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Objective: To determine work participation, social roles, and empowerment of QFS patients ≥10-year after infection. Methods: QFS patients ≥10-year after acute infection, who were of working age, participated in a cross-sectional survey study. Work participation, fulfilment of social roles, and empowerment outcomes were studied for the total population, as well as for subgroups based on employment type and current work status. Associations between empowerment, work and social roles were examined. Results: 291 participants were included. Of the 250 participants who had paid work before Q-fever, 80.4% stopped working or worked less hours due to QFS. For each social role, more than half of the participants (56.6–87.8%) spent less time on the role compared to before Q-fever. The median empowerment score was 41.0 (IQR: 37.0–44.0) out of 60. A higher empowerment score was significantly associated with lower odds of performing all social roles less due to QFS (OR = 0.871–0.933; p<0.001–0.026), except for parenting and informal care provision (p = 0.070–0.460). No associations were found between empowerment and current work status. Conclusion: Work participation and fulfilment of social roles is generally low in QFS patients. Many of the participants stopped working or are working less hours due to QFS, and most spent less time on social roles compared to before Q-fever. Minor variation was seen in total empowerment scores of participants; however, these slight differences were associated with the fulfilment of social roles, but not work participation. This new insight should be further explored in future studies. [ABSTRACT FROM AUTHOR]

Background: Intoxications with alcohol and drugs are common in the Emergency Department. This study aimed to describe the occurrence and characteristics of intoxications (alcohol, Drugs of Abuse (DOA), pharmaceutical and chemical) presented to the Emergency Department and the health care costs of these intoxications. Methods: This was a retrospective medical record study of all patients (≥ 16 years) who presented to the Emergency Department of an inner-city academic hospital in the Netherlands due to single or multiple intoxication(s) as the primary or secondary reason in the year 2016. An intoxication was reported as present if the attending physician described the intoxication in the patient's medical record. Results: A total of 783 patients were included, accounting for 3.2% of the adult Emergency Department population (age ≥ 16 year). In 30% more than one substance was used. Intoxications with alcohol, Drugs of Abuse and pharmaceuticals was reported in respectively 62%, 29% and 21% of the intoxicated patients. The mean costs per patient presenting with an intoxication to the Emergency Department was € 1,490. The mean costs per patient were highest for pharmaceutical intoxications (€ 2,980), followed by Drugs of Abuse (€ 1,140) and alcohol (€ 1,070). Conclusions: Intoxications among patients aged 16 years and older are frequently seen at the Emergency Department and are frequently caused by multiple substances. Alcohol is the most common intoxication. Substantial healthcare costs are involved. Therefore, this study suggests that further research into hazardous alcohol consumption and DOA abuse is warranted. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) can negatively impact patients' lives on many dimensions. Multiple instruments are available for evaluating TBI outcomes, but it is still unclear which instruments are the most sensitive for that purpose. This study examines the sensitivity of nine outcome instruments in terms of their ability to discriminate within and between specific patient groups, selected a priori as identified from the literature, at three different time points within a year after TBI (i.e., 3, 6, and 12 months post injury). The sensitivity of the instruments to sociodemographic (sex, age, education), premorbid (psychological health status), and injury-related (clinical care pathways, TBI and extracranial injury severity) factors was assessed by means of cross-sectional multivariate Wei-Lachin analyses. The Glasgow Outcome Scale Extended (GOSE)-the standard in the field of TBI for measuring functional recovery-demonstrated the highest sensitivity in most group comparisons. However, as single functional scale, it may not be able to reflect the multidimensional nature of the outcome. Therefore, the GOSE was used as a reference for further sensitivity analyses on more specific outcome scales, addressing further potential deficits following TBI. The physical component summary score (PCS) of the generic health-related quality of life (HRQOL) instruments (SF-36v2/-12v2) and the TBI-specific HRQOL instruments (QOLIBRI/-OS) were most sensitive in distinguishing recovery after TBI across all time points and patient groups, followed by the RPQ assessing post-concussion symptoms and the PHQ-9 measuring depression. The SF-36v2/-12v2 mental component summary score and the GAD-7 measuring anxiety were less sensitive in several group comparisons. The assessment of the functional recovery status combined with generic HRQOL (the PCS of the SF-12v2), disease-specific HRQOL (QOLIBRI-OS), and post-concussion symptoms (RPQ) can provide a sensitive, comprehensive, yet time-efficient evaluation of the health status of individuals after TBI in different patient groups., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Johannes Vester is a senior biometric consultant of idv Datenanalyse und Versuchsplanung and received no personal fees related to the submitted work. Integra LifeSciences Corporation (USA) and NeuroTrauma Sciences (USA) provided additional financial support in respect to data curation. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: © 2023 von Steinbuechel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Through improvements in trauma care there has been a decline in injury mortality, as more people survive severe trauma. Patients who survive severe trauma are at risk of long-term disabilities which may place a high economic burden on society. The purpose of this study was to estimate the health care and productivity costs of severe trauma patients up to 24 months after sustaining the injury. Furthermore, we investigated the impact of injury severity level on health care utilization and costs and determined predictors for health care and productivity costs., Methods: This prospective cohort study included adult trauma patients with severe injury (ISS≥16). Data on in-hospital health care use, 24-month post-hospital health care use and productivity loss were obtained from hospital registry data and collected with the iMTA Medical Consumption and Productivity Cost Questionnaire. The questionnaires were completed 1 week and 1, 3, 6, 12 and 24 months after injury. Log-linked gamma generalized linear models were used to investigate the drivers of health care and productivity costs., Results: In total, 174 severe injury patients were included in this study. The median age of participants was 55 years and the majority were male (66.1%). The mean hospital stay was 14.2 (SD = 13.5) days. Patients with paid employment returned to work 21 weeks after injury. In total, the mean costs per patient were €24,760 with in-hospital costs of €11,930, post-hospital costs of €7,770 and productivity costs of €8,800. Having an ISS ≥25 and lower health status were predictors of high health care costs and male sex was associated with higher productivity costs., Conclusions: Both health care and productivity costs increased with injury severity, although large differences were observed between patients. It is important for decision-makers to consider not only in-hospital health care utilization but also the long-term consequences and associated costs related to rehabilitation and productivity loss., Competing Interests: The authors have declared that no competing interests exist.

