Publications by authors named "Hans Groenewoud"

62 Publications

Trends and projections in cutaneous melanoma death in the Netherlands from 1950 to 2045.

Medicine (Baltimore) 2021 Dec;100(48):e27784

Radboud Institute for Health Sciences, Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract: Child sun protection has recently been linked to the future disappearance of fatal melanoma in adults in successive generations. In the Netherlands, however, mortality rates from melanoma have increased gradually from the 1950s, with some indication of stabilisation since 2010, which may be compatible with a birth cohort effect by sun-protective measures and screening. To study the trajectories ahead a trend analysis was applied. Numbers of people with cutaneous melanoma as underlying cause of death from 1950 to 2018 and population data were derived from Statistics Netherlands. A graphical approach was used to explore trends in mortality by age, calendar period, and cohorts born in the successive periods of 1889 to 1979. Age-period-cohort modelling outcomes and population forecasts provided projections of mortality until 2045. Based on 24,151 cases of melanoma death (13,256 men, 10,895 women), age-standardised mortality rates were similar from 1950 to 1989 for both genders, and increased thereafter more in men. The age-curve patterns changed gradually towards higher death rates at older age, implying the existence of a birth cohort effect. The age-period-cohort models showed an increase in melanoma mortality rates in successive generations. For women, the birth cohort effect plateaued for generations born since the mid-1980s. The projected total mortality number was predicted to rise in the next 3 decades.It is concluded that a small future decline of mortality in younger generations can be expected in the Netherlands, but mortality is still rising for the total population.
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http://dx.doi.org/10.1097/MD.0000000000027784DOI Listing
December 2021

Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources.

Lancet Reg Health Eur 2022 Feb 22;13:100266. Epub 2021 Nov 22.

Department of Internal Medicine and Radboudumc Center for Infectious diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.

Background: Biologics directed against the T-helper (Th)-17 pathway have been approved for several inflammatory diseases. Interleukin (IL)-17 is involved in anti- host defense, and clinical trials suggested increased candidiasis incidence during IL-17 inhibitor therapy. We describe the worldwide epidemiology of candidiasis during Th17 inhibitor therapy, and immunological mechanisms involved in candidiasis susceptibility.

Methods: A comprehensive analysis of multiple independent sources reporting adverse events during biologics inhibiting the Th17 pathway was performed. Association between Th17 inhibitors and candidiasis was assessed using safety reports of (1) WHO and (2) EMA, (3) a population-based prescriptions registry, and (4) a psoriasis cohort. In a cohort of psoriasis patients experiencing candidiasis during Th17 inhibitors, killing by immune cells and serum inflammatory proteome were analyzed.

Findings: A strong association between IL-17 inhibitors and candidiasis (ROR 10·20) was found in the WHO database, particularly for cutaneous (ROR 12·28), oropharyngeal (ROR 19·18), and esophageal candidiasis (ROR 21·20). Risk was higher relative to TNF-α inhibitors (4-10-fold, depending on candidiasis type), confirmed by EMA reports (16-33-fold), prescriptions registry (2-42-fold), and a psoriasis cohort (3-25-fold). After start of IL-17 inhibitors, patients' risk of candidiasis requiring antifungals increased 2-16 fold. In the psoriasis cohort, 58% of IL-17 treatment episodes were associated with candidiasis. In Th17 inhibitor recipients, proteins involved in anti- immunity and killing by mononuclear leukocytes were impaired.

Interpretation: IL-17 inhibitors are associated with an increased risk of oropharyngeal, esophageal, and cutaneous candidiasis, posing a significant disease burden for IL-17 inhibitor recipients.

Funding: RadboudUMC.
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http://dx.doi.org/10.1016/j.lanepe.2021.100266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671639PMC
February 2022

Hearing-Related Quality of Life in 75 Patients with a Percutaneous Bone Conduction Device.

Otol Neurotol 2021 Dec 9. Epub 2021 Dec 9.

Department of Otorhinolaryngology, Donders Center for Neurosciences, Radboud University Medical Center, Nijmegen Department of Otorhinolaryngology, St. Antonius Hospital, Nieuwegein Department of Health Evidence, Radboud University Medical Center, Nijmegen Department of Otorhinolaryngology/Head and Neck Surgery, University Medical Center Groningen, University of Groningen, Groningen Research School of Behavioral and Cognitive Neurosciences, Graduate School of Medical Sciences, University of Groningen, Groningen, The Netherlands.

Objective: To evaluate long-term hearing-related quality of life (HRQoL) and device use in bone conduction (BCD) users. Furthermore, to assess differences between indications and changes in HRQoL over time.

Study Design: Prospective questionnaire survey.

Setting: Tertiary referral center.

Patients: Seventy-five patients with a percutaneous BCD.

Main Outcome Measures: Glasgow Benefit Inventory (GBI) at 3 and 12 months postoperatively, Glasgow Health Status Inventory (GHSI) preoperatively, and 6 and 36 months postoperatively, device use at 6, 12, and 36 months. Changes over time were assessed and outcomes were compared between indications.

Results: After implantation, 97% of all patients reported a positive benefit on the GBI total. The GHSI total had improved with median 15 points (Interquartile range [IQR] 12). At 36 months, median device use was 15 hours/day (IQR 10) and one nonuser was reported. Patients with bilateral hearing loss (BHL) showed greater improvement on the GHSI total (median 18 vs 14, p < 0.0001) and used their devices more frequently (median 16 vs 8 h/day, p < 0.0001) than patients with unilateral HL (UHL). Postoperative GHSI and GBI scores were consistent over time, in the entire patient population and for every indication. Between 6 and 36 months, device use was stable over time, except for patients with single-sided deafness (SSD; median -6.4 h/day, p = 0.009).

Conclusion: The BCD improves HRQoL in patients with BHL, in patients with unilateral conductive/mixed hearing loss and in patients with SSD. Patients with BHL experienced a greater improvement in hearing status compared to patients with UHL. Although use decreased over time in SSD patients, device use was high for every indication.
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http://dx.doi.org/10.1097/MAO.0000000000003442DOI Listing
December 2021

Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER): Protocol for a Longitudinal Observational Study.

JMIR Res Protoc 2021 Nov 16;10(11):e31647. Epub 2021 Nov 16.

Department of Dermatology, Radboud University Medical Center, Nijmegen, Netherlands.

Background: One in three patients with psoriasis will develop psoriatic arthritis (PsA). If left untreated, this can lead to pain, impaired function, and irreversible joint damage. Timely recognition and referral to a rheumatologist are therefore key. However, current methods used to screen patients with psoriasis for those who might benefit from referral to a rheumatologist are not performing well enough.

Objective: The Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) study is designed to determine the prevalence of PsA in a psoriasis population and to find parameters that can be used to develop a new or enhance an existing instrument for a rheumatological referral.

