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Background Alternative data sources for surveillance have gained importance in maintaining coronavirus disease 2019 (COVID-19) situational awareness as nationwide testing has drastically decreased. Therefore, we explored whether rates of sick-leave from work are associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) notification trends and at which lag, to indicate the usefulness of sick-leave data for COVID-19 surveillance. Methods We explored trends during the COVID-19 epidemic of weekly sick-leave rates and SARS-CoV-2 notification rates from 1 June 2020 to 10 April 2022. Separate time series were inspected visually. Then, Spearman correlation coefficients were calculated at different lag and lead times of zero to four weeks between sick-leave and SARS-CoV-2 notification rates. We distinguished between four SARS-CoV-2 variant periods, two labour sectors and overall, and all-cause sick-leave versus COVID-19-specific sick-leave. Results The correlation coefficients between weekly all-cause sick-leave and SARS-CoV-2 notification rate at optimal lags were between 0.58 and 0.93, varying by the variant period and sector (overall: 0.83, lag −1; 95% CI [0.76, 0.88]). COVID-19-specific sick-leave correlations were higher than all-cause sick-leave correlations. Correlations were slightly lower in healthcare and education than overall. The highest correlations were mostly at lag −2 and −1 for all-cause sick-leave, meaning that sick-leave preceded SARS-CoV-2 notifications. Correlations were highest mostly at lag zero for COVID-19-specific sick-leave (coinciding with SARS-CoV-2 notifications). Conclusion All-cause sick-leave might offer an earlier indication and evolution of trends in SARS-CoV-2 rates, especially when testing is less available. Sick-leave data may complement COVID-19 and other infectious disease surveillance systems as a syndromic data source. [ABSTRACT FROM AUTHOR]

Background We aimed to determine the noninferiority of fosfomycin compared to ciprofloxacin as an oral step-down treatment for Escherichia coli febrile urinary tract infections (fUTIs) in women. Methods This was a double-blind, randomized, controlled trial in 15 Dutch hospitals. Adult women who were receiving 2–5 days of empirical intravenous antimicrobials for E. coli fUTI were assigned to step-down treatment with once-daily 3g fosfomycin or twice-daily 0.5g ciprofloxacin for 10 days of total antibiotic treatment. For the primary end point, clinical cure at days 6–10 post-end of treatment (PET), a noninferiority margin of 10% was chosen. The trial was registered on Trialregister.nl (NTR6449). Results After enrollment of 97 patients between 2017 and 2020, the trial ended prematurely because of the coronavirus disease 2019 pandemic. The primary end point was met in 36 of 48 patients (75.0%) assigned to fosfomycin and 30 of 46 patients (65.2%) assigned to ciprofloxacin (risk difference [RD], 9.6%; 95% confidence interval [CI]: –8.8% to 28.0%). In patients assigned to fosfomycin and ciprofloxacin, microbiological cure at days 6–10 PET occurred in 29 of 37 (78.4%) and 33 of 35 (94.3%; RD, –16.2%; 95% CI: –32.7 to –0.0%). Any gastrointestinal adverse event was reported in 25 of 48 (52.1%) and 14 of 46 (30.4%) patients (RD, 20.8%; 95% CI: 1.6% to 40.0%), respectively. Conclusions Fosfomycin is noninferior to ciprofloxacin as oral step-down treatment for fUTI caused by E. coli in women. Fosfomycin use is associated with more gastrointestinal events. Clinical Trial Registration Trial NL6275 (NTR6449). [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to gain insight into the epidemiology of burn patients admitted to a hospital without a burn center or referred to a burn center. Methods: This retrospective, nationwide, cohort study included patients with burns or inhalation trauma, admitted between 2014 and 2018, from a national trauma registry. The primary outcome measure was admission to a hospital with or without a burn center. Secondary outcome measures were patient and injury characteristics, Intensive Care Unit (ICU) admission and length of stay, and hospital length of stay (HLOS). Results: Of the 5524 included patients, 2787 (50.4%) were treated at a non-burn center, 1745 (31.6%) were subsequently transferred to a burn center, and 992 (18.0%) were primarily presented and treated at a burn center. The annual number of patients decreased from 1199 to 1055 (− 12.4%). At all admission locations, a clear incidence peak was observed in children ≤ 4 years and in patients of ≥ 80 years. The number of ICU admissions for the entire population increased from 201 to 233 (33.0%). The mean HLOS for the entire population was 8 (SD 14) days per patient. This number remained stable over the years in all groups. Conclusion: Half of all burn patients were admitted in a non-burn center and the other half in a burn center. The number and incidence rate of patients admitted with burns or inhalation trauma decreased over time. An increased incidence rate was found in children and elderly. The number of patients admitted to the ICU increased, whereas mean hospital length of stay remained stable. [ABSTRACT FROM AUTHOR]

Little is known about delirium in elderly burn center patients. The aim of this study is to provide information on the prevalence of delirium and risk factors contributing to the onset of delirium. All patients aged 70 years or older admitted with burn injuries to the Burn Center, Maasstad Hospital, in 2011 to 2017 were eligible for inclusion. We retrospectively collected data regarding the presence of delirium, potential risk factors contributing to the onset of delirium and outcome after delirium. We included elderly 90 patients in this study. The prevalence of delirium in our population was 13% (N = 12). Risk factors for delirium were advanced age, increased American Society for Anesthesiologists score, physical impairment and the use of anticholinergic drugs during admission. Patients with delirium had a poorer outcome, with prolonged hospital stay and increased mortality 6 and 12 months after discharge. Delirium is diagnosed in 13% of the elderly patients admitted to our burn center. Risk factors for delirium found in this study are advanced age, poor physical health status, physical impairment, and the use of anticholinergic drugs. Delirium is related to poor outcomes, including prolonged hospital stay and mortality after discharge. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether nitrofurantoin 50 mg normal-release every 6 h (NF50) and nitrofurantoin 100 mg extended-release every 12 h (NF100) are equally effective for treating cystitis in primary care. In the Netherlands, GP prescription of either option largely depends on pharmacy procurement, rather than on patient-related factors.Methods: GP data between January 2013 and July 2018 were retrospectively collected. Inclusion criteria were the use of nitrofurantoin for uncomplicated cystitis, complicated cystitis or cystitis in pregnancy. Criteria for early and late failure were a second antibiotic prescription for cystitis or pyelonephritis within 14 and 28 days post-prescription, respectively. Crude and confounder-adjusted (CA) risk differences (RDs) were estimated using linear regression. Instrumental variable analysis and CA instrumental variable analysis used GP practice proportion of NF50 versus NF100 use as the instrumental variable.Results: For uncomplicated cystitis (n=46855), treatment with NF50 and NF100 resulted in late failure in 9.7% and 9.6%, respectively. The CA RD, instrumental variable RD and CA instrumental variable RD were 0.2% (95% CI=-0.5 to 0.8), -0.7% (95% CI=-1.7 to 0.3) and 0.0% (95% CI=-0.9 to 1.0), respectively. In complicated cystitis (n=10767), late failure occurred in 10.9% and 11.1% after using NF50 and NF100, respectively [CA RD=0.5% (95% CI=-1.2 to 1.8), instrumental variable RD=-0.8% (95% CI=-3.4 to 1.8) and CA instrumental variable RD=-0.3% (95% CI=-3.0 to 2.4)]. For cystitis in pregnancy (n=1087), NF50 and NF100 resulted in late failure in 13.4% and 7.8%, respectively [CA RD=-5.4% (95% CI=-10.0 to -1.4), instrumental variable RD=-8.9% (95% CI=-16.0 to -1.8) and CA instrumental variable RD=-8.9% (95% CI=-16.0 to -1.7)]. No differences were observed in early failure.Conclusions: In patients with cystitis in pregnancy, NF100 was associated with a lower incidence of late clinical failure compared with NF50. We found no differences in clinical failure between NF50 and NF100 for uncomplicated and complicated cystitis. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome. Methods: In a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity. Results: A total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18‐70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30‐day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later. Conclusions: In a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%). [ABSTRACT FROM AUTHOR]

Objective: People in the Netherlands are legally allowed to celebrate New Year's Eve with consumer fireworks. The aim of this study was to provide detailed information about the patient and injury characteristics, medical and societal costs, and clinical and functional outcome in patients with injuries resulting from this tradition. Methods: A multicenter, prospective, observational case series performed in the Southwest Netherlands trauma region, which reflects 15% of the country and includes a level I trauma center, a specialized burn center, a specialized eye hospital, and 13 general hospitals. All patients with any injury caused by consumer fireworks, treated at a Dutch hospital between December 1, 2017 and January 31, 2018, were eligible for inclusion. Exclusion criteria were unknown contact information or insufficient understanding of Dutch or English language. The primary outcome measure was injury characteristics. Secondary outcome measures included treatment, direct medical and indirect societal costs, and clinical and functional outcome until one year after trauma. Results: 54 out of 63 eligible patients agreed to participate in this study. The majority were males (N = 50; 93%), 50% were children below 16 years of age, and 46% were bystanders. Injuries were mainly located to the upper extremity or eyes, and were mostly burns (N = 38; 48%) of partial thickness (N = 32; 84%). Fifteen (28%) patients were admitted and 11 (20%) patients needed surgical treatment. The mean total costs per patient were €6,320 (95% CI €3,400 to €9,245). The most important cost category was hospital admission. Only few patients reported complaints in patient-reported quality of life and functional outcome after 12 months follow-up. Conclusion: This study found that young males are most vulnerable for fireworks injuries and that most injuries consist of burns, located to the arm and hand, and eye injuries. On the long-term only few patients experienced reduced quality of life and functional limitations. [ABSTRACT FROM AUTHOR]

