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Background If survival could be reliably predicted many patients could be safely managed outside of hospital in an ambulatory care setting. Aim Comparison of common laboratory findings, co-morbidities, mobility and vital signs as predictors of mortality of acutely ill emergency department (ED) attendees. Design Prospective observational study. Methods Secondary analysis of 1334 consenting acutely ill patients attending a Danish ED. Results 67 (5%) out of 1334 patients died within 100 days. After logistic regression seven predictors of 100 days mortality remained significant: an albumin level ≤34 gm/l, D-dimer level >0.51 mg/l, an Asadollahi score (based on admission laboratory data and age) ≥12, a platelet count <159 X 1000/ml, impaired mobility on presentation, a respiratory rate ≥30 bpm and a Charlson co-morbidity index ≥3. Only 5 of the 442 without any of these variables died within 365 days. Only one of the 517 patients with a stable independent gait and normal d-dimer and albumin levels died within 100 days, none died within 30 days of assessment and 12 died within 365 days. Of the remaining 817 patients 66 (8%) died within 100 days. Conclusion These findings suggest that normal gait, albumin and d-dimer levels are the most parsimonious way of identifying low risk ED patients. [ABSTRACT FROM AUTHOR]

Background: Hospital readmissions are increasingly used as a quality indicator with a belief that they are a marker of poor care and have led to financial penalties in UK and USA. Risk scoring systems, such as LACE and HOSPITAL, have been proposed as tools for identifying patients at high risk of readmission but have not been validated in international populations. Aim: To perform an external independent validation of the HOSPITAL and LACE scores. Design: An unplanned secondary cohort study. Methods: Patients admitted to the medical admission unit at the Hospital of South West Jutland (10/2008-2/2009; 2/2010-5/ 2010) and the Odense University Hospital (6/2009-8/2011) were analysed. Validation of the scores using 30 day readmissions as the endpoint was performed. Results: A total of 19277 patients fulfilled the inclusion criteria.Median age was 67 (range 18-107) years and 8977 (46.6%) were female. The LACE score had a discriminatory power of 0.648 with poor calibration and the HOSPITAL score had a discriminatory power of 0.661 with poor calibration. The HOSPITAL score was significantly better than the LACE score for identifying patients at risk of 30 day readmission (P<0.001). The discriminatory power of both scores decreased with increasing age. Conclusion: Readmissions are a complex phenomenon with not only medical conditions contributing but also system, cultural and environmental factors exerting a significant influence. It is possible that the heterogeneity of the population and health care systems may prohibit the creation of a simple prediction tool that can be used internationally. [ABSTRACT FROM AUTHOR]

Background Hyponatraemia is common and its differential diagnosis and consequent therapy management is challenging. The differential diagnosis is mainly based on the routine clinical assessment of volume status, which is often misleading. Mid-regional pro-atrial natriuretic peptide ( MR-pro ANP) is associated with extracellular and cardiac fluid volume. Methods A total of 227 consecutive patients admitted to the emergency department with profound hypo-osmolar hyponatraemia (Na < 125 mmol L−1) were included in this prospective multicentre observational study conducted in two tertiary centres in Switzerland. A standardized diagnostic evaluation of the underlying cause of hyponatraemia was performed, and an expert panel carefully evaluated volaemic status using clinical criteria. MR-pro ANP levels were compared between patients with hyponatraemia of different aetiologies and for assessment of volume status. Results MR-pro ANP levels were higher in patients with hypervolaemic hyponatraemia compared to patients with hypovolaemic or euvolaemic hyponatraemia ( P = 0.0002). The area under the curve ( AUC) to predict an excess of extracellular fluid volume, compared to euvolaemia, was 0.73 [95% confidence interval ( CI) 0.62-0.84]. Additionally, in multivariate analysis, MR-pro ANP remained an independent predictor of excess extracellular fluid volume after adjustment for congestive heart failure ( P = 0.012). MR-pro ANP predicted the syndrome of inappropriate antidiuresis ( SIAD) versus hypovolaemic and hypervolaemic hyponatraemia with an AUC of 0.77 (95% CI 0.69-0.84). Conclusion MR-pro ANP is associated with extracellular fluid volume in patients with hyponatraemia and remains an independent predictor of hypervolaemia after adjustment for congestive heart failure. MR-pro ANP may be a marker for discrimination between the SIAD and hypovolaemic or hypervolaemic hyponatraemia. [ABSTRACT FROM AUTHOR]

