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Key summary points Aim The aim was to develop expert clinical recommendations on Geriatric Emergency Medicine to be disseminated across Europe. Findings Eight posters with expert clinical guidelines on the most important topics in Geriatric Emergency Medicine are now available through https://posters.geriemeurope.eu/. Message Expert clinical recommendations for Geriatric Emergency Medicine in Europe were created and are ready for dissemination across Europe. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00578-1., Purpose Despite the rapidly expanding knowledge in the field of Geriatric Emergency Medicine in Europe, widespread implementation of change is still lacking. Many opportunities in everyday clinical care are missed to improve care for this susceptible and growing patient group. The aim was to develop expert clinical recommendations on Geriatric Emergency Medicine to be disseminated across Europe. Methods A group of multi-disciplinary experts in the field of Geriatric Emergency Medicine in Europe was assembled. Using a modified Delphi procedure, a prioritized list of topics related to Geriatric Emergency Medicine was created. Next, a multi-disciplinary group of nurses, geriatricians and emergency physicians performed a review of recent guidelines and literature to create recommendations. These recommendations were voted upon by a group of experts and placed on visually attractive posters. The expert group identified the following eight subject areas to develop expert recommendations on: Comprehensive Geriatric Assessment in the Emergency Department (ED), age/frailty adjusted risk stratification, delirium and cognitive impairment, medication reviews in the ED for older adults, family involvement, ED environment, silver trauma, end of life care in the acute setting. Results Eight posters with expert clinical recommendations on the most important topics in Geriatric Emergency Medicine are now available through https://posters.geriemeurope.eu/. Conclusion Expert clinical recommendations for Geriatric Emergency Medicine may help to improve care for older patients in the Emergency Department and are ready for dissemination across Europe. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00578-1.

Background:Over half of patients with facial fractures have associated traumatic brain injury. Based on previous force dynamic cadaveric studies, Lefort type 2 and 3 fractures are more associated with severe injury. Whether this correlates to neurosurgical intervention have not been well characterized. The purpose of this retrospective data analysis is to characterize fracture pattern types in patients requiring neurosurgical intervention and to see if this is different from those not requiring intervention. Methods:Retrospective data was collected from the trauma registry from 2010-2019. Inclusion criteria: adults over 18, confirmed facial fracture with available neuroimaging, reported traumatic brain injury, and admission to ICU or floor bed. Exclusion criteria: patients less than 18 years old, patients with no neuroimaging, and patients that were deceased prior to initiation of neurosurgical intervention. Data included: basic demographic data, presenting Glasgow Coma Scale (GCS) score, mechanism of injury, type of traumatic brain injury, neurosurgical intervention, and facial fracture type. Retrospective Contingency Analysis with Fraction of Total Comparison was used with Chi-Square analysis for demographic and injury characteristic data.Results:1172 patients met inclusion criteria. 1001 required no neurosurgical intervention and 171 required intervention. No significant difference was seen between the non-intervention group and intervention group in terms of demographic data or baseline injury characteristics except for presenting GCS. A significant difference was seen between groups for presenting Glasgow Coma Scale (c2=67.71, p2=4.518, p=0.92), however subset analysis did reveal a 2 fold increase in Lefort type 2 fractures and notable increase in Lefort type 3 and panfacial fractures in the intervention group. The intervention group was further divided into those requiring external ventricular drain or intracranial pressure monitor only vs. patients requiring craniectomy, craniotomy, or burr holes with or with external ventricular drain or intracranial pressure monitor. A significant difference was seen between groups (c2=20.02, p=0.03). The craniectomy, craniotomy, or burr hole group was much more likely to have Lefort type 2 or 3 fractures compared to the external ventricular drain or intracranial pressure monitor group only. Conclusions:Lefort type 2 and type 3 fractures are significantly associated with requiring neurosurgical intervention. An improved algorithm for managing these patients has been proposed in the discussion. Ongoing work will focus on validating and refining the algorithm in order to improve patient care for trauma patients with facial fracture and traumatic brain injury.

OBJECTIVE Postoperative urinary retention (POUR) is a common complication after spine surgery and is associated with prolongation of hospital stay, increased hospital cost, increased rate of urinary tract infection, bladder overdistention, and autonomic dysregulation. POUR incidence following spine surgery ranges between 5.6% and 38%; no reliable prediction tool to identify those at higher risk is available, and that constitutes an important gap in the literature. The objective of this study was to develop and validate a preoperative risk model to predict the occurrence of POUR following routine elective spine surgery. METHODS The authors conducted a retrospective chart review of consecutive adults who underwent lumbar spine surgery between June 1, 2017, and June 1, 2019. Patient characteristics, preexisting ICD-10 codes, preoperative pain and opioid use, preoperative alpha-1 blocker use, details of surgical planning, development of POUR, and management strategies were abstracted from electronic medical records. A binomial logistic model and a multilayer perceptron (MLP) were optimized using training and validation sets. The models’ performance was then evaluated on model-naïve patients (not a part of either cohort). The models were then stacked to take advantage of each model’s strengths and to avoid their weaknesses. Four additional models were developed from previously published models adjusted to include only relevant factors (i.e., factors known preoperatively and applied to the lumbar spine). RESULTS Overall, 891 patients were included in the cohort, with a mean of 59.6 ± 15.5 years of age, 52.7% male, BMI 30.4 ± 6.4, American Society of Anesthesiologists class 2.8 ± 0.6, and a mean of 5.6 ± 5.7 comorbidities. The rate of POUR was found to be 25.9%. The two models were comparable, with an area under the curve (AUC) of 0.737 for the regression model and 0.735 for the neural network. By combining the two models, an AUC of 0.753 was achieved. With a regression model probability cutoff of 0.24 and a neural network cutoff of 0.23, maximal sensitivity and specificity were achieved, with specificity 68.2%, sensitivity 72.9%, negative predictive value 88.2%, and positive predictive value 43.4%. Both models individually outperformed previously published models (AUC 0.516–0.645) when applied to the current data set. CONCLUSIONS This predictive model can be a powerful preoperative tool in predicting patients who will be likely to develop POUR. By using a combination of regression and neural network modeling, good sensitivity, specificity, and NPV are achieved.

Breast cancer brain metastases remain largely incurable. Although several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immunocompromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours. As seen by immunohistochemistry, 4T1Br4 tumours and brain metastases display a triple-negative phenotype, consistent with the high propensity of this breast cancer subtype to spread to brain. In vitro assays indicate that 4T1Br4 cells have an enhanced ability to adhere to or migrate across a brain-derived endothelial monolayer and greater invasive response to brain-derived soluble factors compared to 4T1 cells. These properties are likely to contribute to the brain selectivity of 4T1Br4 tumours. Expression profiling and gene set enrichment analyses demonstrate the clinical relevance of the 4T1Br4 model at the transcriptomic level. Pathway analyses implicate tumour-intrinsic immune regulation and vascular interactions in successful brain colonisation, revealing potential therapeutic targets. Evaluation of two histone deacetylase inhibitors, SB939 and 1179.4b, shows partial efficacy against 4T1Br4 metastasis to brain and other sites in vivo, and potent radio-sensitising properties in vitro. The 4T1Br4 model provides a clinically relevant tool for mechanistic studies and to evaluate novel therapies against brain metastasis. This article has an associated First Person interview with Soo-Hyun Kim, joint first author of the paper., Summary: The authors introduce a new syngeneic mouse model of spontaneous breast cancer brain metastasis, demonstrate its phenotypic, functional and transcriptomic relevance to human TNBC brain metastasis, and test novel therapies.

