A comparison of international clinical practice guidelines on adult chronic rhinosinusitis shows considerable variability of recommendations for diagnosis and treatment.

OBJECTIVES: To compare international clinical practice guidelines on adult chronic rhinosinusitis (CRS). DESIGN: Extensive literature search in Embase, PubMed and the internet (Google, websites of well-known guideline organizations) on November 21st 2018. MAIN OUTCOME MEASURES: Guidelines' quality was measured by the AGREE II instrument. A summary and comparison of recommendations on diagnosis and treatment with harmonized levels of evidence (LoE) and grade of recommendations (GoR) is given. RESULTS: We selected ten guidelines on CRS. Five guidelines were of sufficient to high quality according to AGREE II, the remaining guidelines predominantly did not meet AGREE II criteria. We harmonized all guideline recommendations so we could compare them, although three guidelines did not provide a LoE. Five guidelines provided recommendations on diagnosis, all of them recommended performing nasal endoscopy, CT scan and allergy testing (with varying GoRs). All ten guidelines provided recommendations on therapy, one treatment, i.e., the use of intranasal steroids, was recommended by all guidelines (with varying GoRs). Recommendations for surgical treatment of CRS were provided by five guidelines. CONCLUSION: We performed an extensive search and included ten (inter)national guidelines on CRS for adults. According to AGREE II, five were of good or sufficient quality. Overall, there was much variation between guidelines in recommended diagnostic test or treatment, direction of evidence and GoR. We found consensus for nasal endoscopy, CT scan, allergy testing and intranasal steroids. We argue for standardization of guideline development, to increase their quality and improve comparability.

Otolaryngologists adhere to evidence-based guidelines for chronic rhinosinusitis.

PURPOSE: To assess awareness of, opinion about and adherence to evidence-based guidelines on chronic rhinosinusitis among Dutch Otolaryngologists. METHODS: We assessed implementation of two guidelines, one Dutch and one European, that are both intended for diagnosis and treatment of patients with chronic rhinosinusitis. We invited 485 Otolaryngologists to fill out a questionnaire and report on their opinion on and adherence to the guidelines. The adherence was further tested by 4 clinical case scenarios, derived from guideline recommendations. RESULTS: 166 (34%) completed the questionnaire. 99% of the respondents was aware of one or both guidelines. Most respondents (90%) consider the guidelines as directing or supportive for their clinical practice based on the clinical case scenarios, between 62 and 99% of the respondents act according to guidelines. Concerning diagnosis, CT-imaging is performed more and allergy testing less than recommended. Where multiple treatment options are recommended, the responses are more heterogeneous as a result of this. Nonetheless, high recommended treatment was chosen more often. Otolaryngologists were reluctant in surgical treatment as a first option, which is according to the guidelines. CONCLUSIONS: Overall, both the EPOS and CBO guideline are well known among Dutch Otolaryngologists and 90% indicates that the guideline is important in their daily practice. Adherence to the guidelines is sufficient to high. If multiple treatment or diagnostic options are recommended this leads to a more heterogeneous response pattern. Recommendations with a high grade of recommendation were followed up most often.

Improving oral healthcare using academic detailing - design of the ADVOCATE Field Studies.

Background: Academic detailing (AD) is a defined form of educational outreach that can be deployed to intrinsically motivate practitioners towards improving quality of care. This paper describes the design of the ADVOCATE Field Studies. This proof of concept study aims to evaluate the feasibility, acceptability and usefulness of AD, reinforced with feedback information to promote prevention-oriented, patient-centred and evidence-based oral healthcare delivery by general dental practitioners (GDPs). Methods: Six groups of GDPs will be recruited; two groups of six to eight GDPs in each of three countries - the Netherlands, Germany and Denmark. GDPs will meet for four Academic Detailing Group (ADG) meetings for open discussions using comparative feedback data to stimulate debate about their dental practice performance and care delivery. Group meetings will be moderated using the AD methodology. Qualitative data will be collected through focus group interviews, an online discussion forum, field notes and debriefs of ADG meetings and analysed by conventional content analysis using MaxQDA software. Discussion: The results of the study will provide novel information on the feasibility, perceived acceptability and usefulness of AD and feedback data for GDPs to improve oral healthcare delivery.