Objective: During the early stages of the COVID-19 pandemic, medical students were abruptly removed from clinical rotations and transitioned to virtual learning. This study investigates the impact of this shift on students' wellbeing and preparedness for advanced training., Methods: Through qualitative research methods, including semi-structured interviews, the experiences of medical students working on the COVID-19 frontline were explored., Results: The comprehensive findings of the study shed light on the profound emotional journey that medical students embarked upon during the relentless public health crisis. Within the chaos and overwhelming demands of the pandemic, medical students discovered a profound sense of purpose and fulfillment in their contributions to the welfare of the community. Despite the personal sacrifices they had to make, such as long hours, limited social interactions, and potentially risking their own health, students reported feelings of relief and gratitude., Conclusion: Tailored support systems for medical students' wellbeing are crucial for improving healthcare delivery during crises. Medical schools should adopt a holistic curriculum approach, integrating interdisciplinary learning and prioritizing student wellbeing. Recognizing the pandemic's impact on students and implementing targeted support measures ensures resilience and contributes to an improved healthcare system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Klasen, Poljo, Sortino, Bogie, Schoenbaechler, Meienberg, Nickel, Bingisser and LaDonna.)

Background and Aim: Loss of time is a major obstacle to efficient stroke treatment. Our telestroke path intends to optimize prehospital triage using a video link connecting ambulance personnel and a stroke physician. The objectives were as follows: (1) To identify patients suffering a stroke and (2) in particular large vessel occlusion (LVO) strokes as candidates for endovascular treatment. We have chosen the Rapid Arterial Occlusion Evaluation (RACE) scale for this purpose., Methods: This analysis aimed to verify the feasibility of prehospital stroke identification by video assessment. In this prospective telestroke cohort study, we included 97 subjects, in which the RACE score (items: facial palsy, arm and leg motor function, head and gaze deviation, and aphasia or agnosia) was applied, and the assessment videotaped by a trained member of the Emergency Medical Services (EMS) in the field using a mobile device. Each recorded patient video was independently assessed by three experienced stroke physicians from a certified stroke center and compared to the neuroimaging gold standard. Within this feasibility study, the stroke code was not altered by the outcome of the RACE assessment, and all patients underwent the standard procedures within the emergency unit., Results: We analyzed 97 patients (median age 78 years, 53% women), of whom 51 (52.6%) suffered an acute stroke, 12 (23.5%) of which were due to an LVO and 46 patients had symptoms mimicking a stroke. The sensitivity of stroke identification was 77.8%, and specificity was 53.6%. In regard to the identification of an LVO, sensitivity was 69.4% and specificity was 84.3%. The inter-rater agreement in the RACE-score assessment was ICC = 0.82 (intraclass-correlation coefficient)., Conclusion: These results confirm our hypothesis that the local telestroke concept is feasible. It allows correct (i) stroke and (ii) LVO identification in the majority of the cases and thus has the potential to assist in efficient prehospital triage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thilemann, Traenka, Schaub, Nussbaum, Bonati, Peters, Fladt, Nickel, Hunziker, Luethy, Schädelin, Ernst, Engelter, De Marchis and Lyrer.)

Background: Waiting for triage in overburdened emergency departments (ED) has become an increasing problem, which endangers patients. A fast triage system to rapidly identify low-acuity patients should divert care and resources to more urgent cases., Aim: The objective of this study was to compare the performance of the Kitovu Hospital fast triage (KFT) score with the Emergency Severity Index (ESI), using mortality and hospital admission as proxies for the patients' acuity., Design: This is a prospective observational study of consecutive patients presenting to a Swiss academic ED., Methods: Patients were prospectively triaged into one of five ESI strata and retrospectively assessed by the KFT score, which awards one point each for altered mental status, impaired mobility and oxygen saturation <94%., Results: The KFT score had a lower discrimination than the ESI for hospital admission, but a higher discrimination for mortality from 24 h to 1 year after ED presentation. A total of 5544 (67%) patients were assigned to the lowest acuity by the KFT score compared with 2374 (28.7%) by the ESI; there was no significant difference in the 24-h mortality of patients who were deemed low acuity by either score., Conclusion: Compared to the ESI, the KFT score identifies more than twice as many patients at low risk of early death. Therefore, this score might help to identify patients who could be managed through alternative pathways. This may be particularly helpful in situations of ED crowding and access block., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Association of Physicians.)