Introduction The increased use of long-acting reversible contraceptives (LARCs), such as intrauterine devices and hormonal implants, has the potential to reduce unintended pregnancy and abortion rates. However, use of LARCs in Australia is very low, despite clinical practice guidance and statements by national and international peak bodies advocating their increased use. This protocol paper describes the Australian Contraceptive ChOice pRojet (ACCORd), a cluster randomised control trial that aims to test whether an educational intervention targeting general practitioners (GPs) and establishing a rapid referral service are a cost-effective means of increasing LARC uptake. Methods and analysis The ACCORd intervention is adapted from the successful US Contraceptive CHOICE study and involves training GPs to provide ‘LARC First’ structured contraceptive counselling to women seeking contraception, and implementing rapid referral pathways for LARC insertion. Letters of invitation will be sent to 600 GPs in South-Eastern Melbourne. Using randomisation stratified by whether the GP inserts LARCs or not, a total of 54 groups will be allocated to the intervention (online ‘LARC First’ training and rapid referral pathways) or control arm (usual care). We aim to recruit 729 women from each arm. The primary outcome will be the number of LARCs inserted; secondary outcomes include the women's choice of contraceptive method and quality of life (Short Form Health Survey, SF-36). The costs and outcomes of the intervention and control will be compared in a cost-effectiveness analysis. Ethics and dissemination The ACCORd study has been approved by the Monash University Human Research Ethics Committee: CF14/3990-2014002066 and CF16/188-2016000080. Any protocol modifications will be communicated to Ethics Committee and Trial Registration registry. The authors plan to disseminate trial outcomes through formal academic pathways comprising journal articles, nation and international conferences and reports, as well as using more ‘popular’ strategies including seminars, workshops and media engagements. Trial registration number ACTRN12615001346561.

Objectives While still in its early stages, recent scientific research towards a cure for HIV has generated widespread media interest. The aim of this paper was to explore the ways in which this research has been represented in Australian print and online media and discuss implications of this. Methods A search of databases from four selected media outlets was conducted to identify published articles that directly discussed HIV cure research. Content analysis was used to explore the discursive framing of HIV cure research and identify the presence or absence of people living with HIV in articles. Results In total, 95 articles were identified that had been published in print or online between 2007 and 2015. Media reports tended to focus on research breakthroughs or the future potential of HIV cure research, rather than more immediate implications of research findings. While not inaccurate, this focus often implied the field of HIV cure research was more advanced than was generally the case. There was a notable absence of commentary from people living with HIV or community advocates in media reporting. Conclusions Media reporting may generate unrealistic expectations of HIV cure research. This raises ethical concerns that media reporting may inadvertently contribute to therapeutic or curative misconceptions among potential participants in HIV cure-related trials. To address this, scientists, HIV advocates and people living with HIV will need to work collaboratively to engage with reporters and media outlets to provide more consistent input and guidance into reporting about research towards a cure for HIV.

The correlation of neuroinflammation with the development of cerebral vasospasm following subarachnoid hemorrhage has been well documented in the literature; both clinical and preclinical. The exact mechanisms by which this process occurs, however, are poorly elucidated. Recent evidence indicates that interleukin-6 is not only an important prognostic biomarker for subarachnoid hemorrhage and subsequent vasospasm development but also an integral component in the progression of injury following initial insult. In this review, we briefly highlight other pathways under investigation and focus heavily on what has been discovered regarding the role of interleukin 6 and cerebral vasospasm following subarachnoid hemorrhage. A proposed mechanistic pathway is highlighted in written and graphical format. A discussion regarding the human correlative findings and initial pre-clinical mechanistic studies is addressed. Finally, in the future investigation section, innovative developments and a clear description of areas warranting further scientific inquiry are emphasized. This review will catalyze continued discovery in this area of emerging significance and aid in the quest for effective vasospasm treatment where limited clinical therapeutics currently exist.

Kathrin Kahnert,1 Rudolf A Jörres,2 Tanja Lucke,2 Franziska C Trudzinski,3 Pontus Mertsch,1 Christiane Bickert,1 Joachim H Ficker,4 Jürgen Behr,1 Robert Bals,5 Henrik Watz,6 Tobias Welte,7 Claus F Vogelmeier,8 Peter Alter8 On behalf of COSYCONET Study Group1Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany; 3Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany; 4Department of Respiratory Medicine, Nürnberg General Hospital, Paracelsus Medical University, Nürnberg, Germany; 5Department of Internal Medicine V - Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany; 6Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 7Clinic for Pneumology, Hannover Medical School, Member of the German Center for Lung Research (DZL), Hannover, Germany; 8Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg (UMR), Germany, Member of the German Center for Lung Research (DZL), Marburg, GermanyCorrespondence: Kathrin KahnertDepartment of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, GermanyTel +49 89 4400 52590Fax +49 89 4400 54905Email kathrin.kahnert@med.uni-muenchen.deBackground: Patients with chronic obstructive pulmonary disease (COPD) often have osteoporosis and diabetes as comorbid conditions. Anti-diabetic medication, including metformin, has protective effects on osteoporosis in experimental studies. We therefore studied whether patients with COPD receiving anti-diabetic medication had a lower osteoporosis prevalence in a large COPD cohort, COSYCONET.Methods: Assessment of osteoporosis was based on patients’ reports of physician-based diagnoses and the presence of disease-specific medication. The predictive value of physical characteristics, lung function, comorbidities, cardiovascular medication, and the use of anti-inflammatory diabetes medication, including metformin, sulfonylureas, glinides or DPP4I, was evaluated using logistic regression analysis. ClinicalTrials.gov: NCT01245933.Results: In total, 2222 patients were eligible for analysis (863 [39%] female, mean age 65 y), 515 of whom had higher symptoms and exacerbations (Global Initiative for Chronic Obstructive Lung Disease group D). Osteoporosis was present in 15.8% of the overall cohort, and in 24.1% of GOLD D patients. Regression analyses identified the following as associated with osteoporosis (p < 0.05): female sex, higher age, lower body-mass index, asthma, higher air trapping, oral steroids, and cardiovascular medication. Although oral anti-diabetic medication was overall not associated with a lower prevalence of osteoporosis (p = 0.131), anti-inflammatory anti-diabetic medication (p = 0.009) and metformin-containing therapy (p = 0.039) were. This was driven by GOLD D patients.Conclusion: In a large COPD cohort, anti-inflammatory diabetes therapy, including metformin, was associated with a lower prevalence of osteoporosis, especially in patients with higher symptoms and exacerbations. These findings suggest a protective effect of common anti-diabetic medication on osteoporosis, possibly as a result of attenuated systemic inflammation.Keywords: chronic obstructive pulmonary disease, oral corticosteroids, inhaled corticosteroids, anti-inflammatory, metformin, diabetes

