Assessment of spin in the abstracts of randomized controlled trials in dental caries with statistically nonsignificant results for primary outcomes: A methodological study.

The study aimed to assess the prevalence of spin in the titles and abstracts of RCTs in dental caries with statistically nonsignificant primary outcomes and to assess the risk indicators which may be associated with spin. Any original publication reporting a two-arm RCT in dental caries with clearly identified statistically nonsignificant primary outcomes published from January 1, 2015 until October 28, 2022 were included. PubMed was searched electronically to identify the eligible publications. The prevalence of spin in titles and abstracts were assessed and categorized into spin patterns based on a pre-determined classification scheme. The association between spin and the potential risk indicators at study, author, journal, institutional, and national level was assessed. A total of 234 eligible RCT publications were included. The prevalence of spin in the titles and abstracts was 3% (95%CI: 2% to 6%) and 79% (95%CI: 74% to 84%), respectively. The most common spin patterns in the results and conclusion sections, respectively, were results focusing on statistically significant within-group comparisons (23%), and conclusions focusing only on statistically significant results without acknowledgment of statistically nonsignificant results for the primary outcomes (26%). The spin was significantly associated with number of study centers (single-center vs. multicenter) (OR=2.131; 95%CI: 1.092 to 4.158; P=0.03), trial designs (non-parallel designs vs. parallel designs) (OR=0.395; 95%CI: 0.193 to 0.810; P=0.01), and overall H index of institutions for last authors (OR=0.998; 95%CI: 0.996 to 0.999; P<0.01), while it was not significantly associated with the other indicators. In the RCT publications with statistically nonsignificant results for primary outcomes in dental caries, the prevalence of spin may be low in the titles but high in the abstracts. Single-center studies with parallel designs and a lower overall H index of institutions for last authors may be more likely to have spin in the abstracts.

Can a Joint Assessment Provide Relevant Information for National/Local Relative Effectiveness Assessments? An In-Depth Comparison of Pazopanib Assessments.

BACKGROUND: In many European jurisdictions, relative effectiveness assessments (REAs) of pharmaceuticals are performed during the reimbursement decision-making process. International collaboration in the production of these assessments may prevent the duplication of information in various jurisdictions. A first pilot of a joint REA (pazopanib for the treatment of renal cell carcinoma) was published in 2011. OBJECTIVE: The objective was to investigate how well the methods used in the joint REA match the methods used in the national/local assessments on the same topic. METHODS: National/local assessments from European jurisdictions, available in English language, were identified through a literature search and an e-mail request to health technology assessment organizations. Data were abstracted from joint and national/local assessments using a structured data abstraction form. Results were compared for differences and similarities. RESULTS: In total, five national/local reports were included (Belgium, England/Wales, France, The Netherlands, and Scotland). The general methods (indication, main comparator, main end points, main trial) were similar. The details of the assessment (e.g., exact wording of indication, additional comparators, additional trials included, and method of indirect comparison), however, varied. Despite these differences, the joint REA included nearly all comparators, end points, trials, and methods of analysis that were used in national/local REA reports. CONCLUSIONS: This study has shown overlap in the methods national/local REA bodies in Europe have chosen for a pazopanib REA for renal cell carcinoma, except for the use and methods of indirect comparisons. Although some additional comparators and outcomes differed between national/local REAs, they can be captured in a comprehensive joint REA.

COX-2 inhibitors: complex association with lower risk of hospitalization for gastrointestinal events compared to traditional NSAIDs plus proton pump inhibitors.

