Ziekenhuis Bernhoven

An increase in pediatric cases of invasive group A streptococcus (iGAS) disease was noted in the Netherlands starting in early 2022. GAS disease can range from mild to life-threatening invasive infections. Clinical and public health decisions rely on timely and detailed reporting of clinical data. To determine risk factors associated with severe pediatric iGAS, defined as requiring admission to an intensive care unit and/or death, and to analyze pediatric iGAS incidence, presentations, and outcome between pre-COVID-19 pandemic (January 2015 to March 2020), COVID-19 pandemic (April 2020 to December 2021), and post-COVID-19 pandemic (January 2022 to June 2024) periods. This observational, retrospective and prospective cohort study in 20 hospitals (tertiary and nontertiary) in the Netherlands was conducted from January 2015 to June 2024, with real-time reporting of data on the study website since January 2022. Children aged 0 to 17 years with iGAS (positive culture or polymerase chain reaction test and/or clinical presentation) were included. iGAS infection. The primary outcome was risk factors for severe iGAS; secondary outcomes included iGAS incidence rate and clinical phenotypes prior, during, and after the COVID-19 pandemic. Risk factors for severity and mortality were analyzed using univariable and multivariable logistic regression analyses, and incidence rate ratios (IRRs) between pre-COVID-19 and postCOVID-19 pandemic periods were calculated using Poisson regression. Of 617 children included, 351 (56.9%) were aged 0 to 4 years. For the 192 participants with detailed data collection, median (IQR) age was 4.2 (1.7-7.1) years and 91 (47.4%) were male. iGAS cases decreased during the COVID-19 pandemic and increased significantly in the post-COVID-19 period (IRR, 2.93; 95%, 2.46-3.49), as compared with the pre-COVID-19 pandemic period. By late 2023, the incidence of iGAS returned to pre-COVID-19 pandemic levels. Factors associated with increased risk of severe disease included a post-COVID-19 pandemic diagnosis (odds ratio [OR], 3.49; 95% CI, 2.31-6.26), pulmonary involvement (OR, 8.64; 95% CI, 5.50-13.55), streptococcal toxic shock syndrome (STSS; OR, 11.71; 95% CI, 4.39-31.18), and meningitis or encephalitis (OR, 4.38; 95% CI, 4.39-31.18). Clinical factors associated with increased risk of severe disease were reduced consciousness (OR, 7.61; 95% CI, 1.84-34.41), dyspnea (OR, 9.89; 95% CI, 3.04-32.14), abnormal auscultation (OR, 6.32; 95% CI, 2.18-18.32), and elevated C-reactive protein (OR, 6.32; 95% CI, 2.18-18.32), while estimated glomerular filtration rate was associated with a decreased risk (OR, 0.64; 95% CI, 0.49-0.84). Disease severity increased in post-COVID-19-pandemic cases, with higher mortality (13 of 294 cases [4.4%] vs 3 of 218 cases [1.4%]) and intensive care admission rates (113 of 294 cases [38.4%] vs 34 of 218 cases [15.6%]), as compared with pre-COVID-19 pandemic cases. Severity of pulmonary iGAS was similar in both periods. In the post-COVID-19 pandemic period, there was a significant increase in the incidence of pulmonary infections (IRR, 5.04; 95% CI, 3.27-7.97) , STSS (IRR, 10.30; 95% CI, 3.88-35.60), meningitis or encephalitis (IRR, 12.30; 95% CI, 4.14-52.70), and necrotizing fasciitis (IRR, 26.10; 95% CI, 5.14-475.00). In this cohort study, risk factors for a complicated course of iGAS in children included pulmonary or central nervous system involvement, STSS, reduced consciousness or pulmonary clinical signs, elevated CRP, and decreased eGFR. Awareness of these risk factors is important to improve timely recognition of at-risk cases and improve clinical outcomes.