Purpose: To identify preoperative anatomical aortic characteristics that predict seal failures after endovascular aneurysm sealing (EVAS) and compare the incidence of events experienced by patients treated within vs outside the instructions for use (IFU).Methods: Of 355 patients treated with the Nellix EndoVascular Aneurysm Sealing System (generation 3SQ+) at 3 high-volume centers from March 2013 to December 2015, 94 patients were excluded, leaving 261 patients (mean age 76±8 years; 229 men) for regression analysis. Of these, 83 (31.8%) suffered one or more of the following events: distal migration ⩾5 mm of one or both stent frames, any endoleak, and/or aneurysm growth >5 mm. Anatomical characteristics were determined on preoperative computed tomography (CT) scans. Patients were divided into 3 groups: treated within the original IFU (n=166), outside the original IFU (n=95), and within the 2016 revised IFU (n=46). Categorical data are presented as the median (interquartile range Q1, Q3).Results: Neck diameter was significantly larger in the any-event cohort vs the control cohort [23.7 mm (21.7, 26.3) vs 23.0 mm (20.9, 25.2) mm, p=0.022]. Neck length was significantly shorter in the any-event cohort [15.0 mm (10.0, 22.5) vs 19.0 mm (10.0, 21.8), p=0.006]. Maximum abdominal aortic aneurysm (AAA) diameter and the ratio between the maximum AAA diameter and lumen diameter in the any-event group were significantly larger than the control group (p=0.041 and p=0.002, respectively). Regression analysis showed aortic neck diameter (p=0.006), neck length (p=0.001), and the diameter ratio (p=0.011) as significant predictors of any event. In the comparison of events to IFU status, 52 (31.3%) of 166 patients in the inside the original IFU group suffered an event compared to 13 (28.3%) of 46 patients inside the 2016 IFU group (p=0.690).Conclusion: Large neck diameter, short aortic neck length, and the ratio between the maximum AAA and lumen diameters are preoperative anatomical predictors of the occurrence of migration (⩾5 mm), any endoleak, and/or aneurysm growth (>5 mm) after EVAS. Even under the refined 2016 IFU, more than a quarter of patients suffered from an event. Improvements in the device seem to be necessary before this technique can be implemented on a large scale in endovascular AAA repair. [ABSTRACT FROM AUTHOR]

Purpose:To determine reliability of the ABILHAND-Kids, explore sources of variation associated with these measurement results, and generate repeatability coefficients. Method:A reliability study with a repeated measures design was performed in an ambulatory rehabilitation care department from a rehabilitation center, and a center for special education. A physician, an occupational therapist, and parents of 27 children with spastic cerebral palsy independently rated the children’s manual capacity when performing 21 standardized tasks of the ABILHAND-Kids from video recordings twice with a three week time interval (27 first-, and 25 second video recordings available). Parents additionally rated their children’s performance based on their own perception of their child's ability to perform manual activities in everyday life, resulting in eight ratings per child. Results:ABILHAND-Kids ratings were systematically different between observers, sessions, and rating method. Participant × observer interaction (66%) and residual variance (20%) contributed the most to error variance (9%). Test–retest reliability was 0.92. Repeatability coefficients (between 0.81 and 1.82 logit points) were largest for the parents’ performance-based ratings. Conclusion:ABILHAND-Kids scores can be reliably used as a performance- and capacity-based rating method across different raters. Parents’ performance-based ratings are less reliable than their capacity-based ratings. Resulting repeatability coefficients can be used to interpret ABILHAND-Kids ratings with more confidence.Implications for RehabilitationThe ABILHAND-Kids is a valuable tool to assess a child's unimanual and bimanual upper limb activities.The reliability of the ABILHANDS-Kids is good across different observers as a performance- and capacity-based rating method.Parents' performance-based ratings are less reliable than their capacity-based ones.This study has generated repeatability coefficients for clinical decision making. [ABSTRACT FROM PUBLISHER]

Objectives Various configurations of kissing stent (KS) configurations exist and patency rates vary. In response the covered endovascular reconstruction of the aortic bifurcation configuration was designed to minimize mismatch and improve outcome. The aim of the current study is to compare geometrical mismatch of kissing stent with the covered endovascular reconstruction of the aortic bifurcation configuration in vivo. Methods Post-operative computed tomographic data and patient demographics from 11 covered endovascular reconstruction of the aortic bifurcation and 11 matched kissing stent patients were included. A free hand region of interest and ellipse fitting method were applied to determine mismatch areas and volumes. Conformation of the stents to the vessel wall was expressed using the D-ratio. Results Patients were mostly treated for Rutherford category 2 and 3 (64%) with a lesion classification of TASC C and D in 82%. Radial mismatch area and volume for the covered endovascular reconstruction of the aortic bifurcation group was significantly lower compared to the kissing stent configuration ( P < 0.05). The D-ratio did not significantly differ between groups. Measurements were performed with good intra-class correlation. There were no significant differences in the post-procedural aortoiliac anatomy. Conclusions The present study shows that radial mismatch exists in vivo and that large differences in mismatch exist, in favour of the covered endovascular reconstruction of the aortic bifurcation configuration. Future research should determine if the decreased radial mismatch results in improved local flow profiles and subsequent clinical outcome. [ABSTRACT FROM AUTHOR]

Background: To determine the cost-effectiveness of strategies of preferred antibiotic treatment with beta-lactam/macrolide combination or fluoroquinolone monotherapy compared to beta-lactam monotherapy.Methods: Costs and effects were estimated using data from a cluster-randomized cross-over trial of antibiotic treatment strategies, primarily from the reduced third payer perspective (i.e. hospital admission costs). Cost-minimization analysis (CMA) and cost-effectiveness analysis (CEA) were performed using linear mixed models. CMA results were expressed as difference in costs per patient. CEA results were expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per prevented death.Results: A total of 2,283 patients were included. Crude average costs within 90 days from the reduced third payer perspective were €4,294, €4,392, and €4,002 per patient for the beta-lactam monotherapy, beta-lactam/macrolide combination, and fluoroquinolone monotherapy strategy, respectively. CMA results were €106 (95% CI €-697 to €754) for the beta-lactam/macrolide combination strategy and €-278 (95%CI €-991 to €396) for the fluoroquinolone monotherapy strategy, both compared to the beta-lactam monotherapy strategy. The ICER was not statistically significantly different between the strategies. Other perspectives yielded similar results.Conclusions: There were no significant differences in cost-effectiveness of strategies of preferred antibiotic treatment of CAP on non-ICU wards with either beta-lactam monotherapy, beta-lactam/macrolide combination therapy, or fluoroquinolone monotherapy.Trial Registration: The trial was registered with ClinicalTrials.gov, number NCT01660204 , on May 2nd, 2012. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate health status and associated factors in community-dwelling elderly in the Netherlands. Methods: Participants from a placebo-controlled double-blind randomized controlled trial conducted in the Netherlands were invited at the time of enrolment to participate in this study. Data were collected on comorbidities, socio-demographic background and health status, using EQ-5D-3L instrument. EQ-5D-3L summary index values (EQ-5D-indices) was derived using Dutch tariff. Regression analysis was conducted to identify factors associated with EQ-5D-indices and visual analogue scale (EQ-VAS). Results: 48,634 elderly (≥65 years) were included. The most frequently reported complaint was pain/discomfort (29.4%), but for the elder elderly (i.e. ≥85 years) it was mobility (52.9%). The proportion of persons reporting (multiple) problems increased with age from 31.5% for 65-69 years old subjects to 65.9% for elder elderly. The mean EQ-5D-indices and EQ-VAS decreased with age from 0.94 and 84, respectively in those 65 to 69 years old to 0.86 and 76, respectively, in ≥85 years old subjects. Increasing age, female gender, low education, geographic factors and comorbidities were associated with impaired health status. Conclusions: Within community-dwelling elderly large differences in health status exist. Impairment increases rapidly with age, but health status is also associated with socio-demographic variables and comorbidities. Trial Registration: ClinicalTrials.gov, NCT00812084 . [ABSTRACT FROM AUTHOR]