The COVID-19 pandemic caused complex and enduring challenges for healthcare providers and medical educators. The rapid changes to the medical education landscape forced universities across the world to pause traditional medical training. In Basel, Switzerland, however, medical students had the opportunity to work on the COVID-19 frontlines. Our purpose was to understand how they perceived both learning and professional identity development in this novel context. We conducted semi-structured interviews with 21 medical students who worked in a COVID-19 testing facility at the University Hospital of Basel. Using constructivist grounded theory methodology, we collected and analyzed data iteratively using the constant comparative approach to develop codes and theoretical themes. Most participants perceived working on the pandemic frontlines as a positive learning experience, that was useful for improving their technical and communication skills. Participants particularly valued the comradery amongst all team members, perceiving that the hierarchy between faculty and students was less evident in comparison to their usual learning environments. Since medical students reported that their work on the pandemic frontlines positively affected their learning, the need to create more hands-on learning opportunities for medical students challenges curriculum developers. Medical students wish to feel like full-fledged care team members rather than observing sideliners. Performing simple clinical tasks and collaborative moments in a supportive learning environment may promote learning and professional development and should be encouraged in the post-pandemic era.

Background: Chronic pelvic pain with various etiologies and mechanisms affects men and women and is a major challenge. Monotherapy is often unsuccessful for chronic pelvic pain, and combinations of different classes of medications are frequently prescribed, with the expectation of improved outcomes. Although a number of combination trials for chronic pelvic pain have been reported, we are not aware of any systematic reviews of the available evidence on combination drug therapy for chronic pelvic pain., Objective: We have developed a protocol for a systematic review to evaluate available evidence of the efficacy and safety of drug combinations for chronic pelvic pain., Methods: This systematic review will involve a detailed search of randomized controlled trials investigating drug combinations to treat chronic pelvic pain in adults. The databases searched will include the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from their inception until the date the searches are run to identify relevant studies. The primary outcome will be pain relief measured using validated scoring tools. Secondary outcomes, where reported, will include the following: adverse events, serious adverse events, sexual function, quality of life, and depression and anxiety. Methodological quality of each included study will be assessed using the Cochrane Risk of Bias Tool., Results: The systematic review defined by this protocol is expected to synthesize available good quality evidence on combination drug therapy in chronic pelvic pain, which may help guide future research and treatment choices for patients and their health care providers., Conclusions: This review will provide a clearer understanding of the efficacy and safety of combination pharmacological therapy for chronic pelvic pain., Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42020192231; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=192231., International Registered Report Identifier (irrid): PRR1-10.2196/21909., (©Mohammed Mohiuddin, Rex Park, Ursula Wesselmann, Caroline Pukall, Keith Jarvi, Curtis Nickel, Christopher Doiron, Ian Gilron. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 17.05.2021.)

Engineered nanomaterials (ENMs) based on CeO 2 and TiO 2 differ in their effects on the unicellular green alga Raphidocelis subcapitata but these effects do not reflect the physicochemical parameters that characterize such materials in water and other test media. To determine whether interactions with algae can predict the ecotoxicity of ENMs, we studied the attachment of model compounds (three subtypes of CeO 2 and five subtypes of TiO 2 ) to algal cells by light microscopy and electron microscopy. We correlated our observations with EC 50 values determined in growth inhibition assays carried out according to the Organisation for Economic Co-operation and Development (OECD) test guideline 201. Light microscopy revealed distinct patterns of ENM attachment to algal cells according to the type of compound, with stronger interactions leading to greater toxicity. This was confirmed by electron microscopy, which allowed the quantitative assessment of particle attachment. Our results indicate that algal extracellular polymeric substances play an important role in the attachment of ENMs, influencing the formation of agglomerates. The attachment parameters in short-term tests predicted the toxicity of CeO 2 and TiO 2 ENMs and can be considered as a valuable tool for the identification of sets of similar nanoforms as requested by the European Chemicals Agency in the context of grouping and read-across., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Background: Plain radiography (XR) series are standard of care for detection of fall-related fractures in older patients with low-energy falls (LEF) in the emergency department (ED). We have investigated the prevalence of fractures and diagnostic accuracy of XR imaging in the ED., Methods: 2839 patients with LEF, who were presented to two urban level I trauma centers in 2016 and received XR and computed tomography (CT), were consecutively included in this retrospective cohort study. The primary endpoint was the prevalence of fractures of the vertebral column, rib cage, pelvic ring, and proximal long bones. Secondary endpoints were diagnostic accuracy of XR for fracture detection with CT as reference standard and cumulative radiation doses applied., Results: Median age was 82 years (range 65-105) with 64.1% female patients. Results revealed that 585/2839 (20.6%) patients sustained fractures and 452/2839 (15.9%) patients received subsequent XR and CT examinations of single body regions. Cross-tabulation analysis revealed sensitivity of XR of 49.7%, a positive likelihood ratio of 27.6, and negative likelihood ratio of 0.5., Conclusions: XR is of moderate diagnostic accuracy for ruling-out fractures of the spine, pelvic ring, and rib cage in older patients with LEF. Prospective validations are required to investigate the overall risk-benefit of direct CT imaging strategies, considering the trade-off between diagnostic safety, health care costs, and radiation exposure., Competing Interests: The authors declare no conflicts of interest.