Methods: DAPPER is a longitudinal observational study with a 1-year follow-up. Patients with psoriasis (N=300) who are treated at an outpatient dermatological clinic will be screened extensively for signs and symptoms of PsA by a trained rheumatologist. If there is clinical suspicion of PsA and the patient is not yet treated by a rheumatologist, referral to the Department of Rheumatology will follow for confirmation of the diagnosis and further care. After 1 year, data on changes in quality of life and PsA and psoriasis disease activity will be collected from the referred patients. The screening visit will be used to gather demographical and medical data, which can later be used to develop the aforementioned screening instrument.

Results: Inclusion started in June 2019 and finished in June 2021. Follow-up with newly discovered patients with PsA is ongoing.

Conclusions: The DAPPER study is specifically designed to improve the detection of existing PsA in a dermatologic outpatient setting. Although internal validity will be tested, external validity will have to be checked using a second validation cohort. To predict the development of PsA in the future, longitudinal/prospective data collection is required and will be performed in a follow-up study (DAPPER-i).

Trial Registration: Dutch Trial Register NTR7604; https://www.trialregister.nl/trial/7397.

International Registered Report Identifier (irrid): DERR1-10.2196/31647.
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http://dx.doi.org/10.2196/31647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663491PMC
November 2021

N-of-1 Trials in Neurology: A Systematic Review.

Neurology 2021 Oct 21. Epub 2021 Oct 21.

Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands.

ObjectiveTo perform a systematic review of published N-of-1 trials (e.g. single patient cross-over trials) in neurological disorders, including an assessment of methodological quality and reporting.MethodsWe searched PubMed, MEDLINE and Embase, from inception date - the first of December 2019, for reports on N-of-1 trials in neurological disorders. Basic trial information on design, disease, intervention, analysis and treatment success was extracted. Strengths and weaknesses of the N-of-1 trials were assessed using the CONSORT extension for N-of-1 trials (CENT) 2015 criteria checklist and the Jadad score as measures of quality and reporting.ResultsWe retrieved 40 reports of N-of-1 trials in neurological disorders (19 individual N-of-1 trials, 21 series of N-of-1 trials). Most N-of-1 trials were performed in neuromuscular and neurodegenerative / movement disorders. Unlike the majority of trials that studied the main symptom(s) of a chronic stable condition, nine N-of-1 trials studied a stable chronic symptom of a progressive or acute neurological disorder. Besides pharmacological interventions, electrical stimulation protocols and nutritional products were studied. A mean total CENT score of 20.88 (SD, 9.10; range 0-43) and mean total Jadad score of 2.90 (SD, 2.15; range 0-5) were found as methodological measures of quality and reporting across all N-of-1 trialsConclusionsN-of-1 trials have been reported in numerous neurological disorders, not only in chronic stable disorders, but also in progressive or acute disorders with a stable symptom. This indicates the emerging therapeutic area of N-of-1 trials in Neurology.Methodological quality and reporting of N-of-1 trials were found suboptimal and can easily be improved in future trials by appropriately describing the methods of blinding and randomization and follow CENT guidelines. As most N-of-1 trials remain unreported in medical literature, this systematic review probably only represent the tip of the iceberg of conducted N-of-1 trials in neurological disorders. In addition to conventional trial designs, N-of-1 trials can help to bridge the gap between research and clinical care by providing an alternative, personalized level 1 evidence-base for suitable treatments.
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http://dx.doi.org/10.1212/WNL.0000000000012998DOI Listing
October 2021

Treatment goals and preferences of pediatric psoriasis patients, young adults, and parents.

J Dermatolog Treat 2021 Oct 8:1-7. Epub 2021 Oct 8.

Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Treatment needs of young psoriasis patients and parents are not widely studied and could advance patient-centered care.

Objective: To explore treatment goals and preferences of pediatric psoriasis patients, young adults, and parents.

Methods: A web-based survey among Dutch psoriasis patients aged ≥6 to ≤30 years and parents included multiple-choice, open-ended, and 4-point Likert scale questions. Treatment goals and characteristic preferences of pediatric patients (≤17 years) were compared to young adults (≥18 years) and parents.

Results: 195 young patients (20.2 ± 6.3 years) and 45 parents were included. The most important treatment goals were 'preventing lesions', 'reducing lesions', 'no itch', and 'no lesions'. Regarding treatment characteristics, 'long-term safety', 'high effectiveness', and 'short-term safety' were most important. We found differences by age, gender, and current treatment. Pediatric patients rated 'not sticky', 'quick results', and 'no/few blood samples needed' higher than parents and/or young adults. Young adults rated 'feeling more confident' and 'better quality of sleep' higher than pediatric patients. Parents considered safety most important. Psychosocial goals were more important for women and patients on biologics.

Conclusion: Young psoriasis patients and parents mainly strive to clear lesions and itch with effective and safe treatment. However, revealed differences underline the relevance of addressing individual needs.
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http://dx.doi.org/10.1080/09546634.2021.1985058DOI Listing
October 2021

Perfusion measured by laser speckle contrast imaging as a predictor for expansion of psoriasis lesions.

Skin Res Technol 2021 Oct 7. Epub 2021 Oct 7.

Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Skin microvasculature changes are crucial in psoriasis development and correlate with perfusion. The noninvasive Handheld Perfusion Imager (HAPI) examines microvascular skin perfusion in large body areas using laser speckle contrast imaging (LSCI).

Objectives: To (i) assess whether increased perilesional perfusion and perfusion inhomogeneity are predictors for expansion of psoriasis lesions and (ii) assess feasibility of the HAPI system in a mounted modality.

Methods: In this interventional pilot study in adults with unstable plaque psoriasis, HAPI measurements and color photographs were performed for lesions present on one body region at week 0, 2, 4, 6 and 8. The presence of increased perilesional perfusion and perfusion inhomogeneity was determined. Clinical outcome was categorized as increased, stable or decreased lesion surface between visits. Patient feedback was collected on a 10-point scale.

Results: In total, 110 lesions with a median follow-up of 6 (IQR 6.0) weeks were assessed in 6 patients with unstable plaque psoriasis. Perfusion data was matched to 281 clinical outcomes after two weeks. A mixed multinomial logistic regression model revealed a predictive value of perilesional increased perfusion (OR 9.90; p < 0.001) and perfusion inhomogeneity (OR 2.39; p = 0.027) on lesion expansion after two weeks compared to lesion stability. HAPI measurements were considered fast, patient-friendly and important by patients.

Conclusion: Visualization of increased perilesional perfusion and perfusion inhomogeneity by noninvasive whole field LSCI holds potential for prediction of psoriatic lesion expansion. Furthermore, the HAPI is a feasible and patient-friendly tool.
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http://dx.doi.org/10.1111/srt.13098DOI Listing
October 2021

Trends and projections in the incidence of oesophageal cancer in the Netherlands: An age-period-cohort analysis from 1989 to 2041.

Int J Cancer 2022 Feb 16;150(3):420-430. Epub 2021 Oct 16.

Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.

