Publications by authors named "Bjorn Winkens"

197 Publications

The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis.

Authors:
Michelle Bosman Sigrid Elsenbruch Maura Corsetti Jan Tack Magnus Simrén Bjorn Winkens Thimo Boumans Ad Masclee Daniel Keszthelyi

Lancet Gastroenterol Hepatol 2021 Mar 22. Epub 2021 Mar 22.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands.

Background: Clinical trials in irritable bowel syndrome are associated with high placebo response rates. We aimed to identify the magnitude of the placebo response and the contributing factors to this occurrence.

Methods: We did a systematic review and meta-analysis with a search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials between April 1, 1959, and April 30, 2020. We included all randomised controlled trials that compared an active pharmacotherapeutic agent with placebo and had a dichotomous outcome of response to therapy (in terms of global improvement or improvement in abdominal pain) in adults (aged ≥18 years) with irritable bowel syndrome. Exclusion criteria were trials reporting on treatment satisfaction as a dichotomous outcome of response to therapy or clinician-reported outcomes and a treatment duration of less than 4 weeks. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: global improvement, abdominal pain, and US Food and Drug Administration (FDA) endpoints. We extracted information from published reports and pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020170908.

Findings: Of the 6863 publications identified, 70 articles describing 73 randomised controlled trials were included in our analysis. The pooled placebo response rate was 27·3% (95% CI 24·3-30·9) using the global improvement endpoint, 34·4% (31·2-37·8) using the abdominal pain endpoint, and 17·9% (15·2-21·0) using the composite FDA endpoint responder definition, all with substantial heterogeneity between the trials. Studies published before 2006, and those done in Europe, with a parallel design, a run-in period of 2 weeks or less, a dose schedule of three times a day or more, or a smaller sample size of the control group were significantly associated with an increased pooled placebo response rate.

Interpretation: More than a quarter of patients with irritable bowel syndrome had a placebo response in terms of global improvement, with multiple associated moderators. We recommend future trials apply a run-in period of at least 2 weeks and dose once or twice a day to minimise the placebo response rate.

Funding: None.
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http://dx.doi.org/10.1016/S2468-1253(21)00023-6DOI Listing
March 2021

Exhaled volatile organic compounds detect pulmonary exacerbations early in children with cystic fibrosis: results of a 1 year observational pilot study.

Authors:
Marieke van Horck Agnieszka Smolinska Geertjan Wesseling Karin de Winter-de Groot Ilja de Vreede Bjorn Winkens Quirijn Jöbsis Jan Dallinga Edward Dompeling Frederik-Jan van Schooten

J Breath Res 2021 Feb 25;15(2):026012. Epub 2021 Feb 25.

Department of Paediatric Pulmonology, School for Public Health and Primary Health Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.

In patients with cystic fibrosis (CF), pulmonary exacerbations (PEx) have an important influence on well-being, quality of life, and lung function decline. Early detection combined with early treatment may prevent severe PEx. To determine whether early detection of PEx is possible by non-invasive markers (volatile organic compounds) in exhaled breath. In a 1 year prospective observational pilot study, 49 children with CF were studied. At clinical visits with an interval of 2 months, lung function, volatile organic compounds (VOCs) in exhaled breath by means of gas chromatography-time-of-flight-mass spectrometry, and medication use were assessed. PEx were recorded. Random forest (RF) classification modelling was used to select discriminatory VOCs, followed by building of receiver operating characteristic curves. An inverse relation between the predictive power of a set of VOCs and time between exhaled breath sampling and the onset of PEx was found. When this time period was within 7 d, the RF model with the nine most discriminatory VOCs was able to correctly predict 79% of the children with an upcoming PEx or remaining stable (sensitivity 79% and specificity 78%). This result was validated by means of bootstrapping within the RF classification model. PEx in children with CF can be detected at an early stage by means of exhaled VOCs. The highest predictive value was reached if time between sampling and the onset of an exacerbation was no longer than 7 d.
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http://dx.doi.org/10.1088/1752-7163/abda55DOI Listing
February 2021

Correction: Smart Data Collection for the Assessment of Treatment Effects in Irritable Bowel Syndrome: Observational Study.

Authors:
Zsa Zsa R M Weerts Koert G E Heinen Ad A M Masclee Amber B A Quanjel Bjorn Winkens Lisa Vork Paula E L M Rinkens Daisy M A E Jonkers Daniel Keszthelyi

JMIR Mhealth Uhealth 2021 Feb 18;9(2):e27998. Epub 2021 Feb 18.

Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands.

[This corrects the article DOI: 10.2196/19696.].
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http://dx.doi.org/10.2196/27998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932838PMC
February 2021

Rebubbling and graft failure in Descemet membrane endothelial keratoplasty: a prospective Dutch registry study.

Authors:
Suryan Dunker Bjorn Winkens Frank van den Biggelaar Rudy Nuijts Pieter Jan Kruit Mor Dickman

Br J Ophthalmol 2021 Feb 17. Epub 2021 Feb 17.

University Eye Clinic, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Aims: To identify risk factors for rebubbling, and early graft failure after Descemet membrane endothelial keratoplasty (DMEK).

Methods: In this prospective registry study, all consecutive DMEK procedures registered in the Netherlands Organ Transplant Registry were assessed (n=752). Univariable and multivariable analysis was performed using logistic regression. The effect of rebubbling on endothelial cell density was analysed using a linear mixed model.

Results: 144 of 752 (19%) eyes underwent rebubbling. Rebubbling was successful in 101 eyes (70%). In eyes that underwent rebubbling, the graft failure rate was significantly higher than eyes that did not undergo rebubbling (30% vs 9%, respectively; OR: 4.28, 95% CI 2.72 to 6.73, p<0.001). In multivariable analysis, independent risk factors for rebubbling were surgical complication (OR: 2.28, 95% CI 1.20 to 4.33, p=0.012) and older recipient age (OR: 1.04 (per increase of 1 year), 95% CI 1.01 to 1.07, p=0.003). Risk factors for developing graft failure within 3 months were transplant before 2016 (OR: 3.32, 95% CI 1.87 to 5.90, p<0.001), and surgical complication (OR: 2.93, 95% CI 1.42 to 6.04, p=0.004). Throughout the study period, rebubbling and early graft failure were inversely related. Eyes that underwent rebubbling showed significantly lower endothelial cell densities at 3, 6 and 12 months compared with eyes that did not undergo rebubbling (all p<0.001).

Conclusions: This Dutch registry study identified independent risk factors for DMEK graft detachment leading to rebubbling, namely recipient age and surgical complication, and early graft failure, namely transplantation before 2016 and surgical complication. Rebubbling was associated with significantly higher endothelial cell loss in the first year after surgery.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317041DOI Listing
February 2021

The Effect of a Comprehensive, Interdisciplinary Medication Review on Quality of Life and Medication Use in Community Dwelling Older People with Polypharmacy.

Authors:
Donna Bosch-Lenders Jesse Jansen Henri E J H Jelle Stoffers Bjorn Winkens Karin Aretz Mascha Twellaar Jos M G A Schols Paul-Hugo M van der Kuy J André Knottnerus Marjan van den Akker

J Clin Med 2021 Feb 5;10(4). Epub 2021 Feb 5.

Department of Family Medicine, Care and Public Health Research Institute (CAHPRI), Maastricht University, 6200 MD Maastricht, The Netherlands.