The combination of a representative microplastic sampling method and a fast-quantitative analysis using Pyrolysis-GC-MS (Py-GC-MS) for investigation of the microplastic load and mass balances is presented in this work. A representative microplastic filtration requires a method allowing quick extraction of the sample. The developed steel based cascadic microplastic filtration uses steel basket filters with mesh sizes of 100 μm, 50 μm and 10 μm and a mean recovery of 86 % without cross contamination was achieved. Thermoanalytical methods have the advantage of minimal sample preparation with short analysis times. The presented platinum filament-based Py-GC-MS method requires little sample preparation and quantification limits for polystyrene (PS) and polyethylene (PE) were 0.03 μg and 1 μg absolute, respectively. The relative standard deviation of the analytical method is 11 %. The combined method allows representative sampling and analysis of MP from water bodies and waste water treatment plants within 48 h. •Presentation of a validated steel based cascadic microplastic filtration plant.•Fast and reproduceable Py-GC-MS analysis method for microplastic.•Py-GC-MS allows microplastic analysis with little sample preparation., (© 2020 The Authors.)

Objective: To determine the ability of a normal D-dimer level (<0.5 mg/l) to identify emergency department (ED) patients at low risk of 30-day all-cause mortality., Design: In this prospective observational study, D-dimer levels of adult medical patients were assessed at arrival to the ED. Data on 30-day survival status were extracted from the Danish Civil Registration System with complete follow-up., Setting: The Hospital of South West Jutland., Patients: All patients aged 18 years or older who required any blood sample on a clinical indication on arrival to the ED. Participants were required to give written informed consent before enrollment., Main Results: The study population of 1 518 patients with median age 66 years of which 49.4% were female. Of the 791 (52.1%) patients with normal D-dimer levels, 3 (0.4%) died within 30 days; one death resulted from an unrelated traumatic accident. Of the 727 (47.9%) patients with abnormal D-dimer levels (≥0.50 mg/l), 32 (4.4%) died within 30 days. Patients with normal D-dimer levels had a significantly lower 30-day mortality compared to patients with abnormal D-dimer levels (odds ratio 0.08, 95% CI 0.02-0.28): of the 35 patients who died within 30 days, 19 (54.3%) had normal or near normal vital signs when first assessed., Conclusion: Normal D-dimer levels identified patients at low risk of 30-day mortality. Since most patients who died within 30 days presented with normal or near normal vital signs, D-dimer levels appear to provide additional prognostic information., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Sources of data in the intensive care setting are increasing exponentially, but the benefits of displaying multiparametric, high-frequency data are unknown. Decision making may not benefit from this technology if clinicians remain cognitively overburdened by poorly designed data integration and visualization technologies (DIVTs)., Objective: To systematically review and summarize the published evidence on the association of user-centered DIVTs with intensive care clinician performance., Data Sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Web of Science were searched in May 2014 and January 2018., Study Selection: Studies had 3 requirements: (1) the study tested a viable DIVT, (2) participants involved were intensive care clinicians, and (3) the study reported quantitative results associated with decision making in an intensive care setting., Data Extraction and Synthesis: Of 252 records screened, 20 studies, published from 2004 to 2016, were included. The human factors framework to assess health technologies was applied to measure study completeness, and the Quality Assessment Instrument was used to assess the quality of the studies. PRISMA guidelines were adapted to conduct the systematic review and meta-analysis., Main Outcomes and Measures: Study completeness and quality; clinician performance; physical, mental, and temporal demand; effort; frustration; time to decision; and decision accuracy., Results: Of the 20 included studies, 16 were experimental studies with 410 intensive care clinician