Facilitators and Barriers of Adherence to Multi-Disease Exacerbation Action Plans in COPD Patients - A Qualitative Study.

Whereas exacerbation action plans to self-manage Chronic Obstructive Pulmonary Disease (COPD) significantly improve health outcomes, patients' adherence to those action plans is often poor. This study aimed to identify facilitators and barriers of adherence to tailored multi-disease exacerbation action plans. We also explored patients' perspectives toward disease management roles. Individual semi-structured interviews were conducted with a sample of COPD patients who completed a Dutch-Australian self-management intervention evaluating tailored exacerbation action plans for COPD and relevant comorbidities. Interviews were thematically analyzed using a deductive approach guided by the Capability, Opportunity and Motivation of Behavior (COM-B) model. In 2016, ten patients (5 Australian; 5 Dutch; 6 men; age 59-83 years) were interviewed at the end of their one-year follow-up. Facilitators of adherence included improved patients' comprehension of disease and treatment, positive feelings about the intervention, improved self-confidence, and professional support. Barriers included difficulties to recognize symptoms, dislike toward daily symptom monitoring, negative feelings about the intervention, negative mood state, and complexity of symptom diaries and action plans. Patients indicated three distinctive perspectives of their own and their healthcare professional's role in their disease management: 1) patients felt mainly responsible; 2) patients felt shared responsibility with their healthcare professional; and 3) patients felt not responsible as they perceived their healthcare professional to be mainly responsible. We successfully used the COM-B model as a guide to identify facilitators and barriers of patients' adherence to multi-disease exacerbation action plans. Improving patients' adherence in future self-management interventions by targeting specific facilitators or barriers should be considered.

Cost-utility analysis of a structured medication review compared to usual care in Parkinson's disease.

PURPOSE: For controlling symptoms in Parkinson's disease (PD) together with treating additional comorbidities, patients often face complex medication regimens, with suboptimal adherence, drug-related problems, and diminished therapy efficacy as a common consequence. A medication review could potentially tackle these issues, among others by optimizing drug treatment. Even if no change in clinical outcomes is observed, this intervention might decrease health care costs by reducing drug-related problems and hospital admissions. This study aimed to gain more insight in the health benefits and costs of a structured medication review (SMR) in PD. METHODS: A cost-utility analysis was performed, based on a multicenter randomized controlled trial with 202 PD patients with polypharmacy. The intervention group received an SMR, whereas the control group received usual care. The intervention effect after 6 months of follow-up was presented as incremental quality-adjusted life years (QALY) using the EQ-5D-5L questionnaire. Costs were based on real-world data. Missing data was imputed using multiple imputation techniques. Bootstrapping was used to estimate the uncertainty in all health and economic outcomes. RESULTS: The QALY gain in the intervention group compared to the control group was - 0.011 (95% CI - 0.043; 0.020). Incremental costs were €433 (95% CI - 873; 1687). When adapting a willingness-to-pay threshold of €20,000/QALY and €80,000/QALY, the probability of SMRs being cost-effective was 18% and 30%, respectively. CONCLUSION: A community pharmacist-led SMR in PD patients in the current setting shows no apparent benefit and is not cost-effective after 6 months, compared to usual care. TRIAL REGISTRATION: Netherlands Trial Register, NL4360. Registered 17 March 2014.

Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study).

BACKGROUND: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. METHODS: Chemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. RESULTS: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm3, 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm3, 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015). CONCLUSIONS: No exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study).

BACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .

Difference in survival between COPD patients with an impaired immune reaction versus an adequate immune reaction to seasonal influenza vaccination: The COMIC study.

