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Contains fulltext : 208387.pdf (publisher's version ) (Open Access), Reporting of research findings is often selective. This threatens the validity of the published body of knowledge if the decision to report depends on the nature of the results. The evidence derived from studies on causes and mechanisms underlying selective reporting may help to avoid or reduce reporting bias. Such research should be guided by a theoretical framework of possible causal pathways that lead to reporting bias. We build upon a classification of determinants of selective reporting that we recently developed in a systematic review of the topic. The resulting theoretical framework features four clusters of causes. There are two clusters of necessary causes: (A) motivations (e.g. a preference for particular findings) and (B) means (e.g. a flexible study design). These two combined represent a sufficient cause for reporting bias to occur. The framework also features two clusters of component causes: (C) conflicts and balancing of interests referring to the individual or the team, and (D) pressures from science and society. The component causes may modify the effect of the necessary causes or may lead to reporting bias mediated through the necessary causes. Our theoretical framework is meant to inspire further research and to create awareness among researchers and end-users of research about reporting bias and its causes.

Contains fulltext : 203326.pdf (Publisher’s version ) (Closed access), BACKGROUND: Current level of asthma control can be easily assessed by validated instruments, but it is currently difficult to assess individuals' level of future risk. OBJECTIVE: Develop, and validate, a risk prediction score for level of future risk, including patient characteristics and information on early treatment response. METHODS: We used data of 304 adult patients with asthma from a 12-month primary care randomized controlled trial with 3-monthly assessments. With logistic regression we modeled the association between the level of future risk and patient characteristics including early treatment response. Future risk was defined as Asthma Control Questionnaire (ACQ) score of 1.5 or more at 12 months or the experience of at least 1 exacerbation during the final 6 months. We developed a risk prediction score on the basis of regression coefficients. RESULTS: Performance of the risk prediction score improved, taking into account data on early treatment response (area under receiver-operating curve [AUROC] = 0.84) compared with a model containing only baseline characteristics (AUROC = 0.78). The score includes 6 easy-to-obtain predictors: sex, ACQ score and exacerbations in the previous year at baseline and at first follow-up, and smoking status and exacerbations in the previous 3 months (indicating early treatment response). External validation yielded an AUROC of 0.77. The risk prediction score classified patients into 3 risk groups: low (absolute risk, 11.7%), intermediate (47.0%), and high (72.7%). CONCLUSIONS: We developed and externally validated a risk prediction score, quantifying both level of current asthma control and the guideline-defined future risk. Patients' individual risk can now be estimated in an easy way, as proposed but not specified, by asthma management guidelines.

Item does not contain fulltext, BACKGROUND: Several prediction models assessing future risk of exacerbations in adult patients with asthma have been published. Applicability of these models is uncertain because their predictive performance has often not been assessed beyond the population in which they were derived. OBJECTIVE: This study aimed to identify and critically appraise prediction models for asthma exacerbations and validate them in 2 clinically distinct populations. METHODS: PubMed and EMBASE were searched to April 2017 for reports describing adult asthma populations in which multivariable models were constructed to predict exacerbations during any time frame. After critical appraisal, the models' predictive performances were assessed in a primary and a secondary care population for author-defined exacerbations and for American Thoracic Society/European Respiratory Society-defined severe exacerbations. RESULTS: We found 12 reports from which 24 prediction models were evaluated. Three predictors (previous health care utilization, symptoms, and spirometry values) were retained in most models. Assessment was hampered by suboptimal methodology and reporting, and by differences in exacerbation outcomes. Discrimination (area under the receiver-operating characteristic curve [c-statistic]) of models for author-defined exacerbations was better in the primary care population (mean, 0.71) than in the secondary care population (mean, 0.60) and similar (0.65 and 0.62, respectively) for American Thoracic Society/European Respiratory Society-defined severe exacerbations. Model calibration was generally poor, but consistent between the 2 populations. CONCLUSIONS: The preservation of 3 predictors in models derived from variable populations and the fairly consistent predictive properties of most models in 2 distinct validation populations suggest the feasibility of a generalizable model predicting severe exacerbations. Nevertheless, improvement of the models is warranted because predictive performances a

