Autoimmune cytopenias (AIC) following allogeneic haematopoietic stem cell transplant for acquired aplastic anaemia: a joint study of the Autoimmune Diseases and Severe Aplastic Anaemia Working Parties (ADWP/SAAWP) of the European Society for Blood and Marrow Transplantation (EBMT).

This retrospective study explored the incidence of autoimmune cytopenia (AIC) in 530 paediatric and adult patients with acquired aplastic anaemia (aAA) who underwent first allogeneic HSCT between 2002 and 2012. AIC was a rare complication with a cumulative incidence of AIC at 1, 3, 5 and 10 years post HSCT of 2.5% (1.2-3.9 95% CI), 4.4% (2.6-6.2 95% CI), 4.6% (2.8-6.5 95% CI) and 5.1% (3.1-7.2 95% CI). Overall survival at 5 years after diagnosis of AIC was 85.9% (71-100 95% CI). Twenty-five patients were diagnosed with AIC at a median of 10.6 (2.6-91.5) months post HSCT. Eight (32%) patients were diagnosed with immune thrombocytopenia (ITP), seven (28%) with autoimmune haemolytic anaemia (AIHA), seven (24%) with Evans syndrome and four (16%) with autoimmune neutropenia (AIN). Treatment strategies were heterogeneous. Complete responses were seen in 12 of 25 patients, with death in three patients. In multivariable Cox analysis of a subgroup of 475 patients, peripheral blood stem cell (PBSC) transplant was associated with higher risk of AIC compared with bone marrow (BM) when conditioning regimens contained fludarabine and/or alemtuzumab (2.81 [1.06-7.49 95% CI]; p = 0.038), or anti-thymocyte globulin (ATG) (2.86 [1.11-7.37 95% CI]; p = 0.029). Myeloablative conditioning was associated with a lower risk of AIC compared with reduced intensity conditioning (RIC) in fludarabine and/or alemtuzumab (0.34 [0.12-0.98 95% CI]; p = 0.046) and ATG containing regimens (0.34 [0.12-0.95 95% CI]; p = 0.04). These findings provide clinically useful information regarding the incidence of a rare and potentially life-threatening complication of allogeneic HSCT for aAA, and further support for BM as the preferred stem cell source for transplant of patients with aAA

Measuring the Quality of Data Collection in a Large Observational Cohort of HIV and AIDS

The aim of this study was to examine the quality of data collection by studying the validity of collected data. Data were extracted from the clinic charts of two anonymous outpatients by 38 data collectors. A standard for the data to be collected was determined (168 items). The validity was measured by comparing the collected items with the standard; in this way, the percentages of the collected items that were ‘correct’ could be calculated. The percentage ‘correct’ was higher for clinic chart 1 (mean: 83% correct, SD 7%) than for clinic chart 2 (mean: 78% correct, SD 8%). All categories contained incorrectly collected data. These data were divided into missing data, incorrect start-stop dates, and surplus collected data. Almost all start-stop dates would change into ‘correct’ if ‘monthyear’ was considered correct (instead of the standard ‘daymonthyear’). Not all data collectors used specific protocols, and sources other than the written comments were not always checked. This study shows that a high proportion of data was correctly collected. However, the collection of start-stop dates was not optimal, and the collected data included surplus and missing data. Data collectors should be more knowledgeable about HIV disease and trained in the use of difficult protocols, so that they can better recognize what data to collect and how it should be collected. Among physicians, there should be more agreement about what information to record in the charts, to facilitate data extraction for data collectors

Current practice in analysing and reporting binary outcome data—a review of randomised controlled trial reports