AIM: To study the hypothesis that COPD patients who do not achieve seroprotective levels after influenza vaccination, are a less immune-competent group with a higher risk of morbidity and mortality. METHODS: 578 patients included in the COMIC cohort had pre- and post-vaccination stable state blood samples in which influenza-vaccine specific antibodies were measured. Post-vaccination titers of ≥40 were considered protective and indicative of being immuno-competent. Primary outcome was all-cause mortality. Morbidity was defined as time till first severe acute exacerbation in COPD (severe AECOPD) and time till first community acquired pneumonia (CAP). RESULTS: 42% of the patients achieved seroprotective levels to both H1N1 and H3N2 after vaccination. Seroprotective levels to H3N2 were markedly higher (96%) than to H1N1(43%). Having seroprotective levels to both H1N1 and H3N2 was not associated with less morbidity (severe AECOPD HR 0.91 (95% 0.66-1.25; p = 0.564) (CAP HR 1.23 (95% 0.75-2.00; p = 0.412)) or lower mortality (HR 1.10(95% 0.87-1.38; p = 0.433)). CONCLUSION: In a large well-characterized COPD cohort only the minority of patients achieved seroprotective titers to H1N1 and H3N1 after the yearly influenza vaccination. While achieving seroprotection after vaccination can be considered a surrogate marker of being immunocompetent, this was not associated with lower morbidity and mortality. Whether this means that the immune status is not a relevant pheno/endotype in COPD patients for the course of their disease or that seroprotection is not an adequate (surrogate) marker to define the immune status in COPD needs to be further studied.

Limited Impact of Breast Cancer and Non-breast Malignancies on Survival in Older Patients with Early-Stage Breast Cancer: Results of a Large, Single-Centre, Population-Based Study.

AIMS: To analyse the disease-free survival and overall survival in older adults with breast cancer after breast-conserving therapy, focusing on the relevance of non-breast malignancy (NBM) with respect to survival rates. MATERIALS AND METHODS: Analyses were based on 1205 women aged 65 years and older with breast cancer treated with breast-conserving therapy between 1999 and 2015. Patients were divided into three age categories: 65-70, 71-75 and >75 years. Multivariate survival analysis was carried out using Cox regression analysis. RESULTS: The two youngest age categories showed excellent results, with a 12-year disease-free survival of 84.6 and 86.3%, respectively. We noted a 17.2% incidence of NBM, particularly for colon cancer and lung cancer. Most (72.9%) occurred after a diagnosis of breast cancer. Of those 72.9%, about 50% died as a result of NBM within 2 years of the diagnosis of NBM. The overall 12-year NBM-specific survival was 92.0%. The 12-year overall survival was 60.0% for all and for the three abovementioned age categories was 73.3, 54.4 and 28.4%, respectively. The cause of death for all was predominantly non-malignancy-related morbidity. CONCLUSION: The impact of breast cancer on life expectancy was limited, in particularly for women aged 65-75 years. The relevance of NBM on survival was limited.

Using a stepwise approach to simultaneously develop and validate machine learning based prediction models.

Accurate diagnosis of a disease is essential in healthcare. Prediction models, based on classical regression techniques, are widely used in clinical practice. Machine Learning (ML) techniques might be preferred in case of a large amount of data per patient and relatively limited numbers of subjects. However, this increases the risk of overfitting, and external validation is imperative. However, in the field of ML, new and more efficient techniques are developed rapidly, and if recruiting patients for a validation study is time consuming, the ML technique used to develop the first model might have been surpassed by more efficient ML techniques, rendering this original model no longer relevant. We demonstrate a stepwise design for simultaneous development and validation of prediction models based on ML techniques. The design enables - in one study - evaluation of the stability and robustness of a prediction model over increasing sample size as well as assessment of the stability of sensitivity/specificity at a chosen cut-off. This will shorten the time to introduction of a new test in health care. We finally describe how to use regular clinical parameters in conjunction with ML based predictions, to further enhance differentiation between subjects with and without a disease.

Functional or not functional; that's the question: Can we predict the diagnosis functional movement disorder based on associated features?

BACKGROUND AND PURPOSE: Functional movement disorders (FMDs) pose a diagnostic challenge for clinicians. Over the years several associated features have been shown to be suggestive for FMDs. Which features mentioned in the literature are discriminative between FMDs and non-FMDs were examined in a large cohort. In addition, a preliminary prediction model distinguishing these disorders was developed based on differentiating features. METHOD: Medical records of all consecutive patients who visited our hyperkinetic outpatient clinic from 2012 to 2019 were retrospectively reviewed and 12 associated features in FMDs versus non-FMDs were compared. An independent t test for age of onset and Pearson chi-squared analyses for all categorical variables were performed. Multivariate logistic regression analysis was performed to develop a preliminary predictive model for FMDs. RESULTS: A total of 874 patients were eligible for inclusion, of whom 320 had an FMD and 554 a non-FMD. Differentiating features between these groups were age of onset, sex, psychiatric history, family history, more than one motor phenotype, pain, fatigue, abrupt onset, waxing and waning over long term, and fluctuations during the day. Based on these a preliminary predictive model was computed with a discriminative value of 91%. DISCUSSION: Ten associated features are shown to be not only suggestive but also discriminative between hyperkinetic FMDs and non-FMDs. Clinicians can use these features to identify patients suspected for FMDs and can subsequently alert them to test for positive symptoms at examination. Although a first preliminary model has good predictive accuracy, further validation should be performed prospectively in a multi-center study.