Contains fulltext : 193563.pdf (publisher's version ) (Open Access), Background: Previous findings suggest that apathy symptoms independently of depressive symptoms measured using the Geriatric Depression Scale (GDS) are associated with cardiovascular disease (CVD) in older individuals. Aims: To study whether apathy and depressive symptoms in older people are associated with future CVD, stroke, and mortality using individual patient-data meta-analysis. Methods: Medline, Embase, and PsycInfo databases up to September 3, 2013, were systematically searched without language restrictions. We sought prospective studies with older (mean age >/=65 years) community-dwelling populations in which the GDS was employed and subsequent stroke and/or CVD were recorded to provide individual participant data. Apathy symptoms were defined as the three apathy-related subitems of the GDS, with depressive symptoms the remaining items. We used myocardial infarction (MI), stroke, and all-cause mortality as main outcomes. Analyses were adjusted for age, sex, and MI/stroke history. An adaptation of the Newcastle-Ottawa scale was used to evaluate bias. Hazard ratios were calculated using one-stage random-effect Cox regression models. Results: Of the 52 eligible studies, 21 (40.4%) were included, comprising 47,625 older people (mean age [standard deviation] 74 [7.4] years), over a median follow-up of 8.8 years. Participants with apathy symptoms had a 21% higher risk of MI (95% confidence interval [CI] 1.08-1.36), a 37% higher risk of stroke (95% CI 1.18-1.59), and a 47% higher risk of all-cause mortality (95% CI 1.38-1.56). Participants with depressive symptoms had a comparably higher risk of stroke (HR 1.36, 95% CI 1.18-1.56) and all-cause mortality (HR 1.44, 95% CI 1.35-1.53), but not of MI (HR 1.08, 95% CI 0.91-1.29). Associations for isolated apathy and isolated depressive symptoms were comparable. Sensitivity analyses according to risk of bias yielded similar results. Conclusion: Our findings stress the clinical importance of recognizing apathy independent

Item does not contain fulltext, BACKGROUND: Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management. METHODS: We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure. Three models were constructed, based on: (1) history, (2) history+spirometry and (3) history+spirometry+FeNO. Final models were corrected for overoptimism by shrinking the regression coefficients; predictive performance was assessed by the area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test. Models were externally validated in a data set including patients with severe asthma (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes). RESULTS: 80/611 (13.1%) participants experienced >/=1 severe exacerbation. Five predictors (Asthma Control Questionnaire score, current smoking, chronic sinusitis, previous hospital admission for asthma and >/=1 severe exacerbation in the previous year) were retained in the history model (AUROC 0.77 (95% CI 0.75 to 0.80); Hosmer-Lemeshow p value 0.35). Adding spirometry and FeNO subsequently improved discrimination slightly (AUROC 0.79 (95% CI 0.77 to 0.81) and 0.80 (95% CI 0.78 to 0.81), respectively). External validation yielded AUROCs of 0.72 (95% CI 0.70 to 0.73; 71 to 0.74 and 0.71 to 0.73) for the three models, respectively; calibration was best for the spirometry model. CONCLUSIONS: A simple history-based model extended with spirometry identifies patients who are prone to asthma exacerbations. The additional value of FeNO is modest. These models merit an implementation study in clinical practice to assess their utility. TRIAL REGISTRATION NUMBER: NTR 1756.

Contains fulltext : 168210.pdf (publisher's version ) (Open Access), BACKGROUND: Patients visiting their GPs exceptionally often (frequent attenders, FAs) have high rates of somatic disease, emotional distress, psychiatric illnesses and social problems and require a disproportionate amount of their GPs' time. OBJECTIVES: To summarize which types of FA have been studied and what the effects of interventions were on quality of life (QoL), symptom severity of underlying illness(es) and consultation frequency. To discover when patients are considered FAs. METHODS: Systematic review of RCTs using a comprehensive search (MEDLINE, PsycINFO, CINAHL and EMBASE, from 1980 to August 2015) and no language restrictions. Two investigators extracted data. Results were summarized qualitatively. RESULTS: We included 17 RCTs. Heterogeneity at the level of populations, interventions and outcomes precluded statistical pooling. In-depth analysis by GPs assessing a patient's reasons for frequent attendance decreased consultation frequency by four to six per year. A small effect on symptom severity was noted in depressed FAs, although this finding was not replicated in a recent trial. Multi-component therapy and medication in FAs with medically unexplained symptoms (MUS) improved QoL (SF36 odds ratio: 1.92; 95%CI: 1.08-3.40) and morbidity (CES-D 3.17; 95%CI: 1.27-5.08). CONCLUSION: RCTs on intervention effects in frequent attenders to primary care used different patient populations, interventions, comparators and outcome measures. Consistent evidence on the effects of particular interventions in specific patient domains is lacking. A tailored approach based on in-depth analysis among GPs of potential reasons for frequent attendance may decrease consultation frequency. Research involving the screening and treating for FAs with MUS may be useful in future trials.