Background Severe headache, a hallmark of aneurysmal subarachnoid hemorrhage (aSAH), affects up to 90% of patients during hospitalization. Opioids remain the guideline recommended mainstay of acute therapy despite their significant side effects and potential for tolerance and addiction. We evaluated time trends in opioid prescriptions, hypothesizing a decline with increasing recognition of the opioid crisis. Methods We performed a retrospective review of patients with aSAH admitted to a single tertiary care center between 2012 and 2019 and included patients with Hunt-Hess-Grade ≤ 3 who were able to verbalize pain scores. Collected variables included mean and maximum daily headache scores, aneurysm treatment modality, and daily analgesic medication doses. Results Of 340 patients with aSAH, 114 (86 from 2012–2016 and 28 from 2017–2019) were included. Of the included patients, 86/114 (75.4%) were female. Patients in the 2012–2016 had a median age of 55 compared to 63 in the 2017–2019 group (P = 0.02). Otherwise, there was no significant difference in demographic data including time in hospital, treatment option utilized, or aneurysm characteristics. Maximal daily headache score ranged from 6 to 8 for 2012–2016 and 5 to 8 for 2017–2019 cohorts. Average oral morphine equivalents (in mg) administered during hospitalization were similar between groups (2012–2016: 251 ± 345 95% CI [178,323]; 2017–2019: 207 ± 237 95% CI [119,295]; P = 0.319). When prescribed, doses of opioids provided at discharge were less in the more recent group (2012–2016: 84.4 ± 78.9 95% CI [57.5, 111]; 2017–2019: 38.1 ± 20.2 95% CI [33.7, 42.5]; P = 0.004) Conclusion Despite recognition of important drawbacks of opioid use for headache control, and efforts to reduce opioid use during hospitalization, we found that utilization during hospitalization for SAH did not decrease over time. Maximal headache scores remained similar in the studied time periods, indicative of insufficient pain relief. This points out a pressing need to further investigate alternative opioid and narcotic sparing strategies for patients with SAH.

Background and objectives Women’s ability to negotiate condom use helps prevent sexually transmissible infections (STIs) and unintended pregnancies. The aim of this study was to assess the relationship between substance use, risk perception and the certainty of using condoms in several hypothetical situations. Methods This is a secondary analysis from the Australian Contraceptive ChOice pRoject (ACCORd) cluster randomised controlled trial. Descriptive statistics and logistic regression were used for the analysis. Results At baseline, contraceptive questions were answered by 698 women attending 57 general practices in Melbourne, Australia. Condom use was reported by 47%. Of those using condoms as the sole form of contraception (n = 137), 20% used them inconsistently. Dual protection was used by 58% of women (188/325). Condoms and the pill were more frequently used than condoms and longer-acting contraceptives. Women were less likely to be confident negotiating condom use when using substances. Discussion Substance use and the concurrent use of other forms of contraception impact use of condoms. Even when condoms are the sole form of contraception with willing partners, use is inconsistent, leaving women at risk of pregnancy and STI.

Introduction The COPD classification proposed by the Global Initiative for Obstructive Lung Disease was recently revised, and the A to D grouping is now based on symptoms and exacerbations only. Potential associations with comorbidities have not been assessed so far. Thus the aim of the present study was to determine the relationship between the revised (2017) GOLD groups A-D and major comorbidities. Methods We used baseline data from the COPD cohort COSYCONET. Comorbidities were identified from patient self-reports and disease-specific medication: gastrointestinal disorders, asthma, sleep apnea, hyperuricemia, hyperlipidemia, diabetes, osteoporosis, mental disorders, heart failure, hypertension, coronary artery disease. The A-D groups were based on either the COPD Assessment Test or the modified Medical Research Council scale. Exacerbations were also categorized as per GOLD recommendations. Results Data from 2228 patients were analyzed. Using GOLD group A as a reference, group D was associated with nearly all comorbidities, followed by group B and C. When groups A-D were dichotomized as AC vs. BD (symptoms) and AB vs. CD (exacerbations), all comorbidities correlated with symptoms and/or exacerbations. This was true for both mMRC- and CAT-based categorizations. Conclusions These findings suggest that the recently modified GOLD categorization is clinically relevant beyond being purely an assessment of symptoms and exacerbations. As the A-D groups correlated with the risk of important comorbidities, with some differences in terms of the correlation with symptoms and exacerbations, the findings underline the importance of identifying comorbidities in COPD, particularly in non-responders to therapy who have high symptoms and/or exacerbation rates.

Divorce is a life-changing event with financial implications for women. Although large-scale studies have examined the factors associated with financial coping after divorce, little attention has been paid to the lived experience of women over time. In this study, we used mixed methods to examine the financial well-being of divorced women over 20 years from 1996 to 2016. Using data from the Australian Longitudinal Study on Women's Health [ALSWH], we analyzed women's ratings of their ability to manage on available income, and their narrative comments about financial coping over eight waves, beginning in midlife (ages 46-51). The ratings improved over time, particularly as women reached peak career in their 50s or 60s or entered retirement. Despite this upward trajectory, financial strain persisted for ~40% of the cohort who faced poor health or diminishing job prospects. We conclude that, although financial hardship often eases over time, women's early ratings of financial coping predict levels of income security in older age.

Myalgia and mild elevation in muscle enzymes are common side effects of statin therapy. While these symptoms are generally self-limited, in rare cases, statin use is associated with an immune-mediated necrotizing myopathy caused by development of autoantibodies against HMG-CoA reductase. The primary presenting symptom of this condition is progressive symmetric proximal weakness that does not abate or worsens even after cessation of statin therapy and is associated with markedly elevated creatine kinase (CK) levels. To date, no randomized controlled trials have been conducted to identify the most effective treatment for statin-associated autoimmune myopathy. Treatment recommendations involve a combination of steroids and immunosuppressive drugs. This single-center case series highlights the clinicopathologic features diagnostic for statin-associated autoimmune myopathy as well as treatment challenges for the patient population. The series highlights a range of potential presentations, from mildly symptomatic despite highly elevated CK, to severe muscle weakness including dysphagia. Multiple patients required several immunosuppressant medications as well as intravenous immunoglobulin (IVIG) to achieve disease control. In this case series, marked improvement was noted in several diabetic patients with IVIG.