Background: Advance care planning (ACP) supports individuals to define, discuss, and record goals and preferences for future medical treatment and care. Despite being internationally recommended, randomised clinical trials of ACP in patients with advanced cancer are scarce., Methods and Findings: To test the implementation of ACP in patients with advanced cancer, we conducted a cluster-randomised trial in 23 hospitals across Belgium, Denmark, Italy, Netherlands, Slovenia, and United Kingdom in 2015-2018. Patients with advanced lung (stage III/IV) or colorectal (stage IV) cancer, WHO performance status 0-3, and at least 3 months life expectancy were eligible. The ACTION Respecting Choices ACP intervention as offered to patients in the intervention arm included scripted ACP conversations between patients, family members, and certified facilitators; standardised leaflets; and standardised advance directives. Control patients received care as usual. Main outcome measures were quality of life (operationalised as European Organisation for Research and Treatment of Cancer [EORTC] emotional functioning) and symptoms. Secondary outcomes were coping, patient satisfaction, shared decision-making, patient involvement in decision-making, inclusion of advance directives (ADs) in hospital files, and use of hospital care. In all, 1,117 patients were included (442 intervention; 675 control), and 809 (72%) completed the 12-week questionnaire. Patients' age ranged from 18 to 91 years, with a mean of 66; 39% were female. The mean number of ACP conversations per patient was 1.3. Fidelity was 86%. Sixteen percent of patients found ACP conversations distressing. Mean change in patients' quality of life did not differ between intervention and control groups (T-score -1.8 versus -0.8, p = 0.59), nor did changes in symptoms, coping, patient satisfaction, and shared decision-making. Specialist palliative care (37% versus 27%, p = 0.002) and AD inclusion in hospital files (10% versus 3%, p < 0.001) were more likely in the intervention group. A key limitation of the study is that recruitment rates were lower in intervention than in control hospitals., Conclusions: Our results show that quality of life effects were not different between patients who had ACP conversations and those who received usual care. The increased use of specialist palliative care and AD inclusion in hospital files of intervention patients is meaningful and requires further study. Our findings suggest that alternative approaches to support patient-centred end-of-life care in this population are needed., Trial Registration: ISRCTN registry ISRCTN63110516., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BH and LB are developers of Respecting Choices and report personal fees from Gundersen Health, outside the submitted work.

Background: Although the benefits of antithrombotic drugs are indisputable to reduce thrombotic events, they carry a high risk of compromising patient safety. No previous studies investigated the implementation and (cost-) effectiveness of a hospital-based multidisciplinary antithrombotic team on bleeding and thrombotic outcomes. The primary aim of this study was to compare the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization., Methods and Findings: A prospective, multicenter before-after intervention study was conducted in two Dutch hospitals. Adult patients hospitalized between October 2015 and December 2017 treated with anticoagulant therapy were included. The primary aim was to estimate the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization. The intervention was the implementation of a multidisciplinary antithrombotic team focusing on education, medication reviews by pharmacists, implementing of local anticoagulant therapy guidelines based on national guidelines, patient counselling and medication reconciliation at admission and discharge. The primary endpoint was analysed using segmented linear regression. We obtained data for 1,886 patients: 941 patients were included in the usual care period and 945 patients in the intervention period. The S-team study showed that implementation of a multidisciplinary antithrombotic team over time significantly reduced the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs (-1.83% (-2.58% to -1.08%) per 2 month period)., Conclusions: This study shows that implementation of a multidisciplinary antithrombotic team over time significantly reduces the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs., Trial Registration: Trialregister.nl NTR4887., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: FWGL received unrestricted research grants for studies on Von Willebrand disease. He is consultant for uniQure, Takeda and NovoNordisk, of which fees go to the university. He is a DSMB member for a study of Roche. All these potential COI are not related to the current study and does not alter our adherence to PLOS ONE policies on sharing data and materials .ARD, MJHAK, JD, SZ, RB, PGMM, FNC, EK, and PMLAvdB have no conflict of interest.