Item does not contain fulltext, BACKGROUND: Aiming at partly controlled asthma (PCa) instead of controlled asthma (Ca) might decrease asthma medication use. Biomarkers, such as the fraction of exhaled nitric oxide (Feno), allow further tailoring of treatment. OBJECTIVE: We sought to assess the cost-effectiveness and clinical effectiveness of pursuing PCa, Ca, or Feno-driven controlled asthma (FCa). METHODS: In a nonblind, pragmatic, cluster-randomized trial in primary care, adults (18-50 years of age) with a doctor's diagnosis of asthma who were prescribed inhaled corticosteroids were allocated to one of 3 treatment strategies: (1) aiming at PCa (Asthma Control Questionnaire [ACQ] score <1.50); (2) aiming at Ca (ACQ score <0.75); and (3) aiming at FCa (ACQ score <0.75 and Feno value <25 ppb). During 12 months' follow-up, treatment was adjusted every 3 months by using an online decision support tool. Outcomes were incremental cost per quality-adjusted life year gained, asthma control (ACQ score), quality of life (Asthma Quality of Life Questionnaire score), asthma medication use, and severe exacerbation rate. RESULTS: Six hundred eleven participants were allocated to the PCa (n = 219), Ca (n = 203), or FCa (n = 189) strategies. The FCa strategy improved asthma control compared with the PCa strategy (P < .02). There were no differences in quality of life (P >/= .36). Asthma medication use was significantly lower for the PCa and FCa strategies compared with the Ca strategy (medication costs: PCa, $452; Ca, $551; and FCa, $456; P

Item does not contain fulltext, BACKGROUND: Patients who visit their General Practitioner (GP) very frequently over extended periods of time often have multimorbidity and are costly in primary and specialist healthcare. We investigated the impact of patient-level psychosocial and GP-level factors on the persistence of frequent attendance (FA) in primary care. METHODS: Two-year prospective cohort study in 623 incident adult frequent attenders (>90th attendance centile; age and sex-adjusted) in 2009. Information was collected through questionnaires (patients, GPs) and GPs' patient data. We used multilevel, ordinal logistic regression analysis, controlling for somatic illness and demographic factors with FA in 2010 and/or 2011 as the outcome. RESULTS: Other anxiety (odds ratio (OR) 2.00; 95% confidence interval from 1.29 to 3.10) over 3years and the number of life events in 3years (OR 1.06; 1.01-1.10 per event; range of 0 to 12) and, at baseline, panic disorder (OR 5.40; 1.67-17.48), other anxiety (OR 2.78; 1.04-7.46), illness behavior (OR 1.13; 1.05-1.20 per point; 28-point scale) and lack of mastery (OR 1.08; 1.01-1.15 per point; 28-point scale) were associated with persistence of FA. We found no evidence of synergistic effects of somatic, psychological and social problems. We found no strong evidence of effects of GP characteristics. CONCLUSION: Panic disorder, other anxiety, negative life events, illness behavior and lack of mastery are independently associated with persistence of frequent attendance. Effective intervention at these factors, apart from their intrinsic benefits to these patients, may reduce attendance rates, and healthcare expenditures in primary and specialist care.