In Western populations, the incidence of oesophageal squamous cell carcinoma (OSCC) has been declining, whereas the incidence of oesophageal adenocarcinoma (OAC) has been increasing. Our study examines temporal trends in the incidence of oesophageal cancer in the Netherlands between 1989 and 2016, in addition to predicting future trends through 2041. Data from the Netherlands Cancer Registry and Statistics Netherlands were collected to obtain incidence trends of OSCC and OAC for the period 1989 to 2016. Age-period-cohort (APC) modelling was used to estimate the contribution of age, calendar period and birth cohort on the observed incidence trends. To predict the future numbers of new cases of both OSCC and OAC from 2017 to 2041, log-linear APC models were fitted to the trends of 1989 to 2016. The age-standardised incidence rates of OSCC have decreased slightly for men and increased slightly for women. In contrast, a marked increase in the incidence of OAC was observed, ranging from 2.8 per 100 000 persons in 1989 to 10.1 in 2016. This increase in OAC incidence was more prominent in men, and it will result in an increased risk of OAC for successive generations. Future projections indicate that the incidence of OAC will further increase to 13.1 per 100 000 persons in 2037 to 2041, meaning that there will be 13 259 cases of OAC in 2037 to 2041, as compared to 9386 diagnoses in 2017 to 2021. The changing epidemiologic trends in oesophageal cancer in the Netherlands should be reflected in the development of prevention, early detection and treatment strategies.
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http://dx.doi.org/10.1002/ijc.33836DOI Listing
February 2022

N-of-1 trial of salbutamol in hyperkalaemic periodic paralysis.

J Neurol Neurosurg Psychiatry 2021 12 10;92(12):1352-1353. Epub 2021 Jun 10.

Department for Health Evidence, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.

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http://dx.doi.org/10.1136/jnnp-2021-326347DOI Listing
December 2021

Translating Evidence to Advanced Parkinson's Disease Patients: A Systematic Review and Meta-Analysis.

Mov Disord 2021 06 2;36(6):1293-1307. Epub 2021 Apr 2.

Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, the Netherlands.

In the advanced stages of Parkinson's disease (PD), patients frequently experience disabling motor complications. Treatment options include deep brain stimulation (DBS), levodopa-carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusion (CSAI). Choosing among these treatments is influenced by scientific evidence, clinical expertise, and patient preferences. To foster patient engagement in decision-making among the options, scientific evidence should be adjusted to their information needs. We conducted a systematic review from the patient perspective. First, patients selected outcomes for a treatment choice: quality of life, activities of daily living, ON and OFF time, and adverse events. Second, we conducted a systematic review and meta-analysis for each treatment versus best medical treatment using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Finally, the evidence was transformed into comprehensible and comparable information. We converted the meta-analysis results into the number of patients (per 100) who benefit clinically from an advanced treatment per outcome, based on the minimal clinically important difference and the cumulative distribution function. Although this approach allows for a comparison of outcomes across the three device-aided therapies, they have never been compared directly. The interpretation is hindered by the relatively short follow-up time in the included studies, usually less than 12 months. These limitations should be clarified to patients during the decision-making process. This review can help patients integrate the evidence with their own preferences, and with their clinician's expertise, to reach an informed decision. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252410PMC
June 2021

The Additional Effect of Individualized Prescriber-Focused Feedback on General Guideline Instruction in Reducing Antipsychotic Polypharmacy in Inpatients.

J Clin Psychopharmacol 2021 Mar-Apr 01;41(2):129-134

Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands.

Purpose/background: Antipsychotic polypharmacy (APP) is the concurrent use of more than one antipsychotic by a patient. Multiple antipsychotics are often prescribed, although all relevant guidelines discourage this practice. These recommendations are based on a lack of evidence for effectiveness and an increased risk of serious adverse events with APP. Studies on the effects of educational interventions targeted at physicians have demonstrated inconclusive results. Moreover, it is unclear how individualized these interventions need to be. In this study, we aimed to assess the effect of a general intervention and the additional impact of an individualized, prescriber-focused intervention on guidelines adherence, that is, the prescription of APP.

Methods/procedures: We conducted a 36-month 2-step serial intervention study with 4 stages of 9 months each (baseline, general intervention, addition of an individualized intervention, and follow-up) including all 20 inpatient units of one regional mental health organization. The primary outcome was the proportion of patients with regular prescriptions for APP ≥30 consecutive days across all patients with a prescription of at least one antipsychotic. The secondary outcome was the proportion of patient days on APP over the total number of patient days on at least one antipsychotic.

Findings/results: The general intervention was ineffective on both outcome measures. Addition of an individualized intervention decreased the proportion of patients with prescriptions for episodes of persistent APP significantly by 49.6%. The proportion of patient days on APP significantly decreased by 35.4%.

Implications/conclusions: In contrast to a general intervention, the addition of an individualized intervention was effective in improving adherence to guidelines with respect to APP prescription in inpatients.
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http://dx.doi.org/10.1097/JCP.0000000000001355DOI Listing
October 2021

Health Economic Consequences of a Tightly Controlled Dose Reduction Strategy for Adalimumab, Etanercept and Ustekinumab Compared with Standard Psoriasis Care: A Cost-utility Analysis of the CONDOR Study.

Acta Derm Venereol 2020 Dec 1;100(19):adv00340. Epub 2020 Dec 1.

Department of Dermatology, Radboud university medical center, 6525 Nijmegen, The Netherlands. E-mail:

A dose reduction strategy for adalimumab, etanercept and ustekinumab in patients with psoriasis who have stable and low disease activity has recently been compared with usual care in the CONDOR study (CONtrolled DOse Reduction) of biologics in patients with psoriasis with low disease activity. The aim of the current study was to perform a cost-utility analysis with a 12-month time horizon alongside this trial, using prospectively measured healthcare costs and quality-adjusted life years, based on Short-Form Six-Dimension utilities. Bootstrap analys-es were used to calculate the decremental cost-utility ratio and the incremental net monetary benefit. The dose reduction strategy resulted in a mean cost saving of €3,820 (95th percentile -€3,099 to -€4,509) per patient over a period of 12 months. There was an 83% chance that dose reduction would result in a reduction in quality adjusted life years (mean -0.02 (95th percentile -0.06 to 0.02). In conclusion, dose reduction of biologics resulted in substantial cost savings with an acceptable reduction in quality of life.
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http://dx.doi.org/10.2340/00015555-3692DOI Listing
December 2020

The Skin May Clear But the Arthritis Won't Disappear: Focusing on Concomitant and New-Onset Psoriatic Arthritis in a Daily Practice Cohort of Psoriasis Patients on Biologic Therapy.

Psoriasis (Auckl) 2020 5;10:29-37. Epub 2020 Oct 5.

Department of Dermatology, Radboud University Medical Center (Radboudumc), Nijmegen, the Netherlands.

Background: Previously identified risk factors for psoriatic arthritis (PsA); nail dystrophy and scalp lesions are highly prevalent in patients with moderate-to-severe psoriasis. Therefore, these variables may not be useful as predictors for PsA in this population.

Objective: We assessed the predictive value of demographic and clinical characteristics for development of PsA in a cohort of patients with moderate-to-severe psoriasis, currently treated with biologics. Furthermore, we reported the incidence of new-onset PsA in this population and described the characteristics of patients that developed PsA during biologic treatment.