Introduction: Survival after trauma has considerably improved. This warrants research on non-fatal outcome. We aimed to identify characteristics associated with both short and long-term health status (HS) after trauma and to describe the recovery patterns of HS and psychological outcomes during 24 months of follow-up., Methods: Hospitalized patients with all types of injuries were included. Data were collected at 1 week 1, 3, 6, 12, and 24 months post-trauma. HS was assessed with the EuroQol-5D-3L (EQ-5D-3L) and the Health Utilities Index Mark 2 and 3 (HUI2/3). For the screening of symptoms of post-traumatic stress, anxiety and depression, the Impact of Event Scale (IES) and the Hospital Anxiety and Depression Scale (HADS) subscale anxiety (HADSA) and subscale depression (HADSD) were used. Recovery patterns of HS and psychological outcomes were examined with linear mixed model analyses., Results: A total of 4,883 patients participated (median age 68 (Interquartile range 53-80); 50% response rate). The mean (Standard Deviation (SD)) pre-injury EQ-5D-3L score was 0.85 (0.23). One week post-trauma, mean (SD) EQ-5D-3L, HUI2 and HUI3 scores were 0.49 (0.32), 0.61 (0.22) and 0.38 (0.31), respectively. These scores significantly improved to 0.77 (0.26), 0.77 (0.21) and 0.62 (0.35), respectively, at 24 months. Most recovery occurred up until 3 months. At long-term follow-up, patients of higher age, with comorbidities, longer hospital stay, lower extremity fracture and spine injury showed lower HS. The mean (SD) scores of the IES, HADSA and HADSD were respectively 14.80 (15.80), 4.92 (3.98) and 5.00 (4.28), respectively, at 1 week post-trauma and slightly improved over 24 months post-trauma to 10.35 (14.72), 4.31 (3.76) and 3.62 (3.87), respectively., Discussion: HS and psychological symptoms improved over time and most improvements occurred within 3 months post-trauma. The effects of severity and type of injury faded out over time. Patients frequently reported symptoms of post-traumatic stress., Trial Registration: ClinicalTrials.gov identifier: NCT02508675., Competing Interests: The authors have declared that no competing interests exist.