We conducted a comprehensive medication review at the patients' home, using data from electronic patient records, and with input from relevant specialists, general practitioners and pharmacists formulated and implemented recommendations to optimize medication use in patients aged 60+ years with polypharmacy. We evaluated the effect of this medication review on quality of life (QoL) and medication use. Cluster randomized controlled trial (stepped wedge), randomly assigning general practices to one of three consecutive steps. Patients received usual care until the intervention was implemented. Primary outcome was QoL (SF-36 and EQ-5D); secondary outcomes were medication changes, medication adherence and (instrumental) activities of daily living (ADL, iADL) which were measured at baseline, and around 6- and 12-months post intervention. Twenty-four general practices included 360 women and 410 men with an average age of 75 years (SD 7.5). A positive effect on SF-36 mental health (estimated mean was stable in the intervention, but decreased in the control condition with -6.1, = 0.009,) was found with a reduced number of medications at follow-up compared to the control condition. No significant effects were found on other QoL subscales, ADL, iADL or medication adherence. The medication review prevented decrease of mental health (SF36), with no significant effects on other outcome measures, apart from a reduction in the number of prescribed medications.
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http://dx.doi.org/10.3390/jcm10040600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915595PMC
February 2021

[Effects and costs of The Healthy Primary School of the Future].

Authors:
C P van Schayck Maartje Willeboordse Marije Oosterhof Nina Bartelink Patricia van Assema Stef Kremers Bjorn Winkens Hans Savelberg Maria Jansen Manuela Joore Anita C E Vreugdenhil

Ned Tijdschr Geneeskd 2021 01 28;165. Epub 2021 Jan 28.

Universiteit Maastricht/Maastricht Universitair Medisch Centrum+, afd. Kindergeneeskunde,Maastricht.

Objective: To study school lifestyle interventions for elementary school children (The Healthy Primary School of the Future).

Research Question: What are the effects of the introduction of increased physical activity with or without healthy nutrition on health behaviour and BMI of young children and what are the costs of this program?

Design: Prospective controlled non-randomized study with nearly 1700 children in Parkstad (South-East Netherlands).

Results: Preliminary results after two years show that the combination of increased physical activity and healthy nutrition result in a decreased BMIz-score (-0.036), increased physical activity alone in hardly any change (-0.10) while in the control group the BMIz-score increased (0.052). The net societal costs of the combination of physical activity and health nutrition costs were 1 euro per child per day.

Conclusion: The study contributes to the increasing amount of evidence proving that lifestyle interventions are effective in reducing the obesity epidemic. Future studies will show whether a weight reduction in children will result in the prevention of chronic disease later on in life and what the cost reduction related to this result will be.
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January 2021

Prevalence of Upper Extremity Musculoskeletal Disorders in Patients with Type 2 Diabetes in General Practice.

Authors:
Login Ahmed S Alabdali Jasmien Jaeken Geert-Jan Dinant Marjan van den Akker Bjorn Winkens Ramon P G Ottenheijm

Medicines (Basel) 2021 Feb 1;8(2). Epub 2021 Feb 1.

Department of Family Medicine, CAPHRI Care and Public Health Research Institute, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

One of the lesser recognized complications of diabetes mellitus are musculoskeletal (MSK) complications of the upper and lower extremity. No prevalence studies have been conducted in general practice. Thus, the aim of this study was to investigate the prevalence of upper extremity MSK disorders in patients with type 2 diabetes (T2DM) in the Netherlands. We conducted a cross-sectional study with two different approaches, namely a representative Dutch primary care medical database study and a questionnaire study among patients with T2DM. In the database study, 2669 patients with T2DM and 2669 non-diabetes patients were included. MSK disorders were observed in 16.3% of patients with T2DM compared to 11.2% of non-diabetes patients ( < 0.001, OR 1.53, 95% CI 1.31, 1.80). In the questionnaire study, 200 patients with T2DM were included who reported a lifetime prevalence of painful upper extremity body sites for at least four weeks of 67.3%. We found that upper extremity MSK disorders have a high prevalence in Dutch patients with T2DM presenting in general practice. The prevalence ranges from 16% based on GP registered disorders and complaints to 67% based on self-reported diagnosis and pain. Early detection and treatment of these disorders may play a role in preventing the development of chronic MSK disorders.
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http://dx.doi.org/10.3390/medicines8020008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912777PMC
February 2021

Quality of vision and vision-related quality of life after Descemet membrane endothelial keratoplasty: a randomized clinical trial.

Authors:
Suryan L Dunker Mor M Dickman Robert P L Wisse Siamak Nobacht Robert H J Wijdh Marjolijn C Bartels N E Mei-Lie Tang Frank J H M van den Biggelaar Pieter J Kruit Bjorn Winkens Rudy M M A Nuijts

Acta Ophthalmol 2021 Jan 12. Epub 2021 Jan 12.

Maastricht University Medical Center+, University Eye Clinic, Maastricht, the Netherlands.

Purpose: To compare quality of vision and vision-related quality of life (QOL) in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) or ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK).

Methods: Fifty-four eyes of 54 patients with Fuchs' dystrophy from six corneal clinics in the Netherlands were randomized to DMEK or ultrathin DSAEK and examined preoperatively, and 3, 6 and 12 months postoperatively. Main outcome measures were corneal higher-order aberrations (HOAs), contrast sensitivity, straylight and vision-related QOL.

Results: Posterior corneal HOAs decreased after DMEK and increased after ultrathin DSAEK (p ≤ 0.001) 3 months after surgery and correlated positively with best spectacle-corrected visual acuity (12 months: r = 0.29, p = 0.04). Anterior and total corneal HOAs did not differ significantly between both techniques at any time point. Contrast sensitivity was better (p = 0.01), and straylight was lower (p = 0.01) 3 months after DMEK compared with ultrathin DSAEK; 95% confidence interval [CI] of log(cs) 1.10-1.35 versus 95% CI: 0.84 to 1.12, and 95% CI: log(s) 1.18 to 1.43 versus 95% CI: 1.41 to 1.66, respectively. Both were comparable at later time points. Vision-related QOL (scale 0-100) did not differ significantly between both groups at any time point and improved significantly at 3 months (β = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (β = 5 [95% CI: 0 to 9]; p = 0.06).

Conclusions: Descemet membrane endothelial keratoplasty (DMEK) results in lower posterior corneal HOAs compared with ultrathin DSAEK. Contrast sensitivity and straylight recover faster after DMEK but reach similar levels with both techniques at 1 year. Vision-related QOL improved significantly after surgery, but did not differ between both techniques.
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http://dx.doi.org/10.1111/aos.14741DOI Listing
January 2021

Exhaled volatile organic compounds detect pulmonary exacerbations early in children with Cystic Fibrosis: results of a one-year observational pilot study.

Authors:
Marieke van Horck Agnieszka Smolinska Geertjan Wesseling Karin M de Winter-de Groot Ilja de Vreede Bjorn Winkens Quirijn Jöbsis Jan Dallinga Edward Dompeling Frederik Jan van Schooten

J Breath Res 2021 Jan 11. Epub 2021 Jan 11.

Department of Toxicology, Maastricht University, Maastricht, Limburg, NETHERLANDS.

Background: In patients with Cystic fibrosis (CF), pulmonary exacerbations (PEx) have an important influence on well-being, quality of life, and lung function decline. Early detection combined with early treatment may prevent severe PEx.

Aim: To determine whether early detection of PEx is possible by non-invasive markers (volatile organic compounds) in exhaled breath.

Methods: In a one-year prospective observational pilot study, 49 children with CF were studied. At clinical visits with an interval of 2 months, lung function, volatile organic compounds (VOCs) in exhaled breath by means of gas chromatography-time-of-flight-mass spectrometry, and medication use were assessed. PEx were recorded. Random Forest (RF) classification modelling was used to select discriminatory VOCs, followed by building of Receiver Operating Characteristic curves.

