrum and prevalence of comorbidities of endometriosis and irritable bowel syndrome (IBS) overlap? SUMMARY ANSWER: Despite several overlapping symptoms, the most significantly associated comorbidities of endometriosis and IBS are different and are rather related to the organ systems primarily involved in the index diagnosis. WHAT IS KNOWN ALREADY: Endometriosis and IBS both have several similar unspecific symptoms, such as recurrent abdominal pain, cramping and anxiety, and both diseases affect young women and are associated with a number of comorbidities causing a poor quality of life. However, a detailed study, revealing the full spectrum of endometriosis and IBS comorbidities in the same study population, is lacking. STUDY DESIGN, SIZE, DURATION: This article presents a retrospective in silico analysis of the data from a large nationwide biobank-based cohort consisting of 121 773 women. After excluding all first- and second-degree relatives, the data of up to 65 421 women were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: International Classification of Disease-10 diagnosis main codes associated with endometriosis (N80) and IBS (K58) diagnoses were identified from the Estonian Biobank dataset by linking with the Estonian Health Insurance Fund and other relevant registries. The associations between N80 and K58 and other diagnosis codes were tested using logistic regression, adjusting for age at recruitment and 10 genetic principal components to account for potential population stratification. Bonferroni correction was applied to account for multiple testing. MAIN RESULTS AND THE ROLE OF CHANCE: Both women with endometriosis and IBS suffered from more conditions compared to the control group, with 226 and 428 diagnosis codes statistically significantly more frequent in women with respective diagnosis compared to controls. Women suffering from both conditions had 275 significantly associated comorbidities. A remarkable proportion of women with IBS or endometriosis suffered also from endometriosis (9.0%) or IBS (13.6%), respectively. In endometriosis, the most prevalent diagnoses were related to diseases of the genitourinary system (33 N-category codes) and in women with IBS, the most associated diagnoses were related to digestive disorders and gastrointestinal tract (52 codes from K-category). Among the most significant diagnoses in endometriosis were uterine leiomyomas (D25), menstrual disorders (N92) and infertility (N97) (P < 1 × 10-315 for all), and in IBS, lactose intolerance (E73), gastritis and duodenitis (K29) and functional dyspepsia (K30) were in the top list of most significant comorbidities (P < 1 × 10-315 for all). LIMITATIONS, REASONS FOR CAUTION: The information about the severity stages of endometriosis and subtypes of IBS was not available for analysis. The findings may not be fully extrapolated to all female populations, because all participants were from one geographic area and had good access to health services. WIDER IMPLICATIONS OF THE FINDINGS: These findings support previous studies that have found a high prevalence of pre-selected comorbidities in women with endometriosis and IBS. However, taking into account the differences in the full spectrum of comorbidities of endometriosis and IBS may aid in diagnosing these disorders. Women and healthcare providers need to be aware that women with endometriosis are at high risks of complications during pregnancy and should be carefully monitored. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Estonian Research Council (grant PRG1076), Horizon 2020 innovation grant (ERIN, grant no. EU952516), Enterprise Estonia (grant no. EU48695), MSCA-RISE-2020 project TRENDO (grant no. 101008193) and by the European Union through the European Regional Development Fund (Projects no. 2014-2020.4.01.15-0012 and no. 2014-2020.4.01.16-0125). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis.