Background: There are two primary surgical techniques to reconstruct the anterior cruciate ligament (ACL), transtibial (TT) technique and anteromedial portal (AMP) technique. Currently, there is no consensus which surgical technique elicits the best clinical and functional outcomes. MRI-derived measures of the signal intensity (SI) of the ACL graft have been described as an independent predictor of graft properties. The purpose of this study is to compare the MRI derived SI measurements of the ACL graft one year after ACL reconstruction, in order to compare the outcomes of both the AMP and TT ACL reconstruction technique.Methods/design: Thirty-six patients will be included in a randomized controlled trial. Patients who are admitted for primary unilateral ACL reconstruction will be included in the study. Exclusion criteria are a history of previous surgery on the ipsilateral knee, re-rupture of the ipsilateral ACL graft, associated ligamentous injuries or meniscal tear of the ipsilateral knee, unhealthy contralateral knee, contra-indications for MRI and a preference for one of the two surgical techniques and/or orthopaedic surgeon. Primary outcome is MRI Signal intensity ratio (SIR) of the ACL graft. Secondary outcome measures are the International Knee Documentation Committee (IKDC) Knee Examination Form,the Knee injury and Osteoarthritis Outcome Scores (KOOS) and the Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS). Differences between MRI SIR assessment with the current MRI protocol (proton density weighted imaging protocol) and the additional T2*-weighted gradient-echo protocol will be assessed.Discussion: There is no consensus regarding the TT or AMP ACL reconstruction technique. SI measurements with MRI have been used in other clinical studies for evaluation of the ACL graft and maturation after ACL reconstruction compared to clinical and functional outcomes. This randomized controlled trial has been designed to compare the TT technique with the AMP technique with the use of MRI SI of the graft after ACL reconstruction.Trial Registration: Netherlands Trial Registry NTR5410 (registered on August 24, 2015). [ABSTRACT FROM AUTHOR]

A novel low-mast low-power Terrestrial Digital Audio Broadcasting (T-DAB) single frequency network topology is described and evaluated in this paper. For this purpose, a pilot network (band III and L-band) was constructed in Amsterdam, the Netherlands. The performance of the band III pilot network (channel 12B) is compared with the existing traditional high-power high-mast T-DAB network (channel 12C) of the public service broadcaster. An important goal is to investigate whether the pilot network can co-exist with an existing traditional T-DAB network. The field trial shows that a gap filler can effectively neutralize the adjacent channel interference of the pilot network on the existing T-DAB network. Moreover, the L-band pilot network is compared with both band III networks by assessing the indoor coverage of every network. For estimation of the indoor coverage, 34 objects were investigated. Both the indoor penetration loss for band III and L-band was determined for each object. Indoor coverage in a region is reached if 95% of the buildings or more have indoor coverage. Using this definition, the loss for band III is 21.6 dB and for L-band 24.6 dB. As a result we consider the indoor penetration loss values reported in literature as too optimistic. Also other parameters of the pilot network were measured, such as the frequency re-use distance. [ABSTRACT FROM AUTHOR]

Background: The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design: 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion: The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of these two separate trials are: (1) to reduce health care workers (HCWs) absenteeism; and (2) to reduce hospital admission among the elderly during the COVID-19 pandemic through BCG vaccination.Trial Design: Two separate multi-centre placebo-controlled parallel group randomized trials PARTICIPANTS: (1) Health care personnel working in the hospital or ambulance service where they will take care of patients with the COVID-19 infection and (2) elderly ≥60 years. The HCW trial is being undertaken in 9 hospitals. The elderly trial is being undertaken in locations in the community in Nijmegen, Utrecht, and Veghel, in the Netherlands, using senior citizen organisations to facilitate recruitment.Intervention and Comparator: For both trials the intervention group will be randomized to vaccination with 0.1 ml of the licensed BCG vaccine (Danish strain 1331, SSI, Denmark, equivalent to 0.075 mg attenuated M. bovis). The placebo group consists of 0.1 ml 0.9% NaCl, which is the same amount, and has the same colour and appearance as the suspended BCG vaccine.Main Outcomes: (1) Number of days of unplanned work absenteeism in HCWs for any reason which can be continuously measured on a bi-weekly basis, and (2) the cumulative incidence of hospital admission due to documented COVID-19.Randomisation: Participants will be randomized to BCG vaccine or placebo (1;1) centrally using a computer- based system, stratified by study centre.Blinding (masking): Subjects, investigators, physicians and outcome assessors are blinded for the intervention. Only the pharmacist assistant that prepares- and research personnel that administers- study medicines are unblinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): (1) The sample size for the first trial is N=1500 HCWs randomised 1:1 to either BCG vaccine (n=750) and placebo (n=750) and (2) The sample size for the second trial is N=1600 elderly persons randomised to BCG vaccine (n=800) and the placebo group (n=800).Trial Status: HCW: version 4.0, 24-04-2020. Recruitment began 25-03-2020 and was completed on the 23-04-2020. Elderly: version 3.0, 04-04-2020. Recruitment began 16-04- 2020 and is ongoing.Trial Registration: The HCWs trial was registered 31-03-2020 at clinicaltrials.gov (identifier: NCT04328441) and registered 20-03-2020 at the Dutch Trial Registry (trialregister.nl, identifier Trial NL8477). The elderly trial was registered 22-04-2020 at the Dutch trial registry with number NL8547.Full Protocol: The full protocols will be attached as additional files, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. [ABSTRACT FROM AUTHOR]

We conducted a post-hoc analysis of a double blind, randomized, placebo-controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged 65 years or older to assess public health impact. For all outcomes, we included all randomized subjects, using a modified intention-to-treat (mITT) approach to determine vaccine efficacy (VE), vaccine preventable disease incidence (VPDI) defined as control minus vaccinated group incidence, and numbers needed to vaccinate (NNV) (based on a five-year duration of protection). Results are reported for, in order, clinical, adjudicated (clinical plus radiologic infiltrate determined by committee), pneumococcal, and vaccine-type pneumococcal (VT-Sp) community-acquired pneumonia; invasive pneumococcal disease (IPD) and VT-IPD. VEs (95% CI) for all hospital episodes were 8.1% (−0.6%, 16.1%), 6.7% (−4.1%, 16.3%), 22.2% (2.0%, 38.3%), 37.5% (14.3%, 54.5%), 49.3% (23.2%, 66.5%), and 75.8% (47.6%, 88.8%). VPDIs per 100,000 person-years of observation (PYOs) were 72, 37, 25, 25, 20, and 15 with NNVs of 277, 535, 816, 798, 1016, and 1342. For clinical CAP, PCV13 was associated with a reduction of 909 (−115, 2013) hospital days per 100,000 PYOs translating to a reduction over 5 years of one hospital day for every 22 people vaccinated. When comparing at-risk persons (defined by self-report of diabetes, chronic lung disease, or other underlying conditions) to not at-risk persons, VEs were similar or lower, but because baseline incidences were higher the VPDIs were approximately 2–10 times higher and NNVs 50–90% lower. A public health analysis of pneumonia and IPD outcomes in a randomized controlled trial found substantial burden reduction following adult PCV13 immunization implemented in a setting with an ongoing infant PCV7-PCV10 program. VPDIs were higher among at-risk adults. The original study and the current analysis were funded by Pfizer. [ABSTRACT FROM AUTHOR]

• Data on serotype specific PCV13 vaccine efficacy (VE) against CAP have not been published. • We analysed a randomised controlled trial of PCV13 against CAP among elderly adults. • Five of 13 vaccine serotypes had sufficient data for analysis. • Statistically significant VE was found for serotypes 3 and 7F and was positive for all five. Serotype-specific vaccine efficacy (VE) against adult community acquired pneumonia (CAP) remains poorly defined, yet such data are important for assessing the utility of adult pneumococcal conjugate vaccine (PCV) programs. We evaluated the Community Acquired Pneumonia Immunization Trial in Adults to assess serotype-specific VE for CAP. This parallel-arm randomized clinical trial assessed 13-valent PCV (PCV13) VE among community dwelling persons aged ≥65 years in The Netherlands. In the original analysis, PCV13 VE against first episodes of vaccine-type (VT) chest radiology confirmed CAP was 45.6% (95% confidence interval [CI] 21.8–62.5%). Unlike the original analysis, we included any subject that met a clinical definition of CAP regardless of radiographic findings. VT-CAP was identified by culture (sterile or non-sterile) or serotype-specific urinary antigen detection (SSUAD) test. Only the five serotypes with at least 10 episodes in the control arm, based on the original analysis, were included for VE assessment. Of 272 clinical CAP visits with VT serotypes identified, 253 (93%) were identified by SSUAD including 210 (77%) by SSUAD alone. VE was determined for serotypes 1, 3, 6A, 7F, and 19A, with total first episodes of, respectively, 27, 36, 25, 38, and 48. VE (95%CI) for the five evaluated serotypes against first clinical CAP episodes were: serotype 1, 20.0% (−83.1% to 65.8%); serotype 3, 61.5% (17.6–83.4%); serotype 6A, 33.3% (−58.6% to 73.2%); serotype 7F, 73.3% (40.5–89.4%); and serotype 19A, 45.2% (−2.2% to 71.5%). Statistically significant VE was observed for serotypes 3 and 7F for clinical CAP among elderly community dwelling adults. The VE point estimates and CIs for serotypes 1, 6A, and 19A were lower but consistent with the overall VT-CAP VE of 45.6% previously reported. These findings may be relevant in models to accurately account for the potential impact of adult PCV13 immunization. [ABSTRACT FROM AUTHOR]