Results: An inverse relation between the predictive power of a set of VOCs and time between exhaled breath sampling and the onset of PEx was found. When this time period was within 7 days, the RF model with the 9 most discriminatory VOCs was able to correctly predict 79% of the children with an upcoming PEx or remaining stable (sensitivity 79% and specificity 78%). This result was validated by means of bootstrapping within the RF classification model.

Conclusion: PEx in children with CF can be detected at an early stage by means of exhaled VOCs. The highest predictive value was reached if time between sampling and the onset of an exacerbation was no longer than 7 days.
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http://dx.doi.org/10.1088/1752-7163/abda55DOI Listing
January 2021

Lymphedema and Post-Operative Complications after Sentinel Lymph Node Biopsy versus Lymphadenectomy in Endometrial Carcinomas-A Systematic Review and Meta-Analysis.

Authors:
Rianne J A Helgers Bjorn Winkens Brigitte F M Slangen Henrica M J Werner

J Clin Med 2020 Dec 31;10(1). Epub 2020 Dec 31.

Department of Obstetrics and Gynecology, GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands.

: Lymph node dissection (LND) is recommended as staging procedure in presumed low stage endometrial cancer. LND is associated with risk of lower-extremity lymphedema and post-operative complications. The sentinel lymph node (SLN) procedure has been shown to have high diagnostic accuracy, but its effects on complication risk has been little studied. This systematic review compares the risk of lower-extremity lymphedema and post-operative complications in SLN versus LND in patients with endometrial carcinoma. : A systematic search was conducted in PubMed and Cochrane Library. : Seven retrospective and prospective studies (total n = 3046 patients) were included. Only three studies reported the odds ratio of lower-extremity lymphedema after SLN compared to LND, which was 0.05 (95% CI 0.01-0.37; = 0.067), 0.07 (95% CI 0.00-1.21; = 0.007) and 0.54 (95% CI 0.37-0.80; = 0.002) in these studies. The pooled odds ratio of any post-operative complications after SLN versus LND was 0.52 (95% CI 0.36-0.73; I = 48%; < 0.001). For severe post-operative complications the pooled odds ratio was 0.52 (95% CI 0.28-0.96; I = 0%; = 0.04). : There are strong indications that SLN results in a lower incidence of lower-extremity lymphedema and less often severe post-operative complications compared to LND. In spite of the paucity and heterogeneity of studies, direction of results was similar in all studies, supporting the aforementioned conclusion. These results support the increasing uptake of SLN procedures in endometrial cancer.
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http://dx.doi.org/10.3390/jcm10010120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795280PMC
December 2020

A predictive model for estimating the number of erythrocytapheresis or phlebotomy treatments for patients with naïve hereditary hemochromatosis.

Authors:
Eva Rombout-Sestrienkova Bjorn Winkens Marian van Kraaij Cees Th B M van Deursen Mirian C H Janssen Alexander M J Rennings Dorothea Evers Jean-Louis Kerkhoffs Ad Masclee Ger H Koek

J Clin Apher 2020 Dec 24. Epub 2020 Dec 24.

Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.

Background And Aims: Standard treatment for naïve hereditary hemochromatosis patients consists of phlebotomy or a personalized erythrocytapheresis. Erythrocytapheresis is more efficient, but infrequently used because of perceived costs and specialized equipment being needed. The main aim of our study was to develop a model that predicts the number of initial treatment procedures for both treatment methods. This information may help the clinician to select the optimal treatment modality for the individual patient.

Methods: We analyzed retrospective data of 125 newly diagnosed patients (C282Y homozygous), treated either with phlebotomy (n = 54) or erythrocytapheresis (n = 71) until serum ferritin (SF) reached levels ≤100 μg/L. To estimate the required number of treatment procedures multiple linear regression analysis was used for each treatment method separately.

Results: The linear regression model with the best predictive quality (R = 0.74 and 0.73 for erythrocytapheresis and phlebotomy respectively) included initial SF, initial hemoglobin (Hb) level, age, and BMI, where initial SF was independently related to the total number of treatment procedures for both treatment methods. The prediction error expressed in RMSPE and RMSDR was lower for erythrocytapheresis than for phlebotomy (3.8 and 4.1 vs 7.0 and 8.0 respectively), CONCLUSIONS: Although the prediction error of the developed model was relatively large, the model may help the clinician to choose the most optimal treatment method for an individual patient. Generally erythrocytapheresis halves the number of treatment procedures for all patients, where the largest reduction (between 55% and 64%) is reached in patients with an initial Hb level ≥ 9 mmol/L (14.5 g/dL). ClinicalTrials.gov number NCT00202436.
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http://dx.doi.org/10.1002/jca.21867DOI Listing
December 2020

Optical diagnosis of colorectal polyp images using a newly developed computer-aided diagnosis system (CADx) compared with intuitive optical diagnosis.

Authors:
Quirine E W van der Zander Ramon M Schreuder Roger Fonollà Thom Scheeve Fons van der Sommen Bjorn Winkens Patrick Aepli Bu'Hussain Hayee Andreas B Pischel Milan Stefanovic Sharmila Subramaniam Pradeep Bhandari Peter H N de With Ad A M Masclee Erik J Schoon

Endoscopy 2020 Dec 23. Epub 2020 Dec 23.

GROW, School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.

Background:  Optical diagnosis of colorectal polyps remains challenging. Image-enhancement techniques such as narrow-band imaging and blue-light imaging (BLI) can improve optical diagnosis. We developed and prospectively validated a computer-aided diagnosis system (CADx) using high-definition white-light (HDWL) and BLI images, and compared the system with the optical diagnosis of expert and novice endoscopists.

Methods:  CADx characterized colorectal polyps by exploiting artificial neural networks. Six experts and 13 novices optically diagnosed 60 colorectal polyps based on intuition. After 4 weeks, the same set of images was permuted and optically diagnosed using the BLI Adenoma Serrated International Classification (BASIC).

Results:  CADx had a diagnostic accuracy of 88.3 % using HDWL images and 86.7 % using BLI images. The overall diagnostic accuracy combining HDWL and BLI (multimodal imaging) was 95.0 %, which was significantly higher than that of experts (81.7 %,  = 0.03) and novices (66.7 %,  < 0.001). Sensitivity was also higher for CADx (95.6 % vs. 61.1 % and 55.4 %), whereas specificity was higher for experts compared with CADx and novices (95.6 % vs. 93.3 % and 93.2 %). For endoscopists, diagnostic accuracy did not increase when using BASIC, either for experts (intuition 79.5 % vs. BASIC 81.7 %,  = 0.14) or for novices (intuition 66.7 % vs. BASIC 66.5 %,  = 0.95).

Conclusion:  CADx had a significantly higher diagnostic accuracy than experts and novices for the optical diagnosis of colorectal polyps. Multimodal imaging, incorporating both HDWL and BLI, improved the diagnostic accuracy of CADx. BASIC did not increase the diagnostic accuracy of endoscopists compared with intuitive optical diagnosis.
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http://dx.doi.org/10.1055/a-1343-1597DOI Listing
December 2020

Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial.

Authors:
Mark R Hazebroek Michiel T H M Henkens Anne G Raafs Job A J Verdonschot Jort J Merken Robert M Dennert Casper Eurlings Myrurgia A Abdul Hamid Petra F G Wolffs Bjorn Winkens Hans-Peter Brunner-La Rocca Christian Knackstedt Pieter van Paassen Vanessa P M van Empel Stephane R B Heymans

Eur J Heart Fail 2021 Feb 7;23(2):302-309. Epub 2021 Jan 7.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.

Aims: Previous uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)-related dilated cardiomyopathy (DCM). This randomized, double-blind, placebo-controlled, single-centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.