Given the link between systemic inflammation, body composition and insulin resistance (IR), anti-inflammatory therapy may improve IR and body composition in inflammatory joint diseases. This study assesses the IR and beta cell function in rheumatoid arthritis (RA) patients with active disease compared to osteoarthritis (OA) patients and investigates the effect of anti-TNF treatment on IR, beta cell function and body composition in RA. 28 Consecutive RA patients starting anti-TNF treatment (adalimumab), and 28 age, and sex-matched patients with OA were followed for 6 months. Exclusion criteria were use of statins, corticosteroids, and cardiovascular or endocrine co-morbidity. Pancreatic beta cell function and IR, using the homeostasis model assessment (HOMA2), and body composition, using dual-energy X-ray absorptiometry (DXA) were measured at baseline and 6 months. At baseline, IR [1.5 (1.1-1.8) vs. 0.7 (0.6-0.9), 100/%S] and beta cell function (133% vs. 102%) were significantly (p < 0.05) higher in RA patients with active disease as compared to OA patients. After 6 months of anti-TNF treatment, IR [1.5 (1.1-1.8) to 1.4 (1.1-1.7), p = 0.17] slightly improved and beta cell function [133% (115-151) to 118% (109-130), p <0.05] significantly improved. Improvement in IR and beta cell function was most pronounced in RA patients with highest decrease in CRP and ESR. Our observations indicate that IR and increased beta cell function are more common in RA patients with active disease. Anti-TNF reduced IR and beta cell function especially in RA patients with highest decrease in systemic inflammation and this effect was not explained by changes in body composition.

Cognitive behavioral therapy or graded exercise therapy compared with usual care for severe fatigue in patients with advanced cancer during treatment: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue remains a prevalent and burdensome symptom experienced by patients with advanced cancer. Our aim was to assess the effects of cognitive behavioral therapy (CBT) or graded exercise therapy (GET) on fatigue in patients with advanced cancer during treatment with palliative intent. PATIENTS AND METHODS: A randomized controlled trial was conducted from 1 January 2013 to 1 September 2017. Adult patients with locally advanced or metastatic cancer who reported severe fatigue during treatment [Checklist Individual Strength, subscale fatigue severity (CIS-fatigue) ≥35] were accrued across nine centers in The Netherlands. Patients were randomly assigned to either 12 weeks of CBT or GET, or usual care (1 : 1: 1, computer-generated sequence). Primary outcome was CIS-fatigue at 14 weeks. Secondary outcomes included fatigue measured with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30), quality of life, emotional functioning, physical functioning, and functional impairments at baseline, 14, 18, and 26 weeks. RESULTS: Among 134 participants randomized, the mean age was 63 (standard deviation 9) years and 77 (57%) were women. Common diagnoses included: breast (41%), colorectal (28%), and prostate cancer (17%). A total of 126 participants completed assessment at 14 weeks. Compared with usual care, CBT significantly reduced fatigue [difference -7.2, 97.5% confidence interval (CI) -12.7 to -1.7; P = 0.003, d = 0.7], whereas GET did not (-4.7, 97.5% CI -10.2 to 0.9; P = 0.057, d = 0.4). CBT significantly reduced EORTC-QLQ-C30 fatigue (-13.1, 95% CI -22.1 to -4.0; P = 0.005) and improved quality of life (10.2, 95% CI 2.4 to 17.9; P = 0.011) and physical functioning (7.1, 95% CI 0.5 to 13.7; P = 0.036) compared with usual care. Improvement in emotional functioning and decrease in functional impairments failed to reach significance. GET did not improve secondary outcomes compared with usual care. CONCLUSIONS: Among advanced cancer patients with severe fatigue during treatment, a CBT intervention was more effective than usual care for reducing fatigue. Following GET, patients reported lower fatigue, but results were not significant, probably due to a smaller sample size and lower adherence than anticipated. TRIAL REGISTRATION: Netherlands National Trial Register, identifier: NTR3812.

Intraprostatic Cancer Recurrence following Radical Radiotherapy on Transperineal Template Mapping Biopsy: Implications for Focal Ablative Salvage Therapy.

PURPOSE: Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies. MATERIALS AND METHODS: The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement. RESULTS: Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation. CONCLUSIONS: Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.

Healthcare experiences and quality of life of adults with coeliac disease: a cross-sectional study.