Background Randomised controlled trials (RCTs) need to be reported so that their results can be unambiguously and robustly interpreted. Binary outcomes yield unique challenges, as different analytical approaches may produce relative, absolute, or no treatment effects, and results may be particularly sensitive to the assumptions made about missing data. This review of recently published RCTs aimed to identify the methods used to analyse binary primary outcomes, how missing data were handled, and how the results were reported. Methods Systematic review of reports of RCTs published in January 2019 that included a binary primary outcome measure. We identified potentially eligible English language papers on PubMed, without restricting by journal or medical research area. Papers reporting the results from individually randomised, parallel-group RCTs were included. Results Two hundred reports of RCTs were included in this review. We found that 64% of the 200 reports used a chi-squared-style test as their primary analytical method. Fifty-five per cent (95% confidence interval 48% to 62%) reported at least one treatment effect measure, and 38% presented only a p value without any treatment effect measure. Missing data were not always adequately described and were most commonly handled using available case analysis (69%) in the 140 studies that reported missing data. Imputation and best/worst-case scenarios were used in 21% of studies. Twelve per cent of articles reported an appropriate sensitivity analysis for missing data. Conclusions The statistical analysis and reporting of treatment effects in reports of randomised trials with a binary primary endpoint requires substantial improvement. Only around half of the studied reports presented a treatment effect measure, hindering the understanding and dissemination of the findings. We also found that published trials often did not clearly describe missing data or sensitivity analyses for these missing data. Practice for secondary endpoints or observational studies may differ

A comparison of dietary patterns derived by cluster and principal components analysis in a UK cohort of children

Background/Objectives: The objective of this study was to identify dietary patterns in a cohort of 7-year-old children through cluster analysis, compare with patterns derived by principal components analysis (PCA), and investigate associations with sociodemographic variables. Subjects/Methods: The main caregivers in the Avon Longitudinal Study of Parents and Children (ALSPAC) recorded dietary intakes of their children (8279 subjects) using a 94-item food frequency questionnaire. Items were then collapsed into 57 food groups. Dietary patterns were identified using k-means cluster analysis and associations with sociodemographic variables examined using multinomial logistic regression. Clusters were compared with patterns previously derived using PCA. Results: Three distinct clusters were derived: Processed (4177 subjects), associated with higher consumption of processed foods and white bread, Plant-based (2065 subjects), characterized by higher consumption of fruit, vegetables and non-white bread, and Traditional British (2037 subjects), associated with higher consumption of meat, vegetables and full-fat milk. Membership of the Processed cluster was positively associated with girls, younger mothers, snacking and older siblings. Membership of the Plant-based cluster was associated with higher educated mothers and vegetarians. The Traditional British cluster was associated with council housing and younger siblings. The three clusters were similar to the three dietary patterns obtained through PCA; each principal component score being higher on average in the corresponding cluster.Conclusions:Both cluster analysis and PCA identified three dietary patterns very similar both in the foods associated with them and sociodemographic characteristics. Both methods are useful for deriving meaningful dietary patterns. © 2011 Macmillan Publishers Limited All rights reserved