Methods: Demographics and treatment characteristics of psoriasis patients currently using biologic therapy were extracted from the BioCAPTURE database (n=427). Poisson regression was used to calculate incidence rates. Multivariable logistic regression was performed to identify factors independently associated with PsA onset. Patient and treatment characteristics of patients that developed PsA during biologic treatment were described.

Results: The incidence of PsA was 1.0 (95% CI 0.8-1.2) per 100 psoriasis-years. Except for a lower risk for PsA in male gender (OR 0.58, 95% CI 0.34-0.98, p-value 0.04), no clinical factors were significantly associated with an altered risk of developing PsA. During biologic therapy, 32 patients (9.4%) newly developed PsA. In this group, 53.8% had PASI<5 at PsA diagnosis. The incidence rate of PsA was 1.6 (95% CI 1.1-2.2) per 100 years on biologic therapy.

Conclusion: Clinical risk factors might be inaccurate to predict PsA onset in patients with moderate-to-severe psoriasis on biologics. Even with low disease activity, psoriasis patients on biologics are still prone to develop PsA.
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http://dx.doi.org/10.2147/PTT.S270619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547182PMC
October 2020

Reduced neurobehavioral functioning in agricultural workers and rural inhabitants exposed to pesticides in northern Chile and its association with blood biomarkers inhibition.

Environ Health 2020 07 22;19(1):84. Epub 2020 Jul 22.

Laboratorio de Neurotoxicología Ambiental, Facultad de Medicina, Universidad Católica del Norte, Larrondo 1281, 1780000, Coquimbo, Chile.

Background: Previous biomonitoring studies have shown that people in the rural population of Coquimbo, the major agricultural area in northern Chile are being occupationally and environmentally exposed to organophosphate/carbamate (OP/CB) pesticides. Given their harmful effects, this study had two aims; first, to evaluate the effect of cumulative or chronic exposure to OP/CB pesticides on the neurobehavioral performance of agricultural workers and rural inhabitants; second, to determine if changes in the neurobehavioral performance are associated to changes in blood biomarkers of OP/CB pesticides during the spray season, when exposure is higher.

Methods: For the first aim, a cross sectional study of neurobehavioral performance in adult volunteers (men and women, 18-50 years-old, right-handed) was carried out in the pre-spray season. Sampling was done by convenience and a questionnaire was used to categorize participants depending on their level of chronic exposure, as either: occupationally exposed (OE, n = 87), environmentally exposed (EE, n = 81), or non-exposed controls or reference group (RG, n = 100). A neurobehavioral test battery consisting of 21 tests to measure cognitive, motor and emotional state was applied. For the second aim, neurobehavioral measures were taken a second time from EE and OE groups during the spray season, and their exposure corroborated by blood-based biomarker inhibition.

Results: Lower neurobehavioral performance was observed in the pre-spray evaluation of EE and OE groups compared to the non-exposed, OE being the worst performing group. Seasonal exposure impaired performance in both exposure groups on all tests except those on attention and mood. Data modeling of the basal (pre-spray) measurements showed that the level of exposure was the best predictor of performance. During spraying, inhibition of BChE activity in the EE group was the best predictor of low performance in tests measuring logical, auditory and visual memory, inhibitory control of cognitive interference, constructional and planning abilities, executive functions, and motor speed and coordination.

Conclusion: Long-term occupational or environmental exposure to pesticides caused impairment in neurobehavioral functioning, which worsened during the spraying season, mainly in EE. BChE inhibition was the best predictor for seasonal neurobehavioral changes in EE.
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http://dx.doi.org/10.1186/s12940-020-00634-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374955PMC
July 2020

Disease and Treatment Characteristics in Geriatric Psoriasis: A Patient Survey Comparing Age Groups.

Acta Derm Venereol 2020 07 28;100(14):adv00215. Epub 2020 Jul 28.

Department of Dermatology, Radboudumc, 6500 HB Nijmegen, The Netherlands. E-mail:

Little is known about psoriasis in geriatric patients, whereas treating this growing population can be challenging due to comorbidities, comedication and physical impairments. To compare disease and treatment characteristics of psoriasis patients ≥ 65 years old with patients < 65 years old, a self-assessment survey was sent to all members of the Dutch Psoriasis Association (n = 3,310). In total, 985 (29.7%) patients returned the survey, 414 (43.6%) respondents were ≥ 65 years old. Patients ≥ 65 years old had experienced erythrodermic psoriasis significantly more frequently than patients < 65 years old, other disease characteristics were highly comparable. Despite a significantly higher prevalence of comorbidities and comedication use in patients ≥ 65 years old, no difference was seen between the age groups regarding systemic antipsoriatic treatment (38.3% in ≥ 65 years old vs 42.3% in < 65 years old; p = 0.219). Remarkably, treatment-related side-effects were reported more frequently by patients < 65 years old. In conclusion, age alone should not be a limiting factor in psoriasis management, and proper attention must be paid to additional patient-related factors.
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http://dx.doi.org/10.2340/00015555-3569DOI Listing
July 2020

Patients' and gynecologists' views on sentinel lymph node mapping in low- and intermediate-risk endometrial cancer: a Dutch vignette study.

Int J Gynecol Cancer 2020 06 7;30(6):813-818. Epub 2020 May 7.

Obstetrics and Gynecology, Radboudumc, Nijmegen, The Netherlands.

Objective: Sentinel lymph node (SLN) mapping in endometrial cancer is gaining ground. However, patient views on this new technique are unknown. The aim of this study was to determine factors important to patients and gynecologists when considering SLN mapping in low- and intermediate-risk endometrial cancer.

Methods: We performed a vignette study. Patients who underwent a total hysterectomy for low- or intermediate-risk endometrial cancer between 2012 and 2015 were invited. Dutch gynecologists specializing in gynecologic oncology were also invited. We based the selection for attributes in the vignettes on literature and interviews: risk of complications of SLN mapping; chance of finding a metastasis; survival gain; risk of complications after radiotherapy; operation time; and hospital of surgery (travel time). We developed a questionnaire with 18 hypothetical scenarios. Each attribute level varied and for each scenario, participants were asked how strongly they would prefer SLN on a scale from 1 to 7. The strength of preference for each scenario was analyzed using linear mixed effects models.

Results: A total of 38% of patients (41/108) and 33% of gynecologists (42/126) participated in the study. Overall, they had a preference for SLN. The mean preference for patients was 4.29 (95% CI 3.72 to 4.85) and 4.39 (95% CI 3.99 to 4.78) for gynecologists. Patients' preferences increased from 3.4 in the case of no survival gain to 4.9 in the case of 3-year survival gain (P<0.05) and it decreased when travel time increased to >60 min (-0.4, P=0.024), or with an increased risk of complications after adjuvant radiotherapy (-0.6, P=0.002). For gynecologists all attributes except travel time were important.