Aim: The aim of this study was to determine prognostic factors for medical and productivity costs, and return to work (RTW) during the first two years after trauma in a clinical trauma population., Methods: This prospective multicentre observational study followed all adult trauma patients (≥18 years) admitted to a hospital in Noord-Brabant, the Netherlands from August 2015 through November 2016. Health care consumption, productivity loss and return to work were measured in questionnaires at 1 week, 1, 3, 6, 12 and 24 months after injury. Data was linked with hospital registries. Prognostic factors for medical costs and productivity costs were analysed with log-linked gamma generalized linear models. Prognostic factors for RTW were assessed with Cox proportional hazards model. The predictive ability of the models was assessed with McFadden R2 (explained variance) and c-statistics (discrimination)., Results: A total of 3785 trauma patients (39% of total study population) responded to at least one follow-up questionnaire. Mean medical costs per patient (€9,710) and mean productivity costs per patient (€9,000) varied widely. Prognostic factors for high medical costs were higher age, female gender, spine injury, lower extremity injury, severe head injury, high injury severity, comorbidities, and pre-injury health status. Productivity costs were highest in males, and in patients with spinal cord injury, high injury severity, longer length of stay at the hospital and patients admitted to the ICU. Prognostic factors for RTW were high educational level, male gender, low injury severity, shorter length of stay at the hospital and absence of comorbidity., Conclusions: Productivity costs and RTW should be considered when assessing the economic impact of injury in addition to medical costs. Prognostic factors may assist in identifying high cost groups with potentially modifiable factors for targeted preventive interventions, hence reducing costs and increasing RTW rates., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule., Methods and Findings: In a stepped-wedge cluster randomised trial, we included children aged 1-60 months presenting with fever and cough or dyspnoea to 8 EDs in The Netherlands. The EDs were of varying sizes, from diverse geographic and demographic regions, and of different hospital types (tertiary versus general). In the pre-intervention phase, children received usual care, according to the Dutch and NICE guidelines for febrile children. During the intervention phase, a validated clinical prediction model (Feverkidstool) including clinical characteristics and C-reactive protein (CRP) was implemented as a decision rule guiding antibiotic prescription. The intervention was that antibiotics were withheld in children with a low or intermediate predicted risk of bacterial pneumonia (≤10%, based on Feverkidstool). Co-primary outcomes were antibiotic prescription rate and strategy failure. Strategy failure was defined as secondary antibiotic prescriptions or hospitalisations, persistence of fever or oxygen dependency up to day 7, or complications. Hospitals were randomly allocated to 1 sequence of treatment each, using computer randomisation. The trial could not be blinded. We used multilevel logistic regression to estimate the effect of the intervention, clustered by hospital and adjusted for time period, age, sex, season, ill appearance, and fever duration; predicted risk was included in exploratory analysis. We included 999 children (61% male, median age 17 months [IQR 9 to 30]) between 1 January 2016 and 30 September 2018: 597 during the pre-intervention phase and 402 during the intervention phase. Most children (77%) were referred by a general practitioner, and half of children were hospitalised. Intention-to-treat analyses showed that overall antibiotic prescription was not reduced (30% to 25%, adjusted odds ratio [aOR] 1.07 [95% CI 0.57 to 2.01, p = 0.75]); strategy failure reduced from 23% to 16% (aOR 0.53 [95% CI 0.32 to 0.88, p = 0.01]). Exploratory analyses showed that the intervention influenced risk groups differently (p < 0.01), resulting in a reduction in antibiotic prescriptions in low/intermediate-risk children (17% to 6%; aOR 0.31 [95% CI 0.12 to 0.81, p = 0.02]) and a non-significant increase in the high-risk group (47% to 59%; aOR 2.28 [95% CI 0.84 to 6.17, p = 0.09]). Two complications occurred during the trial: 1 admission to the intensive care unit during follow-up and 1 pleural empyema at day 10 (both unrelated to the study intervention). Main limitations of the study were missing CRP values in the pre-intervention phase and a prolonged baseline period due to logistical issues, potentially affecting the power of our study., Conclusions: In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule., Trial Registration: Netherlands Trial Register NTR5326., Competing Interests: The authors have declared that no competing interests exist.

Background: A prominent outcome measure within burn care is health related quality of life (HRQL). Until now, no model for long-term recovery of HRQL exists for adult burn patients which requires large samples with repeated measurements. Re-use and the combination of existing data is a way to achieve larger data samples that enable the estimation of long-term recovery models. The aim of this secondary data analysis was to assess the recovery of HRQL after a burn injury over time., Methods and Findings: Data from ten European studies on generic HRQL assessed in adult burn patients (either with the EQ-5D or SF-36) from five different countries were merged into one dataset. SF-36 outcomes were transformed into EQ-5D outcomes. A 24-month recovery of HRQL (EQ-5D utility) was modeled using a linear mixed-effects model and adjusted for important patient and burn characteristics. Subgroups of patients with mild and intermediate burns (≤20% total body surface area (TBSA) burned) and with major burns (>20% TBSA burned) were compared. The combined database included 1687 patients with a mean age of 43 (SD 15) years and a median %TBSA burned of 9% (IQR 4-18). There was large improvement in HRQL up to six months after burns, and HRQL remained relatively stable afterwards (studied up to 24 months post burn). However, the estimated EQ-5D utility scores remained below the norm scores of the general population. In this large sample, females, patients with a long hospital stay and patients with major burns had a delayed and worse recovery. The proportion of patients that reported problems for the EQ-5D dimensions ranged from 100% (pain/discomfort at baseline in patients with major burns) to 10% (self-care ≥3 months after injury in patients with mild and intermediate burns). After 24 months, both subgroups of burn patients did not reach the level of the general population in the dimensions pain/discomfort and anxiety/depression, and patients with major burns in the dimension usual activities. A main limitation of the study includes that the variables in the model were limited to age, gender, %TBSA, LOS and time since burn as these were the only variables available in all datasets., Conclusions: The 24-month recovery model can be used in clinical practice to inform patients on expected HRQL outcomes and provide clinicians insights into the expected recovery of HRQL. In this way, a delayed recovery can be recognized in an early stage and timely interventions can be started in order to improve patient outcomes. However, external validation of the developed model is needed before implementation into clinical practice. Furthermore, our study showed the benefit of secondary data usage within the field of burns., Competing Interests: The authors have declared that no competing interests exist.