[Costs and financing of oral healthcare in the Netherlands]. / Kosten en financiering van de mondzorg.

In the Netherlands, dental diseases are the third most expensive category of healthcare costs. The total cost of the consumption of oral care gives, however, no insight into the content of the care. Data from health insurers do provide such insight, but due to limitations in reimbursements the data from health insurers represent only part of all the costs of oral care. In this study an attempt was made, by means of an estimation, to gain insight into the total cost of oral care, financed both by basic and supplementary health insurance and by the patients themselves . This estimation was made at the level of UPT clusters and is based on data from the health insurers and a large factoring company for the years 2011, 2013 and 2014. Based on this estimate, one can conclude that on average between 21% and 32% of oral care consumption is financed privately. A complete picture of the costs of oral care is important in determining the contribution of oral care to public health. The structure of the current financial system, however, impedes transparency concerning oral care consumed.

[The content of publications in the Netherlands Journal of Dentistry - an analysis of patterns over time]. / De inhoud van publicaties in het Nederland Tijdschrift voor Tandheelkunde. Een patroonanalyse over de tijd.

In 2018, the Netherlands Journal of Dentistry (NTVT) had been published for 125 years: reason for a systematic look at the subjects that have received attention since 2000. These subjects were subsequently compared to those in Dutch dental publications in international literature and to leading fields in oral health care. The analysis revealed an increase in the attention given to certain fields in the Netherlands Journal of Dentistry, such as public dental health, during the past 18 years and a decrease in the attention given to other subjects, such as basic scientific research. In addition, there was a limited correlation between fields involving the greatest cost of care, such as cariology and preventive dentistry, and research activity. This held true both for international publications and publications in the Netherlands Journal of Dentistry.

Associations of pain intensity and pain-related disability with psychological and socio-demographic factors in patients with temporomandibular disorders: a cross-sectional study at a specialised dental clinic.

The study assessed whether psychological and socio-demographic factors, including somatisation, depression, stress, anxiety, daytime sleepiness, optimism, gender and age, are associated with pain intensity and pain-related disability in patients with temporomandibular disorders (TMDs). In total, 320 TMD patients were involved in the study. The psychological status of each patient was assessed with questionnaires, including the Symptom Checklist-90 (SCL-90), Epworth Sleeping Scale (ESS), stress questionnaire and Life Orientation Test-Revised (LOT-R). TMD pain, including pain intensity and pain-related disability, was assessed with characteristic pain intensity (CPI) and disability points scales. The associations of psychological and socio-demographic factors with pain intensity and pain-related disability were assessed through logistic regression analyses. Higher pain intensity was significantly associated with more severe anxiety (P = 0·004), more severe somatisation (P < 0·001), more severe depression (P < 0·001), more severe stress (P = 0·001) and lower optimism (P = 0·025) in univariate regression analyses. However, multiple regression analysis showed that only somatisation was significantly associated with pain intensity (P < 0·001). Higher pain-related disability was significantly associated with more severe anxiety (P < 0·001), more severe somatisation (P < 0·001), more severe depression (P < 0·001), more severe stress (P < 0·001) and lower optimism (P = 0·003) in univariate regression analyses. However, multiple regression analysis showed that only depression was significantly associated with pain-related disability (P = 0·003). Among the psychological and socio-demographic factors in this study, somatisation was the best predictor of pain intensity, while depression was the best predictor of pain-related disability.

Assessing the sustainability of egg production systems in The Netherlands.

Housing systems for laying hens have changed over the years due to increased public concern regarding animal welfare. In terms of sustainability, animal welfare is just one aspect that needs to be considered. Social aspects as well as environmental and economic factors need to be included as well. In this study, we assessed the sustainability of enriched cage, barn, free-range, and organic egg production systems following a predefined protocol. Indicators were selected within the social, environmental, and economic dimensions, after which parameter values and sustainability limits were set for the core indicators in order to quantify sustainability. Uncertainty in the parameter values as well as assigned weights and compensabilities of the indicators influenced the outcome of the sustainability assessment. Using equal weights for the indicators showed that, for the Dutch situation, enriched cage egg production was most sustainable, having the highest score on the environmental dimension, whereas free-range egg production gave the highest score in the social dimension (covering food safety, animal welfare, and human welfare). In the economic dimension both enriched cage egg and organic egg production had the highest sustainability score. When weights were attributed according to stakeholder outputs, individual differences were seen, but the overall scores were comparable to the sustainability scores based on equal weights. The provided method enabled a quantification of sustainability using input from stakeholders to include societal preferences in the overall assessment. Allowing for different weights and compensabilities helps policymakers in communicating with stakeholders involved and provides a weighted decision regarding future housing systems for laying hens.