The quilt technique results in a significant reduction of postoperative complications after mastectomy. However, concerns remain about the long-term effects on cosmetics, pain, and shoulder function after the quilt technique. This study evaluated long-term patient-reported cosmetic outcomes after mastectomy, comparing the quilt and conventional techniques. This retrospective multicentre evaluation study included 156 patients who underwent mastectomy between October 2018 and October 2022. Patients received quilting sutures (n=81) or conventional closure (n=75). The primary outcome was patient-reported cosmetic outcome, assessed using a 4-point Likert scale. Secondary outcomes were cosmetics evaluated by an expert panel, long-term shoulder function, and surgery-related pain. In the study cohort, the median age was 65±18 years. Unilateral mastectomy was performed in 131 (84.0%) patients and bilateral mastectomy in 25 (16.0%) patients. The median time after surgery was 38±23 months. Long-term cosmetic outcomes were not significantly different between the quilted and non-quilted cohorts (p=0.114): in the quilted cohort, 7.5% of patients rated their cosmetic outcome as poor, 27.5% as fair, 41.3% as good, and 23.8% as excellent, compared to the non-quilted cohort, 20.6% rated their outcome as poor, 23.5% as fair, 39.7% as good, and 16.2% as excellent. Expert panel assessment, long-term shoulder function, and surgery-related pain were comparable between the cohorts. The quilt technique has no long-term deleterious effects regarding cosmetics, shoulder function, and surgery-related pain and can thus be applied safely in mastectomy wound closure. Concerns about long-term safety should be no argument for refraining from quilting.

This study aims to assess the peri- and postoperative outcomes of the vNOTES hysterectomy in the Netherlands during implementation. Nationwide cohort study. vNOTES hysterectomies performed in the Netherlands by 15 hospitals since the implementation of the technique, from August 2019 to September 2024. 673 patients undergoing vNOTES hysterectomy. Descriptive data are presented as frequencies with percentage or mean with range. Logistic regression was used to assess the risk of conversions/complications per BMI group. Peri- and postoperative outcomes such as operating time, conversions, and complications. The mean operating time was 67.4 min (range 24-210). There were 37 (5.5%) conversions and 94 (15.5%) complications. Nineteen (2.8%) complications were perioperative, and 75 (12.7%) postoperative. Ten (1.5%) of the perioperative complications were classified as Clavien-Dindo (CD) 1, and nine (1.3%) as CD3. Postoperatively, 18 patients (3.1%) had a reintervention (N = 17 CD3, N = 1 CD4), and two (0.3%) patients were admitted to the intensive care unit (CD4). The mean blood loss was 127 mL (range 50-2000), and 220 (37%) of patients were discharged the same day. This large nationwide cohort study during implementation of the vNOTES hysterectomy demonstrates the safety and feasibility of this upcoming technique, reporting on a short surgery duration and a similar complication percentage compared to other methods of hysterectomy.

A major lower limb amputation (LLA) for dysvascular disease carries the risk of disturbed wound healing necessitating reamputation at a higher level. A reamputation causes a delay in prosthetic fitting and recovery of walking ability. The combination of a prolonged open wound and inability to walk can worsen the physical and psychological situation. Prevention of reamputation seems therefore important. This study aims to identify risk factors for reamputation, and to evaluate a possible altered mortality rate after a dysvascular major LLA. These issues are crucial for shared decision-making prior to surgery. Retrospective study investigating a Dutch regional cohort of patients with a dysvascular below-knee, through-knee, or above-knee LLA. Five hundred sixteen dysvascular major LLAs were included (2014-2018). One hundred reamputations were performed within 1year after initial amputation (19.4%). Risk factors for ipsilateral reamputation were diabetes mellitus, lipid-lowering drugs usage, and lower level of amputation (P ≤ 0.01, 0.037, and < 0.01, respectively). The 30-day mortality rates were 1% and 12% for the reamputation group and the nonreamputation group, respectively (P≤0.01). The 1-year mortality rates were 23% and 27% for the reamputation group and the nonreamputation group, respectively (P=0.423). Ipsilateral reamputation within 1year after initial amputation is common. Several risk factors for reamputation were identified. The 30-day and 1-year mortality rate is high, but not significantly different after 1year. A clinical decision tool for dysvascular patients needs to be developed to improve shared decision-making, reduce reamputation rates, and improve survival.