participants and 4 were survey-based studies with 1511 respondents. Scores for study completeness ranged from 27 to 43, with a maximum score of 47, and scores for study quality ranged from 46 to 79, with a maximum score of 90. Of 20 studies, DIVTs were evaluated in clinical settings in 2 studies (10%); time to decision was measured in 14 studies (70%); and decision accuracy was measured in 11 studies (55%). Measures of cognitive workload pooled in the meta-analysis suggested that any DIVT was an improvement over paper-based data in terms of self-reported performance, mental and temporal demand, and effort. With a maximum score of 22, median (IQR) mental demand scores for electronic display were 10 (7-13), tabular display scores were 8 (6.0-11.5), and novel visualization scores were 8 (6-12), compared with 17 (14-19) for paper. The median (IQR) temporal demand scores were also lower for all electronic visualizations compared with paper, with scores of 8 (6-11) for electronic display, 7 (6-11) for tabular and bar displays, 7 (5-11) for novel visualizations, and 16 (14.3-19.0) for paper. The median (IQR) performance scores improved for all electronic visualizations compared with paper (lower score indicates better self-reported performance), with scores of 6 (3-11) for electronic displays, 6 (4-11) for tabular and bar displays, 6 (4-11) for novel visualizations, and 14 (11-16) for paper. Frustration and physical demand domains of cognitive workload did not change, and differences between electronic displays were not significant., Conclusions and Relevance: This review suggests that DIVTs are associated with increased integration and consistency of data. Much work remains to identify which visualizations effectively reduce cognitive workload to enhance decision making based on intensive care data. Standardizing human factors testing by developing a repository of open access benchmarked test protocols, using a set of outcome measures, scenarios, and data sets, may accelerate the design and selection of the most appropriate DIVT.

Background: The clinical course of Campylobacter infection varies in symptoms and severity depending on host factors, virulence of the pathogen and initiated therapy. The type VI secretion system (T6SS) has been identified as a novel virulence factor, which mediates contact-dependent injection of enzymes and toxins into competing bacteria or host cells and facilitates the colonisation of a host organism. We aimed to compare the clinical course of Campylobacter infection caused by strains with and without the T6SS and identify possible associations between this putative virulence factor and the clinical manifestations of disease., Methods: From April 2015 to January 2017, patients with detection of Campylobacter spp. were identified at the University Hospital of Basel and the University Children's Hospital of Basel and included in this case-control study. Presence of the T6SS gene cluster was assayed by PCR targeting the hcp gene, confirmed with whole genome sequencing. Pertinent clinical data was collected by medical record review. Differences in disease- and host-characteristics between T6SS-positive (case) and -negative (control) were compared in a uni- and multi-variable analysis. Hospital admission, antibiotic therapy, admission to intensive care unit, development of bacteraemia and in-hospital mortality were considered as clinical endpoints., Results: We identified 138 cases of Campylobacter jejuni infections and 18 cases of Campylobacter coli infections from a paediatric and adult population. Analyses were focused on adult patients with C. jejuni (n = 119) of which 16.8% were T6SS-positive. Comparisons between T6SS-positive and -negative C. jejuni isolates did not reveal significant differences regarding clinical manifestations or course of disease. All clinical endpoints showed a similar distribution in both groups. A higher score in the Charlson Comorbidity Index was associated with T6SS-positive C. jejuni isolates (p < 0.001) and patients were more likely to have a solid organ transplant and to be under immunosuppressive therapy., Conclusions: Our study does not provide evidence that T6SS is associated with a more severe clinical course. Interestingly, T6SS-positive isolates are more commonly found in immunocompromised patients: an observation which merits further investigation.