Meningokokkenziekte in Nederland : Achtergrondinformatie voor de Gezondheidsraad

Meningococcal disease is a very serious infectious disease caused by a bacterium, the meningococcus. There are different types of meningococcus; people become ill mainly from the B, C, W and Y serogroups. Since 2002, vaccination against serogroup C meningococcal disease has been included in the National Immunisation Programme for children of 14 months. As a result, serogroup C meningococcal disease has virtually disappeared. Vaccines against serogroup B have recently become available. In addition, since 2015, there has been a rapid increase in serogroup W meningococcal disease. Multi-component vaccines are available against A, C, W and Y serogroups. Based on these developments, among others, the Health Council will advise the Minister for Health, Welfare and Sport on whether and how the current immunisation programme against meningococcal disease should be adapted. To this end, RIVM has collected background information and recent data on meningococcal disease in the Netherlands. It includes the number of people in the Netherlands who become ill each year, the efficacy and safety of the vaccines, and what the public thinks about vaccination against invasive meningococcal disease. The infection causes a severe medical condition such as meningitis or blood poisoning, which can rapidly develop into shock, frequently causing death. The disease often begins with flu-like symptoms and fever which subsequently worsen very rapidly. The infection is relatively rare in the Netherlands; there are currently 100 to 150 patients a year. Five to ten percent of these patients die despite antibiotics and intensive care. Thirty percent of the patients are left with lifelong impairments such as hearing loss, limb amputation or epilepsy. Meningococcal disease is most common in children under the age of 5, adolescents and the elderly.Meningokokkenziekte is een zeer ernstige infectieziekte die veroorzaakt wordt door een bacterie, de meningokok. Er zijn verschillende typen meningokokken; mensen worden vooral ziek van de serogroepen B, C, W en Y. Vaccinatie tegen meningokokkenziekte serogroep C is in Nederland sinds 2002 opgenomen in het Rijksvaccinatieprogramma voor kinderen van 14 maanden. Hierdoor komt meningokokkenziekte door serogroep C nauwelijks meer voor. Sinds kort zijn vaccins beschikbaar tegen serogroep B. Daarnaast is er sinds 2015 een snelle toename in meningokokkenziekte door serogroep W. Er zijn combinatievaccins beschikbaar tegen serogroep A, C, W en Y. Vanwege ondermeer deze ontwikkelingen gaat de Gezondheidsraad de minister van VWS adviseren of, en op welke manier, het huidige vaccinatieprogramma tegen meningokokkenziekte aangepast moet worden. Daartoe heeft het RIVM achtergrondinformatie en recente data over meningokokkenziekte in Nederland verzameld. Het gaat onder meer om het aantal mensen in Nederland dat jaarlijks ziek wordt, de effectiviteit en veiligheid van de vaccins, en hoe het publiek denkt over vaccinatie tegen invasieve meningokokkenziekte. De infectie geeft een ernstig ziektebeeld zoals hersenvliesontsteking of een bloedvergiftiging, die zich snel kan ontwikkelen tot een shock waar veel mensen aan overlijden. De ziekte begint vaak met griepachtige verschijnselen en koorts die vervolgens zeer snel verergeren. De infectie is in Nederland relatief zeldzaam; op dit moment zijn er 100 tot 150 patiënten per jaar. Van deze patiënten overlijdt 5-10 procent ondanks antibiotica en intensieve zorg. 30 procent van de patiënten houdt er levenslang beperkingen aan over zoals gehoorverlies, amputatie van een ledemaat of epilepsie. Meningokokkenziekte komt het meest voor bij kinderen jonger dan 5 jaar, adolescenten en ouderenMinisterie van VW

Intensive group training protocol versus guideline physiotherapy for patients with chronic low back pain: a randomised controlled trial

Intensive group training using principles of graded activity has been proven to be effective in occupational care for workers with chronic low back pain. Objective of the study was to compare the effects of an intensive group training protocol aimed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain. The study was designed as pragmatic randomised controlled trial with a setup of 105 primary care physiotherapists in 49 practices and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study. In the intensive group training protocol exercise therapy, back school and operant-conditioning behavioural principles are combined. Patients were treated during 10 individual sessions along 20 group sessions. Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain. Main outcome measures were functional disability (Roland Morris disability questionnaire), pain intensity, perceived recovery and sick leave because of low back pain assessed at baseline and after 6, 13, 26 and 52 weeks. Both an intention-to-treat analysis and a per-protocol analysis were performed. Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period, with one exception. After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group, but this difference was absent after 52 weeks. We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain

Protocol of the COSMIN study: COnsensus-based Standards for the selection of health Measurement INstruments

BACKGROUND: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist. METHOD: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist. DISCUSSION: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase

Improved Detection of Bifidobacteria with Optimised 16S rRNA-Gene Based Pyrosequencing

The 16S rRNA gene is conserved across all bacteria and as such is routinely targeted in PCR surveys of bacterial diversity. PCR primer design aims to amplify as many different 16S rRNA gene sequences from as wide a range of organisms as possible, though there are no suitable 100% conserved regions of the gene, leading to bias. In the gastrointestinal tract, bifidobacteria are a key genus, but are often under-represented in 16S rRNA surveys of diversity. We have designed modified, ‘bifidobacteria-optimised’ universal primers, which we have demonstrated detection of bifidobacterial sequence present in DNA mixtures at 2% abundance, the lowest proportion tested. Optimisation did not compromise the detection of other organisms in infant faecal samples. Separate validation using fluorescence in situ hybridisation (FISH) shows that the proportions of bifidobacteria detected in faecal samples were in agreement with those obtained using 16S rRNA based pyrosequencing. For future studies looking at faecal microbiota, careful selection of primers will be key in order to ensure effective detection of bifidobacteria