Item does not contain fulltext, The aim of this study was to establish which cut-off point for the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (i.e. fixed 0.70 or lower limit of normal (LLN) cut-off point) best predicts accelerated lung function decline and exacerbations in middle-aged smokers. We performed secondary analyses on the Lung Health Study dataset. 4045 smokers aged 35-60 years with mild-to-moderate obstructive pulmonary disease were subdivided into categories based on presence or absence of obstruction according to both FEV1/FVC cut-off points. Post-bronchodilator FEV1 decline served as the primary outcome to compare subjects between the categories. 583 (14.4%) subjects were nonobstructed and 3230 (79.8%) subjects were obstructed according to both FEV1/FVC cut-off points. 173 (4.3%) subjects were obstructed according to the fixed cut-off point, but not according to the LLN cut-off point ("discordant" subjects). Mean+/-SE post-bronchodilator FEV1 decline was 41.8+/-2.0 mL.year(-1) in nonobstructed subjects, 43.8+/-3.8 mL.year(-1) in discordant subjects and 53.5+/-0.9 mL.year(-1) in obstructed subjects (p<0.001). Our study showed that FEV1 decline in subjects deemed obstructed according to a fixed criterion (FEV1/FVC <0.70), but non-obstructed by a sex- and age-specific criterion (LLN) closely resembles FEV1 decline in subjects designated as non-obstructed by both criteria. Sex and age should be taken into account when assessing airflow obstruction in middle-aged smokers.

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Background: A setting-specific asthma prediction score for preschool children with wheezing and/or dyspnoea presenting in primary healthcare is needed since existing indices are mainly based on general populations. Aims: To find an optimally informative yet practical set of predictors for the prediction of asthma in preschool children at high risk who present in primary healthcare. Methods: A total of 771 Dutch preschool children at high risk of asthma were followed prospectively until the age of six years. Data on asthma symptoms and environmental conditions were obtained using validated questionnaires and specific IgE was measured. At the age of six years the presence of asthma was assessed based on asthma symptoms, medication, and bronchial hyper-responsiveness. A clinical asthma prediction score (CAPS) was developed using bootstrapped multivariable regression methods. Results: In all, 438 children (56.8%) completed the study; the asthma prevalence at six years was 42.7%. Five parameters optimally predicted asthma: age, family history of asthma or allergy, wheezing-induced sleep disturbances, wheezing in the absence of common colds, and specific IgE. CAPS scores range from 0 to 11 points; scores <3 signified a negative predictive value of 78.4% while scores of ≥7 signified a positive predictive value of 74.3%. Conclusions: We have developed an easy-to-use CAPS for preschool children with symptoms suggesting asthma who present in primary healthcare. After suitable validation, the CAPS may assist in guiding shared decision-making to tailor the need for medical or non-medical interventions. External validation of the CAPS is needed.

Item does not contain fulltext, BACKGROUND: Frequently attending patients to primary care (FA) are likely to cost more in primary care than their nonfrequently attending counterparts. But how much is spent on specialist care of FAs? We describe the healthcare expenditures of frequently attending patients during 1, 2 or 3 years and test the hypothesis that additional costs can be explained by FAs' combined morbidity and primary care physicians' characteristics. METHODS: Record linkage study. Pseudonymised clinical data from the electronic medical records of 16 531 patients from 39 general practices were linked to healthcare insurer's reimbursements data. Main outcome measures were all reimbursed primary and specialist healthcare costs between 2007 and 2009. Multilevel linear regression analysis was used to quantify the effects of the different durations of frequent attendance on three-year total healthcare expenditures in primary and specialist care, while adjusting for age, sex, morbidities and for primary care physicians characteristics. Primary care physicians' characteristics were collected through administrative data and a questionnaire. RESULTS: Unadjusted mean 3-year expenditures were 5044 and 15 824 Euros for non-FAs and three-year-FAs, respectively. After adjustment for all other included confounders, costs both in primary and specialist care remained substantially higher and increased with longer duration of frequent attendance. As compared to non-FAs, adjusted mean expenditures were 1723 and 5293 Euros higher for one-year and three-year FAs, respectively. CONCLUSIONS: FAs of primary care give rise to substantial costs not only in primary, but also in specialist care that cannot be explained by their multimorbidity. Primary care physicians' working styles appear not to explain these excess costs. The mechanisms behind this excess expenditure remain to be elucidated.

1 januari 2012, Contains fulltext : 108014.pdf (publisher's version ) (Closed access), Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future.