Background: The Australian Contraceptive ChOice pRoject (ACCORd) aimed to assess the impact of a complex general practice intervention on the uptake of long-acting reversible contraceptives (LARC). Aims: Using survey data from enrolled women, we aimed to compare the ongoing use and satisfaction of women who chose one of the hormonal LARC methods including the levonorgestrel intrauterine system (LNG-IUS) or levonorgestrel implant compared to the oral contraceptive pill (OCP). Materials and Methods: We used the data from participants’ baseline, six and 12-month surveys to identify new users of implants, LNG-IUS or OCP. We included demographic information, ongoing use of the contraceptive method, reasons for dissatisfaction and discontinuation and experience of side-effects. Proportions were compared using χ tests. Results: Of the 740 women enrolled in ACCORd, 176 started using a hormonal LARC or OCP in the study’s first six months with 76 using the IUS (43%), 60 the implant (34%) and 40 (23%) the OCP. Twelve-month continuation rates for the LNG-IUS, implant and OCP were 93, 83 and 65% respectively (P < 0.001). Satisfaction was highest among the LNG-IUS users; 86% were very/somewhat satisfied compared to 75% of implant users and 61% of OCP users (P < 0.001). Main reasons for method dissatisfaction were irregular bleeding and mood changes which were similar for all methods. Conclusions: This study provides further evidence that hormonal LARC methods have higher continuation and satisfaction rates compared to the OCP with similar side-effects. Since hormonal LARC methods have the highest contraceptive efficacy, these should be offered first-line to women.

OBJECTIVE: To determine the impact of telemedicine visits, compared to in-person visits, on patient satisfaction in an established community hospital-based multidisciplinary central nervous system (CNS) clinic. METHODS: Telemedicine options – virtual visits and teleconferencing – were introduced in July 2020. Both radiation oncologist and neurosurgeon were simultaneously present for the telemedicine visit. Descriptive patient demographics, survey responses, and travel time and distance calculations were analyzed. Satisfaction score was compared to previously published data. RESULTS: A total of twenty-five telemedicine visits (n=22 video; n=3 phone) were completed since July 2020. Patient demographics are as follows: mean age was 59 years (range=22–81), women (9) and men (16), repeat telemedicine visits n=10, malignant CNS disease (17) and benign disease (5). Mean one-way distance traveled was 165.07 miles (median=114; range=0.8–358). Mean roundtrip travel time was estimated at 5h 5min. Mean telemedicine visit duration was 15.3 mins (range=4–46). Mean patient satisfaction score for telemedicine visits was 4.84. CONCLUSION: Patients who opted for the telemedicine visits found them just as effective as in-person visits, saving time and travel costs as well as ensuring patient safety during the current COVID-19 pandemic. The telemedicine visit platform facilitates the multidisciplinary clinic model and should be considered for more widespread utilization (Tab. 3, Fig. 1, Ref. 18). Text in PDF www.elis.sk.

Background & Aims Chronic bowel inflammation increases the risk of colon cancer; colitis-associated cancer (CAC). Thiopurine treatments are associated with a reduction in dysplasia and CAC in inflammatory bowel disease (IBD). Abnormal Wnt/β-catenin signalling is characteristic of >90% of colorectal cancers. Immunosuppression by thiopurines is via Rac1 GTPase, which also affects Wnt/β-catenin signalling. Autophagy is implicated in colonic tumors, and topical delivery of the thiopurine thioguanine (TG) is known to alleviate colitis and augment autophagy. This study investigated the effects of TG in a murine model of CAC and potential mechanisms. Methods Colonic dysplasia was induced by exposure to azoxymethane (AOM) and dextran sodium sulfate (DSS) in wild-type (WT) mice and mice harboring intestinal epithelial cell–specific deletion of autophagy related 7 gene (Atg7ΔIEC). TG or vehicle was administered intrarectally, and the effect on tumor burden and β-catenin activity was assessed. The mechanisms of action of TG were investigated in vitro and in vivo. Results TG ameliorated DSS colitis in wild-type but not Atg7ΔIEC mice, demonstrating that anti-inflammatory effects of locally delivered TG are autophagy-dependent. However, TG inhibited CAC in both wild-type and Atg7ΔIEC mice. This was associated with decreased β-catenin activation/nuclear translocation demonstrating that TG’s inhibition of tumorigenesis occurred independently of anti-inflammatory and pro-autophagic actions. These results were confirmed in cell lines, and the dependency on Rac1 GTPase was demonstrated by siRNA knockdown and overexpression of constitutively active Rac1. Conclusions Our findings provide evidence for a new mechanism that could be exploited to improve CAC chemoprophylactic approaches., Graphical abstract

Railway operators are being challenged by increasing complexity and safeguarding the availability of passenger rolling stock, bringing maintenance and especially emerging technologies into the focus. This paper presents a model for selection and implementation of Industry 4.0 technologies in rolling stock maintenance. The model consists of different stages and considers the main components of rolling stock, the related appropriate maintenance strategies and Industry 4.0 technologies considering the maturity level of the railway operators. Relevant criteria and main prerequisites of the technologies were identified. The model proposes relevant activities and was validated by industry experts.

Das Lipodem ist eine insbesondere beim weiblichen Geschlecht haufig anzutreffende Erkrankung des Unterhautfettgewebes mit noch nicht eindeutig geklarter Pathogenese. Blutungskomplikationen sind in diesem Zusammenhang ebenfalls haufig. In der vorliegenden Arbeit wurde im Zuge der Evaluierung von individuellen Risikoprofilen bei Patienten mit Blutungskomplikationen die jeweils veranlasste erweiterte Gerinnungsdiagnostik mit Blick auf eine mogliche ursachliche Beziehung ausgewertet. Hierbei konnte kein Zusammenhang zwischen einer Blutungsneigung bei Lipodem-Patientinnen und einem Gerinnungsdefekt hergestellt werden, so dass von einer strukturell kutanen Ursache ausgegangen werden muss, die allenfalls durch eine Gerinnungsstorung begunstigt wird.

Immunoglobulin A (IgA) vasculitis nephritis (IgAVN) and IgA nephropathy (IgAN) share many pathological parallels and are viewed as related diseases by many groups. Current treatment guidelines remain vague, controversial, and without consensus, especially regarding the role of immunosuppressive medications. We present five cases of IgAVN encountered at our tertiary care center between 2016 and 2020, which were treated with different immunosuppression regimens. Infection was the leading cause of death in this series. These cases provide evidence that IgAVN should be distinguished from IgAN on a spectrum of IgA-associated glomerulonephritis. The outcomes presented herein suggest that the morbidity and systematic involvement IgAVN is greater than previously believed and that these substantial risks should be reflected in contemporary treatment guidelines.

Relationships and sexuality education (RSE) for young people in Australia and elsewhere is a contentious topic. While focus has been on sexting practices, curriculum and policy and teachers and schools, few studies have examined how discourses of silencing are reflected in what young people want from their RSE. Using thematic analysis on 1258 open-ended comments from a 2018 survey of young people and sexual health and a theoretical framework of ‘Thick Desire,’ this paper explores what students in Australia desire from a RSE program and how they have come to understand those desires. This analysis reveals that young people in Australia understand and are articulate about the gaps in their RSE. Young people are negotiating a ‘silencing’ of knowledge and education around several important factors and are drawing from broader social, cultural and political influences that shape their experiences. Specifically, young people actively desire a RSE that includes more in-depth information about sexually transmissible infections (STIs) and sexual health issues, programs that are inclusive of diverse genders and sexualities, RSE that is delivered by qualified providers and programs that include discussions concerning relationships, consent and pleasure. The findings of this study suggest several important policy recommendations to improve RSE education, particularly focusing on the sexual rights of young people, the lack of consistency and clarity in existing RSE national policy and the impact that silencing can have on young people’s knowledge and safety in engaging in sexual activity.