WEARCON: wearable home monitoring in children with asthma reveals a strong association with hospital based assessment of asthma control.

BACKGROUND: Asthma is one of the most common chronic diseases in childhood. Regular follow-up of physiological parameters in the home setting, in relation to asthma symptoms, can provide complementary quantitative insights into the dynamics of the asthma status. Despite considerable interest in asthma home-monitoring in children, there is a paucity of scientific evidence, especially on multi-parameter monitoring approaches. Therefore, the aim of this study is to investigate whether asthma control can be accurately assessed in the home situation by combining parameters from respiratory physiology sensors. METHODS: Sixty asthmatic and thirty non-asthmatic children were enrolled in the observational WEARCON-study. Asthma control was assessed according to GINA guidelines by the paediatrician. All children were also evaluated during a 2-week home-monitoring period with wearable devices; a physical activity tracker, a handheld spirometer, smart inhalers, and an ambulatory electrocardiography device to monitor heart and respiratory rate. Multiple logistic regression analysis was used to determine which diagnostic measures were associated with asthma control. RESULTS: 24 of the 27 uncontrolled asthmatic children and 29 of the 32 controlled asthmatic children could be accurately identified with this model. The final model showed that a larger variation in pre-exercise lung function (OR = 1.34 95%-CI 1.07-1.68), an earlier wake-up-time (OR = 1.05 95%-CI 1.01-1.10), more reliever use (OR = 1.11 95%-CI 1.03-1.19) and a longer respiratory rate recovery time (OR = 1.12 95%-CI 1.05-1.20) were significant contributors to the probability of having uncontrolled asthma. CONCLUSIONS: Home-monitoring of physiological parameters correlates with paediatrician assessed asthma control. The constructed multivariate model identifies 88.9% of all uncontrolled asthmatic children, indicating a high potential for monitoring of asthma control. This may allow healthcare professionals to assess asthma control at home. TRIAL REGISTRATION: Netherlands Trail Register, NL6087 . Registered 14 February 2017.

Effect of the dr. Bart application on healthcare use and clinical outcomes in people with osteoarthritis of the knee and/or hip in the Netherlands; a randomized controlled trial.

OBJECTIVE: To evaluate the short-term effects of use of the dr. Bart app, compared to usual care, on the number of secondary health care consultations and clinical outcomes in people with knee/hip OA in the Netherlands. METHOD: A randomized controlled design involving participants ≥50 years with self-reported knee and/or hip OA recruited from the community. The number of secondary health care consultations (primary outcome) and secondary outcomes were assessed at baseline, 3 and 6 months via online questionnaires. Data were analyzed using longitudinal mixed models, corrected for baseline values. Due to the design of this study, blinding of participants and researchers was not possible. RESULTS: In total, 427 eligible participants were allocated to either the dr. Bart group (n = 214) or usual care (n = 213). We found no difference between groups in the number of secondary (i.e., orthopaedic surgeon, rheumatologist, or physician assistant) health care consultations (incidence rate ratio (IRR) 1.20 (95% CI: 0.67; 2.19)). We found positive treatment effects of the dr. Bart app on symptoms (2.6 (95% CI: 0.4; 4.9)), pain (3.5 (95% CI: 0.9; 6.0)), and activities of daily living (2.9 (95% CI: 0.2; 5.6)) on a 0-100 scale, higher score indicating less complaints, but not in any other secondary outcome. CONCLUSION: The dr. Bart app did not change the number of secondary health care consultations compared to usual care. However, we found small positive effects (not clinically relevant) on pain, symptoms, and activities of daily living in people with knee/hip OA. TRIAL REGISTRATION: Dutch Trial Register (Trial Number NTR6693/NL6505) (https://www.trialregister.nl/trial/6505).