Background: The recommendations for the treatment of moderate persistent asthma in the Global Initiative for Asthma (GINA) guidelines for paediatric asthma are mainly based on scientific evidence extrapolated from studies in adults or on consensus. Furthermore, clinical decision-making would benefit from formal ranking of treatments in terms of effectiveness.Our objective is to assess all randomized trial-based evidence specifically pertaining to 5-18 year olds with moderate persistent asthma. Rank the different drug treatments of GINA guideline steps 3&4 in terms of effectiveness.Methods: Systematic review with network meta-analysis. After a comprehensive search in Central, Medline, Embase, CINAHL and the WHO search portal two reviewers selected RCTs performed in 4,129 children from 5-18 year old, with moderate persistent asthma comparing any GINA step 3&4 medication options. Further quality was assessed according the Cochrane Collaboration's tool and data-extracted included papers and built a network of the trials. Attempt at ranking treatments with formal statistical methods employing direct and indirect (e.g. through placebo) connections between all treatments.Results: 8,175 references were screened; 23 randomized trials (RCT), comparing head-to-head (n=17) or against placebo (n=10), met the inclusion criteria. Except for theophylline as add-on therapy in step 4, a closed network allowed all comparisons to be made, either directly or indirectly. Huge variation in, and incomplete reporting of, outcome measurements across RCTs precluded assessment of relative efficacies.Conclusion: Evidence-based ranking of effectiveness of drug treatments in GINA steps 3&4 is not possible yet. Existing initiatives for harmonization of outcome measurements in asthma trials need urgent implementation.

Background: In research with long-term follow-up and repeated measurements, quick and complete response to questionnaires helps ensure a study's validity, precision and efficiency. Evidence on the effect of non-monetary incentives on response rates in observational longitudinal research is scarce. Objectives. To study the impact of two strategies to enhance completeness and efficiency in observational cohort studies with follow-up durations of around 2 years. Method and intervention. In a factorial design, 771 children between 2 and 5 years old and their parents participating in a prospective cohort study were randomized to three intervention groups and a control group. Three types of lotteries were run: (i) daytrip tickets for the whole family to a popular amusement park if they returned all postal questionnaires, (ii) 12.50-worth gift vouchers for sending back the questionnaire on time after each questionnaire round and (iii) a combination of (i) and (ii). Main outcome measures. Primary outcome was the proportion of participants who returned all questionnaires without any reminder. Secondary outcomes were '100% returned with or without reminder', 'probability of 100% non-response', 'probability of withdrawal', 'proportion of returned questionnaires' and 'overall number of reminders sent'. Statistical analysis. After testing for interaction between the two lottery interventions, the two trials were analysed separately. We calculated risk differences (RD) and numbers needed to "treat" and their 95% confidence intervals. Results: Daytrip nor voucher intervention had an effect on the proportion of participants who returned all questionnaires (RD -0.01; 95% CI-0.07 - 0.06) and (RD 0.02; 95% CI-0.50 - 0.08), respectively. No effects were found on the secondary outcomes. Conclusion: Our findings do not support the idea that lottery-style incentives lead to more complete response to postal questionnaires in observational cohort studies with repeated data collection and fo

Background: Growing antibiotic resistance warrants studying nonantibiotic prophylaxis for recurrent urinary tract infections (UTIs). Use of lactobacilli appears to be promising. Methods: Between January 2005 and August 2007, we randomized 252 postmenopausal women with recurrent UTIs taking part in a double-blind noninferiority trial to receive 12 months of prophylaxis with trimethoprimsulfamethoxazole, 480 mg, once daily or oral capsules containing 09 colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily. Primary end points were the mean number of symptomatic UTIs, proportion of participants with at least 1 UTI during 12 months, time to first UTI, and development of antibiotic resistance by Escherichia coli. Results: The mean number of symptomatic UTIs in the year preceding randomization was 7.0 in the trimethoprimsulfamethoxazole group and 6.8 in the lactobacilli group. In the intention-to-treat analysis, after 12 months of prophylaxis, these numbers were 2.9 and 3.3, respectively. The betwe