OBJECTIVE Screening for adolescent depression is a quality indicator for pediatric care, and the parent-completed, 17-item Pediatric Symptom Checklist's internalizing (PSC-17P-INT) subscale has been validated for this purpose. The current study assessed the feasibility of PSC-17P-INT screening, the prevalence of risk on 2 consecutive PSC-17P-INTs, and rates of behavioral health (BH) service use before and after screening. METHODS The parent-report PSC-17 was completed on tablet devices before well-child visits (WCVs) with results instantaneously available to clinicians in the electronic health record. Billing data were used to identify adolescents with 2 consecutive WCVs and possible BH service utilization 6 months before and after their first screen. RESULTS In 2017, 1,068 adolescents (12-17 years old) were seen for a WCV, and 637 (59.6%) of them had one in 2018. Most (93.9%; N = 604) completed a PSC at both visits. Patients who scored positively on their first PSC-17P-INT were about 9 times more likely to receive subsequent BH services than patients who screened negative (24.3% vs 2.6%, χ2 = 59.65, p < 0.001). However, risk prevalence increased from the first (11.6%) to the second (14.9%) screen, and only 37.1% of at-risk patients remitted. CONCLUSION The current study demonstrated that screening adolescents for depression using the PSC-17P-INT was feasible and associated with a significant increase in BH treatment rates. The study also demonstrated that the PSC could be used to track adolescents at risk for depression, found that most youth who screened positive remained at risk 1 year later, and supported recent quality guidelines calling for annual depression screening and follow-up for adolescents with depression.

Public health responses to the vaccine-refusal (VR) movement are hindered by inadequate research about the movement's aims, identity and perceived value for its members. This study examined how members of the VR movement in Australia described the movement and what being part of it meant to them. Descriptions of the VR movement by 696 members from across Australia were collected between January and May in 2017 via an online survey. The data were analysed using thematic discourse analysis. Members' understandings of the movement and the beliefs underpinning these understandings were examined. Vaccine refusal was underpinned by distinct epistemic beliefs. Participants believed that mainstream vaccine promotion relies on dishonest communication of compromised research. They saw the VR movement as a science-based movement, researching both 'mainstream' and 'hidden' knowledge, promoting scientific values and advocating for better vaccine studies. Participants believed responsible parenting requires personally researching healthcare choices. Participants constructed the movement's identity in relation to common criticisms of vaccine refusal. These were discredited and repurposed to portray the movement as being brave and righteous. Participants believed people in the movement are astute, informed, responsible and courageous. They believed many members were impacted by vaccine-related harms, from which the movement now saves others. They saw themselves as fighting for an inconvenient truth that the mainstream ignores. Vaccine promotion needs to address the epistemic beliefs associated with vaccine refusal, yet these have been inadequately understood. Our findings contribute to understanding these beliefs. Furthermore, our findings suggest what messages targeting vaccine-refusing people should focus on. This may include acknowledging the significant effort that vaccine-refusing people invest in trying to protect their children, catering to vaccine-refusing people's high engagement and desire for detailed information, and avoiding stigmatising or confrontational vaccine-promotion strategies.

CONTEXT: Unintended pregnancy is common among young women. Understanding how such women use contraceptives- including method combinations-is essential to providing high-quality contraceptive care. METHODS: Data were from a representative cohort of 2,965 Australian women aged 18-23 who participated in the 2012-2013 Contraceptive Use, Pregnancy Intention and Decisions baseline survey, had been heterosexually active in the previous six months, and were not pregnant or trying to conceive. Latent class analysis was employed to characterize women's contraceptive choices; multinomial logistic regression was used to evaluate correlates of membership in the identified classes. RESULTS: The vast majority of women (96%) reported using one or more contraceptives, most commonly short-acting hormonal methods (60%), barrier methods (38%), long-acting contraceptives (16%) and withdrawal (15%). In total, 32 combinations were reported. Four latent classes of method use were identified: no contraception (4% of women); short-acting hormonal methods with supplementation (59%, mostly the pill); high-efficacy contraceptives with supplementation (15%, all long-acting reversible contraceptive users); and low-efficacy contraceptive combinations (21%); supplementation usually involved barrier methods or withdrawal. Class membership differed according to women's characteristics; for example, women who had ever been pregnant were more likely than other women to be in the no-contraception, high-efficacy contraceptive or low-efficacy contraceptive combination classes than in the short-acting hormonal contraceptive class (odds ratios, 2.0-3.0). CONCLUSIONS: The complexity of women's contraceptive choices and the associations between latent classes and such characteristics as pregnancy history highlight the need for individualized approaches to pregnancy prevention and contraceptive care.

Freeze-drying methodology requires an in-depth understanding and characterization for optimal processing of biopharmaceuticals. Particularly the primary drying phase, the longest and most expensive stage of the process, is of interest for optimization. The currently used process analytical technology (PAT) tools give highly valuable insights but come with limitations. Our study describes, for the first time, the application of a heat flux sensor (HFS) to build a primary drying design space and predict the process evolution. First, the heat transfer coefficient (Kv) generated by HFS and by the most accurate, but time-consuming and invasive, gravimetric method were compared. Second, the applicability to generate a design space was tested and verified. Obtained results revealed a good agreement of the values generated from this new and fast HFS compared to the gravimetric determination. Additionally, residual moisture assessed by Karl-Fischer titration and frequency modulated spectroscopy (FMS) support the quality of the obtained predictions. Thus, the HFS approach can substantially accelerate evaluation, development and transfer of a freeze-drying cycle.

In recent years, machine learning algorithms have made a huge development in performance and applicability in industry and especially maintenance. Their application enables predictive maintenance and thus offers significant efficiency increases. However, a successful implementation of such solutions still requires high effort in data preparation to obtain the right information, interdisciplinarity in teams as well as a good communication to employees. Here, small and medium sized enterprises (SME) often lack in experience, competence and capacity. This paper presents a systematic and practice-oriented method for an implementation of machine learning solutions for predictive maintenance in SME, which has already been validated.

Objective To assess clinical outcome in treatment-naive patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods We included adult treatment-naive patients participating in the prospective International CIDP Outcome Study (ICOS) that fulfilled the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria for CIDP. Patients were grouped based on initial treatment with (1) intravenous immunoglobulin (IVIg), (2) corticosteroid monotherapy or (3) IVIg and corticosteroids (combination treatment). Outcome measures included the inflammatory Rasch-built overall disability scale (I-RODS), grip strength, and Medical Research Council (MRC) sum score. Treatment response, treatment status, remissions (improved and untreated), treatment changes, and residual symptoms or deficits were assessed at 1 year. Results Forty patients were included of whom 18 (45%) initially received IVIg, 6 (15%) corticosteroids, and 16 (40%) combination treatment. Improvement on ≥ 1 of the outcome measures was seen in 31 (78%) patients. At 1 year, 19 (48%) patients were still treated and fourteen (36%) patients were in remission. Improvement was seen most frequently in patients started on IVIg (94%) and remission in those started on combination treatment (44%). Differences between groups did not reach statistical significance. Residual symptoms or deficits ranged from 25% for neuropathic pain to 96% for any sensory deficit. Conclusions Improvement was seen in most patients. One year after the start of treatment, more than half of the patients were untreated and around one-third in remission. Residual symptoms and deficits were common regardless of treatment.