Liquid state dynamic nuclear polarization of ethanol at 3.4 T (95 GHz).

Dynamic Nuclear Polarization (DNP) in the liquid state has become the focus of attention to improve the NMR sensitivity of mass limited samples. The Overhauser model predicts a fast reduction in DNP enhancement at high magnetic fields where the electron Larmor frequency exceeds the typical inverse correlation time of the magnetic interaction between an unpaired electron spin of a radical and proton spins of the solvent molecules. The Overhauser hard sphere model is able to predict quantitatively the DNP enhancement for water TEMPOL solutions. The increase in temperature due to dielectric heating of the sample acts to reduce the correlation times and allows a substantial Overhauser DNP. In this paper we extend the work done on water towards other small molecules, such as ethanol. Experimentally we observe a similar enhancement for all three proton groups in the ethanol molecule. The classical interpretation of the low field Overhauser experiments on ethanol invokes a very fast anisotropic rotation of the hydrogen bonded TEMPOL-ethanol complex to explain the fast relaxation of the OH proton. Here we will discuss W-band relaxation and DNP enhancement within this classical model. Although the description can be made quantitative, the invoked parameters do not seem to be realistic. We will propose an alternative model based on the dynamic interaction both in free collision and due to modulation of the hydrogen bond length of the complex.

Deliberative Improvement of Oral Care Quality: The Horizon Europe DELIVER Project.

KNOWLEDGE TRANSFER STATEMENT: The EU DELIVER project aims to enhance the quality of oral health care through codevelopment and coproduction of solutions together with citizens/patients, providers, and policymakers. The unique multicountry nature of the project will facilitate fast-track prototype development and testing of innovative QI approaches in select countries. Reflective learning regarding the transferability of findings between different countries and settings offers unique opportunities to drive progress toward context-specific implementation of innovative oral health care QI approaches. The collective knowledge gained from the 7 European countries involved in DELIVER can also generate knowhow for improving the quality of oral health care in other countries around the globe.

Whisker Sensing by Force and Moment Measurements at the Whisker Base.

We address the theoretical question which forces and moments measured at the base of a whisker (tactile sensor) allow for the prediction of the location in space of the point at which a whisker makes contact with an object. We deal with the general case of three-dimensional deformations as well as with the special case of planar configurations. All deformations are treated as quasi-static, and contact is assumed to be frictionless. We show that the minimum number of independent forces or moments required is three but that conserved quantities of the governing elastic equilibrium equations prevent certain triples from giving a unique solution in the case of contact at any point along the whisker except the tip. The existence of these conserved quantities depends on the material and geometrical properties of the whisker. For whiskers that are tapered and intrinsically curved, there is no obstruction to the prediction of the contact point. We show that the choice of coordinate system (Cartesian or cylindrical) affects the number of suitable triples. Tip and multiple point contact are also briefly discussed. Our results explain recent numerical observations in the literature and offer guidance for the design of robotic tactile sensory devices.

Dental healthcare costs of children living in Amsterdam and associated socio-demographic characteristics.