Methods And Results: Fifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6-min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end-diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (-7;5) vs. placebo -2 (-6;6), P = 0.904] and LVEDV (IVIg -16 ± 49 mL/m vs. placebo -29 ± 40 mL/m ; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups.

Conclusion: Intravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence.

Clinical Trial Registration: ClinicalTrials.gov ID NCT00892112.
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http://dx.doi.org/10.1002/ejhf.2082DOI Listing
February 2021

Functional Disability in Adolescents with Chronic Pain: Comparing an Interdisciplinary Exposure Program to Usual Care.

Authors:
Carolien Dekker Mariëlle Goossens Bjorn Winkens Silvia Remerie Caroline Bastiaenen Jeanine Verbunt

Children (Basel) 2020 Dec 11;7(12). Epub 2020 Dec 11.

Department of Rehabilitation Medicine, Care and Public Health Research Institute, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, The Netherlands.

(1) Background: Chronic musculoskeletal pain (CMP) in adolescents can negatively affect physical, psychological, and social functioning, resulting in functional disability. This randomized controlled trial (RCT) aimed to evaluate the effectiveness of an outpatient rehabilitation program based on graded exposure in vivo (EP) compared with care as usual (CAU: interdisciplinary outpatient rehabilitation care). Both EP and CAU aim to improve functional ability in adolescents with CMP. (2) Methods: Pragmatic multicenter RCT with 12-month follow-up. Adolescents (12-21 years) with CMP were invited to participate. Primary outcome: functional disability; secondary outcomes: perceived harmfulness; pain catastrophizing; pain intensity. Data analysis: intention-to-treat linear mixed model. (3) Results: Sixty adolescents (mean 16 years) were randomized; data for 53 were analyzed. Adolescents in EP showed relevant and significant decreases in functional disability (estimated mean difference at least -8.81, ≤ 0.01) compared with CAU at all times. Significant differences in favor of EP were found for perceived harmfulness at all times ( ≤ 0.002), for pain catastrophizing at 2 months ( = 0.039) and for pain intensity at 4 and 10 months ( ≤ 0.028). (4) Conclusion: EP leads to a significant and clinically relevant decrease in functional disability compared with usual care.
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http://dx.doi.org/10.3390/children7120288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763849PMC
December 2020

Feasibility and Effect of the Exergame BOOSTH Introduced to Improve Physical Activity and Health in Children: Protocol for a Randomized Controlled Trial.

Authors:
Gabrielle Ten Velde Guy Plasqui Maartje Willeboordse Bjorn Winkens Anita Vreugdenhil

JMIR Res Protoc 2020 Dec 11;9(12):e24035. Epub 2020 Dec 11.

Department of Nutrition and Movement Sciences, Maastricht University Medical Centre, Maastricht, Netherlands.

Background: Despite the well-known beneficial health effects of physical activity (PA), the majority of Dutch primary school children do not meet the recommended PA guidelines. Although there is growing evidence on the effectiveness of exergames for PA in children, there is limited evidence on their effect on health outcomes, such as cardiovascular health and health-related quality of life (HRQOL), and on factors influencing their effectiveness and feasibility. The exergame BOOSTH uses a wrist-worn activity tracker to measure steps per day. As a reward for the performed PA, children can unlock levels in the online BOOSTH game. In addition, "BOOSTH battle" enables competition between groups.

Objective: This protocol describes a cluster randomized controlled trial in 16 primary schools in the Netherlands investigating the effect of BOOSTH on moderate-to-vigorous PA (MVPA) using accelerometry. Secondary aims are to investigate the feasibility of BOOSTH (mixed methods: questionnaires and focus group interviews) and its effect on cardiovascular risk factors (anthropometrics, blood pressure, and retinal microvasculature) and HRQOL.

Methods: Stratification variables and relevant variables related to outcomes (such as BMI [z-score], sex, age, and parenting style) and/or missingness will be taken into account. Measurements will be performed at baseline and after 3, 6, and 12 months.

Results: The study has received funding from Province Limburg (SAS-2015-04956) and received ethical approval from the Medical Ethics Committee of Maastricht University Medical Centre (METC172043/NL64324.068.17). The results of the analyses are expected to be published in 2021.

Conclusions: With this study, the ability of the exergame BOOSTH to increase PA and improve health in children of primary school age will be investigated. The insights into effectiveness and feasibility will result in scientific and societal recommendations, which could potentially contribute to widespread implementation of exergames for children.

Trial Registration: ClinicalTrials.gov NCT03440580; https://clinicaltrials.gov/ct2/show/NCT03440580.

International Registered Report Identifier (irrid): DERR1-10.2196/24035.
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http://dx.doi.org/10.2196/24035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762686PMC
December 2020

Metachronous neoplasms in patients with laterally spreading tumours during surveillance.

Authors:
Roel M M Bogie Bjorn Winkens Sean J J Retra Chantal M C le Clercq Mariëlle W Bouwens Eveline J A Rondagh Li-Chun Chang Rogier de Ridder Chantal Hoge Jan-Willem Straathof Danny Goudkade Silvia Sanduleanu-Dascalescu Ad A M Masclee

United European Gastroenterol J 2021 Feb 18. Epub 2021 Feb 18.

Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: Laterally spreading tumours represent a major challenge for endoscopic detection and resection.

Objective: To examine synchronous and metachronous neoplasms in patients with laterally spreading tumours.

Methods: We prospectively collected colonoscopy and histopathology data from patients who underwent colonoscopy in our centre at up to 6 years' follow-up. Post-resection surveillance outcomes between laterally spreading tumours, flat colorectal neoplasms 10 mm or greater, and large polypoid colorectal neoplasms, polypoid colorectal neoplasms 10 mm or greater, were compared.

Results: Between 2008 and 2012, 8120 patients underwent colonoscopy for symptoms (84.6%), screening (6.7%) or surveillance (8.7%). At baseline, 151 patients had adenomatous laterally spreading tumours and 566 patients had adenomatous large polypoid colorectal neoplasms. Laterally spreading tumour patients had more synchronous colorectal neoplasms than large polypoid colorectal neoplasm patients (mean 3.34 vs. 2.34, p < 0.001). Laterally spreading tumour patients significantly more often developed metachronous colorectal neoplasms (71.6% vs. 54.2%, p = 0.0498) and colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients (36.4% vs. 15.8%, p < 0.001). After correction for age and gender, laterally spreading tumour patients were more likely than large polypoid colorectal neoplasm patients to develop a colorectal neoplasm with high grade dysplasia or submucosal invasion (hazard ratio 2.9, 95% confidence interval 1.8-4.6). The risk of metachronous colorectal cancer was not significantly different in laterally spreading tumours compared to large polypoid colorectal neoplasm patients.

Conclusion: Patients with laterally spreading tumours developed more metachronous colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients. Based on these findings endoscopic treatment and surveillance recommendations for patients with laterally spreading tumours should be optimised.
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http://dx.doi.org/10.1177/2050640620965317DOI Listing
February 2021

Effectiveness and cost-effectiveness of the Assessment of Burden of Chronic Conditions (ABCC) tool in patients with COPD, asthma, diabetes mellitus type 2 and heart failure: protocol for a pragmatic clustered quasi-experimental study.

Authors:
Esther A Boudewijns Danny Claessens Manuela Joore Lotte C E M Keijsers Onno C P van Schayck Bjorn Winkens Annerika H M Gidding-Slok

BMJ Open 2020 11 17;10(11):e037693. Epub 2020 Nov 17.

Department of Family Medicine, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.