The Visual Analog Scale detects exercise-induced bronchoconstriction in children with asthma.

Objective: Exercise-induced bronchoconstriction (EIB) is a specific morbidity of childhood asthma and an important sign of uncontrolled asthma. The occurrence of EIB is insufficiently identified by the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT). This study aimed to (1) evaluate the Visual Analog Scale (VAS) for dyspnea as a tool to detect EIB in asthmatic children and (2) assess the value of combining (C-)ACT outcomes with VAS scores. Methods: We measured EIB in 75 asthmatic children (mean age 10.8 years) with a standardized exercise challenge test (ECT) performed in cold and dry air. Children and parents reported VAS dyspnea scores before and after the ECT. Asthma control was assessed by the (C-)ACT. Results: Changes in VAS scores (ΔVAS) of children and parents correlated moderately with fall in forced expiratory volume in 1 second (FEV1), respectively rs=0.57 (p < .001) and rs=0.58 (p < .001). At a ΔVAS cutoff value of ≥3 in children, sensitivity and specificity for EIB were 80% and 79% (AUC 0.82). Out of 38 children diagnosed with EIB, 37 had a (C-)ACT score of ≤19 and/or a ΔVAS of ≥3, corresponding with a sensitivity of 97% and a negative predictive value of 96%. Conclusion: This study shows that the VAS could be an effective additional tool for diagnosing EIB in children. A reported difference in VAS scores of ≥3 after a standardized ECT combined with low (C-)ACT scores was highly effective in detecting and excluding EIB.

A randomized controlled efficacy study of the Medido medication dispenser in Parkinson's disease.

BACKGROUND: Complex medication schedules in Parkinson's disease (PD) result in lower therapy adherence, which contributes to suboptimal therapy and clinical deterioration. Medication reminder systems might improve therapy adherence and subsequently improve symptoms of PD. This randomized controlled study assessed the effect of the electronic medication dispenser Medido on physical disability in PD, as a proxy for changes in therapy adherence.x METHODS: Eighty-seven patients were randomized into the Medido group or control group. The primary outcome of physical disability was measured by the AMC Linear Disability Scale (ALDS). Secondary outcomes were quality of life (QoL) (PDQ-39), health status (EQ5D-5L, VAS), non-motor symptoms (NMS-Quest), and QoL of the caregiver (PDQ-carer). Measurements were performed at baseline, and after 3 and 6 months follow-up. RESULTS: When using the Medido, a non-significant improvement of 3.0 points (95% CI -5.6;11.6) was seen in ALDS. The exploratory subgroup Hoehn & Yahr classification (H&Y) > 2.5 improved significantly on ALDS with 14.7 points (95% CI -28.5;-0.9, p = 0.029 for group x time interaction). QoL deteriorated with 1.0 point in PDQ-39 (p = 0.01 for group x time interaction) in favor of the control group. Non-significant differences were observed for VAS (0.4 points, p = 0.057) and NMS-Quest (1.3 points, p = 0.095) in favor of the Medido group. No changes over time were observed in EQ5D-5L and PDQ-carer. CONCLUSIONS: Based on these data, no firm conclusion can be drawn, but use of the Medido medication dispenser may result in a clinical improvement of physical disability and seems particularly appropriate for more severe patients. TRIAL REGISTRATION: NTR3917 . Registered 19 March 2013.

Differentiation between infected and non-infected wounds using an electronic nose.

OBJECTIVES: The aim of this study was to explore whether an electronic nose, Aetholab, is able to discriminate between infected versus non-infected wounds, based on headspace analyses from wound swabs. METHODS: A total of 77 patients participated in this pilot study. Each wound was assessed for infection based on clinical judgment. Additionally, two wound swabs were taken, one for microbiological culture and one for measurement with Aetholab. Diagnostic properties with 95% confidence intervals (95%CIs) of Aetholab were calculated with clinical judgment and microbiological culture results as reference standards. RESULTS: With clinical judgment as reference standard, Aetholab had a sensitivity of 91% (95%CI 76-98) and a specificity of 71% (95%CI 55-84). Diagnostic properties were somewhat lower when microbiological culture results were used as reference standard: sensitivity 81% (95%CI 64-91), specificity 63% (95%CI 46-77). CONCLUSIONS: Aetholab seems a promising diagnostic tool for wound infection given the diagnostic properties presented in this pilot study. A larger study is needed to confirm our results.