Conclusions: Overall, patients and gynecologists were in favor of SLN mapping in low- and intermediate-risk endometrial cancer. Most important to patients were survival gain, travel time, and complication risk after adjuvant radiotherapy. These preferences should be taken into account when counseling about SLN mapping.
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http://dx.doi.org/10.1136/ijgc-2019-001138DOI Listing
June 2020

Association between cholinesterase's inhibition and cognitive impairment: A basis for prevention policies of environmental pollution by organophosphate and carbamate pesticides in Chile.

Environ Res 2020 07 18;186:109539. Epub 2020 Apr 18.

Laboratory of Environmental Neurotoxicology, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile.

Background: In Chile organophosphate pesticides are widely used in the production of fruits. Pesticides use is regulated for professional practice but there is no regulation regarding exposure to the general population.

Objective: To relate exposure to cholinesterase's inhibitor pesticides during the spray season with neuropsychological impairment in occupationally exposed (OE) and environmentally exposed (EE) groups of people.

Methods: Exposure was assessed through inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity and neuropsychological outcomes were evaluated through a large battery of tests covering general mental status, language, memory, attention, executive function, praxis and psychomotricity. Evaluations were carried out firstly in a period of no/low organophosphate pesticide use and subsequently during the spray season. All parameters were calculated as the relative change from baseline to spray season.

Results: For this study in total 156 participants were recruited divided equally over participants with environmental exposures (EE) and participants with occupational exposure (OE). In the EE, BChE's enzyme activity inhibition ≥30% showed significant association with 10% or more decreased performance in several tests evaluating six of the eight cognitive areas (excepting psychomotricity and mood status); besides, for AChE inhibition in EE, the association was significant in three tests evaluating attention and one of executive function. Whereas, in OE, the inhibition of the BChE ≥30% was associated with a low performance of one attention test and for AChE the exceedance of the standard was associated with diminished performance in one test of memory and attention, respectively. The association between biomarkers of biological effect and cognitive impairment persisted among the EE group after removing confounders. No association was found between biomarkers of biological acute effect and decreased cognitive performance in the OE group.

Conclusions: Increased exposure to pesticides was confirmed by increased inhibition of cholinesterase's in both exposure groups; which was associated with a diminished neuropsychological performance, mainly in the environmentally exposed study group. [310 words].
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http://dx.doi.org/10.1016/j.envres.2020.109539DOI Listing
July 2020

Comparison of Tightly Controlled Dose Reduction of Biologics With Usual Care for Patients With Psoriasis: A Randomized Clinical Trial.

JAMA Dermatol 2020 04;156(4):393-400

Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands.

Importance: Biologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible.

Objective: To investigate whether dose reduction (DR) of biologics in patients with stable psoriasis is noninferior to usual care (UC).

Design, Setting, And Participants: This pragmatic, open-label, prospective, controlled, noninferiority randomized clinical trial was conducted from March 1, 2016, to July 22, 2018, at 6 dermatology departments in the Netherlands. A total of 120 patients with plaque psoriasis and stable low disease activity who were receiving treatment with adalimumab, etanercept, or ustekinumab were studied.

Interventions: Patients were randomized 1:1 to DR (n = 60) or UC (n = 60). In the DR group, injection intervals were prolonged stepwise, leading to 67% and 50% of the original dose.

Main Outcomes And Measures: The primary outcome was between-group difference in disease activity corrected for baseline at 12 months compared with the predefined noninferiority margin of 0.5. Secondary outcomes were Psoriasis Area and Severity Index (PASI) score and health-related quality of life (including Dermatology Life Quality Index [DLQI] and Medical Outcomes Study 36-Item Short Form Health Survey scores), proportion of patients with short and persistent flares (defined as PASI and/or DLQI scores >5 for ≥3 months), and proportion of patients with successful dose tapering.

Results: Of 120 patients (mean [SD] age, 54.0 [13.2] years; 82 [68%] male), 2 patients were lost to follow-up, 2 patients had a protocol violation, and 5 patients had a protocol deviation, leaving 111 patients for the per-protocol analysis (53 in the DR group and 58 in the UC group). The median PASI scores at month 12 were 3.4 (interquartile range [IQR], 2.2-4.5) in the DR group and 2.1 (IQR, 0.6-3.6) in the UC group (mean difference, 1.2; 95% CI, 0.7-1.8). This indicates that noninferiority was not demonstrated for DR compared to UC. The median DLQI score at month 12 was 1.0 (IQR, 0.0-2.0) in the DR group and 0.0 (IQR, 0.0-2.0) in the UC group (mean difference, 0.8; 95% CI, 0.3-1.3), indicating noninferiority for DR compared with UC. No significant difference was found regarding persistent flares between groups (n = 5 in both groups). Twenty-eight patients (53%; 95% CI, 39%-67%) in the DR group tapered their dose successfully at 12 months. No severe adverse events related to the intervention occurred.

Conclusions And Relevance: In this trial, noninferiority was not demonstrated for DR of adalimumab, etanercept, and ustekinumab based on the PASI in patients with psoriasis compared with UC with the chosen noninferiority margin. However, the strategy was noninferior based on the DLQI. Dose tapering did not lead to persistent flares or safety issues.

Trial Registration: ClinicalTrials.gov Identifier: NCT02602925.
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http://dx.doi.org/10.1001/jamadermatol.2019.4897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042801PMC
April 2020

Use of Catheter Lock Solutions in Patients Receiving Home Parenteral Nutrition: A Systematic Review and Individual-Patient Data Meta-Analysis.

JPEN J Parenter Enteral Nutr 2020 09 27;44(7):1198-1209. Epub 2020 Jan 27.

Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands.

Background: Use of catheter lock solutions (CLSs) as a strategy to prevent catheter-related bloodstream infections (CRBSIs) has been evaluated in recent clinical trials. Our aim was to identify the most effective CLS formulation in patients receiving home parenteral nutrition (HPN).

Methods: We conducted a systematic review and individual-patient data meta-analysis (IPDMA). Prospective randomized clinical trials in adult HPN patients using CLS were identified from PubMed, EMBASE, Web of Science, CINAHL, Cochrane library, and ClinicalTrials.gov. Primary outcome was the number of CRBSIs per 1000 catheter days for each CLS. Other outcomes included time to CRBSI and identification of patients with a higher risk for CRBSIs.

Results: In total, 1107 studies were screened for eligibility, of which three studies comprising 162 HPN patients and 45,695 catheter days were included in the IPDMA. CRBSI rates were significantly decreased in patients using taurolidine (rate 0.13; 95% confidence interval [CI], 0.05-0.32) when compared with saline (rate 0.74; 95% CI, 0.31-1.74; P = .002) or heparin (rate 2.01; 95% CI, 1.03-3.91; P < .001). The cumulative proportion of CRBSI-free patients using taurolidine, saline, and heparin after 1 year was 88%, 56%, and 14%, respectively. Three risk factors for CRBSIs were identified: type of CLS, intestinal dysmotility as underlying condition, and use of central venous catheters.