PURPOSE: To compare hospitalization rates for serious upper and lower gastrointestinal (GI) events between chronic and acute users of a traditional non-steroidal anti-inflammatory drugs (tNSAID) + proton pump inhibitor (PPI) and users of a COX-2 selective inhibitor (Coxib). METHODS: The PHARMO Record Linkage System, including linked drug-dispensing and hospital records of approximately 3 million individuals in the Netherlands was used. We selected new Coxib or tNSAID users (01/01/2000-31/12/2004) with > or =1 year history before the first NSAID dispensing and > or =1 year follow-up ending at the first hospitalization for GI event (the outcome), last dispensing, or end of the study period. Chronic users were patients who used any NSAIDs for > or =60 days during the first year (n = 58 770); others were acute users (n = 538 420). Multivariate analysis was performed by Poisson regression adjusted for gender, age, and duration of follow-up, tNSAID and Coxib dose, NSAID/PPI adherence, use of other gastroprotective agents, anticoagulants, acetaminophen, corticosteroids, and cardiovascular disease. RESULTS: The cohort included 23 999 new tNSAIDs + PPI users and 25 977 new Coxib users, with main characteristics: mean +/- SD age 58.1 +/- 15.5 vs. 56.7 +/- 17.5; female 55.3% vs. 62.2%; duration of treatment (days): 137 +/- 217 vs. 138 +/- 179, respectively. Among acute users, adjusted hazard ratios (95% Confidence Interval) were 0.21 (0.14-0.32) for upper and 0.26 (0.16-0.42) for lower GI events, for Coxib versus tNSAIDs + PPI users. Among chronic users, these were 0.35 (0.22-0.55) for upper GI and 0.43 (0.25-0.75) for lower GI events. CONCLUSIONS: Coxib users had significantly lower rates of GI events. Further research should elucidate the possible impact of selection bias.

Large impact of antidiabetic drug treatment and hospitalizations on economic burden of diabetes mellitus in The Netherlands during 2000 to 2004.

OBJECTIVE: To estimate the burden of diabetes mellitus (DM) and its complications in The Netherlands. METHODS: The PHARMO Record Linkage System comprised among others linked drug dispensing, hospital and clinical laboratory data from approximately 2.5 million individuals in The Netherlands. Patients with DM (type 1 and type 2) were included in the study cohort from 2000 to 2004 if they used antidiabetic drugs or had HbA1c >or= 6.5 mmol/L or had a hospitalization for DM or a diabetic complication in the measurement year or in the preceding year. Controls, defined as subjects without a diagnosis of DM and/or subjects not prescribed glucose-lowering medication, were 1:1 matched to patients with diabetes, on birth year, zip code, and gender. Complications (hospitalizations and dispensings for cardiovascular disease/eye problems/amputations) were classified into stages. Complications attributed to DM were estimated as complication stages 1 and 2 among patients minus those among controls. Drug costs were extrapolated to The Netherlands by direct standardization. RESULTS: Among the total population in The Netherlands, the prevalence of DM increased from 2.8% in 2000 to 4.0% in 2004. Severe cardiovascular complications attributed to DM increased from 18,000 to 39,000 patients. Per DM patient the cost of direct treatment attributed to DM increased from Euro 974 in 2000 to Euro 1283 in 2004. Per 100 members of the total population, this increase was from Euro 2764 in 2000 to Euro 5140 in 2004. Most of these costs (65% in 2004) were because of hospitalizations. CONCLUSION: Drug treatment, hospitalizations, and cost attributed to diabetes mellitus have almost doubled between 2000 and 2004, but so did the "background" costs in the general population, perhaps because of preventive efforts.

Topical corticosteroids and the risk of diabetes mellitus: a nested case-control study in the Netherlands.