Purpose While previous studies have identified a range of potential risk factors for postnatal depression (PND), none have examined a comprehensive set of risk factors at a population-level using data collected prospectively. The aim of this study was to explore the relationship between a range of factors and PND and to construct a model of the predictors of PND. Methods Data came from 5219 women who completed Survey 5 of the Australian Longitudinal Study on Women’s Health in 2009 and reported giving birth to a child. Results Over 15% of women reported experiencing PND with at least one of their children. The strongest positive associations were for postnatal anxiety (OR = 13.79,95%CI = 10.48,18.13) and antenatal depression (OR = 9.23,95%CI = 6.10,13.97). Positive associations were also found for history of depression and PND, low SF-36 Mental Health Index, emotional distress during labour, and breastfeeding for less than six months. Conclusions Results indicate that understanding a woman’s mental health history plays an important role in the detection of those who are most vulnerable to PND. Treatment and management of depression and anxiety earlier in life and during pregnancy may have a positive impact on the incidence of PND.

Penetrating traumatic brain injury (pTBI) often occurs with systemic insults such as hemorrhagic shock (HS) and hypoxemic (HX). This study examines rat models of penetrating ballistic-like brain injury (PBBI) and HX+HS to assess whether the blood levels of brain and systemic response biomarkers phosphorylated neurofilament-heavy protein (pNF-H), neurofilament-light protein (NF-L), αII-spectrin, heat shock protein (HSP70), and high mobility group box 1 protein (HMGB1) can distinguish pTBI from systemic insults and guide in pTBI diagnosis, prognosis, and monitoring. Thirty rats were randomly assigned to sham, PBBI, HS+HX, and PBBI+HS+HX groups. PBBI and sham groups underwent craniotomy with and without probe insertion and balloon expansion, respectively. HX and HS was then simulated by blood withdrawal and fraction of inspired oxygen (FIO2) reduction. Biomarker serum concentrations were determined at one (D1) and two (D2) days post-injury with enzyme-linked immunosorbent assay (ELISA) methods. Axonal injury-linked biomarkers pNF-H and NF-L serum levels in PBBI groups were higher than those in sham and HX+HS groups at D1 and D2 post-injury. The same was true for PBBI+HX+HS compared with sham (D2 only for pNF-H) and HX+HS groups. However, pNF-H and NF-L levels in PBBI+HX+HS groups were not different than their PBBI counterparts. At D1, αII-spectrin levels in the HX+HS and PBBI+HS+HX groups were higher than the sham groups. αII-spectrin levels in the HX+HS group were higher than the PBBI group. This suggests HX+HS as the common insult driving αII-spectrin elevations. In conclusion, pNF-H and NF-L may serve as specific serum biomarkers of pTBI in the presence or absence of systemic insults. αII-spectrin may be a sensitive acute biomarker in detecting systemic insults occurring alone or with pTBI.

Purpose Older people often present to the Emergency Department with nonspecific complaints. We aimed (1) to examine characteristics of older patients presenting to the ED triaged with the presentational flowchart 'unwell adult' of the Manchester triage system (MTS) and (2) to assess the different mortality and admission rates among triage categories. Methods Retrospective cohort study including all consecutive patients aged 70 years and older who visited the ED of a tertiary care hospital in the Netherlands during a 1-year period. The primary outcome was 30-day mortality. Secondary outcomes were 7-day mortality, hospital admission and ED length of stay. Results 4255 patients were included in this study. Mean age was 78 years (IQR 73.9-83.4) and 2098 were male (49.3%). The MTS presentational flowchart 'unwell adult' was the most commonly used flowchart (n = 815, 19.3%). After the infrequent flowchart 'major trauma' (n = 9, 13.8%), 'unwell adult' had the highest 30-day mortality (n = 88, 10.8%). When compared to all other flowcharts, patients assigned as 'unwell adult' have significantly higher 30-day mortality rates (OR 1.89 (95%CI 1.46-2.46), p = < 0.001), also when adjusted for age, gender and triage priority (OR 1.75 (95%CI 1.32-2.31), p = < 0.001). Patients from the 'unwell adult' flowchart had the highest hospital admission rate (n = 540, 66.3%), and had among the longest ED length of stay. Conclusions Older ED patients are most commonly assigned the presentational flowchart 'unwell adult' when using the MTS. Patients in this category have the highest non-trauma mortality and highest hospital admission rates when compared to other presenting complaints.Key summary pointsAim Examine characteristics of older patients presenting to the ED triaged with the presentational flowchart 'unwell adult' of the Manchester triage system (MTS) and to assess the different mortality and admission rates among triage categories. Findings Older patients assigned to the 'unwell' flowchart have the highest non-trauma mortality rate, independent of urgency category, and highest admission rates of all presenting complaints. Surprisingly, mortality was also observed in the lowest triage categories. Message Patients in the category 'unwell' have the highest non-trauma 30-day mortality and highest hospital admission rates when compared to other presenting complaints, indicating that the nonspecific disease presentation "unwell" is a serious medical condition.

Posterior circulation aneurysms are difficult to treat with the current methods of coiling and clipping. To address limitations in training, we developed a cadaveric model to train learners on endoscopic clipping of posterior circulation aneurysms. An endoscopic transclival approach (ETA) and a transorbital precaruncular approach (TOPA) to successfully access and clip aneurysms of the posterior circulation are described. The model has flexibility in that a colored silicone compound can be injected into the cadaveric vessels for the purpose of training learners on vascular anatomy. The other option is that the model could be connected to a vascular perfusion pump allowing real-time appreciation of a pulsatile or ruptured aneurysm. This cadaveric model is the first of its kind for training of endoscopic clipping of posterior circulation aneurysms. Learners will develop proficiency in endoscopic skills, appropriate dissection, and appreciation for relative anatomy while developing an algorithm that can be employed in a real operative arena. Going forward, various clinical scenarios can be developed to enhance the realism, allow learners from different specialties to work together, and emphasize the importance of teamwork and effective communication.

Carotid artery injuries are serious complications of endoscopic endonasal surgery. As these occur rarely, simulation training offers an avenue for technique and algorithm development in resident learners. This study develops a realistic cadaveric model for the training of crisis resource management in the setting of cavernous carotid artery injury. An expanded endonasal approach and right cavernous carotid injury is performed on a cadaveric head. The cadaver's right common carotid artery is cannulated and connected to a perfusion pump delivering pressurized simulated blood. A simulation mannequin is incorporated into the model to allow for vital sign feedback. Surgical and anesthesia resident learners are tasked with obtaining vascular control with a muscle patch technique and medical management over the course of 3 clinical scenarios with increasing complexity. Crisis management instructions for an endoscopic endonasal approach to the cavernous carotid artery and blood pressure control were provided to the learners prior to beginning the simulation. An independent reviewer evaluated the learners on communication skills, crisis management algorithms, and implementation of appropriate skill sets. After each scenario, residents were debriefed on how to improve technique based on evaluation scores in areas of situational awareness, decision-making, communications and teamwork, and leadership. After the simulation, learners provided feedback on the simulation and this data was used to improve future simulations. The benefit of this cadaveric model is ease of set-up, cost-effectiveness, and reproducibility.