Can Pediatricians Assess Exercise-Induced Bronchoconstriction From Post-exercise Videos?

Objective: Exercise-induced bronchoconstriction (EIB) is a highly prevalent morbidity of childhood asthma and defined by a transient narrowing of the airways during or after physical exercise. An exercise challenge test (ECT) is the reference standard for the diagnosis of EIB. Video evaluation of EIB symptoms could be a practical alternative for the assessment of EIB. We studied the ability of pediatricians to assess EIB from post-exercise videos. Methods: A clinical assessment was performed in 20 asthmatic children (mean age 11.6 years) and EIB was measured with a standardized ECT performed in cold, dry air. EIB was defined as a fall in forced expiratory volume in 1 s (FEV1) of ≥10% post-exercise. Children were filmed before and after exercise in frontal position and bare chested. The clinical assessment results and videos were shown to 20 pediatricians (mean experience 14.4 years). Each assessed EIB severity in 5 random children providing 100 assessments, scored on a continuous rating scale (0-10) and in severity classifications (no, mild, moderate, severe) using a scoring list including physical asthma symptoms. Correlations between predicted scores and objective scores were calculated with Spearman's rho and Cohen's Kappa. A generalized linear model was used to assess the relationship between physical symptoms and fall in FEV1. Results: Median fall in FEV1 after exercise was 15.1% (IQR 1.2-65.1). Pediatricians detected EIB with a sensitivity of 78% (95% CI 66-87%) and a specificity of 40% (95% CI 27-55%). The positive predictive value for a pediatricians' diagnosis of EIB was 61% (95% CI 50-72%). The negative predictive value was 60% (95% CI 42-76%). The agreement between predicted EIB severity classifications and the validated classifications based on the ECT's, was fair [Kappa = 0.36 (95% CI 0.23-0.48)]. The correlation between predicted EIB severity scored on a continuous rating scale and fall in FEV1 after exercise was weak (rs = 0.39, p < 0.001). Independent predictive variables for fall in FEV1 were wheezing (-11%), supraclavicular retractions (-8.4%) and a prolonged expiratory phase (-8.8%). Conclusion: The ability of pediatricians to assess EIB from post-exercise videos is fair at best, implicating that standardized ECT's are still vital in the assessment of EIB.

Culture results from wound biopsy versus wound swab: does it matter for the assessment of wound infection?

OBJECTIVES: The aim of this study was to determine whether assessment of wound infection differs when culture results from wound biopsy versus wound swab are available in clinical practice. METHODS: For 180 eligible patients, a swab and biopsy were taken from one wound during a regular appointment at a wound care facility in eastern Netherlands. Culture results from both methods were supplemented with clinical information and provided to a panel of six experts who independently assessed each wound as infect or not, separately for swab and biopsy. Assessments for biopsy and swab were compared for the complete expert panel, and for individual experts. RESULTS: The complete expert panel provided the same wound assessment based on (clinical information and) culture results from wound biopsy and wound swab in 158 of 180 wounds (87.8%, kappa 0.67). For individual experts, agreement between biopsy and swab varied between 77% and 96%. However, there were substantial differences between experts: the same assessment was provided in 62 (34.4%) to 76 (42.2%) wounds for swab and biopsy respectively. CONCLUSIONS: Assessment of infection does not significantly differ when culture results from swabs or biopsies are available. The substantial variability between individual experts indicates non-uniformity in the way wounds are assessed. This complicates accurate detection of infection and comparability between studies using assessment of infection as reference standard.

Comparison of outcome in stroke patients admitted during working hours vs. off-hours; a single-center cohort study.