Fluorouracil is among the most used antimetabolite drugs for the chemotherapeutic treatment of various types of gastrointestinal malignancies. Dihydropyrimidine dehydrogenase (DPYD) genotyping prior to fluorouracil treatment is considered standard practice in most European countries. Yet, current pre-therapeutic DPYD genotyping procedures do not identify all dihydropyrimidine dehydrogenase (DPD)-deficient patients. Alternatively, DPD activity can be estimated by determining the DPD phenotype by quantification of plasma concentrations of the endogenous uracil and thymine concentrations and their respective metabolites dihydrouracil (DHU) and dihydrothymine (DHT). Liquid chromatography - mass spectrometry (LC-MS) detection is currently considered as the most adequate method for quantification of low-molecular weight molecules, although the sample preparation method is highly critical for analytical outcome. It was hypothesized that during protein precipitation, the recovery of the molecule of interest highly depends on the choice of precipitation agent and the extent of protein binding in plasma. In this work, the effect of protein precipitation using acetonitrile (ACN) compared to strong acid perchloric acid (PCA) on the recovery of uracil, thymine, DHU and DHT is demonstrated. Upon the analysis of plasma samples, PCA precipitation showed higher concentrations of uracil and thymine as compared to ACN precipitation. Using ultrafiltration, it was shown that uracil and thymine are significantly (60–65 %) bound to proteins compared to DHU and DHT. This shows that before harmonized cut-off levels of DPD phenotyping can be applied in clinical practice, the analytical methodology requires extensive further optimization.

Healthcare systems remain disease oriented despite growing sustainability concerns caused by inadequate management of patients with multimorbidity. Comprehensive care programmes (CCPs) can play an important role in streamlining care delivery, but large differences in setup and results hinder firm conclusions on their effectiveness. Many elements for successful implementation of CCPs are identified, but strategies to overcome barriers and embed programmes within health systems remain unknown. To address this knowledge gap through a detailed study of implementing a CCP in a Dutch hospital setting, including patient experiences, facilitators, barriers and ways to overcome those barriers. Additionally, this study aims to explore effects on patient satisfaction and healthcare use. A qualitative study design with 39 semistructured interviews and focus groups between July 2020 and February 2023 with 16 patients and 17 involved professionals. Additionally, effects on quantitative outcomes for patient satisfaction (PACIC-20) and healthcare use were explored. Professionals expressed a wide range of topics related to implementation and ways to overcome barriers at hospital and system level. Alterations in the design to accommodate varying care demands, focus on inclusions through referrals, and lack of long-term support and appropriate financing were key topics. Patients expressed varying experiences, stated a strong desire for comprehensive information, and emphasised the importance of trust in caregivers. Patient satisfaction showed no effects, while healthcare use showed slight decreases in trends, but patient numbers were limited. The introduction of a CCP is feasible, and exploratory analysis on effectiveness shows lower hospital care use without decreasing patient satisfaction. However, this is accompanied by several challenges that show current fragmented systems still do not support implementation of integrated care initiatives. Overcoming those comes with substantial costs and may require a strong bottom-up implementation within a motivated team and actions on all levels of healthcare systems.

To describe the 12-month mortality of Dutch COVID-19 intensive care unit patients, the total COVID-19 population and various subgroups on the basis of the number of comorbidities, age, sex, mechanical ventilation, and vasoactive medication use. We included all patients admitted with COVID-19 between March 1, 2020, and March 29, 2022, from the Dutch National Intensive Care (NICE) database. The crude 12-month mortality rate is presented via Kaplan-Meier survival curves for each patient subgroup. We used Cox regression models to analyze the effects of patient characteristics on 12-month mortality after hospital discharge. We included 16,605 COVID-19 patients. The in-hospital mortality rate was 28.1%, and the 12-month mortality rate after intensive care unit admission was 29.8%. Among hospital survivors, 12-month mortality after hospital discharge was 2.5% (300/11,931). The hazard of death at 12 months after hospital discharge was greater in patients between 60 and 79 years (HR 4.74; 95%CI 2.23 - 10.06) and ≥ 80 years (HR 22.77; 95%CI 9.91 - 52.28) than in patients < 40 years of age; in male patients than in female patients (HR 1.38; 95%CI 1.07 - 1.78); and in patients with one (adjusted HR 1.95; 95%CI 1.5 - 2.53), two (adjusted HR 4.49; 95%CI 3.27 - 6.16) or more than two comorbidities (adjusted HR 4.99; 95%CI 2.62 - 9.5) than in patients with no comorbidities. Neither vasoactive medication use nor mechanical ventilation resulted in statistically significant results. For Dutch COVID-19 intensive care unit patients, most deaths occurred during their hospital stay. For hospital survivors, the crude 12-month mortality rate was low. Patient age (older than 60), sex and the number of comorbidities were associated with a greater hazard of death at 12 months after hospital discharge, whereas mechanical ventilation and vasoactive medication were not.

Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n= 39) or azathioprine plus prednisolone (n= 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p= 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p= 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p= 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p= 0.018). In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. #NCT02900443.