- [Show abstract] [Hide abstract] ABSTRACT: Safety concerns of the concomitant use of clopidogrel and proton pump inhibitors (PPIs) were published in 2009 and 2010 by the medicines regulatory agencies, including a direct healthcare professional communication. We examined the association between various safety statements and prescription behavior for gastroprotective drugs in naïve patients in the Netherlands during the years 2008–2011. Data from the PHARMO Database Network were analyzed with interrupted time series analyses to estimate the impact of each communication on drug prescriptions. Dispensings were used as a proxy variable for prescription behavior. After the early communication in January 2009, 15.5% (95% CI 7.8, 23.4) more patients started concomitantly with (es)omeprazole and 13.8% (95% CI 6.5, 21.2) less with other PPIs. Directly after the first statement in June 2009, we found a steep increase in histamine 2-receptor antagonists (H2RA) peaking at 25%, placing those patients at risk for gastrointestinal events. This effect for H2RA faded away after a few months. In February 2010, when the official advice via an adjusted statement was to avoid (es)omeprazole, we found a decrease of 11.9% (95% CI 5.7, 18.2) for (es)omeprazole and an increase of +16.0% (95% CI 10.3, 21.7) for other PPIs. Still 22.6% (95% CI 19.5, 25.7) of patients started on (es)omeprazole in February 2010, placing them at risk for cardiovascular events. Advices of regulatory authorities were followed, however, reluctantly and not fully, probably partly because of the existing scientific doubt about the interaction.
- [Show abstract] [Hide abstract] ABSTRACT: To better classify patients with chronic obstructive pulmonary disease (COPD) for prognostic purposes and to tailor treatment, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007 classification was revised in 2011. The primary aim of the current data analyses was to evaluate the accuracy of the GOLD 2007 and 2011 GOLD classifications to predict all-cause mortality and morbidity in a well-described COPD cohort. The prognostic values of both GOLD classifications, expressed as the C-statistic, were assessed in the Cohort of Mortality and Inflammation in COPD (COMIC) study of 795 COPD patients, with a follow-up of 3 years. Outcomes were all-cause mortality and morbidity. Morbidity was defined as time until first COPD-related hospitalisation and time until first community-acquired pneumonia (CAP). The prognostic value of the GOLD 2011 classification was compared between symptom classification based on the modified Medical Research Council (mMRC) score and the Clinical COPD Questionnaire (CCQ) scores with two different thresholds. Although the GOLD 2011 CCQ classification had the highest accuracy to predict mortality and morbidity in our study, the C-statistics differed only numerically. Furthermore, our study showed that the instrument used to determine the level of symptoms in the GOLD 2011 classification has not only important consequences on the mortality prognosis, but also affects the morbidity prognosis in COPD. Therefore, patients' estimated prognosis could alter when different types of tools are used to evaluate the prognosis.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: (1) To study the effects of providing ankle-foot orthoses in subjects with (sub)acute stroke; and (2) to study whether the point in time at which an ankle-foot orthosis is provided post-stroke (early or delayed) influences these effects. Design: Randomized controlled trial. Setting: Rehabilitation centre. Subjects: Unilateral hemiparetic stroke subjects with indication for use of an ankle-foot orthosis and maximal six weeks post-stroke. Interventions: Subjects were randomly assigned to: early provision (at inclusion; Week 1) or delayed provision (eight weeks later; Week 9). Outcome measures: 10-metre walk test, 6-minute walk test, Timed Up and Go Test, stairs test, Functional Ambulation Categories, Berg Balance Scale, Rivermead Mobility Index and Barthel Index; assessed in Weeks 1, 3, 9 and 11. Results: A total of 33 subjects were randomized (16 early, 17 delayed). Positive effects of ankle-foot orthoses were found two weeks after provision, both when provided early (significant effects on all outcomes) or delayed (Berg Balance Scale p = 0.011, Functional Ambulation Categories p = 0.008, 6-minute walk test p = 0.005, Timed Up and Go Test p = 0.028). Comparing effects after early and delayed provision showed that early provision resulted in increased levels of improvement on Berg Balance Scale (+5.1 points, p = 0.002), Barthel Index (+1.9 points, p = 0.002) and non-significant improvements on 10-metre walk test (+0.14 m/s, p = 0.093) and Timed Up and Go Test (-5.4 seconds, p = 0.087), compared with delayed provision. Conclusions: We found positive effects of providing ankle-foot orthoses in (sub)acute stroke subjects that had not used these orthoses before.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Health-related quality of life (HRQoL) is widely used as an outcome measure in the evaluation of treatment interventions in patients with chronic obstructive pulmonary disease (COPD). In order to address challenges associated with existing fixed-length measures (e.g., too long to be used routinely, too short to ensure both content validity and reliability), a COPD-specific item bank (COPD-SIB) was developed. Methods: Items were selected based on literature review and interviews with Dutch COPD patients, with a strong focus on both content validity and item comprehension. The psychometric quality of the item bank was evaluated using Mokken Scale Analysis and parametric Item Response Theory, using data of 666 COPD patients. Results: The final item bank contains 46 items that form a strong scale, tapping into eight important themes that were identified based on literature review and patient interviews: Coping with disease/symptoms, adaptability; Autonomy; Anxiety about the course/end-state of the disease, hopelessness; Positive psychological functioning; Situations triggering or enhancing breathing problems; Symptoms; Activity; Impact.