BACKGROUND: The relationship between topical corticosteroid use, potency, treatment duration, concomitant exposure to systemic corticosteroids, and risk of diabetes has been incompletely studied. OBJECTIVE: To investigate an association between intense, longstanding topical corticosteroid use and diabetes mellitus. METHODS: Data for this nested case-control study were obtained from the PHARMO Record Linkage System, including linked drug dispensing and hospital records of >2.5 million individuals in defined areas of the Netherlands. Users of topical corticosteroids during 1992-2004, without diabetes, with >or=2 topical corticosteroid dispensings and >or=4 years of follow-up were selected. Diabetes onset was defined as first occurrence (index date) of an antidiabetic drug dispensing or hospitalization for diabetes. Cases were matched 1:4 by age and sex to controls, with >or=2 topical corticosteroid dispensings and similar follow-up duration. Use of topical corticosteroids and systemic corticosteroids and/or inhaled corticosteroids as co-medication was classified as current, recent and past/never (4 years ago, respectively). Multivariate regression analyses were adjusted for co-medication and co-morbidity. RESULTS: Among 192,893 incident topical corticosteroid users, 2,212 developed diabetes and could be matched to 8,582 controls. Current topical corticosteroid use was associated with an (unadjusted) 1.24-fold increased risk of diabetes (unadjusted OR 1.24; 95% CI 1.11, 1.40). The odds ratio increased to 1.32 with >180 days of topical corticosteroid use (95% CI 1.14, 1.54) and to 1.44 with a cumulative topical corticosteroid load (combined potency and amount) of 731-1460 mg (95% CI 1.21, 1.72). Among past/never users of systemic corticosteroids and/or inhaled corticosteroids, current use of topical corticosteroids remained associated with a 1.27-fold increased diabetes risk (unadjusted OR 1.27; 95% CI 1.10, 1.47) compared with past users of topical corticosteroids. CONCLUSION: An increased risk of new-onset diabetes may be an important consideration in the treatment of patients with topical corticosteroids, especially when intense skin treatment is needed. Future studies are needed to endorse these findings in other populations.

Gastroprotection among new chronic users of non-steroidal anti-inflammatory drugs: a study of utilization and adherence in The Netherlands.

OBJECTIVE: To describe the use of gastroprotection (GP) among new chronic users of NSAIDs in the Netherlands by gastrointestinal (GI) risk factor (RF) score. METHODS: Data for this retrospective follow-up study were extracted from the PHARMO database. We selected new chronic users of COX-2 inhibitors (coxibs) or traditional NSAIDs (tNSAIDs) between 1st January 2000 and 31st December 2004. GP strategies were defined as: use of proton pump inhibitors (PPI), coxibs or both. GI RF score at index date was based on: history of GI drug use, high dose of NSAIDs, age > 60 years, use of corticosteroids/anticoagulants/SSRIs, rheumatoid arthritis, heart failure or diabetes, with each condition accounting for one factor. Switching was assessed among those with > or = 1 GI RF during the first year of follow-up. RESULTS: Among 58,770 new chronic NSAID users at index date, 80% used tNSAIDs alone, 8% used tNSAID + PPI, 10% used a coxib alone and 2% used coxib + PPI. Mean (SD) number of GI RF among these groups was 1.6 (2.1), 3.1 (1.3), 1.5 (1.5) and 2.8 (1.3), respectively. Among 48 390 patients (82.3%) with a GI RF score of > or = 1, 20.9% used a GP strategy, this increased with number of GI RFs. Within the first year, 5.3% (n = 2067) and 4.8%(n = 1 843) of tNSAID users with > or = 1 GI RF switched to tNSAID+PPI and coxib alone, respectively. CONCLUSIONS: Gastroprotection in users of tNSAIDs was inadequate. Over 80% of NSAID users with > or = 1 GI RF did not receive any gastroprotection, and even when prescribed, a PPI is used only half the time. More research should show if gastroprotection was used for prevention.

LDL-C reductions and goal attainment among naive statin users in the Netherlands: real life results.