Background: Adults hospitalised to a non-intensive care unit (ICU) ward with moderately severe community-acquired pneumonia are frequently treated with broad-spectrum antibiotics, despite Dutch guidelines recommending narrow-spectrum antibiotics. Therefore, we investigated whether an antibiotic stewardship intervention would reduce the use of broad-spectrum antibiotics in patients with moderately severe community-acquired pneumonia without compromising their safety.Methods: In this cross-sectional, stepped-wedge, cluster-randomised, non-inferiority trial (CAP-PACT) done in 12 hospitals in the Netherlands, we enrolled immunocompetent adults (≥18 years) who were admitted to a non-ICU ward and had a working diagnosis of moderately severe community-acquired pneumonia. All participating hospitals started in a control period and every 3 months a block of two hospitals transitioned from the control to the intervention period, with all hospitals eventually ending in the intervention period. The unit of randomisation was the hospital (cluster), and electronic randomisation (by an independent data manager) decided the sequence (the time of intervention) by which hospitals would cross over from the control period to the intervention period. Blinding was not possible. The antimicrobial stewardship intervention was a bundle targeting health-care providers and comprised education, engaging opinion leaders, and prospective audit and feedback of antibiotic use. The co-primary outcomes were broad-spectrum days of therapy per patient, tested by superiority, and 90-day all-cause mortality, tested by non-inferiority with a non-inferiority margin of 3%, and were analysed in the intention-to-treat population, comprising all patients who were enrolled in the control and intervention periods. This trial was prospectively registered at ClinicalTrials.gov, NCT02604628.Findings: Between Nov 1, 2015, and Nov 1, 2017, 5683 patients were assessed for eligibility, of whom 4084 (2235 in the control period and 1849 in the intervention period) were included in the intention-to-treat analysis. The adjusted mean broad-spectrum days of therapy per patient were reduced from 6·5 days in the control period to 4·8 days in the intervention period, yielding an absolute reduction of -1·7 days (95% CI -2·4 to -1·1) and a relative reduction of 26·6% (95% CI 18·0-35·3). Crude 90-day mortality was 10·9% (242 of 2228 died) in the control period and 10·8% (199 of 1841) in the intervention period, yielding an adjusted absolute risk difference of 0·4% (90% CI -2·7 to 2·4), indicating non-inferiority.Interpretation: In patients hospitalised with moderately severe community-acquired pneumonia, a multifaceted antibiotic stewardship intervention might safely reduce broad-spectrum antibiotic use.Funding: None. [ABSTRACT FROM AUTHOR]

Background: Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes.Methods: In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711.Findings: Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0·97, 95% CI 0·62-1·51; p=0·88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1·38, 95% CI 0·53-3·59, p=0·50), nor did any of the major complications included in the primary endpoint.Interpretation: In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference.Funding: The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development. [ABSTRACT FROM AUTHOR]

Objectives: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of nonconsenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in vaccine effectiveness (VE) estimates., Study Design and Setting: National data were used for the period dominated by the SARS-CoV-2 Delta variant (July 11 to November 15, 2021). VE ((1-relative risk)∗100%) against COVID-19 hospitalization and intensive care unit (ICU) admission was estimated for individuals 12 to 49, 50 to 69, and ≥70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iteratively imputing corrected vaccination status. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected/corrected relative risk., Results: A total of 8804 COVID-19 hospitalizations and 1692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the nonconsent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79)., Conclusion: VE estimates can be substantially biased with modest nonconsent percentages for vaccination data registration. Data on covariate-specific nonconsent percentages should be available to correct this bias., Competing Interests: Declaration of competing interest C.H. van Werkhoven declares financial and nonfinancial research support from DaVolterra and bioMérieux; financial research support from LimmaTech; consultancy fees from MSD and Sanofi-Pasteur (all payments to the University Medical Center Utrecht, not related to the current manuscript). There are no competing interests for any other author., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Follow-up guidelines barely diverge from a one-size-fits-all approach, even though the risk of recurrence differs per patient. However, the personalization of breast cancer care improves outcomes for patients. This study explores the variation in follow-up pathways in the Netherlands using real-world data to determine guideline adherence and the gap between daily practice and risk-based surveillance, to demonstrate the benefits of personalized risk-based surveillance compared with usual care., Methods: Patients with stage I-III invasive breast cancer who received surgical treatment in a general hospital between 2005 and 2020 were selected from the Netherlands Cancer Registry and included all imaging activities during follow-up from hospital-based electronic health records. Process analysis techniques were used to map patients and activities to investigate the real-world utilisation of resources and identify the opportunities for improvement. The INFLUENCE 2.0 nomogram was used for risk prediction of recurrence., Results: In the period between 2005 and 2020, 3478 patients were included with a mean follow-up of 4.9 years. In the first 12 months following treatment, patients visited the hospital between 1 and 5 times (mean 1.3, IQR 1-1) and received between 1 and 9 imaging activities (mean 1.7, IQR 1-2). Mammogram was the prevailing imaging modality, accounting for 70% of imaging activities. Patients with a low predicted risk of recurrence visited the hospital more often., Conclusions: Deviations from the guideline were not in line with the risk of recurrence and revealed a large gap, indicating that it is hard for clinicians to accurately estimate this risk and therefore objective risk predictions could bridge this gap., (© 2024. The Author(s).)

Background: New 15- and 20-valent pneumococcal vaccines (PCV15, PCV20) are available for both children and adults, while PCV21 for adults is in development. However, their cost-effectiveness for older adults, taking into account indirect protection and serotype replacement from a switch to PCV15 and PCV20 in childhood vaccination, remains unexamined., Methods: We used a static model for the Netherlands to assess the cost-effectiveness of different strategies with 23-valent pneumococcal polysaccharide vaccine (PPV23), PCV15, PCV20, and PCV21 for a 65-year-old cohort from a societal perspective, over a 15-year time horizon. Childhood vaccination was varied from PCV10 to PCV13, PCV15, and PCV20. Indirect protection was assumed to reduce the incidence of vaccine serotypes in older adults by 80% (except for serotype 3, no effect), completely offset by an increase in non-vaccine serotype incidence due to serotype replacement., Results: Indirect effects from childhood vaccination reduced the cost-effectiveness of vaccination of older adults, depending on the serotype overlap between the vaccines. With PCV10, PCV13, or PCV15 in children, PCV20 was more effective and less costly for older adults than PPV23 and PCV15. PCV20 costs approximately €10,000 per quality-adjusted life year (QALY) gained compared to no pneumococcal vaccination, which falls below the conventional Dutch €20,000/QALY gained threshold. However, with PCV20 in children, PCV20 was no longer considered cost-effective for older adults, costing €22,550/QALY gained. As indirect effects progressed over time, the cost-effectiveness of PCV20 for older adults further diminished for newly vaccinated cohorts. PPV23 was more cost-effective than PCV20 for cohorts vaccinated 3 years after the switch to PCV20 in children. PCV21 offered the most QALY gains, and its cost-effectiveness was minimally affected by indirect effects due to its coverage of 11 different serotypes compared to PCV20., Conclusions: For long-term cost-effectiveness in the Netherlands, the pneumococcal vaccine for older adults should either include invasive serotypes not covered by childhood vaccination or become more affordable than its current pricing for individual use., (© 2024. The Author(s).)

An important aspect of the rehabilitation of burn patients is social participation, including daily activities and work. Detailed information on long-term activity impairment and employment is scarce. Therefore, we investigated activity impairment, work status, and work productivity loss in adults 5-7 years following burn injuries, and investigated associations with burn-specific health-related quality of life (HRQL) domains. Adult participants completed the Work Productivity and Activity Impairment General Health questionnaire and the Burn Specific Health Scale-brief (BSHS-B) 5-7 years post-burn. Outcomes were compared between participants with mild/intermediate and severe burns (>20% total body surface area burned). Seventy-six (36%) of the 213 participants experienced some degree of activity impairment due to burn-related problems 5-7 years post-burn. Seventy percent of the population was employed; 12% of them experienced work productivity loss due to burn-related problems. Nineteen percent reported changes in their work situation (partly) because of the burn injury. A higher proportion of participants with severe burns had activity impairments (56% vs 29%; P = .001) and work productivity loss (26% vs 8%; P < .001) compared to participants with mild/intermediate burns. Activity impairment and work productivity loss were both associated with burn-related work problems and lower mood, measured with the BSHS-B. In conclusion, a substantial part of the study population experienced activity impairment and work productivity loss, was unemployed, and/or reported changes in their work situation due to their injury. Particularly patients with severe burns reported productivity loss and had lower employment rates. This subscribes the importance of addressing work-related functioning in the rehabilitation of burn patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association.)