Background: Well-advised priority setting in prevention and treatment of injuries relies on detailed insight into costs of injury. This study aimed to provide a detailed overview of medical and productivity costs due to injury up to two years post-injury and compare these costs across subgroups for injury severity and age., Methods: A prospective longitudinal cohort study followed all adult (≥18 years) injury patients admitted to a hospital in Noord-Brabant, the Netherlands. Patients filled out questionnaires 1 week, 1, 3, 6, 12 and 24 months after trauma, including items on health care consumption from the medical consumption questionnaire (iMCQ) and productivity loss from the productivity cost questionnaire (PCQ). Furthermore, injury severity was defined by Injury Severity Score (ISS). Data on diagnostics was retrieved from hospital registries. We calculated medical costs, consisting of in-hospital costs and post-hospital medical costs, and productivity costs due to injury up to two years post-injury., Results: Approximately 50% (N = 4883) of registered patients provided informed consent, and 3785 filled out at least one questionnaire. In total, the average costs per patient were €12,190. In-hospital costs, post-hospital medical costs and productivity costs contributed €4810, €5110 and €5830, respectively. Total costs per patient increased with injury severity, from €7030 in ISS1-3 to €23,750 in ISS16+ and were lowest for age category 18-24y (€7980), highest for age category 85 years and over (€15,580), and fluctuated over age groups in between., Conclusion: Both medical costs and productivity costs generally increased with injury severity. Furthermore, productivity costs were found to be a large component of total costs of injury in ISS1-8 and are therefore a potentially interesting area with regard to reducing costs., Competing Interests: The authors have declared that no competing interests exist.

Children attending kindergarten are at high risk for contracting infections, for which hand hygiene (HH) has been recognized as the most cost-effective prevention measure globally. Kindergarten teachers' HH behavior plays a vital role in encouraging favorable hygiene techniques and environment. This study aims to evaluate the effectiveness of a multimodal intervention at changing kindergarten teachers' HH behavior and social cognitive factors that influences HH behavior in China. The intervention named "Clean Hands, Happy Life" includes HH products with refills, reminders and cues for action, a kick-off event with awards, and training programs. We evaluated the intervention using a self-administrative questionnaire with a stratified random sample of 12 kindergartens. Two surveys was completed by 176 teachers at baseline and 185 after the 6-month intervention. Compared with the baseline scores, there was a significant improvement in the overall self-reported HH compliance of teachers (9.38 vs. 9.68 out of 10, p = 0.006), as well as teachers' perceived disease susceptibility, disease severity and behavioral control after the intervention (p<0.05). We found that teachers' HH compliance was likely to be higher among those who have better HH guideline awareness (β = 0.48, p<0.01) and perceived behavioral control (β = 0.26, p = 0.01), which explained 24.2% of the variance of self-reported compliance of teachers at baseline. The assessed intervention may provide Chinese kindergarten teachers with behavioral skills and cognitions that associated with the compliance of HH behavior. We thus recommend future intervention studies consider our HH behavior change techniques, address multiple social cognitive determinants of HH behavior and include the change of targeted influences in the impact evaluation., Competing Interests: The hand hygiene products used in this study were jointly sponsored by Essity Hygiene Corporate and Vinda China Group. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development, or marketed products to declare.

Background: The in-hospital treatment of patients with traumatic brain injury (TBI) is considered to be expensive, especially in patients with severe TBI (s-TBI). To improve future treatment decision-making, resource allocation and research initiatives, this study reviewed the in-hospital costs for patients with s-TBI and the quality of study methodology., Methods: A systematic search was performed using the following databases: PubMed, MEDLINE, Embase, Web of Science, Cochrane library, CENTRAL, Emcare, PsychINFO, Academic Search Premier and Google Scholar. Articles published before August 2018 reporting in-hospital acute care costs for patients with s-TBI were included. Quality was assessed by using a 19-item checklist based on the CHEERS statement., Results: Twenty-five out of 2372 articles were included. In-hospital costs per patient were generally high and ranged from $2,130 to $401,808. Variation between study results was primarily caused by methodological heterogeneity and variable patient and treatment characteristics. The quality assessment showed variable study quality with a mean total score of 71% (range 48% - 96%). Especially items concerning cost data scored poorly (49%) because data source, cost calculation methodology and outcome reporting were regularly unmentioned or inadequately reported., Conclusions: Healthcare consumption and in-hospital costs for patients with s-TBI were high and varied widely between studies. Costs were primarily driven by the length of stay and surgical intervention and increased with higher TBI severity. However, drawing firm conclusions on the actual in-hospital costs of patients sustaining s-TBI was complicated due to variation and inadequate quality of the included studies. Future economic evaluations should focus on the long-term cost-effectiveness of treatment strategies and use guideline recommendations and common data elements to improve study quality., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The overestimation of survival predictions in the ageing trauma population results in negative benchmark numbers in hospitals that mainly treat elderly patients. The aim of this study was to develop and validate a modified Trauma and Injury Severity Score (TRISS) for accurate survival prediction in the ageing blunt trauma population., Methods: This retrospective study was conducted with data from two Dutch Trauma regions. Missing values were imputed. New prediction models were created in the development set, including age (continuous or categorical) and Anesthesiologists Physical Status (ASA). The models were externally validated. Subsets were created based on age (≥75 years) and the presence of hip fracture. Model performance was assessed by proportion explained variance (Nagelkerke R2), discrimination (Area Under the curve of the Receiver Operating Characteristic, AUROC) and visually with calibration plots. A final model was created based on both datasets., Results: No differences were found between the baseline characteristics of the development dataset (n = 15,530) and the validation set (n = 15,504). The inclusion of ASA in the prediction models showed significant improved discriminative abilities in the two subsets (e.g. AUROC of 0.52 [95% CI: 0.46, 0.58] vs. 0.74 [95% CI: 0.69, 0.78] for elderly patients with hip fracture) and an increase in the proportion explained variance (R2 = 0.32 to R2 = 0.35 in the total cohort). The final model showed high agreement between observed and predicted survival in the calibration plot, also in the subsets., Conclusions: Including ASA and age (continuous) in survival prediction is a simple adjustment of the TRISS methodology to improve survival predictions in the ageing blunt trauma population. A new model is presented, through which even patients with isolated hip fractures could be included in the evaluation of trauma care., Competing Interests: The authors have declared that no competing interests exist.