Background: End-of-life decisions (EOLD) represent potentially highly consequential decisions often made in acute situations, such as 'do not attempt resuscitation' (DNAR) choices at emergency presentation., Aim: We investigated DNAR decisions in an emergency department (ED) to assess prevalence, associated patient characteristics, potential medical and economic consequences and estimate contributions of patients and physicians to DNAR decisions., Design: Single-centre retrospective observation, including ED patients with subsequent hospitalization between 2012 and 2016. Primary outcome was a DNAR decision and associated patient characteristics. Secondary outcomes were mortality, admission to intensive care unit and use of resources., Methods: Associations between DNAR and patient characteristics were analysed using logistic mixed effects models, results were reported as odds ratios (OR). Median odds ratios (MOR) were used to estimate patient and physician contributions to variability in DNAR., Results: Patients of 10 458 were attended by 315 physicians. DNAR was the choice in 23.3% of patients. Patients' characteristics highly associated with DNAR were age (OR = 4.0, 95% CI = 3.6-4.3) and non-trauma presentation (OR = 2.3, 95% CI = 1.9-2.9). In-hospital mortality was significantly higher (OR = 5.4, CI = 4.0-7.3), and use of resources was significantly lower (OR = 0.7, CI = 0.6-0.8) in patients choosing DNAR. There was a significant effect on DNAR by both patient (MOR = 1.8) and physician (MOR = 2.0)., Conclusions: DNAR choices are common in emergency patients and closely associated with age and non-trauma presentation. Mortality was significantly higher, and use of resources significantly lower in DNAR patients. Evidence of a physician effect raises questions about the choice autonomy of emergency patients in the process of EOLD., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Policy makers struggle with unplanned readmissions as a quality indicator since integrating preventability in such indicators is difficult. Most studies on the preventability of readmissions questioned physicians whether they consider a given readmission to be preventable, from which conclusions on factors predicting preventable readmissions were derived. There is no literature on the interobserver agreement of physician judgement., Aim: To assess the degree of agreement among physicians regarding predictability and preventability of medical readmissions., Design: An online survey based on eight real-life case scenarios was distributed to European physicians., Methods: Physicians were requested to rate from the first four (index admission) scenarios whether they expected these patients to be readmitted within 30 days (the predictability). The remaining four cases, describing a readmission, were used to assess the preventability. The main outcome was the degree of agreement among physicians determined using the intra class correlation coefficient (ICC)., Results: 526 European medical physicians completed the survey. Most physicians had internal medicine as primary specialism. The median years of clinical experience was 11. ICC for predictability of readmission was 0.67 (moderate to good) and ICC for preventability of readmission was 0.13 (poor)., Conclusion: There was moderate to good agreement among physicians on the predictability of readmissions while agreement on preventability was poor. This study indicates that assessing preventability of readmissions based solely on the judgement of physicians is far from perfect. Current literature on the preventability of readmissions and conclusions derived on the basis of physician opinion should be interpreted with caution.

Aims: The objective of this meta-analysis was to determine whether gestational use of hydroxychloroquine (HCQ) for autoimmune disorders leads to an increase in the risk for adverse pregnancy outcomes., Methods: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched from inception to November 21 2014. Studies which reported the outcomes of pregnant women after exposure to HCQ during pregnancy and including a control (unexposed) group were included. Two independent reviewers carried out the review and the quality assessment using the Methodological Index for Non-Randomized Studies (MINORS). A random effects method was used to calculate the odds ratios (OR) for the outcomes., Results: The meta-analysis reported no significant increases in rates of major congenital (OR 1.13, 95% confidence interval (CI) 0.59, 2.17), craniofacial (OR 0.62, 95% CI 0.13, 3.03), cardiovascular (OR 1.06, 95% CI 0.29, 3.86), genitourinary (OR 1.38, 95% CI 0.42, 4.53), nervous system malformations (OR 1.81, 95% CI 0.31, 10.52), stillbirth (OR 0.69, 95% CI 0.35, 1.34), low birth weight (OR 0.69, 95% CI 0.21, 2.27) or prematurity (OR 1.75, 95% CI 0.95, 3.24). The rate of spontaneous abortions, however, was found to be significantly increased in HCQ exposed pregnancies (OR 1.85, 95% CI 1.10, 3.13). No significant heterogeneity was detected among the studies for the evaluated outcomes except prematurity., Conclusions: Prenatal exposure to HCQ for autoimmune diseases does not appear to increase the risk of adverse pregnancy outcomes except spontaneous abortion rate, which may be associated with the underlying disease activity (bias by indication) and needs further investigation., (© 2015 The British Pharmacological Society.)