Introduction: Ampullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016., Methods: Patients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease., Results: In total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989-1995 to 0.68 per 100,000in 2010-2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989-1995 to 63.9% in 2010-2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9-22.8) in 1989-1995 to 29.1% (26.0-31.2) in 2010-2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6-5.0) to 5.9 months (4.7-7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients., Conclusion: Both incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy., Competing Interests: Declaration of competing interest Drs. de Vos-Geelen reports grants, personal fees and non-financial support from Servier, personal fees from AstraZeneca, personal fees from MSD, personal fees from Pierre Fabre, personal fees from Amgen, outside the submitted work. Dr. ir. Geurts reports grants from Roche, grants from Pfizer, grants from Novartis, grants from Eisai, grants from Lilly, outside the submitted work. Dr. Haj Mohammad reports non-financial support from Servier, non-financial support from MSD, non-financial support from BMS, non-financial support from Eli Lily, non-financial support from Astra Zeneca, outside the submitted work. Dr. van Laarhoven reports grants and non-financial support from BMS, grants and non-financial support from Celgene, grants and non-financial support from Lilly, grants and non-financial support from Nordic, grants and non-financial support from Servier, grants from Bayer, grants from Merck Serono, grants from MSD, grants from Philips, outside the submitted work. Dr. Tjan-Heijnen reports grants and personal fees from Roche, grants and personal fees from Novartis, grants and personal fees from Pfizer, grants and personal fees from Lilly, personal fees from Accord Healthcare, grants from AstraZeneca, grants from Eisai, grants from Daiichi Sankyo, outside the submitted work. Dr. Valkenburg-van Iersel reports non-financial support from Servier, non-financial support from Pierre Fabre, non-financial support from Roche, outside the submitted work. Dr. Wilmink reports grants and non-financial support from Servier, non-financial support from MSD, non-financial support from AstraZeneca, grants and non-financial support from Celgene, grants from Halozyme, grants from Merck, grants from Roche, grants from Pfizer, grants from Amgen, grants from Novartis, outside the submitted work. The other authors have declared no conflicts of interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The primary aim of this study was to evaluate the number of patients reported to a hospital with injuries from consumer fireworks in the months December-January in the past 10 years, and to describe the association between the type of fireworks, injury pattern, treatment, and permanent impairment., Methods: A multicenter, retrospective, observational case series. Patients were selected from two hospitals in the Southwest Netherlands: a level 1 trauma center and a specialized burn center. All patients with any fireworks-related injuries treated between December 1 and January 31, during 2007 (December) to 2017 (January), were eligible for participation. The primary outcome was the number of patients with any type of injury caused by fireworks. The secondary outcome measures were patient and injury characteristics, treatment details, and whole person impairment (WPI). The percentage WPI expresses a patient's degree of permanent impairments as a result of fireworks-related injuries., Results: Of the 297 eligible patients, 272 patients were included. From 2007 to 2017, between 21 and 40 patients were treated, and no clear increase or decrease was observed in the number of patients and in the number of patients per type of fireworks. Explosive fireworks mainly caused upper extremity (N = 65; 68%) injuries, while rockets (N = 24; 41%) and aerials (N = 7; 41%) mainly affected the head/neck. Decorative fireworks predominantly resulted in burns (N = 82; 68%), and explosive fireworks in soft tissue lacerations (N = 24; 25%), fractures (N = 16; 17%), and amputations (N = 14; 15%). Patients injured by explosive and homemade fireworks were most often admitted to a hospital (respectively N = 24; 36% and N = 12; 80%), and resulted in the highest proportion undergoing surgical procedures (respectively N = 22; 33% and N = 7; 47%). WPI found in this study was between 0 to 95%, with a median of 0%. In 34 (14%) patients, the injuries resulted in a WPI of ≥1%, mostly as a result of explosive fireworks (N = 18; 53%)., Conclusion: This study found no increase or decrease in the number of patients treated in two specialized hospitals. Explosive and homemade fireworks could be considered as most dangerous, as they result into the most hospital admissions, surgical procedures, and into the most injuries with permanent impairment as a result.

Objectives There is a global increase in infections caused by Gram-negative bacteria. The majority of research is on bacteremic Gram-negative infections (GNI), leaving a knowledge gap on the burden of non-bacteremic GNI. Our aim is to describe characteristics and determine the burden of bacteremic and non-bacteremic GNI in hospitalized patients in the Netherlands. Methods We conducted a prospective cohort study of patients in eight hospitals with microbiologically confirmed GNI, between June 2013 and November 2015. In each hospital the first five adults meeting the eligibility criteria per week were enrolled. We estimated the national incidence and mortality of GNI by combining the cohort data with a national surveillance database for antimicrobial resistance. Results 1,954 patients with GNI were included of which 758 (39%) were bloodstream infections (BSI). 243 GNI (12%) involved multi-drug resistant pathogens. 30-day mortality rate was 11.1% (n = 217) Estimated national incidences of non-bacteremic GNI and bacteremic GNI in hospitalized adults were 74 (95% CI 58 - 89) and 86 (95% CI 72-100) per 100,000 person years, yielding estimated annual numbers of 30-day all-cause mortality deaths of 1,528 (95% CI 1,102-1,954) for bacteremic and 982 (95% CI 688 - 1,276) for non-bacteremic GNI. Conclusion GNI form a large mortality burden in a low-resistance country. A third of the associated mortality occurs after non-bacteremic GNI., Competing Interests: Conflicts of Interest None reported., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome., Methods: In a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity., Results: A total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18-70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30-day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later., Conclusions: In a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%)., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

There exists little to no data on the development of donor-site scars that remain after split skin graft harvesting. The objectives of this study were to (a) examine changes in characteristics of donor-site scar quality over time and (b) assess the agreement between patient-reported and observer-reported donor-site scar quality in a burn population. A prospective cohort study was conducted including patients who underwent split skin grafting for their burn injury. Patients and observers completed the Patient and Observer Scar Assessment Scale (POSAS) for the first harvested donor site at 3 and 12 months post-surgery. This study included 80 patients with a median age of 34 years. At 3 months post-surgery, the patients scored the POSAS items itch and color as most deviant from normal skin, both improved between 3 and 12 months (3.1 vs 1.5 and 5.0 vs 3.5, respectively [P < .001]). Other scar characteristics did not show significant change over time. The patients' overall opinion score improved from 3.9 to 3.2 (P < .001). Observers rated the items vascularization and pigmentation most severe, only vascularization improved significantly between both time points. Their overall opinion score decreased from 2.7 to 2.3 (P < .001). The inter-observer agreement between patients and observers was considered poor (ICC < 0.4) at both time points. Results of current study indicate that observers underestimate the impact of donor-site scars. This has to be kept in mind while guiding therapy and expectations. LEVEL OF EVIDENCE: II, prospective cohort study., (© 2020 by the Wound Healing Society.)

Bacille Calmette-Guérin (BCG) induces long-term boosting of innate immunity, termed trained immunity, and decreases susceptibility to respiratory tract infections. BCG vaccination trials for reducing SARS-CoV-2 infection are underway, but concerns have been raised regarding the potential harm of strong innate immune responses. To investigate the safety of BCG vaccination, we retrospectively assessed coronavirus disease 2019 (COVID-19) and related symptoms in three cohorts of healthy volunteers who either received BCG in the last 5 years or did not. BCG vaccination is not associated with increased incidence of symptoms during the COVID-19 outbreak in the Netherlands. Our data suggest that BCG vaccination might be associated with a decrease in the incidence of sickness during the COVID-19 pandemic (adjusted odds ratio [AOR] 0.58, p < 0.05), and lower incidence of extreme fatigue. In conclusion, recent BCG vaccination is safe, and large randomized trials are needed to reveal if BCG reduces the incidence and/or severity of SARS-CoV-2 infection., Competing Interests: M.G.N. and L.A.B.J. are scientific founders of TTxD., (© 2020 The Author(s).)

Background: Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed., Methods: This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005-2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0-5 years after resection was calculated using the Kaplan-Meier method. A prediction model was constructed., Results: Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17-18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics., Conclusions: This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via www.pancreascalculator.com to inform patients and caregivers.

Little is known about delirium in elderly burn center patients. The aim of this study is to provide information on the prevalence of delirium and risk factors contributing to the onset of delirium. All patients aged 70 years or older admitted with burn injuries to the Burn Center, Maasstad Hospital, in 2011 to 2017 were eligible for inclusion. We retrospectively collected data regarding the presence of delirium, potential risk factors contributing to the onset of delirium and outcome after delirium. We included elderly 90 patients in this study. The prevalence of delirium in our population was 13% (N = 12). Risk factors for delirium were advanced age, increased American Society for Anesthesiologists score, physical impairment and the use of anticholinergic drugs during admission. Patients with delirium had a poorer outcome, with prolonged hospital stay and increased mortality 6 and 12 months after discharge. Delirium is diagnosed in 13% of the elderly patients admitted to our burn center. Risk factors for delirium found in this study are advanced age, poor physical health status, physical impairment, and the use of anticholinergic drugs. Delirium is related to poor outcomes, including prolonged hospital stay and mortality after discharge., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Burn Association.)