Emergency Departments (EDs) are increasingly seeing more seriously unwell older people living with frailty. In the context of limited resources and increasing demand it’s the ED practitioner’s challenge to unpick this constellation of physical, psychological, functional and social issues.To properly assess older people living with frailty at the ED it is crucial to use an holistic approach. This consists of triage with algorithms sensitive to the higher risk of older people living with frailty, a frailty assessment, and an assessment with the help of the principles of Comprehensive Geriatric Assessment. Multi-disciplinary care, a tailor-made treatment plan, based on what the person values most, will help the ED practitioner to deliver appropriate and valuable care during the ED stay, but also in transition from hospital to home.

Soil fertility must be viewed as a dynamic concept that involves the constant cycling of nutrients between organic and inorganic forms. In this context, it refers also to supply adequate amounts of water and aeration for plant growth. Soil fertility under arid and semi-arid lands is constrained not only by limited water availability but also by small organic matter contents. Most fertility assessment systems are based on organic matter contents as the main parameter. However, crop experiments from various irrigated arid and semi-arid soils indicate that productivity is less-affected by organic matter contents than assumed. Therefore, we propose a new soil fertility system for dryland soils. It is a rule-based set of algorithms, mainly using additions and subtractions. Soil, climate, and landscape factors are integrated to calculate the numerical value of fertility for a given soil. We expect the system, which is focused on soil properties that keep or increase optimum soil moisture (such as texture), to be applicable in arid and semi-arid lands and to provide more realistic estimates of fertility regarding agricultural purposes. The manuscript will provide an outline of the main aspects of the system, illustrated by various case applications.

Optimizing emergency care for the aging population is an important future challenge, as the proportion of older patients at the emergency department (ED) rapidly increases. Older patients, particularly those who are frail, have a high risk of adverse outcomes after an ED visit, such as functional decline, institutionalization, and death. The ED can have a key position in identifying frail older patients who benefit most from comprehensive geriatric care [including delirium preventive measures, early evaluation of after-discharge care, and a comprehensive geriatric assessment (CGA)]. However, performing extensive frailty assessment is not suitable at the ED. Therefore, quick and easy-to-use instruments are needed to identify older patients at risk for adverse outcomes. This narrative review outlines the importance and complexity of frailty assessment at the ED. It aligns the available screening instruments, including clinical judgment as frailty assessment, and summarizes arguments for and against frailty assessment at the ED.

Fornicotomy has been used to treat intractable temporal lobe epilepsy with mixed success historically; however, modern advances in stereotactic, neurosurgical, and imaging techniques offer new opportunities to target the fornix with greater precision and safety. In this review, we discuss the historical uses and quantify the outcomes of fornicotomy for the treatment of temporal lobe epilepsy, highlight the potential mechanisms of benefit, and address what is known about the side effects of the procedure. We find that fornicotomy, with or without anterior commissurotomy, resulted in 61% (83/136) of patients having some seizure control benefit. We discuss the potential operative approaches for targeting the fornix, including laser ablation and the use of focused ultrasound ablation. More work is needed to address the true efficacy of fornicotomy in the modern surgical setting. This review is intended to serve as a framework for developing this approach.

Using questionnaires, administrative claims, and chart review data, the current study explored the impact of using an electronic medical record system to administer, score, and store the Pediatric Symptom Checklist (PSC-17) during annual pediatric well-child visits. Within a sample of 1773 Medicaid-insured outpatients, the electronic system demonstrated that 90.5% of cases completed a PSC-17 screen electronically, billing codes indicating a screen was administered agreed with the existence of a questionnaire in the chart in 98.8% of cases, the classification of risk based on PSC-17 scores agreed with the classification of risk based on the Current Procedural Terminology code modifiers in 72.9% of cases, and 90.0% of clinicians’ progress notes mentioned PSC-17 score in treatment planning. Using an electronic approach to psychosocial screening in pediatrics facilitated the use of screening information gathered during the clinical visit and allowed for enhanced tracking of outcomes and quality monitoring.

Background Adherence to COPD medication is often considered to be lower than in other chronic diseases. In view of the frequent comorbidities of COPD, the economic impact of nonadherence and the potential for adverse effects, a direct comparison between the adherence to respiratory and nonrespiratory medication in the same patients seems of particular interest. Objectives We aimed to investigate the intake of respiratory and nonrespiratory medication in the same patients with COPD and frequent comorbidities. Method Within the COPD cohort COSYCONET, we contacted 1042 patients, mailing them a list with all medication regarding all their diseases, asking for regular, irregular and non-intake. Results Valid responses were obtained in 707 patients covering a wide spectrum of drugs. Intake of LABA, LAMA or ICS was regular in 91.9% of patients, even higher for cardiovascular and antidiabetes medication but lower for hyperlipidemia and depression/anxiety medication. Regular intake of respiratory medication did not depend on GOLD groups A-D or grades 1-4, was highest in patients with concomitant cardiovascular disorders and was lowest for concomitant asthma. It was slightly larger for LAMA and LABA administered via combined compared to single inhalers, and lower when similar compounds were prescribed twice. Most differences did not reach statistical significance owing to the overall high adherence. Conclusion Our results indicate a high adherence to respiratory medication in participants of a COPD cohort, especially in those with cardiovascular comorbidities. Compared to the lower adherence reported in the literature for COPD patients, our observations still suggest some room for improvement, possibly through disease management programs.

Hip fractures in elderly patients are associated with increased postoperative morbidity and mortality. We evaluated whether a perioperative multi-system optimization protocol can reduce postoperative complications in these patients.Immediately after diagnosis of hip fracture, patients ≥ 60 yr were randomized to an intervention or control group. Patients in the intervention group were admitted to our postanesthesia care unit where they were treated with goal-directed hemodynamic management, optimized pain therapy, oxygen therapy, and optimized nutrition. Patients in the control group were managed according to our usual standard of care on a regular ward. Postoperative complications during hospital stay included pre-determined cardiovascular, respiratory, neurologic, renal, or surgical events.The incidence of at least one postoperative complication (primary outcome) was seen in 32 of 65 (49%) controls compared with 24 of 62 (39%) in the intervention group (relative risk [RR], 0.79; 95% confidence interval [CI], 0.53 to 1.17; P = 0.23). The secondary unadjusted outcomes showed that patients in the intervention group received more Ringer's acetate compared with controls (median difference, 1.3 L; 95% CI, 0.6 to 2.1 L; P0.001), had more frequently a mean arterial pressure70 mmHg (57% control vs 75% intervention; median percentage difference, 16%; 95% CI, 7 to 25%; P = 0.001), better pain control (numeric rating scale4 at all postoperative measurements; 25% control vs 81% intervention; RR, 0.26; 95% CI, 0.15 to 0.43; P0.001), and possibly a lower incidence of acute renal failure (RR, 0.37; 95% CI, 0.14 to 0.98; P = 0.04).The implementation of a perioperative multi-system optimization protocol algorithm did not significantly reduce the risk of postoperative complications. Nevertheless, we likely over-estimated the potential treatment effect in our study design and thus were under-powered to show an effect.Clinicaltrials.gov (NCT01673776). Registered 23 August, 2012.