OBJECTIVES: The aim of this study was to assess associations between socio-demographic characteristics and dental costs of children living in Amsterdam. Having incurred dental costs was an indicator for having visited the dentist. Having incurred low or high dental costs may indicate the type of dental care provided (periodic examination, preventive care or restorative treatment). METHODS: This study followed a cross-sectional, observational design. The research population contained all children up until 17 years living in Amsterdam in 2016. Dental costs from all Dutch healthcare insurance companies were obtained via Vektis, and socio-demographic data were obtained from Statistics Netherlands (CBS). The study population was stratified into age groups: 0-4 and 5-17 years. Dental costs were classified as no dental costs (0 euros), low dental costs (>0 to <100 euros) or high dental costs (≥100 euros). Univariable and multivariable logistic regression analyses were performed to study the distribution of dental costs and associations with socio-demographic child and parent variables. RESULTS: In the population of 142 289 children, 44 887 (31.5%) incurred no dental costs, 32 463 (22.8%) incurred low dental costs and 64 939 (45.6%) incurred high dental costs. Among children of 0-4 years, a much larger proportion (70.2%) incurred no dental costs, compared to those of 5-17 years (15.8%). In both age groups, migration background (adjusted Odds Ratio (aOR) range 1.23-1.98), low(er) household income (aOR range 0.45-0.93), low(er) parental educational level (aOR range 0.51-0.87) and living in a single-parent household (aOR range 0.89-0.91) were strongly associated with incurring high (vs. low) dental costs. Furthermore, in 5-17-year-old children, a lower level of secondary or vocational education (aOR range 1.12-1.17) and living in households receiving social benefits (aOR 1.23) were associated with incurring high dental costs. CONCLUSIONS: Among children living in Amsterdam in 2016, one in three children did not visit a dentist. For children that did visit a dentist, those with a migration background, low parental educational level and from a low household income were more likely to incur high dental costs, which could be indicative for additional restorative treatment. Hence, patterns of oral healthcare consumption, specified by type of dental care over time, and their association with oral health status, are targets for future research.

High fat diet-induced obesity prolongs critical stages of the spermatogenic cycle in a Ldlr-/-.Leiden mouse model.

Obesity can disturb spermatogenesis and subsequently affect male fertility and reproduction. In our study, we aim to elucidate at which cellular level of adult spermatogenesis the detrimental effects of obesity manifest. We induced high fat diet (HFD) obesity in low-density lipoprotein receptor knock-out Leiden (Ldlr-/-.Leiden) mice, and studied the morphological structure of the testes and histologically examined the proportion of Sertoli cells, spermatocytes and spermatids in the seminiferous tubules. We examined sperm DNA damage and chromatin condensation and measured plasma levels of leptin, testosterone, cholesterol and triglycerides. HFD-induced obesity caused high plasma leptin and abnormal testosterone levels and induced an aberrant intra-tubular organisation (ITO) which is associated with an altered spermatids/spermatocytes ratio (2:1 instead of 3:1). Mice fed a HFD had a higher level of tubules in stages VII + VIII in the spermatogenic cycle. The stages VII + VII indicate crucial processes in spermatogenic development like initiation of meiosis, initiation of spermatid elongation, and release of fully matured spermatids. In conclusion, HFD-induced obese Ldlr-/-.Leiden mice develop an aberrant ITO and alterations in the spermatogenic cycle in crucial stages (stages VII and VII). Thereby, our findings stress the importance of lifestyle guidelines in infertility treatments.

A de novo paradigm for male infertility.

De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10-5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10-4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.

Quantitative analysis of high field liquid state Dynamic Nuclear Polarization.

Dynamic Nuclear Polarization (DNP) in the liquid state has become the focus of attention to improve the NMR sensitivity of mass limited samples. The Overhauser model predicts a fast reduction in DNP enhancement at high magnetic fields where the Electron Larmor frequency exceeds the typical inverse correlation time of the magnetic interaction between a radical spin and proton spins of the water molecules. Recent experiments have shown that an appreciable DNP enhancement in the liquid state is possible also at magnetic fields of 3 to 9 Tesla. At present it is not clear whether the Overhauser model needs to be adapted to explain these results. In the present paper we aim to resolve this question by a combination of in situ temperature dependent NMR relaxation measurements, EPR and DNP experiments. Enhancement factors of up to -165 are obtained with microwave powers below 500 mW. We conclude that at 3.4 Tesla (95 GHz) the various measurements are consistent with each other and in quantitative agreement with Overhauser theory. Microwave heating of the sample does play an important role to reduce the correlation times and allow a substantial Overhauser DNP. The typical enhancement factors may allow new applications in microfluidic NMR.

In vivo repair of DNA damage induced by X-rays in the early stages of mouse fertilization, and the influence of maternal PARP1 ablation.