Background: Burden of disease estimates are an important resource in public health. Currently, robust estimates are not available for the burn population. Our objectives are to adapt a refined methodology (INTEGRIS method) to burns and to apply this new INTEGRIS-burns method to estimate, and compare, the burden of disease of burn injuries in Australia, New Zealand and the Netherlands., Methods: Existing European and Western-Australian health-related quality of life (HRQL) datasets were combined to derive disability weights for three homogenous burn injury groups based on percentage total body surface area (%TBSA) burned. Subsequently, incidence data from Australia, New Zealand, and the Netherlands from 2010 to 2017 were used to compute annual non-fatal burden of disease estimates for each of these three countries. Non-fatal burden of disease was measured by years lived with disability (YLD)., Results: The combined dataset included 7159 HRQL (EQ-5D-3 L) outcomes from 3401 patients. Disability weights ranged from 0.046 (subgroup < 5% TBSA burned > 24 months post-burn) to 0.497 (subgroup > 20% TBSA burned 0-1 months post-burn). In 2017 the non-fatal burden of disease of burns for the three countries (YLDs/100,000 inhabitants) was 281 for Australia, 279 for New Zealand and 133 for the Netherlands., Conclusions: This project established a method for more precise estimates of the YLDs of burns, as it is the only method adapted to the nature of burn injuries and their recovery. Compared to previous used methods, the INTEGRIS-burns method includes improved disability weights based on severity categorization of burn patients; a better substantiated proportion of patients with lifelong disability based; and, the application of burn specific recovery timeframes. Information derived from the adapted method can be used as input for health decision making at both the national and international level. Future studies should investigate whether the application is valid in low- and middle- income countries.

Background: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the implementation and outcome of MILS on a nationwide scale., Methods: Electronic patient files were reviewed in all Dutch liver surgery centers and all patients undergoing MILS between 2011 and 2016 were selected. Operative outcomes were stratified based on extent of the resection and annual MILS volume., Results: Overall, 6951 liver resections were included, with a median annual volume of 50 resections per center. The overall use of MILS was 13% (n = 916), which varied from 3% to 36% (P < 0.001) between centers. The nationwide use of MILS increased from 6% in 2011 to 23% in 2016 (P < 0.001). Outcomes of minor MILS were comparable with international studies (conversion 0-13%, mortality <1%). In centers which performed ≥20 MILS annually, major MILS was associated with less conversions (14 (11%) versus 41 (30%), P < 0.001), shorter operating time (184 (117-239) versus 200 (139-308) minutes, P = 0.010), and less overall complications (37 (30%) versus 58 (42%), P = 0.040)., Conclusion: The nationwide use of MILS is increasing, although large variation remains between centers. Outcomes of major MILS are better in centers with higher volumes., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: It is unknown whether nitrofurantoin 50 mg normal-release every 6 h (NF50) and nitrofurantoin 100 mg extended-release every 12 h (NF100) are equally effective for treating cystitis in primary care. In the Netherlands, GP prescription of either option largely depends on pharmacy procurement, rather than on patient-related factors., Methods: GP data between January 2013 and July 2018 were retrospectively collected. Inclusion criteria were the use of nitrofurantoin for uncomplicated cystitis, complicated cystitis or cystitis in pregnancy. Criteria for early and late failure were a second antibiotic prescription for cystitis or pyelonephritis within 14 and 28 days post-prescription, respectively. Crude and confounder-adjusted (CA) risk differences (RDs) were estimated using linear regression. Instrumental variable analysis and CA instrumental variable analysis used GP practice proportion of NF50 versus NF100 use as the instrumental variable., Results: For uncomplicated cystitis (n=46855), treatment with NF50 and NF100 resulted in late failure in 9.7% and 9.6%, respectively. The CA RD, instrumental variable RD and CA instrumental variable RD were 0.2% (95% CI=-0.5 to 0.8), -0.7% (95% CI=-1.7 to 0.3) and 0.0% (95% CI=-0.9 to 1.0), respectively. In complicated cystitis (n=10767), late failure occurred in 10.9% and 11.1% after using NF50 and NF100, respectively [CA RD=0.5% (95% CI=-1.2 to 1.8), instrumental variable RD=-0.8% (95% CI=-3.4 to 1.8) and CA instrumental variable RD=-0.3% (95% CI=-3.0 to 2.4)]. For cystitis in pregnancy (n=1087), NF50 and NF100 resulted in late failure in 13.4% and 7.8%, respectively [CA RD=-5.4% (95% CI=-10.0 to -1.4), instrumental variable RD=-8.9% (95% CI=-16.0 to -1.8) and CA instrumental variable RD=-8.9% (95% CI=-16.0 to -1.7)]. No differences were observed in early failure., Conclusions: In patients with cystitis in pregnancy, NF100 was associated with a lower incidence of late clinical failure compared with NF50. We found no differences in clinical failure between NF50 and NF100 for uncomplicated and complicated cystitis., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Objective: To determine the cost-effectiveness of selective digestive decontamination (SDD) as compared to selective oropharyngeal decontamination (SOD) in intensive care units (ICUs) with low levels of antimicrobial resistance., Design: Post-hoc analysis of a previously performed individual patient data meta-analysis of two cluster-randomised cross-over trials., Setting: 24 ICUs in the Netherlands., Participants: 12 952 ICU patients who were treated with ≥1 dose of SDD (n=6720) or SOD (n=6232)., Interventions: SDD versus SOD., Primary and Secondary Outcome Measures: The incremental cost-effectiveness ratio (ICER; ie, costs to prevent one in-hospital death) was calculated by comparing differences in direct healthcare costs and in-hospital mortality of patients treated with SDD versus SOD. A willingness-to-pay curve was plotted to reflect the probability of cost-effectiveness of SDD for a range of different values of maximum costs per prevented in-hospital death., Results: The ICER resulting from the fixed-effect meta-analysis, adjusted for clustering and differences in baseline characteristics, showed that SDD significantly reduced in-hospital mortality (adjusted absolute risk reduction 0.0195, 95% CI 0.0050 to 0.0338) with no difference in costs (adjusted cost difference €62 in favour of SDD, 95% CI -€1079 to €935). Thus, SDD yielded significantly lower in-hospital mortality and comparable costs as compared with SOD. At a willingness-to-pay value of €33 633 per one prevented in-hospital death, SDD had a probability of 90.0% to be cost-effective as compared with SOD., Conclusion: In Dutch ICUs, SDD has a very high probability of cost-effectiveness as compared to SOD. These data support the implementation of SDD in settings with low levels of antimicrobial resistance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Mortality in burn intensive care unit (ICU) has been decreasing and treatment appears to be changing. The aims of this study: (1) examine outcome in burn patients, (2) examine changes in ICU indication and (3) explore the influence of a changing case-mix., Methods: Retrospective study in patients admitted to ICU (1987-2016). Four groups were specified: major burns (≥15% TBSA), inhalation injury with small injury (<15% TBSA, inhalation injury), watchful waiting (<15% TBSA, without inhalation injury), tender loving care (patients withheld from treatment). Logistic regression was performed to evaluate the relation between case-mix and outcome., Results: Overall mortality decreased to 7%. Mortality of major burns decreased by 15%. The major burn group decreased by 36%. The inhalation injury and watchful waiting group increased by 9% and 21%. The percentage of ventilated patients increased by 14% in the major burn group. 40% of patients were ventilated in the watchful waiting group., Conclusions: After correction for case-mix, survival improved, mainly in the major burn group. Case-mix shifted towards inhalation injury and watchful waiting. Growth of the watchful waiting group is not necessarily harmful. However, the increase of mechanical ventilation could be. We suggest raising awareness for risks and consequences of mechanical ventilation., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Scar formation is an important adverse consequence of burns. How patients appraise their scar quality is often studied shortly after sustaining the injury, but information in the long-term is scarce. Our aim was, therefore, to evaluate long-term patient-reported quality of burn scars. Adults with a burn center admission of ≥1 day between August 2011 and September 2012 were invited to complete a questionnaire on long-term consequences of burns. We enriched this sample with patients with severe burns (>20% total body surface area [TBSA] burned or TBSA full thickness >5%) treated between January 2010 and March 2013. Self-reported scar quality was assessed with the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS). Patients completed this scale for their-in their opinion-most severe scar ≥5 years after burns. This study included 251 patients with a mean %TBSA burned of 10%. The vast majority (91.4%) reported at least minor differences with normal skin (POSAS item score ≥2) on one or more scar characteristics and 78.9% of the patients' overall opinion was that their scar deviated from normal skin. Patients with severe burns had higher POSAS scores, representing worse scar quality, than patients with mild/intermediate burns, except for color, which was high in both groups. A longer hospital stay predicted reduced scar quality (both mean POSAS and mean overall opinion of the scar) in multivariate analyses. In addition, female gender was also associated with a poorer overall opinion of the scar. In conclusion, this study provides new insights in long-term scar quality. Scars differed from normal skin in a large part of the burn population more than 5 years after burns, especially in those with severe burns. Female gender is associated with a poorer patients' overall opinion of their scar, which may be an indication of gender differences in perception of scar quality after burns., (© 2019 The Authors. Wound Repair and Regeneration published by Wiley Periodicals, Inc. on behalf of by the Wound Healing Society.)