The objectives were to (a) assess the diagnostic value of testing clinically affected and unaffected limbs with nerve conduction studies (NCS) in patients with the asymmetric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant and to define the most useful strategy for diagnosis, and (b) describe treatment response and long-term outcome. We performed a retrospective study and included patients with a multifocal distribution of symptoms and signs, who met the probable or definite EFNS/PNS diagnostic categories for CIDP. We included 34 patients and 32 NCS datasets were available. Of these 32 patients, 25 (78%) met the electrodiagnostic criteria for definite or probable CIDP and seven (22%) for possible CIDP. Patients fulfilling the possible electrodiagnostic criteria and a supportive criterion were considered as probable CIDP. NCS of the clinically affected forearm and leg led to a probable or definite diagnosis in 13 patients (41%). Measuring both arms up to Erb's point led to a probable or definite diagnosis in 25 patients (78%), after which NCS of both legs did not contribute to additional probable or definite diagnoses. In total, 30% of patients treated with dexamethasone and 94% of patients treated with intravenous immunoglobulins (IVIg) responded. IVIg withdrawal attempts were successful in 21% of patients. After measuring the clinically affected arm up to Erb's point, NCS of the unaffected arm to Erb's point has the highest additional diagnostic yield in patients with asymmetric CIDP. Patients seem to respond better to IVIg than to corticosteroids and long-term treatment is often required, although IVIg withdrawal was successful in 21%.

Hypoxic–ischemic encephalopathy (HIE) remains a significant cause of mortality and neurodevelopmental impairment despite treatment with therapeutic hypothermia. Magnetic resonance H1-spectroscopy measures concentrations of cerebral metabolites to detect derangements in aerobic metabolism. We assessed MR spectroscopy in neonates with HIE within 18–24 h of initiating therapeutic hypothermia and at 5–6 days post therapeutic hypothermia. Eleven neonates with HIE underwent MR spectroscopy of the basal ganglia and white matter. We compared metabolite concentrations during therapeutic hypothermia and post-therapeutic hypothermia and between moderate and severe HIE. During therapeutic hypothermia, neonates with severe HIE had decreased basal ganglia N-acetylaspartate (NAA; 0.62±0.08 vs. 0.72±0.05; P=0.02), NAA + N-acetylaspartylglutamate (NAAG; 0.66±0.11 vs. 0.77±0.06; P=0.05), glycerophosphorylcholine + phosphatidylcholine (GPC+PCh; 0.28±0.05 vs. 0.38±0.06; P=0.02) and decreased white matter GPC+PCh (0.35±0.13 vs. 0.48±0.04; P=0.02) compared to neonates with moderate HIE. For all subjects, basal ganglia NAA decreased (−0.08±0.07; P=0.01), whereas white matter GPC+PCh increased (0.03±0.04; P=0.04) from therapeutic hypothermia MRI to post-therapeutic-hypothermia MRI. All metabolite values are expressed in mmol/L. Decreased NAA and GPC+PCh were associated with greater HIE severity and could distinguish neonates who might benefit most from targeted additional neuroprotective therapies.

Background Cerebrospinal fluid rhinorrhea from a lateral skull base defect refractory to spontaneous healing and/or conservative management is most commonly managed via open surgery. Approach for repair is dictated by location of the defect, which may require surgical exploration. The final common pathway is the eustachian tube (ET). Endoscopic ET obliteration via endonasal and lateral approaches is under development. Whereas ET anatomy has been studied, surgical landmarks have not been previously described or quantified. We aimed to define surgical parameters of specific utility to endoscopic ET obliteration. Methods A literature review was performed of known ET anatomic parameters. Next, using a combination of endoscopic and open techniques in cadavers, we cannulated the intact ET and dissected its posterior component to define the major curvature position of the ET, defined as the genu, and quantified the relative distances through the ET lumen. The genu was targeted as a major obstacle encountered when cannulating the ET from the nasopharynx. Results Among 10 ETs, we found an average distance of 23 ± 5 mm from the nasopharynx to the ET genu, distance of 24 ± 3 mm from the genu to the anterior aspect of the tympanic membrane and total ET length of 47 ± 4 mm. Conclusions Although membranous and petrous components of the ET are important to its function, the genu may be a more useful surgical landmark. Basic surgical parameters for endoscopic ET obliteration are defined.

Sexuality education is a trusted source of information and guidance for adolescents and young people on sexual health, sexuality and relationships, and it can improve the sexual health of this population. Such education is most effective when informed by the views of young people themselves; however, there is limited research that investigates young people’s experiences of school-based sexuality education. This paper presents findings related to sexuality education from the Fifth National Survey of Secondary Students and Sexual Health, which surveyed 2,193 Australian Year 10, 11 and 12 students from diverse school systems. Descriptive analyses were used to describe the nature of sexuality education the students report having received. Chi-square and T-test analysis were used to determine associations between the relevance of sexuality education, the nature of sexuality education and demographic characteristics, as well as associations between students’ knowledge of HIV, STIs and HPV and their receipt of sexuality education. Additionally, a thematic analysis of the open-ended qualitative responses was performed to provide additional context to the quantitative results. Findings from the study elucidate students’ own perceptions of their school-based sexuality education and provide valuable insight for designing and implementing school-based sexuality education based on students’ opinions and needs.

Common narratives of 'decline' in Jordan and Syria during the Islamic periods are based on diminishing evidence of construction and maintenance of monumental architecture, and often consider man-made degradation of the environment, such as soil erosion due to mismanage­ment, as a key factor of reduced productivity. This contribution tackles the question of historic landscape change with a case study of the site of Abila in northern Jordan, and reviews the literature on the matter. Sediments in the Wadi Queilbeh near Abila suggest that two periods of rapid and significant deposition took place during the 6th and 14th-15th century AD, which were connected with extreme rainfalls induced by global climate variations. After the 6th century, a trend to general drier conditions is discernible. Other periods are characterized by absence of sedimentation, and soil distribution in the vicinity suggests stable and fertile conditions where water availability determines the agricultural potential. Changes of settlement and environment can be explained with reduced rainfalls during the Islamic periods that led to a shift of land use from market-orient agriculture towards subsistence farming. This reduced surpluses and thus less monumental buildings were built. The practice of a mixed economy with an increasing share of pastoralism was connected with natural reforestation of some areas, and seasonal use of many areas may have led to incorrect perceptions of 'empty' lands by European travelers. Tribes settled when they could realize the benefits of agriculture. Climate fluctuations most likely represent the underlying drivers of environmental and economic changes in northern Jordan during the Islamic periods.