Are children with prolonged fever at a higher risk for serious illness? : A prospective observational study

Funding Information: This project received funding from the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No 668303). The research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. RGN was funded by NIHR ACL award (ACL-2018-021-007). Funding Information: This project received funding from the European Union's Horizon 2020 research and innovation programme (Grant Agreement No 668303). The research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. RGN was funded by NIHR ACL award (ACL-2018- 021-007). Publisher Copyright: © 2023 Author(s) (or their employer(s)).Objectives: To describe the characteristics and clinical outcomes of children with fever ≥5 days presenting to emergency departments (EDs). Design: Prospective observational study. Setting: 12 European EDs. Patients: Consecutive febrile children 0.90, but were observed infrequently (range: 0.4%-17%). Absence of warning signs was not sufficiently reliable to rule out SBI (sensitivity 0.92 (95% CI 0.87-0.95), negative likelihood ratio (LR) 0.34 (0.22-0.54)). CRP <20 mg/L was useful for ruling out SBI (negative LR 0.16 (0.11-0.24)). There were 66 cases (1.7%) of non-infectious serious illnesses, including 21 cases of Kawasaki disease (0.6%), 28 inflammatory conditions (0.7%) and 4 malignancies. Conclusion: Children with prolonged fever have a higher risk of SBI, warranting a careful clinical assessment and diagnostic workup. Warning signs of SBI occurred infrequently but, if present, increased the likelihood of SBI. Although rare, clinicians should consider important non-infectious causes of prolonged fever.Peer reviewe

Missing not at random in end of life care studies : multiple imputation and sensitivity analysis on data from the ACTION study

Background: Missing data are common in end-of-life care studies, but there is still relatively little exploration of which is the best method to deal with them, and, in particular, if the missing at random (MAR) assumption is valid or missing not at random (MNAR) mechanisms should be assumed. In this paper we investigated this issue through a sensitivity analysis within the ACTION study, a multicenter cluster randomized controlled trial testing advance care planning in patients with advanced lung or colorectal cancer. Methods: Multiple imputation procedures under MAR and MNAR assumptions were implemented. Possible violation of the MAR assumption was addressed with reference to variables measuring quality of life and symptoms. The MNAR model assumed that patients with worse health were more likely to have missing questionnaires, making a distinction between single missing items, which were assumed to satisfy the MAR assumption, and missing values due to completely missing questionnaire for which a MNAR mechanism was hypothesized. We explored the sensitivity to possible departures from MAR on gender differences between key indicators and on simple correlations. Results: Up to 39% of follow-up data were missing. Results under MAR reflected that missingness was related to poorer health status. Correlations between variables, although very small, changed according to the imputation method, as well as the differences in scores by gender, indicating a certain sensitivity of the results to the violation of the MAR assumption. Conclusions: The findings confirmed the importance of undertaking this kind of analysis in end-of-life care studies

Regression discontinuity was a valid design for dichotomous outcomes in three randomized trials

Pathophysiology, epidemiology and therapy of agein

Mapping European Association of Urology Guideline Practice Across Europe: An Audit of Androgen Deprivation Therapy Use Before Prostate Cancer Surgery in 6598 Cases in 187 Hospitals Across 31 European Countries