- [Show abstract] [Hide abstract] ABSTRACT: Background Both chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under discussion. The aim of this study is to further investigate the association of statin use with clinical outcomes in a well-described COPD cohort. Methods 795 patients of the Cohort of Mortality and Inflammation in COPD (COMIC) study were divided into statin users or not. Statin use was defined as having a statin for at least 90 consecutive days after inclusion. Outcome parameters were 3-year survival, based on all-cause mortality, time until first hospitalisation for an acute exacerbation of COPD (AECOPD) and time until first community-acquired pneumonia (CAP). A sensitivity analysis was performed without patients who started a statin 3 months or more after inclusion to exclude immortal time bias. Results Statin use resulted in a better overall survival (corrected HR 0.70 (95% CI 0.51 to 0.96) in multivariate analysis), but in the sensitivity analysis this association disappeared. Statin use was not associated with time until first hospitalisation for an AECOPD (cHR 0.95, 95% CI 0.74 to 1.22) or time until first CAP (cHR 1.1, 95% CI 0.83 to 1.47). Conclusions In the COMIC study, statin use is not associated with a reduced risk of all-cause mortality, time until first hospitalisation for an AECOPD or time until first CAP in patients with COPD.
- [Show abstract] [Hide abstract] ABSTRACT: It is unknown whether heterogeneity in effects of self-management interventions in patients with chronic obstructive pulmonary disease (COPD) can be explained by differences in programme characteristics. This study aimed to identify which characteristics of COPD self-management interventions are most effective.Systematic search in electronic databases identified randomised trials on self-management interventions conducted between 1985 and 2013. Individual patient data were requested for meta-analysis by generalised mixed effects models.14 randomised trials were included (67% of eligible), representing 3282 patients (75% of eligible). Univariable analyses showed favourable effects on some outcomes for more planned contacts and longer duration of interventions, interventions with peer contact, without log keeping, without problem solving, and without support allocation. After adjusting for other programme characteristics in multivariable analyses, only the effects of duration on all-cause hospitalisation remained. Each month increase in intervention duration reduced risk of all-cause hospitalisation (time to event hazard ratios 0.98, 95% CI 0.97-0.99; risk ratio (RR) after 6 months follow-up 0.96, 95% CI 0.92-0.99; RR after 12 months follow-up 0.98, 95% CI 0.96-1.00).Our results showed that longer duration of self-management interventions conferred a reduction in all-cause hospitalisations in COPD patients. Other characteristics are not consistently associated with differential effects of self-management interventions across clinically relevant outcomes.