Conclusions: Taurolidine was the most effective CLS formulation in HPN patients for the prevention of CRBSIs. We suggest discussing with patients the benefits and risks when starting taurolidine, especially in patients who are considered to have a higher risk for CRBSIs.
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http://dx.doi.org/10.1002/jpen.1761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540581PMC
September 2020

Association Between Quality of Life and Improvement in Psoriasis Severity and Extent in Pediatric Patients.

JAMA Dermatol 2020 01;156(1):72-78

Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands.

Importance: Treatment of psoriasis is associated with improved quality of life (QOL) in those with the disease. However, in daily clinical practice, the association between the degree of psoriasis clearance and QOL has not been studied to date, especially in the pediatric population.

Objectives: To identify the association between the degree of psoriasis improvement (as measured by the Psoriasis Area Severity Index [PASI] and body surface area [BSA] response) and QOL (as measured by the Children's Dermatology Life Quality Index [CDLQI]) in pediatric psoriasis, and to assess the association of treatment type with QOL, independent of psoriasis improvement.

Design, Setting, And Participants: Data used in this single-center cohort study were extracted from the Child-CAPTURE (Continuous Assessment of Psoriasis Treatment Use Registry), a prospective, observational, daily clinical practice cohort of all children (aged <18 years) with a psoriasis diagnosis who attended the outpatient clinic of the Department of Dermatology at the Radboud University Medical Center in Nijmegen, the Netherlands, between September 3, 2008, and May 4, 2018. All records of treatment episodes with CDLQI, PASI, and BSA scores were included in the analysis.

Exposures: Patients were treated according to daily clinical care. Treatments were clustered into topical, dithranol, conventional systemic, and biological treatments. Because of low numbers of UV-B phototherapy, this treatment was not assessed.

Main Outcomes And Measures: Primary outcomes were mean change of CDLQI scores per PASI and BSA response categories (0 to <50, 50 to <75, 75 to <90, and ≥90) and mean CDLQI change per treatment categories.

Results: In total, 319 patients (median [interquartile range] age, 10.0 [7.0] years; 183 female [57.4%]) were analyzed for PASI score improvement (399 treatment episodes) and improvement in BSA involvement (366 treatment episodes). The greatest improvements in CDLQI scores were seen in the PASI ≥90 response category, with an estimated marginal mean change in CDLQI score of -6.6 (95% CI, -7.5 to -5.7). The greatest improvements in CDLQI scores were also observed in the BSA ≥90 response category, with an estimated marginal mean change in CDLQI score of -6.8 (95% CI, -7.5 to -6.1). Systemic treatment demonstrated a greater degree of improvement of CDLQI compared with topical treatment, independent of PASI response categories.

Conclusions And Relevance: This cohort study in a real-world setting found that the greatest improvements in QOL were associated with PASI 90 or greater, a decrease in BSA involvement of 90% or greater, and systemic treatments. These findings suggest that reaching PASI 90 or greater and decreasing BSA involvement by at least 90% may be clinically meaningful treatment goals that will help pediatric patients with psoriasis reach optimal QOL.
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http://dx.doi.org/10.1001/jamadermatol.2019.3717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902114PMC
January 2020

Unraveling Hepcidin Plasma Protein Binding: Evidence from Peritoneal Equilibration Testing.

Pharmaceuticals (Basel) 2019 Aug 23;12(3). Epub 2019 Aug 23.

Department of Laboratory Medicine, Radboud University Medical Center, 6525 Nijmegen, The Netherlands.

Peptide hormone hepcidin regulates systemic iron metabolism and has been described to be partially bound to α2-macroglobulin and albumin in blood. However, the reported degree of hepcidin protein binding varies between <3% and ≈89%. Since protein-binding may influence hormone function and quantification, better insight into the degree of hepcidin protein binding is essential to fully understand the biological behavior of hepcidin and interpretation of its measurement in patients. Here, we used peritoneal dialysis to assess human hepcidin protein binding in a functional human setting for the first time. We measured freely circulating solutes in blood and peritoneal fluid of 14 patients with end-stage renal disease undergoing a peritoneal equilibration test to establish a curve describing the relation between molecular weight and peritoneal clearance. Calculated binding percentages of total cortisol and testosterone confirmed our model. The protein-bound fraction of hepcidin was calculated to be 40% (±23%). We, therefore, conclude that a substantial proportion of hepcidin is freely circulating. Although a large inter-individual variation in hepcidin clearance, besides patient-specific peritoneal transport characteristics, may have affected the accuracy of the determined binding percentage, we describe an important step towards unraveling human hepcidin plasma protein binding in vivo including the caveats that need further research.
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http://dx.doi.org/10.3390/ph12030123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789442PMC
August 2019

Adrenal venous sampling: cosyntropin stimulation or not?

Eur J Endocrinol 2019 Sep;181(3):D15-D26

Department of Medicine - DIMED, Padova, Italy.

Notwithstanding the high prevalence of primary aldosteronism (PA), probably the most common form of secondary hypertension, the diagnosis of PA is often neglected or delayed, thus precluding target treatment, which is curative in many cases. For selection of the most appropriate treatment, a fundamental step is the distinction between a lateralized form, mainly aldosterone-producing adenoma (APA), and bilateral adrenocortical hyperplasia (BAH), also known as idiopathic hyperaldosteronism (IHA). To this aim all current guidelines recommend adrenal vein sampling (AVS), a technically challenging procedure that often fails, particularly in non-experienced hands. Cosyntropin (synthetic ACTH) is administered in the attempt to maximize adrenal cortisol secretion and avoid pulsatile adrenocortical hormone secretion in about 40% of the referral centres around the world. However, the Endocrine Society guidelines do not advise about the use or not of cosyntropin as stimulus during AVS, as there are arguments in favour and against its use. These arguments are presented in this debate article reflecting the views of groups that currently use and do not use cosyntropin.
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http://dx.doi.org/10.1530/EJE-18-0844DOI Listing
September 2019

Impact of molecular point-of-care testing on clinical management and in-hospital costs of patients suspected of influenza or RSV infection: a modeling study.

J Med Virol 2019 08 14;91(8):1408-1414. Epub 2019 Apr 14.

Department of Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: At hospital admission, patients suspected of infection with influenza or respiratory syncytial virus (RSV) are placed in isolation, pending the outcome of diagnostics. In a significant number, isolated care proves unnecessary. We investigated the potential impact of molecular point-of-care (POC) diagnostics on patient management and in-hospital costs.

Method: Prospective collection of data on resource utilization within the hospital from consecutive patients 18 years or older presenting at our university medical center with symptoms of respiratory tract infection from December 2016 to April 2017. A cost analysis was conducted using Markov modeling comparing the actual course of events (on the basis of routine diagnostic tests) with two hypothetical scenarios: when POC would impact time to diagnosis only (scenario 1) or on discharge from the hospital, too (scenario 2).