BACKGROUND: Coeliac disease affects many aspects of quality of life and treatment can be burdensome. Access to healthcare services is necessary for the diagnosis and management of coeliac disease. The present study aimed to investigate the healthcare experiences of adults with coeliac disease and explore the relationship between experiences and quality of life. METHODS: A cross-sectional postal survey was sent to 800 members of Coeliac UK and contained questions about diagnosis, dietary advice, follow-up appointments, prescriptions, knowledge and information provision, and quality of life [Coeliac Disease Assessment Questionnaire (CDAQ)]. Descriptive statistics were calculated. A total problem score summarised the number of problems experienced with healthcare services. Multiple linear regression analyses were conducted to investigate experiential and demographic factors associated with quality of life. RESULTS: An average of 5.5 problems with healthcare services was reported, with females reporting significantly more problems than males (6.5 versus 5.0, P = 0.003). The total problem score was significantly related to the CDAQ overall index score and all CDAQ dimension scores (stigma, dietary burden, symptoms, social isolation, and worries and concerns) (P < 0.001). The analyses highlighted four key areas of healthcare experiences that were significantly related to quality of life: information provision, general practioners' knowledge, communication with health professionals and access to prescriptions. CONCLUSIONS: Poorer experiences of healthcare services in coeliac disease are related to worse quality of life. Improving services in the four key areas identified may help adults with coeliac disease to achieve a better quality of life.

Withdrawing gluten-free food from prescriptions in England: a mixed-methods study to examine the impact of policy changes on quality of life.

BACKGROUND: Some local areas in England stopped have gluten-free prescriptions for coeliac disease. An explanatory mixed-methods study has investigated the impact of these changes. METHODS: A cross-sectional survey with 1697 participants was followed by 24 qualitative interviews. The survey included questions on the use of prescriptions and healthcare services, as well as the Coeliac Disease Assessment Questionnaire (CDAQ) to assess quality of life. The survey data were analysed by descriptive statistics, analysis of variance and regression analysis, and the interviews were analysed by thematic analysis. Findings from the interviews guided the survey analysis. RESULTS: Dietary burden was significantly different between prescribing and nonprescribing areas, with little impact on other aspects of quality of life. Survey participants in nonprescribing areas who felt more impacted by the prescription changes reported a lower quality of life. Satisfaction with and use of services was lower in nonprescribing areas. Interviews indicated that, after initial frustrations, most people adapted to the changed prescription policy. However, there was a clear preference for gluten-free prescriptions to be available, in particular for staple foods. CONCLUSIONS: The main quality of life impact was on Dietary burden. It is encouraging that most participants in the present study maintained a good quality of life. However, issues of worse experiences of care, lower follow-up opportunities and inequity arose, and these should be taken into consideration in decisions on gluten-free food prescriptions. The new guidelines for the National Health Service in England have retained prescriptions for bread and flour mixes, which is more limited than the range of staple foods preferred in the present study.

A randomized controlled TRIal of cognitive BEhavioral therapy for high Catastrophizing in patients undergoing lumbar fusion surgery: the TRIBECA study.

BACKGROUND: Around 20% of patients undergoing spinal fusion surgery have persistent back or leg pain despite surgery. Pain catastrophizing is the strongest psychological predictor for chronic postsurgical pain. Psychological variables are modifiable and could be target for intervention. However, randomized controlled trials evaluating the effectiveness of psychological interventions to reduce chronic pain and disability after spinal fusion in a population of patients with high preoperative pain catastrophizing scores are missing. The aim of our study is to examine whether an intervention targeting pain catastrophizing mitigates the risk of chronic postsurgical pain and disability. Our primary hypothesis is that targeted perioperative cognitive behavioral therapy decreases the risk of chronic postsurgical pain and disability after spinal fusion surgery in high catastrophizing patients. METHODS: We will perform a two-center prospective, single-blind, randomized, controlled study comparing lumbar spinal fusion surgery outcome between 2 cohorts. Adult patients selected for lumbar spinal fusion with decompression surgery and a minimum score of 24 on the pain catastrophizing scale will be randomized with 1:1 allocation for either perioperative cognitive behavioral therapy (intervention group) or a perioperative education plus progressive exercise program (control group). Patients randomized to the intervention group will receive six individual sessions of cognitive behavioral therapy, two sessions before the operation and four after. Primary outcome is the Core Outcome Measures Index at 12 months. Secondary outcomes include pain, disability, depression and quality of life. DISCUSSION: This is the first trial that evaluates the effectiveness of cognitive behavioral therapy as a perioperative tool to improve pain and disability after spinal fusion surgery in comparison with an educational/exercise control intervention, in patients with high levels of pain catastrophizing. If perioperative cognitive behavioral therapy proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcome after spinal fusion surgery. TRIAL REGISTRATION: Clinicaltrials ( NCT03969602 ). Registered 31 May 2019.