Contains fulltext : 97659.pdf (publisher's version ) (Open Access), BACKGROUND: Despite the availability of effective therapies, asthma remains a source of significant morbidity and use of health care resources. The central research question of the ACCURATE trial is whether maximal doses of (combination) therapy should be used for long periods in an attempt to achieve complete control of all features of asthma. An additional question is whether patients and society value the potential incremental benefit, if any, sufficiently to concur with such a treatment approach. We assessed patient preferences and cost-effectiveness of three treatment strategies aimed at achieving different levels of clinical control: 1. sufficiently controlled asthma 2. strictly controlled asthma 3. strictly controlled asthma based on exhaled nitric oxide as an additional disease marker DESIGN: 720 Patients with mild to moderate persistent asthma from general practices with a practice nurse, age 18-50 yr, daily treatment with inhaled corticosteroids (more then 3 months usage of inhaled corticosteroids in the previous year), will be identified via patient registries of general practices in the Leiden, Nijmegen, and Amsterdam areas in The Netherlands. The design is a 12-month cluster-randomised parallel trial with 40 general practices in each of the three arms. The patients will visit the general practice at baseline, 3, 6, 9, and 12 months. At each planned and unplanned visit to the general practice treatment will be adjusted with support of an internet-based asthma monitoring system supervised by a central coordinating specialist nurse. Patient preferences and utilities will be assessed by questionnaire and interview. Data on asthma control, treatment step, adherence to treatment, utilities and costs will be obtained every 3 months and at each unplanned visit. Differences in societal costs (medication, other (health) care and productivity) will be compared to differences in the number of limited activity days and in quality adjusted life years (Dutch

Item does not contain fulltext, OBJECTIVE: Newly presented unexplained complaints (UCs) are common in general practice. Factors influencing the transition of newly presented into persistent UCs have been scarcely investigated. We studied the number and the nature of diagnoses made over time, as well as factors associated with UCs becoming persistent. Finally, we longitudinally studied factors associated with quality of life (QoL). METHODS: Prospective cohort study in general practice of patients presenting with a new UC. Data sources were case record forms, patient questionnaires and electronic medical registries at inclusion, 1, 6 and 12 months. Presence of complaints and diagnoses made over time were documented. Potential risk factors were assessed in mixed-effect logistic and linear regression models. RESULTS: Sixty-three GPs included 444 patients (73% women; median age 42) with unexplained fatigue (70%), abdominal complaints (14%) and musculoskeletal complaints (16%). At 12 months, 43% of the patients suffered from their initial complaints. Fifty-seven percent of the UCs remained unexplained. UCs had (non-life-threatening) somatic origins in 18% of the patients. QoL was often poor at presentation and tended to remain poor. Being a male [odds ratio (OR) 0.6; 95% confidence interval (CI) 0.4-0.8] and GPs' being more certain about the absence of serious disease (OR 0.9; 95% CI 0.8-0.9) were the strongest predictors of a diminished probability that the complaints would still be present and unexplained after 12 months. The strongest determinants of complaint persistence [regardless of (un)explicability] were duration of complaints >4 weeks before presentation (OR 2.6; 95% CI 1.6-4.3), musculoskeletal complaint at baseline (OR 2.3; 1.2-4.5), while the passage of time acted positively (OR 0.8 per month; 95% CI 0.78-0.84). Musculoskeletal complaints, compared to fatigue, decreased QoL on the physical domain (4.6 points; 2.6-6.7), while presence of psychosocial factors decreased mental QoL (5.0; 3.1-6.

Item does not contain fulltext, BACKGROUND: Unexplained fatigue is frequently encountered in general practice. Because of the low prior probability of underlying somatic pathology, the positive predictive value of abnormal (blood) test results is limited in such patients. AIM: The study objectives were to investigate the relationship between established diagnoses and the occurrence of abnormal blood test results among patients with unexplained fatigue; to survey the effects of the postponement of test ordering on this relationship; and to explore consultation-related determinants of abnormal test results. DESIGN OF STUDY: Cluster randomised trial. SETTING: General practices of 91 GPs in the Netherlands. METHOD: GPs were randomised to immediate or postponed blood-test ordering. Patients with new unexplained fatigue were included. Limited and expanded sets of blood tests were ordered either immediately or after 4 weeks. Diagnoses during the 1-year follow-up period were extracted from medical records. Two-by-two tables were generated. To establish independent determinants of abnormal test results, a multivariate logistic regression model was used. RESULTS: Data of 325 patients were analysed (71% women; mean age 41 years). Eight per cent of patients had a somatic illness that was detectable by blood-test ordering. The number of false-positive test results increased in particular in the expanded test set. Patients rarely re-consulted after 4 weeks. Test postponement did not affect the distribution of patients over the two-by-two tables. No independent consultation-related determinants of abnormal test results were found. CONCLUSION: Results support restricting the number of tests ordered because of the increased risk of false-positive test results from expanded test sets. Although the number of re-consulting patients was small, the data do not refute the advice to postpone blood-test ordering for medical reasons in patients with unexplained fatigue in general practice.