- [Show abstract] [Hide abstract] ABSTRACT: Background and Aims Individuals with mild or borderline intellectual disability (MBID) are at risk of substance use (SU). At present, it is unclear which strategy is the best for assessing SU in individuals with MBID. This study compares three strategies, namely self-report, collateral-report, and biomarker analysis. Methods and Procedures In a sample of 112 participants with MBID from six Dutch facilities providing care to individuals with intellectual disabilities, willingness to participate, SU rates, and agreement between the three strategies were explored. The Substance use and misuse in Intellectual Disability -Questionnaire (SumID-Q; self-report) assesses lifetime use, use in the previous month, and recent use of tobacco, alcohol, cannabis, and stimulants. The Substance use and misuse in Intellectual Disability - Collateral-report questionnaire (SumID-CR; collateral-report) assesses staff members' report of participants' SU over the same reference periods as the SumID-Q. Biomarkers for SU, such as cotinine (metabolite of nicotine), ethanol, tetrahydrocannabinol (THC), and its metabolite THC-COOH, benzoylecgonine (metabolite of cocaine), and amphetamines were assessed in urine, hair, and sweat patches. Results Willingness to provide biomarker samples was significantly lower compared to willingness to complete the SumID-Q (p < .001). Most participants reported smoking, drinking alcohol, and using cannabis at least once in their lives, and about a fifth had ever used stimulants. Collateral-reported lifetime use was significantly lower. However, self-reported past month and recent SU rates did not differ significantly from the rates from collateral-reports or biomarkers, with the exception of lower alcohol use rates found in biomarker analysis. The agreement between self-report and biomarker analysis was substantial (kappas .60 - .89), except for alcohol use (kappa .06). Disagreement between SumID-Q and biomarkers concerned mainly over-reporting of the SumID-Q. The agreement between SumID-CR and biomarker analysis was moderate to substantial (kappas .48 - .88), again with the exception of alcohol (kappa .02). Conclusions and Implications In this study, the three strategies that were used to assess SU in individuals with MBID differed significantly in participation rates, but not in SU rates. Several explanations for the better-than-expected performance of self- and collateral-reports are presented. We conclude that for individuals with MBID, self-report combined with collateral-report can be used to assess current SU, and this combination may contribute to collaborative, early intervention efforts to reduce SU and its related harms in this vulnerable group.
- [Show abstract] [Hide abstract] ABSTRACT: Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD). However, choice of parameters and score complexity restrict clinical applicability. Our aim was to provide and validate a simplified COPD risk index independent of lung function.The PROMISE study (n=530) was used to develop a novel prognostic index. Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality. External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C. It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05). Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively). External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk.
- [Show abstract] [Hide abstract] ABSTRACT: There is an urgent need for consensus on what defines a chronic obstructive pulmonary disease (COPD) self-management intervention. We aimed to obtain consensus regarding the conceptual definition of a COPD self-management intervention by engaging an international panel of COPD self-management experts using Delphi technique features and an additional group meeting.In each consensus round the experts were asked to provide feedback on the proposed definition and to score their level of agreement (1=totally disagree; 5=totally agree). The information provided was used to modify the definition for the next consensus round. Thematic analysis was used for free text responses and descriptive statistics were used for agreement scores.In total, 28 experts participated. The consensus round response rate varied randomly over the five rounds (ranging from 48% (n=13) to 85% (n=23)), and mean definition agreement scores increased from 3.8 (round 1) to 4.8 (round 5) with an increasing percentage of experts allocating the highest score of 5 (round 1: 14% (n=3); round 5: 83% (n=19)).In this study we reached consensus regarding a conceptual definition of what should be a COPD self-management intervention, clarifying the requisites for such an intervention. Operationalisation of this conceptual definition in the near future will be an essential next step.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: To assess the capacity of the postcoital test (PCT) to predict pregnancy in WHO II anovulatory women who are ovulatory on clomiphene citrate (CC). In these women, an abnormal PCT result could be associated with lower pregnancy chances, but this has never been proven or refuted. Study design: Prospective cohort study was performed between December 2009 and September 2012 for all women who started ovulation induction with CC in one university clinic and two teaching hospitals in the Netherlands. A PCT was performed in one of the first three ovulatory cycles. Ovulation induction with CC was continued for at least six cycles. The PCT was judged to be positive if at least one progressive motile spermatozo was seen in one of five high power fields at 400× magnification. The primary outcome was time to ongoing pregnancy, within six ovulatory cycles. Results: In 152 women the PCT was performed. 135 women had a reliable, well-timed PCT. The ongoing pregnancy rate was 44/107 (41%) for a positive and 10/28 (36%) for a negative PCT. The hazard rate for ongoing pregnancy was 1.3 (95% CI 0.64-2.5) for a positive versus a negative PCT. Thirty five of 77 (46%) women with clear mucus had an ongoing pregnancy versus 12 of 45 (27%) women in whom the mucus was not clear (HR 2.0; 95% CI 1.02-3.84, p=0.04). Conclusion: The present study suggests that the outcome of the postcoital test in women with WHO-II anovulation that undergo ovulation induction with CC does not have a large effect on ongoing pregnancy chances over time.