Prospective Follow-Up of Cortical Interruptions, Bone Density, and Micro-structure Detected on HR-pQCT: A Study in Patients with Rheumatoid Arthritis and Healthy Subjects.

OBJECTIVES: The purpose of the study was to prospectively investigate change (repair or progression) in the number, surface area and volume of cortical interruptions, bone density (vBMD) and micro-structural parameters assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in finger joints of patients with rheumatoid arthritis (RA) treated with synthetic disease modifying anti-rheumatic drugs (sDMARDs) and/or biologic DMARDs (bDMARDs) over a 1-year follow-up period, and in comparison with healthy subjects (HS). METHODS: Thirty-two patients with RA (221 joints, 53% on bDMARDs) and 32 HS (117 joints) were assessed at baseline and after 1 year using semi-automatic analysis of HR-pQCT images. Mean changes (group level) and the proportion of joints (joint level) with changes beyond the least significant change were calculated. RESULTS: At baseline, 530 interruptions were identified in patients, and 136 in HS. The mean of the interruption parameters did not significantly change in either group Mean vBMD decreased more in patients than in HS (- 4.4 versus - 1.1 mgHA/cm3, respectively). In patients versus HS, proportionally more joints showed repair in interruption volume (6.6% versus 1.7%, respectively) and loss of vBMD (26.7% versus 12.9%, respectively). In patients on sDMARDs versus patients on bDMARDs, proportionally more joints showed progression in the number of interruptions and loss of vBMD (6.1% versus 1.8% and 31.3% versus 17.2%, respectively). CONCLUSIONS: HR-pQCT is able to quantify bone repair and progression. Cortical interruption-, vBMD-, and micro-structure were impaired in RA, of which vBMD and micro-structure further deteriorated, particularly in patients on sDMARDs.

Treating benign ureteroenteric strictures: 27-year experience comparing endourological techniques with open surgical approach.

PURPOSE: To compare open surgical anastomotic revision with endourological techniques for the treatment of ureteroenteric strictures in patients with urinary diversions. METHODS: All records of patients treated for ureteroenteric strictures in our clinic between 1989 and 2016 were retrospectively reviewed. In 76 patients, 161 completed procedures were analyzed: 26 open revisions vs. 135 endourological treatments, including balloon dilation, Wallstent and/or laser vaporization. RESULTS: Median follow-up was 34 months. At 60 months, patency rates were 69% (95% CI 52-92%) after open vs. 27% (95% CI 19-39%) after endo-treatment (p = 0.003); median patency duration was 15.5 vs. 5 months, respectively (p = 0.014). Eventually, 15% of patients required open surgery after primary endo-treatment and 21% received endoscopic re-treatment after primary open surgery. Cox regression analysis revealed no confounding factors among the risk factors added to the model. Complication rates were higher after open surgery (27% Clavien 2, 12% Clavien 3-4 vs. 5% Clavien 1-2, 3% Clavien 3, p = 0.528). Median postoperative hospital stay was 14 days (open) vs. 2 days (endo), p < 0.001. Mean estimated glomerular filtration rate improved with + 17 (open) vs. + 8.1 (endo), p = 0.024. Renal function was compromised in 8% of patients in the open surgery group vs. 6% in the endo-treatment group. CONCLUSIONS: In these patients, in terms of patency and patency duration, open surgery was superior to endourology. Nevertheless, endourological treatments offer a safe and less-invasive alternative to delay or avoid open surgery, especially in patients who are unfit for open surgery.

Prescription patterns of lipid lowering agents among older patients in general practice: an analysis from a national database in the Netherlands.

