[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.
Full-text · Article · Jan 2016 · COPD Journal of Chronic Obstructive Pulmonary Disease
[Show abstract][Hide abstract] ABSTRACT: Objective:
To study the influence of type of inhalation device on medication adherence of COPD patients.
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.
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.
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.
Full-text · Article · Dec 2015 · Expert Opinion on Drug Delivery
[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.
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.
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.
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.
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.
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.
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.
No preview · Article · Dec 2015 · COPD Journal of Chronic Obstructive Pulmonary Disease
[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.
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.
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).
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.
Full-text · Article · Nov 2015 · Quality of Life Research
[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.
Setting and participants:
A total of 1,861 employees comprising healthy blue- and white-collar workers in two representative plants in the Netherlands from a worldwide consumer electronic company were approached to participate.
Employees were invited to complete various sleep questionnaires, and undergo separate single nasal flow recording and home polysomnography on 2 separate nights.
Measurements and 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.
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.
Development and validation of a screening instrument for Obstructive Sleep Apnea Syndrome in healthy workers. Netherlands Trial Register (www.trailregister.nl), number: NTR2675.
Full-text · Article · Oct 2015 · Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine
[Show abstract][Hide abstract] ABSTRACT: Background:
The aim of this study is to analyze the impact of first degree relative (FDR) of young breast cancer patients.
Data were used from our prospective population-based cohort study which started in 1983. The family history (FH) was registered with regard to FDR: the presence or absence of invasive breast cancer in none vs. one or more FDRs at any age.
A total of 1109 women, ≤50 years with 1128 breast conserving treatments was seen. The incidence of FDR was 17.0% for one FDR and 3.2% ≥2 FDR. The three groups, none, 1 or ≥2 FDR, were comparable. The local failure rate is comparable for all three groups. Women with a positive FH and metachronous bilateral breast cancer (MBBC) showed a lower local failure (HR 0.2; 95% CI 0.05-0.8). A positive FH was an independent predictor for a better disease-specific survival (HR 0.6; 95% CI 0.4-0.9).
A positive FH, based on FDR implies a better prognosis in relation to survival for young women treated with BCT. In contrast to no FH for FDR, MBBC in women with a positive FH was not associated with an increased risk of local recurrence.
[Show abstract][Hide abstract] ABSTRACT: Physical inactivity and overweight are risk factors for postmenopausal breast cancer. The effect of physical activity may be partially mediated by concordant weight loss. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise.
Overweight, insufficiently active women were randomised to a diet (N = 97), mainly exercise (N = 98) or control group (N = 48). The goal of both interventions was to achieve 5-6 kg of weight loss by following a calorie-restricted diet or an intensive exercise programme combined with only a small caloric restriction. Primary outcomes after 16 weeks were serum sex hormones and sex hormone-binding globulin (SHBG). Body fat and lean mass were measured by dual-energy X-ray absorptiometry.
Both the diet (-4.9 kg) and mainly exercise (-5.5 kg) groups achieved the target weight loss. Loss of body fat was significantly greater with exercise versus diet (difference -1.4 kg, P < 0.001). In the mainly exercise arm, the reduction in free testosterone was statistically significantly greater than that of the diet arm (treatment effect ratio [TER] 0.92, P = 0.043), and the results were suggestive of a difference for androstenedione (TER 0.90, P = 0.064) and SHBG (TER 1.05, P = 0.070). Compared with the control arm, beneficial effects were seen with both interventions, diet and mainly exercise, respectively, on oestradiol (TER 0.86, P = 0.025; TER 0.83, P = 0.007), free oestradiol (TER 0.80, P = 0.002; TER 0.77, P < 0.001), SHBG (TER 1.14; TER 1.21, both P < 0.001) and free testosterone (TER 0.91, P = 0.069; TER = 0.84, P = 0.001). After adjustment for changes in body fat, intervention effects attenuated or disappeared.
Weight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk. Weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones. The greater fat loss likely explains the observed larger effects on sex hormones.
ClinicalTrials.gov identifier: NCT01511276 . Registered on 12 January 2012.