Results: A total of 283 patients were included, of whom 217 (76.7%) were admitted. Influenza and RSV were detected in 31% and 7% of the patients, respectively. Fifty-four percent of patients tested negative, of which 79% were kept in isolated care waiting for test results, with a median duration of 24 hours. Median length of stay was 6.0 days. Mean total in-hospital costs per patient were € 5243. Introducing POC would lower mean costs per patient to € 4904 (scenario 1) and € 4206 (scenario 2). At the hospital level, this would result in a total cost reduction of € 95 937 to € 293 471 in a single influenza season.

Conclusions: Introducing POC testing for patients presenting with symptoms of viral respiratory tract infection can reduce time-to-diagnosis, hospital stay and, thereby, in-hospital costs.
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http://dx.doi.org/10.1002/jmv.25479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166495PMC
August 2019

Effect of Mexiletine on Muscle Stiffness in Patients With Nondystrophic Myotonia Evaluated Using Aggregated N-of-1 Trials.

JAMA 2018 12;320(22):2344-2353

Department of Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.

Importance: In rare diseases it is difficult to achieve high-quality evidence of treatment efficacy because of small cohorts and clinical heterogeneity. With emerging treatments for rare diseases, innovative trial designs are needed.

Objective: To investigate the effectiveness of mexiletine in nondystrophic myotonia using an aggregated N-of-1 trials design and compare results between this innovative design and a previously conducted RCT.

Design, Setting, And Participants: A series of aggregated, double-blind, randomized, placebo-controlled N-of-1-trials, performed in a single academic referral center. Thirty Dutch adult patients with genetically confirmed nondystrophic myotonia (38 patients screened) were enrolled between February 2014 and June 2015. Follow-up was completed in September 2016.

Interventions: Mexiletine (600 mg daily) vs placebo during multiple treatment periods of 4 weeks.

Main Outcomes And Measures: Reduction in daily-reported muscle stiffness on a scale of 1 to 9, with higher scores indicating more impairment. A Bayesian hierarchical model aggregated individual N-of-1 trial data to determine the posterior probability of reaching a clinically meaningful effect of a greater than 0.75-point difference.

Results: Among 30 enrolled patients (mean age, 43.4 [SD, 15.24] years; 22% men; 19 CLCN1 and 11 SCN4A genotype), 27 completed the study and 3 dropped out (1 because of a serious adverse event). In 24 of the 27 completers, a clinically meaningful treatment effect was found. In the Bayesian hierarchical model, mexiletine resulted in a 100% posterior probability of reaching a clinically meaningful reduction in self-reported muscle stiffness for the nondystrophic myotonia group overall and the CLCN1 genotype subgroup and 93% posterior probability for the SCN4A genotype subgroup. In the total nondystrophic myotonia group, the median muscle stiffness score was 6.08 (interquartile range, 4.71-6.80) at baseline and was 2.50 (95% credible interval [CrI], 1.77-3.24) during the mexiletine period and 5.56 (95% CrI, 4.73-6.39) during the placebo period; difference in symptom score reduction, 3.06 (95% CrI, 1.96-4.15; n = 27) favoring mexiletine. The most common adverse event was gastrointestinal discomfort (21 mexiletine [70%], 1 placebo [3%]). One serious adverse event occurred (1 mexiletine [3%]; allergic skin reaction). Using frequentist reanalysis, mexiletine compared with placebo resulted in a mean reduction in daily-reported muscle stiffness of 3.12 (95% CI, 2.46-3.78), consistent with the previous RCT treatment effect of 2.69 (95% CI, 2.12-3.26).

Conclusions And Relevance: In a series of N-of-1 trials of mexiletine vs placebo in patients with nondystrophic myotonia, there was a reduction in mean daily-reported muscle stiffness that was consistent with the treatment effect in a previous randomized clinical trial. These findings support the efficacy of mexiletine for treatment of nondystrophic myotonia as well as the feasibility of N-of-1 trials for assessing interventions in some chronic rare diseases.

Trial Registration: ClinicalTrials.gov Identifier: NCT02045667.
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http://dx.doi.org/10.1001/jama.2018.18020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583079PMC
December 2018

A prediction model for primary aldosteronism when the salt loading test is inconclusive.

Endocr Connect 2018 Dec;7(12):1308-1314

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Objective: To develop a prediction model to confirm or exclude primary aldosteronism (PA) in patients with an inconclusive salt loading test (SLT).

Context: Diagnosis in patients with a suspicion of PA can be confirmed using an SLT. In case of inconclusive test results the decision about how to manage the patient is usually based on contextual clinical data.

Design: We included a retrospective cohort of 276 patients in the final analysis.

Methods: All patients underwent an SLT between 2005 and 2016 in our university medical center. The SLT was inconclusive (post-infusion aldosterone levels 140-280 pmol/L) in 115 patients. An expert panel then used contextual clinical data to diagnose PA in 45 of them. Together with 101 patients with a positive SLT this resulted in a total of 146 patients with PA. A total of 11 variables were used in a multivariable logistic regression analysis. We assessed internal validity by bootstrapping techniques.

Results: The following variables were independently associated with PA: more intense potassium supplementation, lower plasma potassium concentration, lower plasma renin concentration before SLT and higher plasma aldosterone concentration after SLT. The resulting prediction model had a sensitivity of 84.4% and a specificity of 94.3% in patients with an inconclusive SLT. The positive and negative predictive values were 90.5 and 90.4%, respectively.

Conclusions: We developed a prediction model for the diagnosis of PA in patients with an inconclusive SLT that results in a diagnosis that was in high agreement with that of an expert panel.
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http://dx.doi.org/10.1530/EC-18-0358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240140PMC
December 2018

The Use of N-of-1 Trials to Individualize Treatment in Patients With Renal Magnesium Wasting.

Am J Kidney Dis 2019 02 11;73(2):288-290. Epub 2018 Oct 11.

Department of Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands.

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http://dx.doi.org/10.1053/j.ajkd.2018.08.010DOI Listing
February 2019

Clinical outcomes of home parenteral nutrition patients using taurolidine as catheter lock: A long-term cohort study.

Clin Nutr 2019 10 20;38(5):2210-2218. Epub 2018 Sep 20.

Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands.

Background & Aims: Central venous access device (CVAD)-related complications, such as central-line associated bloodstream infections (CLABSIs), CVAD-related venous thromboses (CRVTs) and -occlusions frequently occur in home parenteral nutrition (HPN) patients. A preventive strategy to decrease the incidence of CLABSIs is the use of CVAD lock solutions, such as 2% taurolidine. The aim of this study was to evaluate long-term clinical outcomes of our HPN cohort while using taurolidine as lock solution. In addition, we explored risk factors associated with CVAD-related complications.

Methods: We conducted a retrospective analysis of complications (CLABSIs, CRVTs and CVAD occlusions) and adverse events in adult HPN patients while using taurolidine as lock solution. Patients with a benign underlying disease leading to intestinal failure were included between 2006 and 2017 at our tertiary referral centre for intestinal failure. Primary outcome was the effectiveness of taurolidine, as described by complication incidence rates. Secondary objectives were to assess adverse events of taurolidine, complication rates of patients who subsequently discontinued taurolidine and started using 0.9% saline alternatively, and risk factors associated with complications.