Background: Hospital readmissions are increasingly used as a quality indicator with a belief that they are a marker of poor care and have led to financial penalties in UK and USA. Risk scoring systems, such as LACE and HOSPITAL, have been proposed as tools for identifying patients at high risk of readmission but have not been validated in international populations., Aim: To perform an external independent validation of the HOSPITAL and LACE scores., Design: An unplanned secondary cohort study., Methods: Patients admitted to the medical admission unit at the Hospital of South West Jutland (10/2008-2/2009; 2/2010-5/2010) and the Odense University Hospital (6/2009-8/2011) were analysed. Validation of the scores using 30 day readmissions as the endpoint was performed., Results: A total of 19 277 patients fulfilled the inclusion criteria. Median age was 67 (range 18-107) years and 8977 (46.6%) were female. The LACE score had a discriminatory power of 0.648 with poor calibration and the HOSPITAL score had a discriminatory power of 0.661 with poor calibration. The HOSPITAL score was significantly better than the LACE score for identifying patients at risk of 30 day readmission (P < 0.001). The discriminatory power of both scores decreased with increasing age., Conclusion: Readmissions are a complex phenomenon with not only medical conditions contributing but also system, cultural and environmental factors exerting a significant influence. It is possible that the heterogeneity of the population and health care systems may prohibit the creation of a simple prediction tool that can be used internationally., (© The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Nanomaterials are commonly used in everyday life products and during their life cycle they can be released into the environment. Soils and sediments are estimated as significant sinks for those nanomaterials. To investigate and assess the behaviour of nanomaterials in soils and sediments standardized test methods are needed. In this study the applicability of two existing international standardized test guidelines for the testing of nanomaterials, OECD TG 106 "Adsorption/Desorption using a Bath Equilibrium Method" and the OECD TG 312 "Leaching in Soil Columns", were investigated. For the study one coated and two uncoated TiO2 nanomaterials were used, respectively. The results indicate that the OECD TG 106 is not applicable for nanomaterials. However, the test method according to OECD TG 312 was found to be applicable if nano-specific adaptations are applied. The mobility investigations of the OECD TG 312 indicated a material-dependent mobility of the nanomaterials, which in some cases may lead to an accumulation in the upper soil layers. Whereas no significant transport was observed for the uncoated materials for the double-coated material (coating with dimethicone and aluminiumoxide) a significant transport was detected and attributed to the coating., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Acute appendicitis is the most common surgical emergency in children. Despite this, there is no core outcome set (COS) described for randomised controlled trials (RCTs) in children with appendicitis and hence no consensus regarding outcome selection, definition and reporting. We aimed to identify outcomes currently reported in studies of paediatric appendicitis., Methods: Using a defined, sensitive search strategy, we identified RCTs and systematic reviews (SRs) of treatment interventions in children with appendicitis. Included studies were all in English and investigated the effect of one or more treatment interventions in children with acute appendicitis or undergoing appendicectomy for presumed acute appendicitis. Studies were reviewed and data extracted by two reviewers. Primary (if defined) and all other outcomes were recorded and assigned to the core areas 'Death', 'Pathophysiological Manifestations', 'Life Impact', 'Resource Use' and 'Adverse Events', using OMERACT Filter 2.0., Results: A total of 63 studies met the inclusion criteria reporting outcomes from 51 RCTs and nine SRs. Only 25 RCTs and four SRs defined a primary outcome. A total of 115 unique and different outcomes were identified. RCTs reported a median of nine outcomes each (range 1 to 14). The most frequently reported outcomes were wound infection (43 RCTs, nine SRs), intra-peritoneal abscess (41 RCTs, seven SRs) and length of stay (35 RCTs, six SRs) yet all three were reported in just 25 RCTs and five SRs. Common outcomes had multiple different definitions or were frequently not defined. Although outcomes were reported within all core areas, just one RCT and no SR reported outcomes for all core areas. Outcomes assigned to the 'Death' and 'Life Impact' core areas were reported least frequently (in six and 15 RCTs respectively)., Conclusions: There is a wide heterogeneity in the selection and definition of outcomes in paediatric appendicitis, and little overlap in outcomes used across studies. A paucity of studies report patient relevant outcomes within the 'Life Impact' core area. These factors preclude meaningful evidence synthesis, and pose challenges to designing prospective clinical trials and cohort studies. The development of a COS for paediatric appendicitis is warranted.