Full-text · Article · Sep 2015 · Breast cancer research: BCR
[Show abstract][Hide abstract] ABSTRACT: The aims of this study were twofold: to analyze the incidence of patients having synchronous or metachronous bilateral invasive breast cancer (SBBC and MBBC) and to assess the characteristics and outcome compared to those having unilateral breast cancer (UBC). The used data were obtained from our prospective population-based cohort study which had been started in 1983. Bilateral breast cancer (BBC) was categorized as SBBC (≤3 months of the first primary) or MBBC (>3 months after the first primary). The incidence of SBBC was 1 % and that of MBBC 7.0 %. Patients with UBC showed more ductal carcinoma compared to patients with BBC. MBBC status was an independent significant predictor of local failure (HR 1.9; 95 % CI 1.3-2.7). SBBC status was an independent predictor of distant metastases (HR 2.6; 95 % CI 1.4-4.5). Overall survival (OS) was better for MBBC (HR 0.6; 95 % CI 0.4-0.8) and worse for SBBC (HR 2.3; 95 % CI 1.5-3.6) compared to UBC. We noted: (1) MBBC showed a significant higher local failure compared to UBC, (2) SBBC, compared to MBBC and UBC had a significant higher distant metastases rate, (3) disease-specific survival and OS were significantly worse for SBBC compared to UBC and MBBC, and (4) that the OS for MBBC compared to UBC, was significantly better.
No preview · Article · Aug 2015 · Breast Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: Objective:
To determine whether a double dose of intraarticular triamcinolone acetonide is more effective for knee arthritis than a 40-mg dose.
In this 12-week randomized controlled clinical trial, 40 mg and 80 mg of intraarticular triamcinolone acetonide were compared in patients with knee arthritis. Evaluated variables included a Likert burden scale, visual analog scale pain scale, degree of arthritis activity, presence of swelling, and presence of functional limitation.
Ninety-seven patients were randomized. No significant differences were observed between the groups regarding any outcomes.
An 80-mg dose of triamcinolone acetonide had no additional benefit compared with 40 mg as treatment for knee arthritis.
Nederlands Trial Register; trial registration number: NTR2298.
No preview · Article · Aug 2015 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: Many patients with eating disorders do not receive help for their symptoms, even though these disorders have severe morbidity. The Internet may offer alternative low-threshold treatment interventions.
This study evaluated the effects of a Web-based cognitive behavioral therapy (CBT) intervention using intensive asynchronous therapeutic support to improve eating disorder psychopathology, and to reduce body dissatisfaction and related health problems among patients with eating disorders.
A two-arm open randomized controlled trial comparing a Web-based CBT intervention to a waiting list control condition (WL) was carried out among female patients with bulimia nervosa (BN), binge eating disorder (BED), and eating disorders not otherwise specified (EDNOS). The eating disorder diagnosis was in accordance with the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and was established based on participants' self-report. Participants were recruited from an open-access website, and the intervention consisted of a structured two-part program within a secure Web-based application. The aim of the first part was to analyze participant's eating attitudes and behaviors, while the second part focused on behavioral change. Participants had asynchronous contact with a personal therapist twice a week, solely via the Internet. Self-report measures of eating disorder psychopathology (primary outcome), body dissatisfaction, physical health, mental health, self-esteem, quality of life, and social functioning were completed at baseline and posttest.
A total of 214 participants were randomized to either the Web-based CBT group (n=108) or to the WL group (n=106) stratified by type of eating disorder (BN: n=44; BED: n=85; EDNOS: n=85). Study attrition was low with 94% of the participants completing the posttest assignment. Overall, Web-based CBT showed a significant improvement over time for eating disorder psychopathology (F97=63.07, P<.001, d=.82) and all secondary outcome measures (effect sizes between d=.34 to d=.49), except for Body Mass Index. WL participants also improved on most outcomes; however, effects were smaller in this group with significant between-group effects for eating disorder psychopathology (F201=9.42, P=.002, d=.44), body dissatisfaction (F201=13.16, P<.001, d=.42), physical health (F200=12.55, P<.001, d=.28), mental health (F203=4.88, P=.028, d=.24), self-esteem (F202=5.06, P=.026, d=.20), and social functioning (F205=7.93, P=.005, d=.29). Analyses for the individual subgroups BN, BED, and EDNOS showed that eating disorder psychopathology improved significantly over time among Web-based CBT participants in all three subgroups; however, the between-group effect was significant only for participants with BED (F78=4.25, P=.043, d=.61).