Background: Infected necrosis complicates 10% of all acute pancreatitis episodes and is associated with 15-20% mortality. The current standard treatment for infected necrotizing pancreatitis is the step-up approach (catheter drainage, followed, if necessary, by minimally invasive necrosectomy). Catheter drainage is preferably postponed until the stage of walled-off necrosis, which usually takes 4 weeks. This delay stems from the time when open necrosectomy was the standard. It is unclear whether such delay is needed for catheter drainage or whether earlier intervention could actually be beneficial in the current step-up approach. The POINTER trial investigates if immediate catheter drainage in patients with infected necrotizing pancreatitis is superior to the current practice of postponed intervention., Methods: POINTER is a randomized controlled multicenter superiority trial. All patients with necrotizing pancreatitis are screened for eligibility. In total, 104 adult patients with (suspected) infected necrotizing pancreatitis will be randomized to immediate (within 24 h) catheter drainage or current standard care involving postponed catheter drainage. Necrosectomy, if necessary, is preferably postponed until the stage of walled-off necrosis, in both treatment arms. The primary outcome is the Comprehensive Complication Index (CCI), which covers all complications between randomization and 6-month follow up. Secondary outcomes include mortality, complications, number of (repeat) interventions, hospital and intensive care unit (ICU) lengths of stay, quality-adjusted life years (QALYs) and direct and indirect costs. Standard follow-up is at 3 and 6 months after randomization., Discussion: The POINTER trial investigates if immediate catheter drainage in infected necrotizing pancreatitis reduces the composite endpoint of complications, as compared with the current standard treatment strategy involving delay of intervention until the stage of walled-off necrosis., Trial Registration: ISRCTN, 33682933 . Registered on 6 August 2015. Retrospectively registered.

Objective: To report the number of patients with firework-related injuries treated in December 2017 and January 2018 in a hospital in the south-west Netherlands trauma region, and to provide details about the types of firework used and the specific injuries., Design: A prospective multicentre cohort study (NTR6793)., Methods: Patients of all ages with firework-related injuries were eligible for inclusion. The injury had to have been sustained between 1 December 2017 and 31 January 2018, and treated at a hospital in the south-west Netherlands trauma region (approximately 2.5 million inhabitants). Data were extracted from patients' medical files and additional information was obtained from patient interviews., Results: Fifty-four patients were included. The majority were male (93%) and the median age was 15 years. Twenty-five (46%) patients were bystanders and 12 (22%) were injured by illegal fireworks. Fifty patients were injured by bangers (n=22) or decorative fireworks (n=28). The patients had a total of 79 injuries, of which 29 (37%) were localised to the upper extremity and 19 (24%) to the eyes. Most upper extremity injuries were burns (69%), primarily partial thickness. Of the eye injuries, 14 were caused by blunt trauma, seven by chemical trauma, and one by penetrating trauma. Three patients sustained indirect firework-related injuries., Conclusion: Between 1 December 2017 and 31 January 2018 in the south-west Netherlands trauma region mainly teenage males and bystanders sustained firework-related injuries. Most injuries were upper extremity burns and eye injuries, mainly due to legal fireworks and bangers or decorative fireworks. The extent of the sample indicates that the study findings can be extrapolated to the rest of the Netherlands.

Introduction: The Emergency Management of Severe Burns (EMSB) referral criteria have been implemented for optimal triaging of burn patients. Admission to a burn centre is indicated for patients with severe burns or with specific characteristics like older age or comorbidities. Patients not meeting these criteria can also be treated in a hospital without burn centre. Limited information is available about the organisation of care and referral of these patients. The aims of this study are to determine the burn injury characteristics, treatment (costs), quality of life and scar quality of burn patients admitted to a hospital without dedicated burn centre. These data will subsequently be compared with data from patients with<10% total bodysurface area (TBSA) burned who are admitted (or secondarily referred) to a burn centre. If admissions were in agreement with the EMSB, referral criteria will also be determined., Methods and Analysis: In this multicentre, prospective, observational study (cohort study), the following two groups of patients will be followed: 1) all patients (no age limit) admitted with burn-related injuries to a hospital without a dedicated burn centre in the Southwest Netherlands or Brabant Trauma Region and 2) all patients (no age limit) with<10% TBSA burned who are primarily admitted (or secondarily referred) to the burn centre of Maasstad Hospital. Data on the burn injury characteristics (primary outcome), EMSB compliance, treatment, treatment costs and outcome will be collected from the patients' medical files. At 3 weeks and at 3, 6 and 12 months after trauma, patients will be asked to complete the quality of life questionnaire (EuroQoL-5D), and the patient-reported part of the Patient and Observer Scar Assessment Scale (POSAS). At those time visits, the coordinating investigator or research assistant will complete the observer-reported part of the POSAS., Ethics and Dissemination: This study has been exempted by the medical research ethics committee Erasmus MC (Rotterdam, The Netherlands). Each participant will provide written consent to participate and remain encoded during the study. The results of the study are planned to be published in an international, peer-reviewed journal., Trial Registration Number: NTR6565., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma., Methods: We did a multicentre, randomised controlled trial at four academic centres in the Netherlands. Patients who were aged at least 18 years with potentially resectable perihilar cholangiocarcinoma requiring major liver resection, and biliary obstruction of the future liver remnant (defined as a bilirubin concentration of >50 μmol/L [2·9 mg/dL]), were randomly assigned (1:1) to receive endoscopic biliary drainage or percutaneous transhepatic biliary drainage through the use of computer-generated allocation. Randomisation, done by the trial coordinator, was stratified for previous (attempted) biliary drainage, the extent of bile duct involvement, and enrolling centre. Patients were enrolled by clinicians of the participating centres. The primary outcome was the number of severe complications between randomisation and surgery in the intention-to-treat population. The trial was registered at the Netherlands National Trial Register, number NTR4243., Findings: From Sept 26, 2013, to April 29, 2016, 261 patients were screened for participation, and 54 eligible patients were randomly assigned to endoscopic biliary drainage (n=27) or percutaneous transhepatic biliary drainage (n=27). The study was prematurely closed because of higher mortality in the percutaneous transhepatic biliary drainage group (11 [41%] of 27 patients) than in the endoscopic biliary drainage group (three [11%] of 27 patients; relative risk 3·67, 95% CI 1·15-11·69; p=0·03). Three of the 11 deaths among patients in the percutaneous transhepatic biliary drainage group occurred before surgery. The proportion of patients with severe preoperative drainage-related complications was similar between the groups (17 [63%] patients in the percutaneous transhepatic biliary drainage group vs 18 [67%] in the endoscopic biliary drainage group; relative risk 0·94, 95% CI 0·64-1·40). 16 (59%) patients in the percutaneous transhepatic biliary drainage group and ten (37%) patients in the endoscopic biliary drainage group developed preoperative cholangitis (p=0·1). 15 (56%) patients required additional percutaneous transhepatic biliary drainage after endoscopic biliary drainage, whereas only one (4%) patient required endoscopic biliary drainage after percutaneous transhepatic biliary drainage., Interpretation: The study was prematurely stopped because of higher all-cause mortality in the percutaneous transhepatic biliary drainage group. Post-drainage complications were similar between groups, but the data should be interpreted with caution because of the small sample size. The results call for further prospective studies and reconsideration of indications and strategy towards biliary drainage in this complex disease., Funding: Dutch Cancer Foundation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The feasibility of the liver-first approach for synchronous colorectal liver metastases (CRLM) has been established. We sought to assess the short-term and long-term outcomes for these patients., Methods: Outcomes of patients who underwent a liver-first approach for CRLM between 2005 and 2015 were retrospectively evaluated from a prospective database., Results: Of the 92 patients planned to undergo the liver-first strategy, the paradigm could be completed in 76.1%. Patients with concurrent extrahepatic disease failed significantly more often in completing the protocol (67% versus 21%; p = 0.03). Postoperative morbidity and mortality were 31.5% and 3.3% following liver resection and 30.9% and 0% after colorectal surgery. Of the 70 patients in whom the paradigm was completed, 36 patients (51.4%) developed recurrent disease after a median interval of 20.9 months. The median overall survival on an intention-to-treat basis was 33.1 months (3- and 5-year overall survival: 48.5% and 33.1%). Patients who were not able to complete their therapeutic paradigm had a significantly worse overall outcome (p = 0.03)., Conclusion: The liver-first approach is feasible with acceptable perioperative morbidity and mortality rates. Despite the considerable overall-survival-benefit, recurrence rates remain high. Future research should focus on providing selection tools to enable the optimal treatment sequence for each patient with synchronous CRLM., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Deep dermal burns require tangential excision of non-viable tissue and skin grafting to improve wound healing and burn-scar quality. Tangential excision is conventionally performed with a knife, but during the last decade hydrosurgery has become popular as a new tool for tangential excision. Hydrosurgery is generally thought to be a more precise and controlled manner of burn debridement leading to preservation of viable tissue and, therefore, better scar quality. Although scar quality is considered to be one of the most important outcomes in burn surgery today, no randomized controlled study has compared the effect of these two common treatment modalities with scar quality as a primary outcome. The aim of this study is, therefore, to compare long-term scar quality after hydrosurgical versus conventional tangential excision in deep dermal burns., Methods/design: A multicenter, randomized, intra-patient, controlled trial will be conducted in the Dutch burn centers of Rotterdam, Beverwijk, and Groningen. All patients with deep dermal burns that require excision and grafting are eligible. Exclusion criteria are: a burn wound < 50 cm 2 , total body surface area (TBSA) burned > 30%, full-thickness burns, chemical or electrical burns, infected wounds (clinical symptoms in combination with positive wound swabs), insufficient knowledge of the Dutch or English language, patients that are unlikely to comply with requirements of the study protocol and follow-up, and patients who are (temporarily) incompetent because of sedation and/or intubation. A total of 137 patients will be included. Comparable wound areas A and B will be appointed, randomized and either excised conventionally with a knife or with the hydrosurgery system. The primary outcome is scar quality measured by the observer score of the Patient and Observer Scar Assessment Scale (POSAS); a subjective scar-assessment instrument, consisting of two separate six-item scales (observer and patient) that are both scored on a 10-point rating scale., Discussion: This study will contribute to the optimal surgical treatment of patients with deep dermal burn wounds., Trial Registration: Dutch Trial Register, NTR6232 . Registered on 23 January 2017.