The early pronucleus stage of the mouse zygote has been characterised in vitro as radiosensitive, due to a high rate of induction of chromosome-type chromosome abnormalities (CA). We have investigated the repair of irradiation induced double strand DNA breaks in vivo by γH2AX foci and first cleavage metaphase analysis. Breaks were induced in sperm and in the early zygote stages comprising sperm chromatin remodelling and early pronucleus expansion. Moreover, the role of PARP1 in the formation and repair of spontaneous and radiation-induced double strand breaks in the zygote was evaluated by comparing observations in C57BL/6J and PARP1 genetically ablated females. The results confirmed in vivo that the rate of chromosome aberration induction by X-rays was approximately 3-fold higher in the zygote than in mouse lymphocytes. This finding was related to a diminished efficiency of double strand break signalling, as shown by a lower rate of γH2AX radiation-induced foci compared to that measured in most other somatic cell types. The spontaneous frequency of CA in PARP1 depleted zygotes was slightly but significantly higher than in wild type zygotes. Also, these zygotes showed some impairment of the radiation-induced DNA Damage Response when exposed closer to the start of S-phase, revealed by a higher number of γH2AX foci and a longer cell cycle delay. The rate of chromosome aberrations, however, was not elevated over that of wild type zygotes, possibly thanks to backup repair pathways and/or selection mechanisms against damaged cells. When comparing with the literature data on irradiation induced CA in mouse zygotes in vitro, the levels of induction were strikingly similar as was the frequency of misrepair of double strand breaks (γH2AX foci). This result can be reassuring for in vitro human gamete and embryo handling, because it shows that culture conditions do not significantly affect double strand DNA break repair.

Diagnosing acute coronary syndrome in primary care: comparison of the physicians' risk estimation and a clinical decision rule.

BACKGROUND: Diagnosing acute coronary syndrome (ACS) in a primary care setting poses a diagnostic dilemma for physicians. OBJECTIVE: We directly compared the diagnostic accuracy of a clinical decision rule (CDR) based on history taking and physical examination in suspected ACS with the risk estimates of the attending GP. METHODS: In a prospective multicenter study, patients suspected of ACS were included by the GP. GPs were asked to estimate the probability (0%-100%) of the presence of ACS. GPs collected patient data, but they were not aware of the CDR and did not score the patient accordingly. RESULTS: Two hundred and ninety-eight patients were included (52% female, mean age 66 years, 22% ACS). The area under the receiver operating characteristic (ROC) curve (AUC) was 0.75 [95% confidence interval (CI) 0.68-0.82] for the GP risk estimate and 0.66 (95% CI 0.58-0.73) for the CDR. There was an agreement between the risk estimation of the GP and a CDR in 51% and the prevalence of ACS in predefined low-, intermediate- and high-risk groups was similar for the GP and CDR estimates. In the low-risk group, according to the GP, four patients (8.2%) suffered an ACS. These four patients were all identified by the decision rule as high risk. CONCLUSIONS: The GP classified patients as ACS or no ACS more adequately than the CDR, judged by the AUC. However, the use of a CDR in patients that are considered at low risk for ACS by the GP could reduce the amount of missed myocardial infarctions.

Exploring Associations between Oral Health and Frailty in Community-Dwelling Older People.

BACKGROUND: In frail older people with natural teeth factors like polypharmacy, reduced salivary flow, a decrease of oral self-care, general healthcare issues, and a decrease in dental care utilization contribute to an increased risk for oral complications. On the other hand, oral morbidity may have a negative impact on frailty. OBJECTIVE: This study explored associations between oral health and two frailty measures in community-dwelling older people. DESIGN: A cross-sectional study. SETTING: The study was carried out in a Primary Healthcare Center (PHC) in The Netherlands. PARTICIPANTS: Of the 5,816 persons registered in the PHC, 1,814 persons were eligible for participation at the start of the study. MEASUREMENTS: Two frailty measures were used: 1. Being at risk for frailty, using Electronical Medical Record (EMR) data, and: 2. Survey-based frailty using 'The Groningen Frailty Indicator' (GFI). For oral health measures, dental-record data (dental care utilization, dental status, and oral health information) and self-reported oral problems were recorded. Univariate regression analyses were applied to determine the association between oral health and frailty, followed by age- and sex-adjusted multivariate logistic regressions. RESULTS: In total 1,202 community-dwelling older people were included in the study, 45% were male and the mean age was 73 years (SD=8). Of all participants, 53% was at risk for frailty (638/1,202), and 19% was frail based on the GFI (222/1,202). A dental emergency visit (Odds Ratio (OR)= 2.0, 95% Confidence Interval (CI)=1.33;3.02 and OR=1.58, 95% CI=1.00;2.49), experiencing oral problems (OR=2.07, 95% CI=1.52;2.81 and OR=2.87, 95% CI= 2.07;3.99), and making dietary adaptations (OR=2.66, 95% CI=1.31;5.41 and OR=5.49, 95% CI= 3.01;10.01) were associated with being at risk for frailty and survey-based frailty respectively. CONCLUSIONS: A dental emergency visit and self-reported oral health problems are associated with frailty irrespective of the approach to its measurement. Healthcare professionals should be aware of the associations of oral health and frailty in daily practice.