Background: Evidence-practice gaps exist in urology. We previously surveyed European Association of Urology (EAU) guidelines for strong recommendations underpinned by high-certainty evidence that impact patient experience for which practice variations were suspected. The recommendation "Do not offer neoadjuvant androgen deprivation therapy (ADT) before surgery for patients with prostate cancer" was prioritised for further investigation. ADT before surgery is neither clinically effective nor cost effective and has serious side effects. The first step in improving implementation problems is to understand their extent. A clear picture of practice regarding ADT before surgery across Europe is not available. Objective: To assess current ADT use before prostate cancer surgery in Europe. Design, setting, and participants: This was an observational cross-sectional study. We retrospectively audited recent ADT practices in a multicentre international setting. We used nonprobability purposive sampling, aiming for breadth in terms of low- versus high-volume, academic, versus community and public versus private centres. Outcome measurements and statistical analysis: Our primary outcome was adherence to the ADT recommendation. Descriptive statistics and a multilevel model were used to investigate differences between countries across different factors (volume, centre type, and funding type). Subgroup analyses were performed for patients with low, intermediate, and high risk, and for those with locally advanced prostate cancer. We also collected reasons for nonadherence. Results and limitations: We included 6598 patients with prostate cancer from 187 hospitals in 31 countries from January 1, 2017 to May 1, 2020. Overall, nonadherence was 2%, (range 0-32%). Most of the variability was found in the high-risk subgroup, for which nonadherence was 4% (range 0-43%). Reasons for nonadherence included attempts to improve oncological outcomes or preoperative tumour parameters; attempts to control the cancer because of long waiting lists; and patient preference (changing one's mind from radiotherapy to surgery after neoadjuvant ADT had commenced or feeling that the side effects were intolerable). Although we purposively sampled for variety within countries (public/private, academic/community, high/low-volume), a selection bias toward centres with awareness of guidelines is possible, so adherence rates may be overestimated. Conclusions: EAU guidelines recommend against ADT use before prostate cancer surgery, yet some guideline-discordant ADT use remains at the cost of patient experience and an additional payer and provider burden. Strategies towards discontinuation of inappropriate preoperative ADT use should be pursued. Patient summary: Androgen deprivation therapy (ADT) is sometimes used in men with prostate cancer who will not benefit from it. ADT causes side effects such as weight gain and emotional changes and increases the risk of cardiovascular disease, diabetes, and osteoporosis. Guidelines strongly recommend that men opting for surgery should not receive ADT, but it is unclear how well the guidance is followed. We asked urologists across Europe how patients in their institutions were treated over the past few years. Most do not use ADT before surgery, but this still happens in some places. More research is needed to help doctors to stop using ADT in patients who will not benefit from it

Gynaecologists estimate and experience laparoscopic hysterectomy as more difficult compared with abdominal hysterectomy

The level of difficulty of various types of hysterectomy differs and may influence the choice of either approach. When surgeons consider one specific approach to hysterectomy as more difficult, they may be reluctant to perform this type of hysterectomy. The main objective of this study was to investigate the potential different levels of difficulty for laparoscopic and abdominal hysterectomy. Furthermore, the accuracy of estimating the level of difficulty was examined. In a randomized controlled trial between laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH), gynaecologists were asked to record the preoperatively estimated and postoperatively experienced level of difficulty on a Visual Analogue Scale (VAS). Differences between LH and AH were examined and the correlation between the estimated uterine weight on bimanual palpation and the actual uterine weight was calculated. A difference on the VAS of three points or more (ΔVAS ≥ 3) was considered clinically relevant. In 72 out of 76 cases, both VAS scores were recorded. LH was estimated and experienced as significantly more difficult as compared with AH. In 13 (18%) cases, ΔVAS was ≥3, equally distributed between LH (n = 6) and AH (n = 7). Eleven of these 13 cases had a positive ΔVAS ≥3, meaning that surgery was experienced as more difficult than it was estimated. Surgeon’s estimation of uterine size correlated well with the actual uterine weight. LH is considered as more difficult than AH, which might be a reason for its slow implementation. In a large proportion of cases, gynaecologists seem to be able to estimate the level of difficulty of hysterectomy accurately

MSC encapsulation in alginate microcapsules prolongs survival after intra-articular injection, a longitudinal in vivo cell and bead integrity tracking study

Mesenchymal stem cells (MSC) are promising candidates for use as a biological therapeutic. Since locally injected MSC disappear within a few weeks, we hypothesize that efficacy of MSC can be enhanced by prolonging their presence. Previously, encapsulation in alginate was suggested as a suitable approach for this purpose. We found no differences between the two alginate types, alginate high in mannuronic acid (High M) and alginate high in guluronic acid (High G), regarding MSC viability, MSC immunomodulatory capability, or retention of capsule integrity after subcutaneous implantation in immune competent rats. High G proved to be more suitable for production of injectable beads. Firefly luciferase-expressing rat MSC were used to track MSC viability. Encapsulation in high G alginate prolonged the presence of metabolically active allogenic MSC in immune competent rats with monoiodoacetate-induced osteoarthritis for at least 8 weeks. Encapsulation of human MSC for local treatment by intra-articular injection did not significantly influence the effect on pain, synovial inflammation, or cartilage damage in this disease model. MSC encapsulation in alginate allows for an injectable approach which prolongs the presence of viable cells subcutaneously or in an osteoarthritic joint. Further fine tuning of alginate formulation and effective dosage for might be required in order to improve therapeutic efficacy depending on the target disease. [Figure not available: see fulltext.]

Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments : MOFICHE, a prospective observational study

Funding Information: Funding This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 668303. The research was supported by the National Institute for Health Research Biomedical Research Centres at Imperial College London, Newcastle Hospitals NHS Foundation Trust and Newcastle University. Publisher Copyright: © 2021 Archives of Disease in ChildhoodObjectives: To develop and cross-validate a multivariable clinical prediction model to identify invasive bacterial infections (IBI) and to identify patient groups who might benefit from new biomarkers. Design: Prospective observational study. Setting: 12 emergency departments (EDs) in 8 European countries. Patients: Febrile children aged 0-18 years. Main outcome measures: IBI, defined as bacteraemia, meningitis and bone/joint infection. We derived and cross-validated a model for IBI using variables from the Feverkidstool (clinical symptoms, C reactive protein), neurological signs, non-blanching rash and comorbidity. We assessed discrimination (area under the receiver operating curve) and diagnostic performance at different risk thresholds for IBI: sensitivity, specificity, negative and positive likelihood ratios (LRs). Results: Of 16 268 patients, 135 (0.8%) had an IBI. The discriminative ability of the model was 0.84 (95% CI 0.81 to 0.88) and 0.78 (95% CI 0.74 to 0.82) in pooled cross-validations. The model performed well for the rule-out threshold of 0.1% (sensitivity 0.97 (95% CI 0.93 to 0.99), negative LR 0.1 (95% CI 0.0 to 0.2) and for the rule-in threshold of 2.0% (specificity 0.94 (95% CI 0.94 to 0.95), positive LR 8.4 (95% CI 6.9 to 10.0)). The intermediate thresholds of 0.1%-2.0% performed poorly (ranges: sensitivity 0.59-0.93, negative LR 0.14-0.57, specificity 0.52-0.88, positive LR 1.9-4.8) and comprised 9784 patients (60%). Conclusions: The rule-out threshold of this model has potential to reduce antibiotic treatment while the rule-in threshold could be used to target treatment in febrile children at the ED. In more than half of patients at intermediate risk, sensitive biomarkers could improve identification of IBI and potentially reduce unnecessary antibiotic prescriptions.publishersversionPeer reviewe

Psychometric test of the Team Climate Inventory-short version investigated in Dutch quality improvement teams

Abstract BACKGROUND: Although some studies have used the Team Climate Inventory within teams working in health care settings, none of these included quality improvement teams. The aim of our study is to investigate the psychometric properties of the 14-item version of the Team Climate Inventory in healthcare quality improvement teams participating in a Dutch quality collaborative. METHODS: This study included quality improvement teams participating in the Care for Better improvement program for home care, care for the handicapped and the elderly in the Netherlands between 2006 and 2008. As part of a larger evaluation study 270 written questionnaires from team members were collected at baseline and 139 questionnaires at end measurement. Confirmatory factor analyses, reliability, Pearson correlations and paired samples t-tests were conducted to investigate construct validity, reliability, predictive validity and temporal stability. RESULTS: Confirmatory factor analyses revealed the expected four-factor structure and good fit indices. For the four subscales--vision, participative safety, task orientation and support for innovation--acceptable Cronbach's alpha coefficients and high inter-item correlations were found. The four subscales all proved significant predictors of perceived team effectiveness, with participatory safety being the best predictor. As expected the four subscales were found to be stable over time; i.e. without significant changes between baseline and end measurement. CONCLUSION: The psychometric properties of the Dutch version of the TCI-14 are satisfactory. Together these results show that the TCI-14 is a useful instrument to assess to what extent aspects of team climate influence perceived team effectiveness of quality improvement teams