Results: In total, 270 HPN patients used taurolidine during 338521 catheter days. CLABSIs, CRVTs and CVAD occlusions occurred at a rate of 0.60 (CI95% 0.52-0.69), 0.28 (CI95% 0.23-0.34), and 0.12 (CI95% 0.08-0.16) events per 1000 catheter days, respectively. In 24 (9%) patients, mild to moderate adverse events resulted in discontinuation of 2% taurolidine. A subsequent switch to 0.9% saline resulted in an increased CLABSI rate (adjusted rate ratio 4.01 (95%CI 1.23-13.04), P = 0.02). Several risk factors were identified for CLABSIs (a lower age, nontunneled catheters, infusion frequency), CRVTs (site of vein insertion), and CVAD occlusions (type of CVAD).

Conclusion: Complication rates remained low in the long-term, and use of taurolidine was generally safe. The identified risk factors may help to create new strategies to further prevent CVAD-related complications and improve HPN care in the future.
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http://dx.doi.org/10.1016/j.clnu.2018.09.020DOI Listing
October 2019

Nail Involvement as a Predictor of Disease Severity in Paediatric Psoriasis: Follow-up Data from the Dutch ChildCAPTURE Registry.

Acta Derm Venereol 2019 Feb;99(2):152-157

Department of Dermatology, Radboud university medical center, 6500 HB Nijmegen, The Netherlands.

Little is known about the relationship between nail psoriasis and psoriasis severity in children, and there has been no longitudinal assessment of psoriasis severity related to nail psoriasis. The aim of this study was to assess whether nail psoriasis could serve as a predictor for a more severe disease course. De-identified data were obtained from the ChildCAPTURE registry, a daily clinical practice cohort of children with psoriasis, from September 2008 to November 2015. Cross-sectional analyses were performed at baseline. Longitudinal data until 2-year follow-up were analysed by linear mixed models. Nail psoriasis was present in 19.0% of all 343 patients at baseline and cross-sectionally associated with higher Psoriasis Area and Severity Index (PASI) (p = 0.033). Longitudinal analysis demonstrated higher PASI (p <0.001) during 2-year follow-up in patients with nail involvement at baseline. These findings suggest that nail psoriasis is a potential clinical predictor for more severe disease course over time in paediatric psoriasis.
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http://dx.doi.org/10.2340/00015555-3036DOI Listing
February 2019

Repair of damaged central venous catheters is safe and doubles catheter survival: a home parenteral nutrition patient cohort study.

Clin Nutr 2019 08 14;38(4):1692-1699. Epub 2018 Aug 14.

Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands.

Background & Aims: Repeated central venous catheter loss due to complications, including material breakage, compromises the options to obtain adequate vascular access in home parenteral nutrition (HPN) patients. It remains unclear whether repair of damaged catheters is an effective strategy to extend catheter survival, avoid surgical replacement and maintain venous access. The aim of this study was to evaluate the effectiveness and safety of catheter repair in our cohort of intestinal failure patients.

Methods: We conducted a retrospective analysis of all catheter repairs that were performed between 2006 and 2017 at our tertiary referral centre for intestinal failure. Primary outcome was the additional median catheter survival after catheter repair, as calculated with Kaplan-Meier analyses. Secondary outcomes included risk for central line-associated bloodstream infections (CLABSIs) and risk factors for catheter damage, as calculated with Poisson regression analyses. CLABSI rates in post-repair periods were compared with pre-repair periods. Pre- and post-repair periods were either short-term (30 days), or long-term (whole catheter period).

Results: A total of 58 repairs in 41 catheters of 35 HPN patients were included in the analysis. The median time to first repair was 452 days (interquartile range (IQR) 206-1134). After first repair, catheter survival additionally increased by 510 days (IQR 147-1195). Repairs did not increase the short-term risk for CLABSIs: incidence rates were 1.23 and 1.26 CLABSIs/1000 catheter days for the 30 days pre- and post-repair periods, respectively (rate ratio, 1.05; 95%CI, 0.15-7.44; P = 0.96). For the whole pre- and post-repair catheter period, incidence rates were 0.12 and 0.59 CLABSIs/1000 catheter days, respectively (rate ratio, 3.55; 95%CI, 1.10-11.45; P = 0.03). The overall CLABSI incidence rates in undamaged versus repaired catheters were 0.84 and 0.31 CLABSIs/1000 catheter days, respectively (rate ratio, 0.47; 95%CI, 0.23-0.94; P = 0.03). A lower age at catheter start and femoral catheterization were associated with a higher risk for catheter damage.

Conclusions: Repair of damaged catheters is often successful and an effective strategy to prolong and maintain venous access in HPN patients. On the short-term, no increase in CLABSI incidence was observed. Despite a possible increase in CLABSI incidence on the long-term, overall CLABSI rates of repaired catheters remained well below the overall CLABSI incidence of undamaged catheters. The identification of two risk factors for catheter damage may help to prevent future catheter damage.
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http://dx.doi.org/10.1016/j.clnu.2018.08.005DOI Listing
August 2019

Prediction of clinically relevant adverse drug events in surgical patients.

PLoS One 2018 23;13(8):e0201645. Epub 2018 Aug 23.

Department of clinical pharmacy, Canisius Wilhelmina hospital, Nijmegen, the Netherlands.

Background: Risk stratification of hospital patients for adverse drug events would enable targeting patients who may benefit from interventions aimed at reducing drug-related morbidity. It would support clinicians and hospital pharmacists in selecting patients to deliver a more efficient health care service. This study aimed to develop a prediction model that helps to identify patients on the day of hospital admission who are at increased risk of developing a clinically relevant, preventable adverse drug event during their stay on a surgical ward.

Methods: Data of the pre-intervention measurement period of the P-REVIEW study were used. This study was designed to assess the impact of a multifaceted educational intervention on clinically relevant, preventable adverse drug events in surgical patients. Thirty-nine variables were evaluated in a univariate and multivariate logistic regression analysis, respectively. Model performance was expressed in the Area Under the Receiver Operating Characteristics. Bootstrapping was used for model validation.

Results: 6780 admissions of patients at surgical wards were included during the pre-intervention period of the PREVIEW trial. 102 patients experienced a clinically relevant, adverse drug event during their hospital stay. The prediction model comprised five variables: age, number of biochemical tests ordered, heparin/LMWH in therapeutic dose, use of opioids, and use of cardiovascular drugs. The AUROC was 0.86 (95% CI 0.83-0.88). The model had a sensitivity of 80.4% and a specificity of 73.4%. The positive and negative predictive values were 4.5% and 99.6%, respectively. Bootstrapping generated parameters in the same boundaries.

Conclusions: The combined use of a limited set of easily ascertainable patient characteristics can help physicians and pharmacists to identify, at the time of admission, surgical patients who are at increased risk of developing ADEs during their hospital stay. This may serve as a basis for taking extra precautions to ensure medication safety in those patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201645PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107128PMC
January 2019
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