INTRODUCTION: We aimed to disprove an in-hospital off-hour effect in stroke patients by adjusting for disease severity and poor prognostic findings on imaging. PATIENTS AND METHODS: Our study included 5378 patients from a single center prospective stroke registry of a large teaching hospital in the Netherlands, admitted between January 2003 and June 2015. Patients were categorized by admission time, off-hours (OH) or working hours (WH). The in-hospital mortality, 7-day mortality, unfavorable functional outcome (modified Rankin scale > 2) and discharge to home were analyzed. Results were adjusted for age, sex, stroke severity (NIHSS score) and unfavorable findings on imaging of the brain (midline shift and dense vessel sign). RESULTS: Overall, 2796 patients (52%) were admitted during OH, which had a higher NIHSS score [3 (IQR 2-8) vs. 3 (IQR 2-6): p < 0.01] and had more often a dense vessel sign at admission (7.9% vs. 5.4%: p < 0.01). There was no difference in mortality between the OH-group and WH-group (6.2% vs. 6.0%; p = 0.87). The adjusted hazard ratio of in-hospital mortality during OH was 0.87 (95% CI: 0.70-1.08). Analysis of 7-day mortality showed similar results. Unadjusted, the OH-group had an unfavorable outcome [OR: 1.14 (95% CI: 1.02-1.27)] and could less frequently be discharged to home [OR: 1.16 (95% CI: 1.04-1.29)], which was no longer present after adjustment. DISCUSSION AND CONCLUSIONS: The overall outcome of stroke patients admitted to a large Dutch teaching hospital is not influenced by time of admission. When studying OH effects, adjustment for disease severity and poor prognostic findings on imaging is crucial before drawing conclusions on staffing and material.

The effect of a structured medication review on quality of life in Parkinson's disease: The study protocol.

BACKGROUND: Treatment of Parkinson's disease (PD) is symptomatic and frequently consists of complicated medication regimes. This negatively influences therapy adherence, resulting in lower benefit of treatment, drug related problems and decreased quality of life (QoL). A potential effective intervention strategy is a structured medication review, executed by community pharmacists. However, little is known about the effects on clinical endpoints like QoL, as well as on feasibility and cost-effectiveness in PD patients. OBJECTIVES: To assess the effect of a structured medication review on QoL in PD patients. Secondary objectives are measurements of physical disability, activities in daily life, non-motor symptoms, health state, personal carers' QoL and cost-effectiveness. Furthermore, a better insight in the process of performing medication reviews will be obtained from the perspective of community pharmacists. METHODS: In this multicenter randomized controlled trial we aim to enroll 200 PD patients from the outpatient clinic of three Dutch hospitals. Community pharmacists will perform a structured medication review in half of the assigned patients; the other half will receive usual care. Data obtained by use of six validated questionnaires will be collected at baseline and after 3 and 6 months of follow-up. Semi-structured interviews with community pharmacists will be conducted till data saturation has been reached. DISCUSSION: This trial targets a high-risk patient group for whom optimizing therapy by a structured medication review might be of added value. If effectiveness is proven, this could further promote the implementation of pharmaceutical care in a primary care setting.

Multi-centre prospective study on diagnosing subtypes of lung cancer by exhaled-breath analysis.

OBJECTIVES: Lung cancer is a leading cause of mortality. Exhaled-breath analysis of volatile organic compounds (VOC's) might detect lung cancer early in the course of the disease, which may improve outcomes. Subtyping lung cancers could be helpful in further clinical decisions. MATERIALS AND METHODS: In a prospective, multi-centre study, using 10 electronic nose devices, 144 subjects diagnosed with NSCLC and 146 healthy subjects, including subjects considered negative for NSCLC after investigation, breathed into the Aeonose™ (The eNose Company, Zutphen, Netherlands). Also, analyses into subtypes of NSCLC, such as adenocarcinoma (AC) and squamous cell carcinoma (SCC), and analyses of patients with small cell lung cancer (SCLC) were performed. RESULTS: Choosing a cut-off point to predominantly rule out cancer resulted for NSCLC in a sensitivity of 94.4%, a specificity of 32.9%, a positive predictive value of 58.1%, a negative predictive value (NPV) of 85.7%, and an area under the curve (AUC) of 0.76. For AC sensitivity, PPV, NPV, and AUC were 81.5%, 56.4%, 79.5%, and 0.74, respectively, while for SCC these numbers were 80.8%, 45.7%, 93.0%, and 0.77, respectively. SCLC could be ruled out with a sensitivity of 88.9% and an NPV of 96.8% with an AUC of 0.86. CONCLUSION: Electronic nose technology with the Aeonose™ can play an important role in rapidly excluding lung cancer due to the high negative predictive value for various, but not all types of lung cancer. Patients showing positive breath tests should still be subjected to further diagnostic testing.