BACKGROUND: Dutch cardiovascular risk management guidelines state almost every older adult (≥70 years) is eligible for a lipid lowering drug (LLD). However, life expectancy, frailty or comorbidities may influence this treatment decision. OBJECTIVE: investigate how many older adults, according to age, frailty (Drubbel-frailty index) and comorbidities were prescribed LLDs. METHODS: data of 244,328 adults ≥70 years from electronic health records of 415 Dutch general practices from 2011-15 were used. Number of LLD prescriptions in patients with (n = 55,309) and without (n = 189,019) cardiovascular disease (CVD) was evaluated according to age, frailty and comorbidities. RESULTS: about 69% of adults ≥70 years with CVD and 36% without CVD were prescribed a LLD. LLD prescriptions decreased with age; with CVD: 78% aged 70-74 years and 29% aged ≥90 years were prescribed a LLD, without CVD: 37% aged 70-74 years and 12% aged ≥90 years. In patients with CVD and within each age group, percentage of LLD prescriptions was 20% point(pp) higher in frail compared with non-frail. In patients without CVD, percentage of LLD prescriptions in frail patients was 11pp higher in adults aged 70-74 years and 40pp higher in adults aged ≥90 years compared to non-frail. Similar trends were seen in the analyses with number of comorbidities. CONCLUSION: in an older population, LLD prescriptions decreased with age but-contrary to our expectations-LLD prescriptions increased with higher frailty levels.

Rituximab in routine care of severe active rheumatoid arthritis : A prospective, non-interventional study in Germany.

OBJECTIVE: To assess safety, effectiveness and onset of effect of rituximab (RTX) in routine clinical treatment of severe, active rheumatoid arthritis (RA). METHODS: Prospective, multi-centre, non-interventional study in rheumatological outpatient clinics or private practices in Germany. RTX-naïve adult patients were to receive RTX according to marketing authorisation and at their physician's discretion. Also according to their physician's discretion, patients could receive a second cycle of RTX (re-treatment = treatment continuation). Major outcome was the change in Disease Activity Score based on 28-joints count and erythrocyte sedimentation rate (DAS28-ESR) over 24 weeks and during 6 months of re-treatment. RESULTS: Overall, 1653 patients received at least one cycle RTX; 99.2% of these had received disease-modifying antirheumatic drugs (DMARD) pre-treatment and 75.5% anti-tumor necrosis factor(TNF)­α pre-treatment. After a mean interval of 8.0 months, 820 patients received RTX re-treatment. Mean DAS28-ESR decreased from 5.3 at baseline to 3.8 after 24 weeks (-1.5 [95% confidence interval, CI: -1.6; -1.4]), and from 4.1 at start of cycle 2 to 3.5 at study end (change from baseline: -1.8 [95% CI: -2.0; -1.7]). Improvements in DAS28-ESR and Health Assessment Questionnaire (HAQ) score occurred mainly during the first 12 weeks of RTX treatment, with further DAS28-ESR improvement until week 24 or month 6 of re-treatment. Improvements in DAS28-ESR and EULAR responses were more pronounced in seropositive patients. RF was a predictor of DAS28-ESR change to study end. Safety analysis showed the established profile of RTX. CONCLUSION: RTX was safe and effective in a real-life setting with rapid and sustained improvement in RA signs and symptoms.

Aids to management of headache disorders in primary care (2nd edition) : on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache.

The Aids to Management are a product of the Global Campaign against Headache, a worldwide programme of action conducted in official relations with the World Health Organization. Developed in partnership with the European Headache Federation, they update the first edition published 11 years ago.The common headache disorders (migraine, tension-type headache and medication-overuse headache) are major causes of ill health. They should be managed in primary care, firstly because their management is generally not difficult, and secondly because they are so common. These Aids to Management, with the European principles of management of headache disorders in primary care as the core of their content, combine educational materials with practical management aids. They are supplemented by translation protocols, to ensure that translations are unchanged in meaning from the English-language originals.The Aids to Management may be individually downloaded and, as is the case for all products of the Global Campaign against Headache, are available without restriction for non-commercial use.