- [Show abstract] [Hide abstract] ABSTRACT: The safety and tolerability of nebulized amoxicillin clavulanic acid were determined in patients with stable COPD and during severe exacerbations of COPD. Nine stable COPD patients received doses ranging from 50:10 mg up to 300:60 mg amoxicillin clavulanic acid and eight patients hospitalised for a COPD exacerbation received fixed doses 200/40 mg twice daily. Safety was evaluated by spirometry before and after inhalation. Tolerability was evaluated by questionnaire. Plasma and expectorated sputum samples were assayed for amoxicillin content. Seventeen patients underwent in total 100 nebulizations with amoxicillin clavulanic acid. In this safety and tolerability study no clinically relevant deteriorations in FEV1 were observed. Nebulized amoxicillin clavulanic acid produces sputum concentrations well above the Minimal Inhibiting Concentration of 90% for potential pathogenic micro-organisms, with low concentrations in the central compartment (low systemic exposure). Based on spirometry and reported side effects, inhalation of nebulized amoxicillin clavulanic acid seems to be safe and well tolerated, both in stable patients with COPD as in those experiencing a severe exacerbation. Levels of amoxicillin were adequate.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: To study the influence of type of inhalation device on medication adherence of COPD patients. Methods: Adherence to inhalation medication of 795 patients was recorded from pharmacy records over 3 years. It was expressed as percentage and deemed good at ≥75-≤125%, sub-optimal ≥50-<75%, and poor <50% (underuse) or >125% (overuse). Since most patients used more than one device, 1379 medication periods were analyzed. Results: Patients using a Metered Dose Inhaler (MDI) or Diskus had a 2.3-fold and 2.2-fold increased risk, respectively, of suboptimal adherence versus good adherence, compared to Handihaler and a 2.1-fold and 2.2-fold increased risk, respectively, of underuse versus good adherence compared to Handihaler. Turbuhaler, MDI, Respimat had a 7.9-fold, 3.5-fold, and 2.0-fold increased risk, of overuse versus good adherence compared to Handihaler. Conclusions: In COPD, adherence to inhalation medication is device-related. Overuse was most pronounced for devices without a dose counter, devices with the ability to load a dosage without actual inhalation, or devices lacking feedback of correct inhalation. The design of the device seems to be related to underuse and overuse of inhaled medication. Future research might investigate whether prescribing a different device with similar medication improves therapy adherence.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objective: Long-term effectiveness of action plans in patients with chronic obstructive pulmonary disease (COPD) is minimally investigated. We have evaluated the (cost-)effectiveness of a self-management programme with or without self-treatment of exacerbations after 2 years follow-up. Methods: Self-management with or without self-treatment of exacerbations was randomly assigned to patients. All patients participated in four self-management meetings. Patients in the self-treatment group (STG) also learned to use an action plan to start a course of prednisolone and/or antibiotics in case of worsening of symptoms. Primary outcome was the duration and severity of exacerbations. Results: Data of 70 COPD patients in the STG and 72 patients in the control group (CG) were analysed. Over 2 years, the median number of exacerbation days was significantly lower in the STG (50, IQR: 32-115) compared with the CG (82, IQR: 22-186) (P = 0.047), as was the mean symptom score of an exacerbation (STG: 43.4, IQR 27.2-68.6 vs CG: 55.9, IQR: 31.2-96.8) (P = 0.029). Also, patients in the STG visited the respiratory physician and emergency department less frequently than patients in the CG with incidence rate ratios of 1.52 (95% CI: 1.28-1.79) and 2.27 (95% CI: 1.11-4.62), respectively. Direct medical costs per patient over 2 years were €1078 lower in the STG. Conclusion: Self-treatment of exacerbations is beneficial in COPD patients without significant comorbidities because it reduces exacerbation duration, exacerbation severity and health-care utilization leading to considerable cost savings.