Background: Panic disorder is associated with high productivity costs. These costs, which should be included in cost-effectiveness analyses (CEA) from a societal perspective, have a considerable impact on cost-effectiveness estimates. However, they are often omitted in published CEAs. It is therefore uncertain whether choosing a societal perspective changes priority setting in future research as compared to a healthcare perspective., Objectives: To identify research priorities regarding the cost-effectiveness of an early intervention for subthreshold panic disorder using value of information (VOI) analysis and to investigate to what extent priority setting depends on the perspective., Methods: We calculated the cost-effectiveness of an early intervention for panic disorder from a healthcare perspective and a societal perspective. We performed a VOI analysis, which estimates the expected value of eliminating the uncertainty surrounding cost-effectiveness estimates, for both perspectives., Results: From a healthcare perspective the early intervention was more effective at higher costs compared to usual care (€17,144 per QALY), whereas it was cost-saving from a societal perspective. Additional research to eliminate parameter uncertainty was valued at €129.7 million from a healthcare perspective and €29.5 million from a societal perspective. Additional research on the early intervention utility gain was most valuable from a healthcare perspective, whereas from a societal perspective additional research would generate little added value., Conclusions: Priority setting for future research differed substantially according to the perspective. Our study underlines that the health-economic perspective of CEAs on interventions for panic disorder must be chosen carefully in order to avoid inappropriate choices in research priorities., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Measurement of health-related quality of life (HRQL) is essential to qualify the subjective burden of burns in survivors. We performed a systematic review of HRQL studies in adult burn patients to evaluate study design, instruments used, methodological quality, and recovery patterns., Methods: A systematic review was performed. Relevant databases were searched from the earliest record until October 2016. Studies examining HRQL in adults after burn injuries were included. Risk of bias was scored using the Quality in Prognostic Studies tool., Results: Twenty different HRQL instruments were used among the 94 included studies. The Burn Specific Health Scale-Brief (BSHS-B) (46%), the Short Form-36 (SF-36) (42%) and the EuroQol questionnaire (EQ-5D) (9%) were most often applied. Most domains, both mentally and physically orientated, were affected shortly after burns but improved over time. The lowest scores were reported for the domains 'work' and 'heat sensitivity' (BSHS-B), 'bodily pain', 'physical role limitations' (SF-36), and 'pain/discomfort' (EQ-5D) in the short-term and for 'work' and 'heat sensitivity', 'emotional functioning' (SF-36), 'physical functioning' and 'pain/discomfort' in the long-term. Risk of bias was generally low in outcome measurement and high in study attrition., Conclusion: Consensus on preferred validated methodologies of HRQL measurement in burn patients would facilitate comparability across studies, resulting in improved insights in recovery patterns and better estimates of HRQL after burns. We recommend to develop a guideline on the measurement of HRQL in burns. Five domains representing a variety of topics had low scores in the long-term and require special attention in the aftermath of burns., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Traumatic brain injuries (TBIs) are a major public health, medical, and societal challenge globally. They present a substantial burden to victims, their families, and the society as a whole. Although indicators such as incidence or death rates provide insight into the occurrence and outcome of TBIs in various populations, they fail to quantify the full extent of their public health and societal impact. Measures such as years of life lost (YLLs), which quantifies the number of years of life lost because the person dies prematurely due to a disease or injury, should be employed to better quantify the population impact. The aim of this study was to provide an in-depth analysis of the burden of deaths due to TBI by calculating TBI-specific YLLs in 16 European countries, analyzing their main causes and demographic patterns, using data extracted from death certificates under unified guidelines and collected in a standardized manner., Methods and Findings: A population-wide, cross-sectional epidemiological study was conducted in 16 European countries to estimate TBI YLLs for the year 2013. The data used for all analyses in this study were acquired from the statistical office of the European Union (Eurostat). A specifically tailored dataset of micro-level data was provided that listed the external cause of death (International Classification of Diseases-10th Revision [ICD-10] codes V01-Y98), the specific nature of injury (ICD-10 codes S00-T98), the age at death, and sex for each death. Overall number of TBI YLLs, crude and age-standardized TBI YLL rates, and TBI YLLs per case were calculated stratified for country, sex, and age. Pooled analyses were performed in order to estimate summary age-standardized rates of TBI YLLs. In order to evaluate the relative importance of TBI in the context of all injuries, proportions of TBI YLLs out of overall injury YLLs were calculated. The total number of TBI YLLs was estimated by extrapolating the pooled crude rate of TBI YLLs in the 16 analyzed countries to the total population of the 28 member states of the EU (EU-28). We found that a total of 17,049 TBI deaths occurred in 2013 in the 16 analyzed countries. These translated into a total of 374,636 YLLs. The pooled age-standardized rate of YLLs per 100,000 people per year was 259.1 (95% CI: 205.8 to 312.3) overall, 427.5 (95% CI: 290.0 to 564.9) in males, and 105.4 (95% CI: 89.1 to 121.6) in females. Males contributed substantially more to TBI YLLs than females (282,870 YLLs, 76% of all TBI YLLs), which translated into a rate ratio of 3.24 (95% CI: 3.22 to 3.27). Each TBI death was on average associated with 24.3 (95% CI: 22.0 to 26.6) YLLs overall, 25.6 (95% CI: 23.4 to 27.8) in males and 20.9 (17.9 to 24.0) in females. Falls and traffic crashes were the most common external causes of TBI YLLs. TBI contributed on average 41% (44% in males and 34% in females) to overall injury YLLs. Extrapolating our findings, about 1.3 million YLLs were attributable to TBI in the EU-28 in 2013 overall, 1.1 million in males and 271,000 in females. This study is based on administratively collected data from 16 countries, and despite the efforts to harmonize them to the greatest possible extent, there may be differences in coding practices or reporting between countries. If present, these would be inherited into our findings without our ability to control for them. The extrapolation of the pooled rates from the 16 countries to the EU-28 should be interpreted with caution., Conclusions: Our study showed that TBI-related deaths and YLLs have a substantial impact at the individual and population level in Europe and present an important societal and economic burden that must not be overlooked. We provide information valuable for policy-makers, enabling them to evaluate and plan preventive activities and resource allocation, and to formulate and implement strategic decisions. In addition, our results can serve as a basis for analyzing the overall burden of TBI in the population.