OBJECTIVE: The effectiveness of statin therapy in a real life setting may differ from that in clinical trials, as physicians make non-randomised treatment decisions for patients with less uniform and possibly different characteristics. We therefore performed a study to compare the effectiveness of different statins and doses in routine clinical practice with respect to total serum cholesterol and LDL-cholesterol (LDL-C) reduction and goal attainment according to European guidelines on the prevention of cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Naive statin users starting treatment in 2003 and 2004 with LDL-C measurements at baseline and between 30 and 365 days after start of treatment were extracted from the PHARMO database. During treatment with their initial statin dose LDL-C reduction and attainment of cholesterol goals were compared between different statins and doses. RESULTS: Of 2303 identified naive patients, approximately 30% were allocated to the high CVD-risk group. Average LDL-C reductions were 48%, 42%, 39%, and 32% at mean doses of 11 mg rosuvastatin, 17 mg atorvastatin, 22 mg simvastatin and 35 mg pravastatin, respectively. The proportion of patients attaining cholesterol goals was 75% for rosuvastatin, 68% for atorvastatin, 56% for simvastatin, and 42% for pravastatin. Dose comparisons showed greater LDL-C reduction and increased goal attainment for rosuvastatin 10 mg compared to other statins at most doses (adjusted p < 0.05). CONCLUSIONS: In a real life setting, both LDL-C reduction and the proportion of patients attaining cholesterol goals appear to be significantly increased among users of rosuvastatin compared to other statins. These results confirm and extend reported clinical trial results to a real world setting.

Large-scale stopping and switching treatment with COX-2 inhibitors after the rofecoxib withdrawal.

PURPOSE: To compare treatment changes after the rofecoxib withdrawal with changes occurring normally and to re-assess 12 months afterwards. METHODS: The PHARMO database comprised medication and hospital discharge records of over 3 million inhabitants in the Netherlands. The Study cohort included chronic coxib users with a coxib prescription on 30th September 2004; the Reference cohort others with a coxib prescription on 1st June 2004. Initial treatment changes were based on first new prescription since cohort entry. Twelve-month changes were studied within the Study cohort only. RESULTS: The Study cohort (n = 6974) and Reference cohort (n = 5393) had similar demographics, stratified on type of coxib. In the Study cohort, 3341 (48%) initially stopped coxibs, of whom 1121 (16%) stopped all analgesic, versus 13 and 5% in the Reference cohort (p < 0.001). Among 'other coxib' users 32% stopped coxibs, and 15% stopped all analgesics, versus 14% and 4%, p < 0.001 in the Reference cohort. Among those who stopped coxibs, 34% switched to non-selective non-steroidal anti-inflammatory drug (nsNSAID) without PPI, 21% to nsNSAID with PPI, and 45% stopped NSAID treatment (Reference cohort: 35, 20, and 44%, respectively). These rates for 'other coxib users' were: switching to nsNSAID without PPI 23% (Study Cohort) versus 35% (Reference Cohort), 13 versus 28%, and 64 versus 37% respectively (p < 0.001). Twelve months later, stopping NSAID increased to 43%, stopping all analgesics to 32%. Rheumatologists continued coxibs more frequently than other caregivers (87, 65, 54%, respectively). CONCLUSIONS: The rofecoxib withdrawal resulted in a large proportion of patients who discontinued analgesic treatment altogether regardless of original coxib therapy.

Development of a case-based system for grouping diagnoses in general practice.

INTRODUCTION: This article describes the development of EPICON; an application to group ICPC-coded diagnoses from electronic medical records in general practice into episodes of care. These episodes can be used to estimate prevalence and incidence rates. METHODS: We used data from 89 practices that participated in the Dutch National Survey of General Practice. Additionally, we held interviews with seven experts, and studied documentation to establish the requirements of the application and to develop the design. We then performed a formative evaluation by assessing incorrectly grouped diagnoses. RESULTS: EPICON is based on a combination of logical expressions, a decision table, and information extracted from individual cases by case-based reasoning. EPICON is able to group all diagnoses in the selected 89 practices, and groups 95% correctly. CONCLUSION: The results cautiously indicate that EPICONs performance will probably be adequate for the purpose of estimating morbidity rates in general practice.

The association between H63D mutations in HFE and amyotrophic lateral sclerosis in a Dutch population.