Introduction: The number of people that have one or multiple condition(s) with a chronic course is rising, which consequently challenges healthcare systems. Healthcare geared to long-term care should focus on patient-centredness, shared decision making and self-management. The Assessment of Burden of Chronic Conditions (ABCC) tool was developed to integrate these elements in daily healthcare practice. The ABCC tool assesses and visualises burden of disease(s), helps to make shared decisions and stimulates self-management. The present paper documents a protocol for a quasi-experimental study investigating the effectiveness and cost-effectiveness of the ABCC tool for people with chronic obstructive pulmonary disease, asthma, type 2 diabetes mellitus and/or heart failure.

Methods And Analysis: The study has a pragmatic clustered quasi-experimental design and will be conducted in the Netherlands. The intervention will be allocated at the level of general practice. The intervention group (18 general practices, 180 patients) will use the ABCC tool during regular consultations; the control group (18 general practices, 180 patients) will maintain usual care. Outcomes include change in quality of care (Patient Assessment of Chronic Illness Care), quality of life (EuroQol-5D-5L), capability well-being (ICEpop CAPability measure for Adults), patients' activation (Patient Activation Measure) and costs. Follow-up time will be 18 months. Outcomes will be analysed using linear mixed models.

Ethics And Dissemination: Ethical approval was obtained from the Medical Ethics Committee Zuyderland-Zuyd Heerlen, the Netherlands (METCZ20180131). Results will be published in peer-reviewed journals and will be presented at national and international conferences.

Trial Registration Number: ClinicalTrials.gov Registry (NCT04127383).
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http://dx.doi.org/10.1136/bmjopen-2020-037693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674093PMC
November 2020

The Effects of Chronic Dialysis on Physical Status, Quality of Life, and Arterial Stiffness: A Longitudinal Study in Prevalent Dialysis Patients.

Authors:
Rens J R Gadaen Jeroen P Kooman Tom Cornelis Frank M van der Sande Bjorn J Winkens Natascha J H Broers

Nephron 2021 27;145(1):44-54. Epub 2020 Oct 27.

Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center+, Maastricht, The Netherlands.

Introduction: It is widely known that dialysis patients have significantly impaired functional outcomes and arterial stiffness, but still few studies have investigated the effects of dialysis longitudinally by a multidimensional approach. We aimed to assess longitudinal patterns of physical activity (PA), physical functioning (PF), health-related quality of life (HrQoL), body composition (BC), and arterial stiffness in prevalent dialysis patients.

Materials And Methods: Thirty-nine prevalent dialysis patients (23 conventional hemodialysis [CHD] and 16 peritoneal dialysis) with a mean vintage of 25.7 (±22.1) months were included in this observational prospective study with a 2-year follow-up, and at baseline 20 healthy controls were included. Measurements were performed every 6 months. HrQoL was assessed using the Short Form-36 (SF-36) questionnaire. PA was assessed using the SenseWear™ Pro3 accelerometer. PF was assessed by walking speed, the PF subscale of the SF-36, and handgrip strength (HGS). BC was assessed using the Body Composition Monitor® and arterial stiffness by measuring carotid-femoral pulse wave velocity (PWV). The longitudinal trend was assessed using linear mixed models, correcting for sex, age, and dialysis vintage. For PWV, the trend was additionally corrected for diabetes and systolic blood pressure.

Results: After correction, no statistically significant changes over time were observed for the parameters of PA, PF, HrQoL, and BC. In the combined group and in the group of CHD patients only, a significant change was observed for PWV (overall trend: p = 0.007 and p = 0.008, respectively). A statistically significant difference at baseline was observed between dialysis patients and healthy controls in all parameters, except for HGS and PWV.

Discussion/conclusion: We observed no statistically significant changes in functional outcomes during a 2-year follow-up period, but a significant increase was observed for arterial stiffness. These results might suggest that after a certain period in time, a relatively stable course is present in functional outcomes, but an ongoing deterioration in arterial stiffness occurs, which might increase the risk of cardiovascular disease and all-cause mortality in these patients.
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http://dx.doi.org/10.1159/000510624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845435PMC
October 2020

Left Ventricular Geometrical Changes in Severely Obese Adolescents: Prevalence, Determinants, and Clinical Implications.

Authors:
Ali Talib Yvonne G M Roebroek Givan F Paulus Kris van Loo Bjorn Winkens Nicole D Bouvy Ernst L W E van Heurn

Pediatr Cardiol 2021 Feb 20;42(2):331-339. Epub 2020 Oct 20.

Department of Surgery, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands.

Left ventricular hypertrophy (LVH) is independently associated with a higher risk of cardiovascular morbidity and mortality in adults. Adiposity is a risk factor for LVH, independent of blood pressure. Potential causes of this nonhemodynamic pathogenesis identified in adults include adverse body fat distribution, insulin resistance, dyslipidemia, and obstructive sleep apnea syndrome (OSA). In severely obese adolescents, the determinants of obesity-induced changes in left ventricular structure are poorly characterized. Cardiac ultrasonographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in adolescents with severe obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with LVH and without LVH were evaluated using independent samples t, chi-square, or Fisher's exact test. Multivariable linear regression analysis was performed to evaluate associations with left ventricular structural changes, corrected for body mass index (BMI) z score. Forty-three patients entered analysis, of whom 24 (55.8%) showed LVH. The most common geometrical change was eccentric LVH (eLVH), occurring in 21 subjects (48.8%). Demographic and anthropometric variables did not differ between patients with and without LVH. Independent of BMI z score, left ventricular mass index was significantly associated with apnea-hypopnea index (AHI) (regression parameter B = 0.8; 95% CI 0.3 to 1.2). Interventricular septum thickness (IVST) was significantly associated with HOMA-IR values (B = 0.1; 95% CI 0.04 to 0.2), HDL-cholesterol (B = - 1.2; 95% CI - 2.2 to 0.1), and triglyceride levels (B = 0.5; 95% CI 0.001 to 0.9). LVH, especially eLVH, is highly prevalent amongst severely obese adolescents. Adverse changes in cardiac structure, increased IVST in particular, are independently associated with several nonhemodynamic comorbidities that are common in this population, namely OSA, insulin resistance, and dyslipidemia.
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http://dx.doi.org/10.1007/s00246-020-02487-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907012PMC
February 2021

The effect of olive leaf extract on cardiovascular health markers: a randomized placebo-controlled clinical trial.

Authors:
Yala Stevens Bjorn Winkens Daisy Jonkers Adrian Masclee

Eur J Nutr 2020 Oct 9. Epub 2020 Oct 9.

Department of Internal Medicine, Division of Gastroenterology-Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, P. O. Box 616, 6200, Maastricht, The Netherlands.

Purpose: Overweight and obesity are associated with many health problems, including cardiovascular disease (CVD). Evidence from previous studies has shown that extracts from olive leaves rich in olive phenolics are able to positively affect CVD risk factors, such as high blood pressure and dyslipidemia. The aim of this study was to investigate the effect of 8-week olive leaf extract (OLE) administration on blood lipid profiles in overweight/obese subjects with mildly elevated cholesterol levels.

Methods: In this randomized, double-blind, placebo-controlled study, 77 healthy adult overweight/obese subjects (aged 56 ± 10 years and BMI 29.0 ± 2.7 kg/m) with total cholesterol levels of 5.0-8.0 mmol/L (5.9 ± 0.7 mmol/L) were randomly assigned to receive 500 mg of OLE (n = 39) or placebo (n = 38) for 8 weeks. In total, 74 subjects completed the entire study protocol. At baseline, after 4 weeks, and after 8 weeks of supplementation, blood lipid profiles, oxidized low-density lipoprotein (oxLDL), blood pressure, glucose, and insulin levels were assessed. In addition, liver function parameters were measured at baseline and after 8 weeks.