Introduction: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study., Methods: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions., Results: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers., Conclusion: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches., Competing Interests: The authors have declared that no competing interests exist.

Background: Costly biologicals in palliative oncology are emerging at a rapid pace. For example, in patients with advanced esophageal squamous cell carcinoma addition of cetuximab to a palliative chemotherapy regimen appears to improve survival. However, it simultaneously results in higher costs. We aimed to determine the incremental cost-effectiveness ratio of adding cetuximab to first-line chemotherapeutic treatment of patients with advanced esophageal squamous cell carcinoma, based on data from a randomized controlled phase II trial., Methods: A cost effectiveness analysis model was applied based on individual patient data. It included only direct medical costs from the health-care perspective. Quality-adjusted life-years and incremental cost-effectiveness ratios were calculated. Sensitivity analysis was performed by a Monte Carlo analysis., Results: Adding cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma resulted in an the incremental cost-effectiveness ratio of €252,203 per quality-adjusted life-year. Sensitivity analysis shows that there is a chance of less than 0.001 that the incremental cost-effectiveness ratio will be less than a maximum willingness to pay threshold of €40,000 per quality-adjusted life-year, which is representative for the threshold used in The Netherlands and other developed countries., Conclusions: Addition of cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma is not cost-effective when appraised according to currently accepted criteria. Cost-effectiveness analyses using outcome data from early clinical trials (i.c. a phase II trial) enable pharmaceutical companies and policy makers to gain early insight into whether a new drug meets the current eligibility standards for reimbursement and thereby potential admittance for use in regular clinical practice.