Usage and Scientific Properties of the ADVOCATE Oral Health Care Measures.

BACKGROUND: Feedback information about the quality of oral health care is important for reflective learning by oral health care professionals and the wider health system. To this end, a list of 48 topics describing oral health and oral health care was recently agreed as part of the EU H2020 ADVOCATE project. OBJECTIVE: This article reports on the formulation of measures based on the ADVOCATE topics and provides information on usage, reporting, validity, and reliability of the measures. METHODS: The AIRE instrument was used to guide the methodological approach adopted. The appropriateness of the measures was tested among 39 general dental practitioners (GDPs) in Denmark, Germany, and the Netherlands. Data were collected from a convenience sample of patients via a questionnaire deployed in an online application in their practice. Feasibility, acceptability, and usefulness of the measures were evaluated through focus group interviews with GDPs. Face validity and test-retest reliability of the measures were assessed. RESULTS: For 46 of the 48 topics, a measure could be defined by constructing a definition and a numerator and denominator. Data collection for all 46 measures was feasible and acceptable for patients using the online questionnaire. The practicalities of using claims data for the purpose of giving feedback to individual and groups of GDPs proved to be challenging in terms of timely access of such data, the granularity of the data, and matching the content of the data with the consented items on quality of oral health care. Face validity was considered appropriate, as the patients found the questionnaire easy to understand. Test-retest reliability was found to be acceptable for 36 of 46 measures. CONCLUSION: The broad range of the ADVOCATE oral health care measures could make a useful contribution to a more transparent, evidence-based, and patient-centered oral health care system. KNOWLEDGE TRANSFER STATEMENT: This study shows the usage, reliability, and validity of 46 oral health care measures. The measures, which include patient experience and health behaviors, were found to be useful to stimulate discussions about clinical practice. The measures can provide essential information for quality improvement strategies and useful and relevant feedback information for GDPs.

Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis.

OBJECTIVES: To systematically analyse the literature on reported adverse events of low- to medium-dose glucocorticoids during >or=1 month for inflammatory diseases. METHODS: Data were systematically retrieved and selected from PUBMED, EMBASE and CINAHL databases (6097 hits). RESULTS: A total of 28 studies (2382 patients) met the inclusion criteria. The risk of adverse events over all studies was 150 per 100 patient-years (95% confidence interval (CI) 132 to 169). Psychological and behavioural adverse events (eg, minor mood disturbances) were most frequently reported, followed by gastrointestinal events (eg, dyspepsia, dysphagia). In 14 studies comprising 796 patients with rheumatoid arthritis the risk of adverse events was 43/100 patient-years (95% CI 30 to 55), in 4 studies of 167 patients with polymyalgia rheumatica the risk of adverse events was 80/100 patient-years (95% CI 15 to 146), and in 10 studies of 1419 patients with inflammatory bowel disease the risk of adverse events was 555/100 patient-years (95% CI 391 to 718). High rates of adverse events were reported in high-quality studies with short follow-up, notably in studies of patients with inflammatory bowel disease. CONCLUSIONS: The risk of adverse events depends on study design and disease. Studies on inflammatory bowel disease were often of short duration with frequent documentation of adverse events which resulted in higher adverse event rates whereas, in studies of rheumatoid arthritis, the longer follow-up may have resulted in lower adverse event rates. In most studies aimed at efficacy of glucocorticoids or other drugs, adverse events were not systematically assessed. Clear guidelines on assessment of adverse events are lacking.