Results: OLE supplementation did not significantly affect blood lipid levels after 4 weeks or after 8 weeks compared to placebo (all p > 0.05). For oxLDL, blood pressure, glucose, and insulin levels and liver function parameters, also no statistically significant differences were found between the two intervention groups (all p > 0.05).

Conclusions: Blood lipid profiles were not significantly affected by 8 weeks OLE supplementation in overweight/obese subjects with mildly elevated cholesterol levels.

Trial Registered: The trial has been registered at ClinicalTrials.gov (NCT02990637).
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http://dx.doi.org/10.1007/s00394-020-02397-9DOI Listing
October 2020

Smart Data Collection for the Assessment of Treatment Effects in Irritable Bowel Syndrome: Observational Study.

Authors:
Zsa Zsa R M Weerts Koert G E Heinen Ad A M Masclee Amber B A Quanjel Bjorn Winkens Lisa Vork Paula E L M Rinkens Daisy M A E Jonkers Daniel Keszthelyi

JMIR Mhealth Uhealth 2020 11 2;8(11):e19696. Epub 2020 Nov 2.

Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, Netherlands.

Background: End-of-day symptom diaries are recommended by drug regulatory authorities to assess treatment response in patients with irritable bowel syndrome. We developed a smartphone app to measure treatment response.

Objective: Because the employment of an app to measure treatment response in irritable bowel syndrome is relatively new, we aimed to explore patients' adherence to diary use and characteristics associated with adherence.

Methods: A smartphone app was developed to serve as a symptom diary. Patients with irritable bowel syndrome (based on Rome IV criteria) were instructed to fill out end-of-day diary questionnaires during an 8-week treatment. Additional online questionnaires assessed demographics, irritable bowel syndrome symptom severity, and psychosocial comorbidities. Adherence rate to the diary was defined as the percentage of days completed out of total days. Adherence to the additional web-based questionnaires was also assessed.

Results: Overall, 189 patients were included (age: mean 34.0 years, SD 13.3 years; female: 147/189, 77.8%; male: 42/189, 22.2%). The mean adherence rate was 87.9% (SD 9.4%). However, adherence to the diary decreased over time (P<.001). No significant association was found between adherence and gender (P=.84), age (P=.22), or education level (lower education level: P=.58, middle education level: P=.46, versus high education level), while higher anxiety scores were associated with lower adherence (P=.03). Adherence to the online questionnaires was also high (>99%). Missing data due to technical issues were limited.

Conclusions: The use of a smartphone app as a symptom diary to assess treatment response resulted in high patient adherence. The data-collection framework described led to standardized data collection with excellent completeness and can be used for future randomized controlled trials. Due to the slight decrease in adherence to diary use throughout the study, this method might be less suitable for longer trials.
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http://dx.doi.org/10.2196/19696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669448PMC
November 2020

Economic evaluation of prevention of cystoid macular edema after cataract surgery in nondiabetic patients: ESCRS PREMED study report 4.

Authors:
Rob W P Simons Laura H P Wielders Carmen D Dirksen Claudette A Veldhuizen Frank J H M van den Biggelaar Bjorn Winkens Jan S A G Schouten Rudy M M A Nuijts

J Cataract Refract Surg 2020 Sep 24. Epub 2020 Sep 24.

From the University Eye Clinic Maastricht, Maastricht University Medical Center+ (Simons, Wielders, Veldhuizen, van den Biggelaar, Schouten, Nuijts), Maastricht, The Netherlands, Department of Ophthalmology, Zuyderland Medical Center Heerlen (Simons, Wielders, Schouten, Nuijts), Sittard-Geleen, The Netherlands, Department of Clinical Epidemiology and Medical Technology Assessment, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center+ (Dirksen), Maastricht, The Netherlands, Department of Methodology and Statistics, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Center+ (Winkens), The Netherlands, Department of Ophthalmology, Canisius Wilhelmina Hospital (Schouten), Nijmegen, The Netherlands.

Purpose: To investigate the cost-effectiveness of prophylactic treatments against cystoid macula edema (CME) after cataract surgery in nondiabetic patients.

Setting: Seven ophthalmology clinics in the Netherlands and Belgium.

Design: Prospective cost-effectiveness analysis using data from a European multicenter randomized clinical trial (ESCRS PREMED).

Methods: Nondiabetic patients planned for expected uncomplicated cataract surgery were randomized to topical bromfenac (Yellox, n=242), topical dexamethasone (n=242), or a combination treatment (n=238). All relevant resources from a healthcare perspective were included in the cost analysis within a time horizon of 12 weeks postoperatively. The main effectiveness outcome was quality-adjusted life years (QALYs). The main cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) based on the cost per QALY.

Results: The study comprised 722 nondiabetic patients. Total healthcare costs and QALYs were &OV0556; 447 (US$ 562) and 0.174 in the bromfenac group, &OV0556; 421 (US$ 529) and 0.179 in the dexamethasone group, and &OV0556; 442 (US$ 555) and 0.182 in the combination group. Bromfenac was most costly and least effective (ie, strongly dominated). The ICER was &OV0556; 6544 (US$ 8221) per QALY for the combination group compared to the dexamethasone group. Assuming the willingness-to-pay is &OV0556; 20,000 (US$ 25,126) per QALY, the cost-effectiveness probability was 3%, 32%, and 65% in the bromfenac, dexamethasone, and combination groups, respectively.

Conclusions: In nondiabetic patients, combination treatment with topical bromfenac and dexamethasone was effective and cost-effective in preventing CME after cataract surgery, compared to treatment with either drug alone.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000449DOI Listing
September 2020

The (cost-)effectiveness and cost-utility of a novel integrative care initiative for patients with chronic musculoskeletal pain: the pragmatic trial protocol of Network Pain Rehabilitation Limburg.

Authors:
Cynthia Lamper Ivan P J Huijnen Mariëlle E J B Goossens Bjorn Winkens Dirk Ruwaard Jeanine A M C F Verbunt Mariëlle E Kroese

Health Qual Life Outcomes 2020 Oct 1;18(1):320. Epub 2020 Oct 1.

Department of Health Services Research, School for Public Health and Primary Care (CAPHRI), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.

Background: Rehabilitation care for patients with chronic musculoskeletal pain (CMP) is not optimally organized. The Network Pain Rehabilitation Limburg 2.0 (NPRL2.0) provides integrated care with a biopsychosocial approach and strives to improve the Quadruple Aim outcomes: pain-related disability of patients with CMP; experiences of care of patients with CMP; meaning in the work of healthcare professionals; and healthcare costs. Firstly, in this study, the effectiveness (with regard to the functioning and participation of patients) of primary care for patients with CMP will be assessed, comparing care organized following the NPRL2.0 procedure with usual care. Secondly, the cost-effectiveness and cost-utility with regard to health-related quality of life and healthcare costs will be assessed. And thirdly, the effect of duration of participation in a local network in primary care will be studied.

Methods: In this pragmatic study, it is expected that two local networks with 105 patients will participate in the prospective cohort study and six local networks with 184 patients in the stepped-wedge based design. Healthcare professionals in the local networks will recruit patients.

Inclusion Criteria: age ≥ 18 years; having CMP; willing to improve functioning despite pain; and adequate Dutch literacy.

Exclusion Criteria: pregnancy; and having a treatable medical or psychiatric disease. Patients will complete questionnaires at baseline (T1), 3 months (T2), 6 months (T3), and 9 months (T4). Questionnaires at T1 and T4 will include the Pain Disability Index and Short Form Health Survey. Questionnaires at T1, T2, T3, and T4 will include the EQ-5D-5L, and iMTA Medical Consumption and Productivity Cost Questionnaires. Outcomes will be compared using linear mixed-model analysis and costs will be compared using bootstrapping methods.