- [Show abstract] [Hide abstract] ABSTRACT: Introduction: Information regarding cost-effectiveness of community-based exercise programmes in COPD is scarce. Therefore, we have investigated whether a community-based exercise programme is a cost-effective component of self-management for patients with COPD after 2 years of follow-up. Methods: All included COPD patients participated in four self-management sessions. Additionally, patients in the COPE-active group participated in an 11-month community-based exercise programme led by physiotherapists. Patients trained 3 times/week for 6 months and two times/week during the subsequent 5 months. In both periods, one of these weekly training sessions was home-based (unsupervised). No formal physiotherapy sessions were offered to COPE-active patients in the second year. A decision analytical model with a 24-month perspective was used to evaluate cost-effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated and cost-effectiveness planes were created. Results: Data of 77 patients participating in the exercise programme and 76 patients in the control group were analysed. The ICER for an additional patient prevented from deteriorating at least 47.5 meters on the ISWT was €6257. The ICER for an additional patient with a clinically relevant improvement (≥ 500 steps/day) in physical activity was €1564, and the ICER for an additional quality-adjusted life year (QALY) was €10 950. Conclusion: Due to a lack of maintenance of beneficial effects on our primary outcome exercise capacity after 2 years of follow-up and higher costs of the programme, the community-based exercise programme cannot be considered cost-effective compared to self-management programmes only. Nevertheless, the ICERs for the secondary outcomes physical activity and QALY are generally considered acceptable.
- [Show abstract] [Hide abstract] ABSTRACT: Purpose: The aim of this study was to assess the experiences of patients with chronic obstructive pulmonary disease (COPD) while they were completing the St. George's Respiratory Questionnaire for COPD patients (SGRQ-C), using qualitative research methods. Methods: Twenty Dutch COPD patients were recruited through pulmonary physicians [13 women; mean age = 63.3 years (SD = 11.4)]. A trained interviewer applied the Three-Step Test Interview which allowed the interviewer to follow the thought process of the patient filling out the SGRQ-C. The official Dutch translation of the SGRQ-C was used. Results: Patients missed a recall period for the Symptoms subscale; were uncertain how to interpret specific words and phrases like "good days", "games", and "housework"; were confused by long-item stems that included a list of activities; and were frustrated by the dichotomous format used for the majority of SGRQ-C items (true/false). Conclusions: Overall, patients were satisfied with the SGRQ-C. Nevertheless, making minor adjustments could further increase its quality. This includes reintroducing a recall period in the first set of items such as used in the previous version and splitting up items consisting of multiple activities. Furthermore, we recommend using the same response format (4 or 5 response categories) for all items.
- [Show abstract] [Hide abstract] ABSTRACT: Study Objectives: To develop and evaluate a screening questionnaire and a two-step screening strategy for obstructive sleep apnea syndrome (OSAS) in healthy workers. Methods: This is a cross-sectional study of 1,861 employees comprising healthy blue- and white-collar workers in two representative plants in the Netherlands from a worldwide consumer electronic company who were approached to participate. Employees were invited to complete various sleep questionnaires, and undergo separate single nasal flow recording and home polysomnography on two separate nights. Results: Of the 1,861 employees, 249 provided informed consent and all nasal flow and polysomnography data were available from 176 (70.7%). OSAS was diagnosed in 65 (36.9%). A combination of age, absence of insomnia, witnessed breathing stops, and three-way scoring of the Berlin and STOPBANG questionnaires best predicted OSAS. Factor analysis identified a six-factor structure of the resulting new questionnaire: snoring, snoring severity, tiredness, witnessed apneas, sleep quality, and daytime well-being. Subsequently, some questions were removed, and the remaining questions were used to construct a new questionnaire. A scoring algorithm, computing individual probabilities of OSAS as high, intermediate, or low risk, was developed. Subsequently, the intermediate risk group was split into low and high probability for OSAS, based on nasal flow recording. This two-step approach showed a sensitivity of 63.1%, and a specificity of 90.1%. Specificity is important for low prevalence populations. Conclusion: A two-step screening strategy with a new questionnaire and subsequent nasal flow recording is a promising way to screen for OSAS in a healthy worker population.
Medisch Spectrum Twente
Enschede, Overijssel, Netherlands
- • Medical School Twente
- • Cardiology Department
University of Twente
Enschede, Overijssel, Netherlands
- Department of Research Methodology, Measurement and Data Analysis (OMD)
Saxion University of Applied SciencesEnschede, Overijssel, Netherlands