Objectives: The American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale is among the most used questionnaires for measuring functional recovery after a hindfoot injury. Recently, this instrument was translated and culturally adapted into a Dutch version. In this study, the measurement properties of the Dutch language version (DLV) were investigated in patients with a unilateral hindfoot fracture., Design: Multicentre, prospective observational study., Setting: This multicentre study was conducted in three Dutch hospitals., Participants: In total, 118 patients with a unilateral hindfoot fracture were included. Three patients were lost to follow-up., Primary and Secondary Outcome Measures: Patients were asked to complete the AOFAS-DLV, the Foot Function Index and the Short Form-36 on three occasions. Descriptive statistics (including floor and ceiling effects), reliability (ie, internal consistency), construct validity, reproducibility (ie, test-retest reliability, agreement and smallest detectable change (SDC)) and responsiveness were determined., Results: Internal consistency was inadequate for the AOFAS-DLV total scale (α=0.585), but adequate for the function subscale (α=0.863). The questionnaire had adequate construct validity (82.4% of predefined hypotheses were confirmed), but inadequate longitudinal validity (70.6%). No floor effects were found, but ceiling effects were present in all AOFAS-DLV (sub)scales, most pronounced from 6 to 24 months after trauma onwards. Responsiveness was only adequate for the pain and alignment subscales, with a SDC of 1.7 points., Conclusions: The AOFAS Ankle-Hindfoot Scale DLV has adequate construct validity and is reliable, making it a suitable instrument for cross-sectional studies investigating functional outcome in patients with a hindfoot fracture. The inadequate longitudinal validity and responsiveness, however, hamper the use of the questionnaire in longitudinal studies and for assessing long-term functional outcome., Trial Registration Number: NTR5613; Post-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: In adults hospitalized with community-acquired pneumonia (CAP) after >48 h of outpatient beta-lactam monotherapy, coverage of atypical pathogens is recommended based on expert opinion., Methods: In a post-hoc analysis of a large study of CAP treatment we included patients who received beta-lactam monotherapy for >48 h before hospitalization. Length of hospital stay (LOS), 30-day mortality, and number of treatment escalations were compared for those that continued beta-lactam monotherapy and those that received atypical coverage at admission., Results: Of 179 patients (median age 66 years (IQR 50-78), 100 (56%) male), 131 (73%) received additional atypical coverage at admission. These patients were younger, had less comorbidities, and longer symptom duration, compared to those that continued beta-lactam monotherapy. In crude analysis, median (IQR) LOS was 6 (4-8) and 6 (4-9) days, mortality was 2% and 4%, and treatment escalations occurred in 8 (17%) and 11 (8%) patients without and with atypical coverage, respectively. Adjusted effect ratios for absence of atypical coverage on LOS, mortality, and treatment escalation were 0.77 (95% CI 0.61-0.97), 0.37 (0.04-3.67), and 2.75 (0.94-8.09), respectively., Conclusion: In adults hospitalized with CAP after >48 h of outpatient beta-lactam monotherapy, not starting antibiotics with atypical coverage was associated with a trend towards more treatment escalations, without evidence of increased LOS or mortality., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Postoperative liver failure (PLF) is a dreaded complication after partial hepatectomy. The peak bilirubin criterion (>7.0 mg/dL or ≥120 μmol/L) is used to define PLF. This study aimed to validate the peak bilirubin criterion as postoperative risk indicator for 90-day liver-related mortality., Methods: Characteristics of 956 consecutive patients who underwent partial hepatectomy at the Maastricht University Medical Centre or Royal Free London between 2005 and 2012 were analyzed by uni- and multivariable analyses with odds ratios (OR) and 95% confidence intervals (95%CI)., Results: Thirty-five patients (3.7%) met the postoperative peak bilirubin criterion at median day 19 with a median bilirubin level of 183 [121-588] μmol/L. Sensitivity and specificity for liver-related mortality after major hepatectomy were 41.2% and 94.6%, respectively. The positive predictive value was 22.6%. Predictors of liver-related mortality were the peak bilirubin criterion (p < 0.001, OR = 15.9 [95%CI 5.2-48.7]), moderate-severe steatosis and fibrosis (p = 0.013, OR = 8.5 [95%CI 1.6-46.6]), ASA 3-4 (p = 0.047, OR = 3.0 [95%CI 1.0-8.8]) and age (p = 0.044, OR = 1.1 [95%CI 1.0-1.1])., Conclusion: The peak bilirubin criterion has a low sensitivity and positive predictive value for 90-day liver-related mortality after major hepatectomy., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Centralization of a pancreatoduodenectomy (PD) leads to a lower post-operative mortality, but is unclear whether it also leads to improved radical (R0) or overall resection rates., Methods: Between 2004 and 2009, pathology reports of 1736 PDs for pancreatic and peri-ampullary neoplasms from a nationwide pathology database were analysed. Pre-malignant lesions were excluded. High-volume hospitals were defined as performing ≥ 20 PDs annually. The relationship between R0 resections, PD-volume trends, quality of pathology reports and hospital volume was analysed., Results: During the study period, the number of hospitals performing PDs decreased from 39 to 23. High-volume hospitals reported more R0 resections in the pancreatic head and distal bile duct tumours than low-volume hospitals (60% versus 54%, P = 0.035) although they operated on more advanced (T3/T4) tumours (72% versus 58%, P < 0.001). The number of PDs increased from 258 in 2004 to 394 in 2009 which was partly explained by increased overall resection rates of pancreatic head and distal bile duct tumours (11.2% in 2004 versus 17.5% in 2009, P < 0.001). The overall reported R0 resection rate of pancreatic head and distal bile duct tumours increased (6% in 2004 versus 11% in 2009, P < 0.001). Pathology reports of low-volume hospitals lacked more data including tumour stage (25% versus 15%, P < 0.001)., Conclusions: Centralization of PD was associated with both higher resection rates and more reported R0 resections. The impact of this finding on overall survival should be further assessed., (© 2015 International Hepato-Pancreato-Biliary Association.)

Background: Pyogenic liver abscesses are currently treated by either percutaneous computer tomography (CT)-guided drainage or by laparoscopic and a conventional liver resection when conservative treatment fails but may be associated with substantial morbidity and mortality., Methods: A minimally invasive technique involving debridement of right liver abscesses was employed using a minimally invasive video-assisted hepatic abscess debridement (VAHD) after unsuccessful percutaneous CT-guided drainage. Clinical data, complication rates and outcomes of patients were recorded retrospectively., Results: Between 2011 and 2014, VAHD was performed on 10 patients at two centres with no observed recurrence of a liver abscess. The median age of the patients was 57 years (range 42-78) with a median pre-operative size of a liver abscess of 78 mm (range 40-115). The median operation time was 47 min (range 23-75), and the median postoperative hospital stay was 9 days (range 7-69). One patient developed a subcutaneous abscess that required further surgery. No patient died, and there were no major complications related to the VAHD., Conclusions: Video-assisted hepatic abscess debridement is a feasible technique that shows promising results for the treatment of a recurrent right liver abscess., (© 2015 International Hepato-Pancreato-Biliary Association.)

Background: The impact of body composition on outcomes after surgery for colorectal liver metastases (CRLM) remains unclear. The aim of the present study was to determine the influence of sarcopenia, obesity and sarcopenic obesity on morbidity, disease-free (DFS) and overall survival (OS)., Method: Between 2005 and 2012, all patients undergoing a partial liver resection for CRLM in the Maastricht University Medical Centre, and who underwent computed tomography (CT) imaging within 3 months before liver surgery, were included. Body composition was primarily based on pre-operative CT measurements. Sarcopenia was based on total muscle area at the level of the third lumbar vertebra and predefined body mass index (BMI)- and gender-specific cut-off values for sarcopenia were used. Body fat percentages were calculated and the top 40% for men and women were considered obese., Results: Of the 171 included patients undergoing liver surgery for CRLM, 80 (46.8%) patients were sarcopenic, 69 (40.4%) obese and 49 (28.7%) sarcopenic obese. The presence of sarcopenia, obesity or sarcopenic obesity did not affect the complication rates. However, readmission rates were significantly increased in patients with (sarcopenic) obesity (P < 0.05). Surprisingly, obesity seemed to prolong OS (P = 0.021) and was identified as an independent predictor [hazard ratio (HR):0.58 and P = 0.046] for better OS. Sarcopenia and sarcopenic obesity did not affect DFS or OS., Conclusion: Sarcopenia, obesity and sarcopenic obesity did not worsen DFS, OS and complication rates after a partial liver resection for CRLM., (© 2014 International Hepato-Pancreato-Biliary Association.)