BACKGROUND: Mutations in HFE, a gene defect that can disrupt iron metabolism, have been implicated in increasing the risk of developing amyotrophic lateral sclerosis (ALS). OBJECTIVE: To further establish the association between ALS and HFE mutations by investigating whether HFE mutations are associated with an increased risk of developing ALS in a population in The Netherlands and by pooling our results with those from previous studies. DESIGN: Retrospective study. SETTING: Tertiary referral center for neuromuscular disorders. PARTICIPANTS: Genotyping for 2 common HFE mutations was performed in 289 patients with ALS and 5886 population-based controls in The Netherlands between January 1, 2000, and December 31, 2004. MAIN OUTCOME MEASURES: Development of ALS and clinical phenotype were compared among the different HFE genotypes, adjusting for known prognostic factors such as age at onset and sex. RESULTS: Homozygosity for H63D was associated with an increased risk of developing ALS (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1-4.1). After pooling our results with those from previous studies, a positive association between H63D homozygotes (OR, 2.7; 95% CI, 1.7-4.4), heterozygotes (OR, 1.5; 95% CI, 1.0-2.1), and mutation carriers (OR, 1.7; 95% CI, 1.1-2.5) was found. Within the patient group, heterozygosity for the H63D mutation was associated with a higher age at onset. CONCLUSIONS: These findings suggest that H63D mutations in HFE play a role in the pathogenesis of ALS in various populations. This association might involve a later-onset subset of ALS.

Increasing incidence of skin disorders in children? A comparison between 1987 and 2001.

BACKGROUND: The increasing proportion of skin diseases encountered in general practice represents a substantial part of morbidity in children. Only limited information is available about the frequency of specific skin diseases. We aimed to compare incidence rates of skin diseases in children in general practice between 1987 and 2001. METHODS: We used data on all children aged 0-17 years derived from two consecutive surveys performed in Dutch general practice in 1987 and 2001. Both surveys concerned a longitudinal registration of GP consultations over 12 months. Each disease episode was coded according to the International Classification of Primary Care. Incidence rates of separate skin diseases were calculated by dividing all new episodes for each distinct ICPC code by the average study population at risk. Data were stratified for socio-demographic characteristics. RESULTS: The incidence rate of all skin diseases combined in general practice decreased between 1987 and 2001. Among infants the incidence rate increased. Girls presented more skin diseases to the GP. In the southern part of the Netherlands children consulted their GP more often for skin diseases compared to the northern part. Children of non-Western immigrants presented relatively more skin diseases to the GP. In general practice incidence rates of specific skin diseases such as impetigo, dermatophytosis and atopic dermatitis increased in 2001, whereas warts, contact dermatitis and skin injuries decreased. CONCLUSION: The overall incidence rate of all skin diseases combined in general practice decreased whereas the incidence rates of bacterial, mycotic and atopic skin diseases increased.

Prevalence estimates of asthma or COPD from a health interview survey and from general practitioner registration: what's the difference?

BACKGROUND: The aim of this study was to compare prevalence estimates of asthma or chronic obstructive pulmonary disease (COPD) derived from self-report in a health interview survey and from general practitioners' (GPs') medical records, and to explain any differences. METHODS: the presence of asthma or COPD was measured by self-report in a random sample of 104 general practices in the Netherlands (n = 19 685) participating in the second Dutch National Survey of General Practice (DNSGP-2). This was compared with the presence of GP-diagnosed asthma or COPD in the same population as recorded using the International Classification of Primary Care by their GPs during a 12-month period. Gender, age, health insurance, ethnic background, educational level, tobacco exposure, and other symptoms and conditions were evaluated as explanatory variables using logistic models. RESULTS: The prevalence of self-reported asthma or COPD (9.7%) was almost twice as high as the prevalence based on GP information (5.2%). The medical records of patients who reported having asthma or COPD, without having a diagnosis in their medical records, usually included other respiratory conditions. Patients reporting no asthma or COPD but whose medical records carried a diagnosis of asthma or COPD, were relatively older (P < 0.01) and tended to be exposed to smoking in their home (P < 0.05). CONCLUSIONS: Two methods for estimating prevalence of asthma or COPD yielded different results: compared with GP medical records, self-reported prevalence shows an overestimation in people who suffer from other respiratory conditions and an underestimation in elderly persons living in a smoky environment.