Working while unwell: Workplace impairment in people with severe asthma.

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

All-optical microscope autofocus based on an electrically tunable lens and a totally internally reflected IR laser.

Microscopic imaging at high spatial-temporal resolution over long time scales (minutes to hours) requires rapid and precise stabilization of the microscope focus. Conventional and commercial autofocus systems are largely based on piezoelectric stages or mechanical objective actuators. Objective to sample distance is either measured by image analysis approaches or by hardware modules measuring the intensity of reflected infrared light. We propose here a truly all-optical microscope autofocus taking advantage of an electrically tunable lens and a totally internally reflected infrared probe beam. We implement a feedback-loop based on the lateral position of a totally internally reflected infrared laser on a quadrant photodetector, as an indicator of the relative defocus. We show here how to treat the combined contributions due to mechanical defocus and deformation of the tunable lens. As a result, the sample can be kept in focus without any mechanical movement, at rates up to hundreds of Hertz. The device requires only reflective optics and can be implemented at a fraction of the cost required for a comparable piezo-based actuator.

Low levels of hybridization in two species of African driver ants.

Hybridization in ants can have consequences different from those observed in most other species, with many of the potential deleterious effects being mitigated due to haplodiploidy and eusociality. In some species where colonies are either headed by multiple queens or single queens that mate with many males, hybridization is associated with genetic caste determination, where hybrids develop into workers and purebred individuals develop into queens. A previous study suggested that hybridization occurs between two Dorylus army ant species with multiply mated queens. However, the extent and exact pattern of hybridization have remained unclear, and its possible effect on caste determination has not been investigated. In this study, we aimed to determine the extent and direction of hybridization by measuring how frequently hybrids occur in colonies of both species, and to investigate the possibility of genetic caste determination. We show that hybridization is bidirectional and occurs at equal rates in both species. Hybrid workers make up only 1-2% of the population, and successful interspecific matings represent approximately 2% of all matings in both species. This shows that, although interspecific matings that give rise to worker offspring occur regularly, they are much rarer than intraspecific mating. Finally, we find no evidence of an association between hybridization and genetic caste determination in this population. This means that genetic caste determination is not a necessary outcome of hybridization in ants, even in species where queens mate with multiple males.

Male gender, school attendance and sports participation are positively associated with health-related quality of life in children and adolescents with congenital bleeding disorders.

BACKGROUND: This study assesses health-related quality of life (HRQOL), and variables associated with HRQOL, in children and adolescents with haemophilia and congenital bleeding disorders (CBD) in the Netherlands. METHODS: Patients <18 years with CBD under treatment at the Hemophilia Comprehensive Care Center of the Academic Medical Center were included. Participants completed generic HRQOL questionnaires (TAPQOL 0-5 years; PedsQL 6-18 years). Differences and effect sizes in HRQOL compared to healthy peers, and between hemophilia severity groups, were tested using Mann Whitney U-tests. Multivariate regression analyses were performed to assess variables associated with HRQOL. RESULTS: Data of 145 patients (81%) were analyzed (N = 32 with severe haemophilia). Children (0-12 years) show no significant impairments in HRQOL compared to healthy peers. Adolescent boys (13-18 years) with CBD report a slightly higher HRQOL on the total and emotional functioning scales than healthy peers (small-moderate effect sizes). In contrast, adolescent girls experience lower HRQOL on total, social functioning and psychosocial health scales compared to healthy peers (moderate effect sizes). No differences between severity groups were found in HRQOL, but more problem behaviour was found in young boys (0-5 years) with severe haemophilia. Male gender, participation in sports and school attendance are positively associated with HRQOL. Parental country of birth, type of treatment and number of bleeds are not associated with HRQOL. CONCLUSION: Continuing monitoring HRQOL in daily clinical practice for children with CBD is important, since possible influencing psychosocial factors can change over time, with special focus on adolescent girls, sports participation and school absence.