Discussion: NPRL2.0 is a multidimensional, complex intervention, executed in daily practice, and therefore needing a pragmatic study design. The current study will assess NPRL2.0 with respect to the Quadruple Aim outcomes: patient health and costs. This will provide more information on the (cost-) effectiveness of the organization of care in a network structure regarding patients with CMP. The other two Quadruple Aim outcomes will be examined alongside this study. Trial registration Netherlands Trial Register: NL7643. https://www.trialregister.nl/trial/7643 .
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http://dx.doi.org/10.1186/s12955-020-01569-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528600PMC
October 2020

The Short-Term Value of the "Healthy Primary School of the Future" Initiative: A Social Return on Investment Analysis.

Authors:
Marije Oosterhoff Onno C P van Schayck Nina H M Bartelink Hans Bosma Maartje Willeboordse Bjorn Winkens Manuela A Joore

Front Public Health 2020 21;8:401. Epub 2020 Aug 21.

Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands.

This study examines the social return on investment (SROI) of the "Healthy Primary School of the Future" initiative after 2 years. Healthy Primary Schools of the Future (HPSF) provide a healthy lunch and daily structured physical activity sessions, whereas Physical Activity Schools (PAS) focus on physical activity only. We evaluated the 2-years investments and effects ( = 1,676 children) of both school environments (four schools) compared to control schools (four schools). Investments and outcomes were grouped within the healthcare, education, household & leisure, and labor & social security sector. Outcomes that could be expressed in monetary terms were used for the calculation of social return on investment. HPSF and PAS created outcomes for the healthcare sector by favorable changes in health behaviors, body mass index [both significant], and medical resource use [not significant]. Outcomes for the education sector included a favorable impact on perceived social behaviors and school satisfaction, and absenteeism from school [latter not significant], and more engagement with the community was experienced. The per child investments, €859 (HPSF) and €1017 (PAS), generated a benefit of €8 (HPSF) and €49 (PAS) due to reduced school absenteeism and medical resource use. Within 2 years of intervention implementation, the HPSF initiative created outcomes in several sectors, but the benefits did not outweigh the investments. Follow-up assessments as well as modeling long-term outcomes are needed to assess the total value of the interventions. Until then, the SROI framework can inform strategies for obtaining stakeholder support and intervention implementation. The study was registered in the ClinicalTrials.gov database on 14 June 2016 (NCT02800616).
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http://dx.doi.org/10.3389/fpubh.2020.00401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472552PMC
August 2020

Circulating miR-216a as a biomarker of metabolic alterations and obesity in women.

Authors:
Indira G C Vonhögen Zenab Mohseni Bjorn Winkens Ke Xiao Thomas Thum Martina Calore Paula A da Costa Martins Leon J de Windt Marc E A Spaanderman Chahinda Ghossein-Doha

Noncoding RNA Res 2020 Sep 22;5(3):144-152. Epub 2020 Aug 22.

Department of Obstetrics and Gynecology, School for Oncology & Developmental Biology (GROW), Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Centre (MUMC+), the Netherlands.

Obesity leads to an amplified risk of disease and contributes to the occurrence of type 2 diabetes, fatty liver disease, coronary heart disease, stroke, chronic kidney disease and various types of cancer. MicroRNAs (miRNAs), small non-coding RNA molecules of 20-25 nucleotides, can remain stable in plasma and have been studied as potential (predictive) biomarkers for obesity and related metabolic disorders. The aim of this study was to identify circulating miRNAs as biomarkers for obesity status and metabolic alterations in women. Circulating miR-216a and miR-155-5p were selected by miRNA expression profiling and validated by real time quantitative PCR in a validation cohort of 60 obese women and 60 normal weight-age-matched control women. This was supplemented by correlation analysis of the candidate miRNA and anthropometric variables, blood biochemistry and lipid profile markers. Circulating miR-216a was validated as a biomarker of obesity status with significantly reduced levels in obese women. Interestingly, this was associated with a negative correlation between the plasma miR-216a content and body mass index (BMI), waist circumference, mean arterial pressure (MAP), triglycerides, ratio of total cholesterol/high density lipoprotein (HDL)-cholesterol and high sensitivity-C reactive protein (hs-CRP).Taken together, we provide evidence for an abnormally expressed circulating miRNA, miR-216a, with additive value as a predictive marker for obesity that correlates with metabolic alterations presented by lipid profile and inflammatory markers.
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http://dx.doi.org/10.1016/j.ncrna.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479169PMC
September 2020

Opportunistic screening versus usual care for detection of atrial fibrillation in primary care: cluster randomised controlled trial.

Authors:
Steven B Uittenbogaart Nicole Verbiest-van Gurp Wim A M Lucassen Bjorn Winkens Mark Nielen Petra M G Erkens J André Knottnerus Henk C P M van Weert Henri E J H Stoffers

BMJ 2020 09 16;370:m3208. Epub 2020 Sep 16.

Department of Family Medicine, Care and Public Health Research Institute, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Netherlands.

Objective: To investigate whether opportunistic screening in primary care increases the detection of atrial fibrillation compared with usual care.

Design: Cluster randomised controlled trial.

Setting: 47 intention-to-screen and 49 usual care primary care practices in the Netherlands, not blinded for allocation; the study was carried out from September 2015 to August 2018.

Participants: In each practice, a fixed sample of 200 eligible patients, aged 65 or older, with no known history of atrial fibrillation in the electronic medical record system, were randomly selected. In the intention-to-screen group, 9218 patients eligible for screening were included, 55.0% women, mean age 75.2 years. In the usual care group, 9526 patients were eligible for screening, 54.3% women, mean age 75.0 years.

Interventions: Opportunistic screening (that is, screening in patients visiting their general practice) consisted of three index tests: pulse palpation, electronic blood pressure measurement with an atrial fibrillation algorithm, and electrocardiography (ECG) with a handheld single lead electrocardiographic device. The reference standard was 12 lead ECG, performed in patients with at least one positive index test and in a sample of patients (10%) with three negative tests. If 12 lead ECG showed no atrial fibrillation, patients were invited for more screening by continuous monitoring with a Holter electrocardiograph for two weeks.

Main Outcome Measures: Difference in the detection rate of newly diagnosed atrial fibrillation over one year in intention-to-screen versus usual care practices.

Results: Follow-up was complete for 8874 patients in the intention-to-screen practices and for 9102 patients in the usual care practices. 144 (1.62%) new diagnoses of atrial fibrillation in the intention-to-screen group versus 139 (1.53%) in the usual care group were found (adjusted odds ratio 1.06 (95% confidence interval 0.84 to 1.35)). Of 9218 eligible patients in the intention-to-screen group, 4106 (44.5%) participated in the screening protocol. In these patients, 12 lead ECG detected newly diagnosed atrial fibrillation in 26 patients (0.63%). In the 266 patients who continued with Holter monitoring, four more diagnoses of atrial fibrillation were found.

Conclusions: Opportunistic screening for atrial fibrillation in primary care patients, aged 65 and over, did not increase the detection rate of atrial fibrillation, which implies that opportunistic screening for atrial fibrillation is not useful in this setting.

Trial Registration: Netherlands Trial Register No NL4776 (old NTR4914).
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http://dx.doi.org/10.1136/bmj.m3208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492823PMC
September 2020

Early ICU-mortality in sepsis - causes, influencing factors and variability in clinical judgement: a retrospective cohort study.

Authors:
Rob G H Driessen Nanon F L Heijnen Riquette P M G Hulsewe Johanna W M Holtkamp Bjorn Winkens Marcel C G van de Poll Iwan C C van der Horst Dennis C J J Bergmans Ronny M Schnabel

Infect Dis (Lond) 2021 Jan 15;53(1):61-68. Epub 2020 Sep 15.