Web-based CBT proved to be effective in improving eating disorder psychopathology and related health among female patients with eating disorders.
Nederlands Trial Register (NTR): NTR2415; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2415 (Archived by WebCite at http://www.webcitation.org/6T2io3DnJ).
Full-text · Article · Jun 2015 · Journal of Medical Internet Research
[Show abstract][Hide abstract] ABSTRACT: Web-based alcohol interventions have demonstrated efficacy in randomized controlled trials. However, most studies have involved self-help interventions without therapeutic support.
To examine the results of a 3-month web-based alcohol treatment program using intensive, asynchronous (non-simultaneous) therapeutic support ( www.alcoholdebaas.nl ) at 9-month follow-up assessment.
This study reports the follow-up results of 144 problem drinking participants who received a web-based alcohol treatment program. We investigated whether the intervention effects at treatment completion (3 months) continued to exist at 6 and 9 months of follow-up. The primary outcome measure was weekly alcohol consumption. Repeated measures analysis with a mixed model approach was used to address loss to follow-up.
Weekly alcohol consumption significantly improved between baseline and 9 months (F(1,74) = 85.6, p < 0.001). Post-hoc tests revealed that the reduction occurred during the first 3 months (from 39.9-11.4 standard units a week). Although alcohol consumption had risen to 19.5 units per week at 9 months, it still decreased by more than 20 units compared to baseline drinking. Significant improvements with medium to large effect sizes were found on the secondary outcomes (depression, general health, and quality of life) at 9 months.
The web-based alcohol treatment with intensive asynchronous therapeutic support has been shown to be effective in reducing alcohol consumption and improving health status at post treatment assessments. The present study showed that most of these improvements were sustained after 9 months. Despite the lack of a control group and the high dropout rate, our findings suggest that web-based treatment can achieve relevant health gains in the long term.
eprint link: http://www.tandfonline.com/eprint/qtMPs2FTKXVyNtPNKae5/full
No preview · Article · Jun 2015 · The American Journal of Drug and Alcohol Abuse
[Show abstract][Hide abstract] ABSTRACT: Antimicrobial resistance rates are increasing. This is, among others, caused by incorrect or inappropriate use of antimicrobials. To target this, a multidisciplinary antimicrobial stewardship-team (A-Team) was implemented at the University Medical Center Groningen on a urology ward. Goal of this study is to evaluate the clinical effects of the case-audits done by this team, looking at length of stay (LOS) and antimicrobial use.
Automatic e-mail alerts were sent after 48 h of consecutive antimicrobial use triggering the case-audits, consisting of an A-Team member visiting the ward, discussing the patient's therapy with the bed-side physician and together deciding on further treatment based on available diagnostics and guidelines. Clinical effects of the audits were evaluated through an Interrupted Time Series analysis and a retrospective historic cohort.
A significant systemic reduction of antimicrobial consumption for all patients on the ward, both with and without case-audits was observed. Furthermore, LOS for patients with case-audits who were admitted primarily due to infections decreased to 6.20 days (95% CI: 5.59-6.81) compared to the historic cohort (7.57 days; 95% CI: 6.92-8.21; p = 0.012). Antimicrobial consumption decreased for these patients from 8.17 DDD/patient (95% CI: 7.10-9.24) to 5.93 DDD/patient (95% CI: 5.02-6.83; p = 0.008). For patients with severe underlying diseases (e.g., cancer) these outcome measures remained unchanged.
The evaluation showed a considerable positive impact. Antibiotic use of the whole ward was reduced, transcending the intervened patients. Furthermore, LOS and mean antimicrobial consumption for a subgroup was reduced, thereby improving patient care and potentially lowering resistance rates.
Full-text · Article · Jun 2015 · Frontiers in Microbiology