Objective: To conduct a systematic review evaluating the effectiveness of a folate-fortified oral contraceptive preparation in increasing blood folate concentrations to levels providing optimal protection against neural tube defects (> 906 nmol/L)., Methods: We searched Medline, EMBASE, Web of Science, and the Cochrane Library for human studies published from inception to June 2013 that evaluated oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. Efficacy and bioequivalence data were evaluated from included studies., Results: Overall, efficacy and bioequivalence data for the folate-fortified oral contraceptive show that it is at least as effective as folic acid alone in raising blood folate concentrations, and that the concomitant administration of folate with the oral contraceptive component does not affect its absorption or kinetics., Conclusion: A folate-fortified oral contraceptive preparation provides an option for women to maintain blood folate levels, especially those who may be planning a family after the cessation of oral contraceptive therapy.

Most chloroplast resident proteins are equipped with N-terminal transit peptides to ensure targeting from the cytosol to the organelle. Import rates can be modulated by phosphorylation and 14-3-3 binding within the transit peptides. Using the phosphorylatable preprotein pHCF136, a photosystem II assembly factor, we investigated the function of preprotein phosphorylation in vivo by complementing the seedling lethal hcf136 mutant. HCF136 constructs containing mutations within the 14-3-3 binding site were generated, either abolishing or mimicking phosphorylation. Interestingly, phosphomimicking reduced the import rate and the hcf136 phenotype could only be partially rescued, as shown by hampered photosystem II complex accumulation, which was most prominently observed in cotyledons., (Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Objective: To conduct a systematic review and meta-analysis of the effect of oral contraceptive use on plasma and red blood cell (RBC) folate concentrations., Methods: We searched Medline, EMBASE, Web of Science, and the Cochrane library for human studies published from inception to June 2013 evaluating oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. A random-effects model of outcomes was used for the meta-analysis., Results: A total of 2831 women in 17 studies were included in the analysis. In those whose plasma folate concentrations were available, there was a significant folate-lowering effect of oral contraceptives observed (mean reduction 1.27 µg/L; 95% CI 1.85 to 0.69, P < 0.001). Similarly, after analyzing data from 1389 women in 12 studies whose RBC folate concentrations were available, significantly lower folate status was observed among oral contraceptive users (mean reduction 59.32 µg/L; 95% CI 58.03 to 23.04, P < 0.001)., Conclusion: Because of the reduction in blood folate concentrations associated with the use of oral contraceptives, it is critical for women of childbearing age to continue folate supplementation during oral contraceptive use.

The association between the physician's first clinical impression of a patient with nonspecific complaints and morbidity and mortality is unknown. The aim was to evaluate the association of the physician's first clinical impression with acute morbidity and mortality. We conducted a prospective observational study with a 30-day follow-up. This study was performed at the emergency departments (EDs) of 1 secondary and 1 tertiary care hospital, from May 2007 to February 2011. The first clinical impression ("looking ill"), expressed on a numerical rating scale from 0 to 100, age, sex, and the Charlson Comorbidity Index (CCI) were evaluated. The association was determined between these variables and acute morbidity and mortality, together with receiver operating characteristics, and validity. Of 217,699 presentations to the ED, a total of 1278 adult nontrauma patients with nonspecific complaints were enrolled by a study team. No patient was lost to follow-up. A total of 84 (6.6%) patients died during follow-up, and 742 (58.0%) patients were classified as suffering from acute morbidity. The variable "looking ill" was significantly associated with mortality and morbidity (per 10 point increase, odds ratio 1.23, 95% confidence interval [CI] 1.12-1.34, P < 0.001, and odds ratio 1.19, 95% CI 1.14-1.24, P < 0.001, respectively). The combination of the variables "looking ill," "age," "male sex," and "CCI" resulted in the best prediction of these outcomes (mortality: area under the curve [AUC] 0.77, 95% CI 0.72-0.82; morbidity: AUC 0.68, 95% CI 0.65-0.71). The physician's first impression, with or without additional variables such as age, male sex, and CCI, was associated with morbidity and mortality. This might help in the decision to perform further diagnostic tests and to hospitalize ED patients.