Department of Intensive Care Medicine, Maastricht University Medical Center +, Maastricht, The Netherlands.

Background: Sepsis is a global health care problem with a high mortality. Early death seems common; however, data are sparse. The objective of the present study was to report causes and influencing factors of early death in sepsis and septic shock.

Methods: All septic ICU patients were included from 2012 to 2017. Early death was predefined as occurring within 48 h. Causes and factors leading up to death were reported by a panel of four intensivists, independently reviewing the medical files. Following factors were assessed: (1) delay in ICU admission; (2) futile ICU treatment; (3) missed diagnosis or inadequate treatment on the ICU. Fleiss kappa was used to assess inter-observer agreement.

Results: 1107 septic patients (APACHE II score 25 ± 8) were included. 344 patients died of which 97 (28%) within 48 h. In 33% an autopsy was performed. Primary causes of early death were multiple organ failure, mesenteric ischaemia and death after cardio-pulmonary resuscitation (CPR). Delay in ICU admission was scored in 32% of early deaths with slight agreement (κ = 0.180), futile ICU treatment in 29% with moderate agreement (κ = 0.415) and missed diagnosis or treatment in 7% of cases with slight agreement (κ = 0.122).

Conclusions: Early death after ICU admission in sepsis is common and primarily caused by multiple organ failure, mesenteric ischaemia and death after unsuccessful CPR. Influencing factors were delay in ICU admission and futile ICU admission. Fleiss kappa indicates substantial variability in clinical judgement between intensivists, strengthening the necessity for shared decision making.
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http://dx.doi.org/10.1080/23744235.2020.1821912DOI Listing
January 2021

Obstructive sleep apnea in obese adolescents referred for bariatric surgery: association with metabolic and cardiovascular variables.

Authors:
Ali Talib Yvonne G M Roebroek Dick A van Waardenburg Chris P M van der Grinten Bjorn Winkens Nicole D Bouvy Ernst L W E van Heurn

Sleep Med 2020 11 6;75:246-250. Epub 2020 Mar 6.

Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands; NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands; Department of Pediatric Surgery, Amsterdam University Medical Centers, Amsterdam, The Netherlands. Electronic address:

Background: obstructive sleep apnea syndrome (OSA) is a well-described disease entity in adults, with a higher prevalence in severely obese individuals, while at the same time associated with several comorbidities independently of BMI. Literature regarding OSA in severely obese adolescents is qualitatively and quantitatively limited, possibly resulting in suboptimal diagnosis and treatment.

Methods: polysomnographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in 56 adolescents with morbid obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with no/mild (apnea-hypopnea index (AHI) 0-4.9) and moderate/severe OSA (AHI ≥ 5.0) were evaluated using independent-samples t, chi-square or Fisher's exact tests. Multivariable linear regression analysis was performed to evaluate the association of several variables with AHI, corrected for BMI z-score.

Results: of the 53 included subjects, 48 (90.6%) showed some degree of sleep disordered breathing and 20 (37.7%) had moderate/severe OSA. Patients with moderate/severe OSA had on average a higher neck circumference (42.4 versus 40.1 cm, p = 0.008), higher BMI z-score (3.7 versus 3.4, p = 0.003), higher plasma triglyceride level (2.2 versus 1.5 mmol/L, p = 0.012), and lower IGF (29.6 versus 40.2 mmol/L, p = 0.010) than those with no/mild OSA. BMI z-score and plasma triglyceride levels were independently related to AHI.

Conclusions: OSA is highly prevalent amongst morbidly obese adolescents and is strongly associated with BMI z-score. Elevated plasma triglyceride levels are associated with AHI, independent of BMI z-score.
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http://dx.doi.org/10.1016/j.sleep.2020.02.026DOI Listing
November 2020

Effect of a high protein/low glycaemic index diet on insulin resistance in adolescents with overweight/obesity-A PREVIEW randomized clinical trial.

Authors:
Elke Dorenbos Mathijs Drummen Tanja Adam Jesse Rijks Bjorn Winkens J Alfredo Martínez Santiago Navas-Carretero Gareth Stratton Nils Swindell Pauline Stouthart Kelly Mackintosh Melitta Mcnarry Angelo Tremblay Mikael Fogelholm Anne Raben Margriet Westerterp-Plantenga Anita Vreugdenhil

Pediatr Obes 2021 Jan 17;16(1):e12702. Epub 2020 Jul 17.

NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.

Background: Pubertal insulin resistance (IR) is associated with increased risk of type 2 diabetes mellitus development in adolescents with overweight/obesity.

Objectives: The PREVIEW study was a randomized parallel trial assessing the change in IR, analyzed by Homeostatic Model Assessment of IR (HOMA-IR), at 2 years after randomization to a high protein vs a moderate protein diet in adolescents with overweight/obesity. It was hypothesized that a high protein/low glycaemic index diet would be superior in reducing IR compared to a medium protein/medium GI diet, in insulin resistant adolescents with overweight or obesity.

Methods: Adolescents with overweight/obesity and IR from the Netherlands, United Kingdom and Spain were randomized into a moderate protein/moderate GI (15/55/30En% protein/carbohydrate/fat, GI ≥ 56) or high protein/low GI (25/45/30En% protein/carbohydrate/fat, GI < 50) diet. Anthropometric and cardiometabolic parameters, puberty, dietary intake and physical activity (PA) were measured and effects on HOMA-IR were analyzed.

Results: 126 adolescents were included in this study (13.6 ± 2.2 years, BMI z-score 3.04 ± 0.66, HOMA-IR 3.48 ± 2.28, HP n = 68, MP n = 58). At 2 years, changes in protein intake were not significantly different between timepoints or intervention groups and no effects of the intervention on IR were observed. The retention rate was 39%, while no compliance to the diets was observed.

Conclusions: The PREVIEW study observed no effect of a high protein/low GI diet on IR in adolescents with overweight/obesity and IR because of lack of feasibility, due to insufficient retention and dietary compliance after 2 years.
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http://dx.doi.org/10.1111/ijpo.12702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757177PMC
January 2021

Patients with Head-and-Neck Cancer: Dysphagia and Affective Symptoms.

Authors:
Iris Krebbers Sorina R Simon Walmari Pilz Bernd Kremer Bjorn Winkens Laura W J Baijens

Folia Phoniatr Logop 2020 Jul 3:1-8. Epub 2020 Jul 3.

Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.

Objective: Affective symptoms are common in patients with head-and-neck cancer. This study determined the association between the presence of aspiration and symptoms of anxiety and depression, as well as patient characteristics in patients with head-and-neck cancer and dysphagia.

Methods: Eighty-four patients with head-and-neck cancer and dysphagia completed the Hospital Anxiety and Depression Scale and underwent a standardized fiberoptic endoscopic evaluation of swallowing. Linear regression analysis was performed to explore the associations.

Results: Fifty-two (61.9%) patients presented clinically relevant symptoms of anxiety or depression. Forty-eight (57.1%) patients presented with aspiration during fiberoptic endoscopic evaluation of swallowing. A significant negative association was found between the presence of aspiration and affective (anxiety and depression) symptoms (p = 0.04). Male patients presented significantly lower symptom scores of anxiety compared to females (p = 0.04).

Conclusions: Clinically relevant affective symptoms were present in more than half of all patients with head-and-neck cancer and dysphagia. Surprisingly, a significant negative association was found between the presence of aspiration and these affective symptoms. Gender was also significantly associated with affective symptoms. These results suggest that there is a need for further investigation into the impact of psychological distress on patients with head-and-neck cancer and dysphagia.
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http://dx.doi.org/10.1159/000508367DOI Listing
July 2020