Objectives: To assess the impact of a clinical decision model for febrile children at risk for serious bacterial infections (SBI) attending the emergency department (ED)., Methods: Randomized controlled trial with 439 febrile children, aged 1 month-16 years, attending the pediatric ED of a Dutch university hospital during 2010-2012. Febrile children were randomly assigned to the intervention (clinical decision model; n = 219) or the control group (usual care; n = 220). The clinical decision model included clinical symptoms, vital signs, and C-reactive protein and provided high/low-risks for "pneumonia" and "other SBI". Nurses were guided by the intervention to initiate additional tests for high-risk children. The clinical decision model was evaluated by 1) area-under-the-receiver-operating-characteristic-curve (AUC) to indicate discriminative ability and 2) feasibility, to measure nurses' compliance to model recommendations. Primary patient outcome was defined as correct SBI diagnoses. Secondary process outcomes were defined as length of stay; diagnostic tests; antibiotic treatment; hospital admission; revisits and medical costs., Results: The decision model had good discriminative ability for both pneumonia (n = 33; AUC 0.83 (95% CI 0.75-0.90)) and other SBI (n = 22; AUC 0.81 (95% CI 0.72-0.90)). Compliance to model recommendations was high (86%). No differences in correct SBI determination were observed. Application of the clinical decision model resulted in less full-blood-counts (14% vs. 22%, p-value < 0.05) and more urine-dipstick testing (71% vs. 61%, p-value < 0.05)., Conclusions: In contrast to our expectations no substantial impact on patient outcome was perceived. The clinical decision model preserved, however, good discriminatory ability to detect SBI, achieved good compliance among nurses and resulted in a more standardized diagnostic approach towards febrile children, with less full blood-counts and more rightfully urine-dipstick testing., Trial Registration: Nederlands Trial Register NTR2381.

Objective: To determine associations between the number of injuries sustained and three measures of disability 12-months post-injury for hospitalised patients., Methods: Data from 27,840 adult (18+ years) participants, hospitalised for injury, were extracted for analysis from the Validating and Improving injury Burden Estimates (Injury-VIBES) Study. Modified Poisson and linear regression analyses were used to estimate relative risks and mean differences, respectively, for a range of outcomes (Glasgow Outcome Scale-Extended, GOS-E; EQ-5D and 12-item Short Form health survey physical and mental component summary scores, PCS-12 and MCS-12) according to the number of injuries sustained, adjusted for age, sex and contributing study., Findings: More than half (54%) of patients had an injury to more than one ICD-10 body region and 62% had sustained more than one Global Burden of Disease injury type. The adjusted relative risk of a poor functional recovery (GOS-E<7) and of reporting problems on each of the items of the EQ-5D increased by 5-10% for each additional injury type, or body region, injured. Adjusted mean PCS-12 and MCS-12 scores worsened with each additional injury type, or body region, injured by 1.3-1.5 points and 0.5 points, respectively., Conclusions: Consistent and strong relationships exist between the number of injury types and body regions injured and 12-month functional and health status outcomes. Existing composite measures of anatomical injury severity such as the NISS or ISS, which use up to three diagnoses only, may be insufficient for characterising or accounting for multiple injuries in disability studies. Future studies should consider the impact of multiple injuries to avoid under-estimation of injury burden.

Objective: Traumatic brain injury (TBI) is a major cause of death and disability, leading to great personal suffering and huge costs to society. Integrated knowledge on epidemiology, economic consequences and disease burden of TBI is scarce but essential for optimizing healthcare policy and preventing TBI. This study aimed to estimate incidence, cost-of-illness and disability-adjusted life years (DALYs) of TBI in the Netherlands., Methods: This study included data on all TBI patients who were treated at an Emergency Department (ED - National Injury Surveillance System), hospitalized (National Medical Registration), or died due to their injuries in the Netherlands between 2010-2012. Direct healthcare costs and indirect costs were determined using the incidence-based Dutch Burden of Injury Model. Disease burden was assessed by calculating years of life lost (YLL) owing to premature death, years lived with disability (YLD) and DALYs. Incidence, costs and disease burden were stratified by age and gender., Results: TBI incidence was 213.6 per 100,000 person years. Total costs were €314.6 (USD $433.8) million per year and disease burden resulted in 171,200 DALYs (on average 7.1 DALYs per case). Men had highest mean costs per case (€19,540 versus €14,940), driven by indirect costs. 0-24-year-olds had high incidence and disease burden but low economic costs, whereas 25-64-year-olds had relatively low incidence but high economic costs. Patients aged 65+ had highest incidence, leading to considerable direct healthcare costs. 0-24-year-olds, men aged 25-64 years, traffic injury victims (especially bicyclists) and home and leisure injury victims (especially 0-5-year-old and elderly fallers) are identified as risk groups in TBI., Conclusions: The economic and health consequences of TBI are substantial. The integrated approach of assessing incidence, costs and disease burden enables detection of important risk groups in TBI, development of prevention programs that target these risk groups and assessment of the benefits of these programs.

Background: With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy., Methods: We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER) between the standard multidrug therapy (MDT) program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case., Findings: Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214), slightly less cost-effective in next door neighbours (ICER $497) and least cost-effective among household contacts (ICER $856)., Conclusion: Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world.