Item does not contain fulltext, BACKGROUND: Approximately 13% of consultations in general practice involve patients with unexplained complaints (UCs). These consultations often end with general practitioners (GPs) ordering blood tests of questionable diagnostic informativeness. OBJECTIVE: We studied factors potentially associated with GPs' decisions to order blood tests. METHODS: Cross-sectional study. Twenty-seven GPs completed registration forms after each consultation concerning newly presented UCs. RESULTS: Of the 100 analysable patients, 59 had at least one blood test ordered. The median number of ordered tests was 10 (interpercentile range [IPR-90] 2-15). Compared to abdominal complaints, the blood test ordering (BTO) probability for fatigue was five times higher (relative risk [RR] 5.2). Duration of complaints for over 4 weeks also increased this probability (RR 1.6). Factors associated with a lower BTO probability were: likelihood of background psychosocial factors (RR 0.4) and GPs having a syndrome rather than symptom type of working hypothesis (RR 0.5). CONCLUSION: We found a high rate of BTO among GPs confronted with patients with UCs. Furthermore, a considerable number of tests were ordered. The selectivity in BTO behaviour of GPs can be improved upon.

Contains fulltext : 57502.pdf (publisher's version ) (Closed access), BACKGROUND AND OBJECTIVE: To evaluate the value of balanced incomplete block designs in quality improvement research, and their capacity to control for the Hawthorne effect. METHODS: General practitioners teams were randomized into three arms and received an intervention on test ordering, relating to tests for two groups of clinical problems (A tests and B tests). In the two trials within the block design, we tried to control for the Hawthorne effect by comparing the complete intervention in both arms on either the A (arm I) or B tests (arm II); the arms acted as blind controls for each other. In the classical trial, the complete intervention on B tests (arm II) was compared with a control arm without any intervention on B tests (arm III). RESULTS: The trials with the block design yielded statistically significant changes in the numbers of A tests ordered (P=.013), but not in the numbers of B tests ordered (P=.29). In the classical design, the complete intervention reached a marginally significant change in the B tests (P=.068). The Hawthorne effect was the same for both arms of the block design. In the classical design, the effect could to some extent be attributed to the Hawthorne effect. CONCLUSION: Our block design allowed us to control for the Hawthorne effect. Suitable use of block designs may further our knowledge of nonspecific effects in quality improvement research.

Contains fulltext : 59105.pdf (publisher's version ) (Closed access), OBJECTIVE: The aim of this study was to describe GPs' test ordering behaviour, and to establish professional and context-related determinants of GPs' inclination to order tests. METHODS: A cross-sectional analysis was carried out of 229 GPs in 40 local GP groups from five regions in The Netherlands of the combined number of 19 laboratory and eight imaging tests ordered by GPs, collected from five regional diagnostic centres. In a multivariable multilevel regression analysis, these data were linked with survey data on professional characteristics such as knowledge about and attitude towards test ordering, and with data on context-related factors such as practice type or experience with feedback on test ordering data. The main outcome measure was the percentage point differences associated with professional and context-related factors. RESULTS: The total median number of tests per GP per year was 998 (interquartile range 663-1500), with significant differences between the regions. The response to the survey was 97%. At the professional level, 'individual involvement in developing guidelines' (yes versus no), and at the context-related level 'group practice' (versus single-handed and two-person practices) and 'more than 1 year of experience working with a problem-oriented laboratory order form' (yes versus no) were associated with 27, 18 and 41% lower numbers of tests ordered, respectively. CONCLUSION: In addition to professional determinants, context-related factors appeared to be strongly associated with the numbers of tests ordered. Further studies on GPs' test ordering behaviour should include local and regional factors.