Between-centre differences and treatment effects in randomized controlled trials: A case study in traumatic brain injury

BACKGROUND: In Traumatic Brain Injury (TBI), large between-centre differences in outcome exist and many clinicians believe that such differences influence estimation of the treatment effect in randomized controlled trial (RCTs). The aim of this study was to assess the influence of between-centre differences in outcome on the estimated treatment effect in a large RCT in TBI. METHODS: We used data from the MRC CRASH trial on the efficacy of corticosteroid infusion in patients with TBI. We analyzed the effect of the treatment on 14 day mortality with fixed effect logistic regression. Next we used random effects logistic regression with a random intercept to estimate the treatment effect taking into account between-centre differences in outcome. Between-centre differences in outcome were expressed with a 95% range of odds ratios (OR) for centres compared to the average, based on the variance of the random effects (tau2). A random effects logistic regression model with random slopes was used to allow the treatment effect to vary by centre. The variation in treatment effect between the centres was expressed in a 95% range of the estimated treatment ORs. RESULTS: In 9978 patients from 237 centres, 14-day mortality was 19.5%. Mortality was higher in the treatment group (OR = 1.22, p = 0.00010). Using a random effects model showed large between-centre differences in outcome (95% range of centre effects: 0.27- 3.71), but did not substantially change the estimated treatment effect (OR = 1.24, p = 0.00003). There was limited, although statistically significant, between-centre variation in the treatment effect (OR = 1.22, 95% treatment OR range: 1.17-1.26). CONCLUSION: Large between-centre differences in outcome do not necessarily affect the estimated treatment effect in RCTs, in contrast to current beliefs in the clinical area of TBI

Severe traumatic injury during long duration spaceflight: Light years beyond ATLS

Traumatic injury strikes unexpectedly among the healthiest members of the human population, and has been an inevitable companion of exploration throughout history. In space flight beyond the Earth's orbit, NASA considers trauma to be the highest level of concern regarding the probable incidence versus impact on mission and health. Because of limited resources, medical care will have to focus on the conditions most likely to occur, as well as those with the most significant impact on the crew and mission. Although the relative risk of disabling injuries is significantly higher than traumatic deaths on earth, either issue would have catastrophic implications during space flight. As a result this review focuses on serious life-threatening injuries during space flight as determined by a NASA consensus conference attended by experts in all aspects of injury and space flight

A clinician’s guide to management of intra-abdominal hypertension and abdominal compartment syndrome in critically ill patients

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

WSES-AAST guidelines: management of inflammatory bowel disease in the emergency setting

Background Despite the current therapeutic options for the treatment of inflammatory bowel disease, surgery is still frequently required in the emergency setting, although the number of cases performed seems to have decreased in recent years. The World Society of Emergency Surgery decided to debate in a consensus conference of experts, the main pertinent issues around the management of inflammatory bowel disease in the emergent situation, with the need to provide focused guidelines for acute care and emergency surgeons. Method A group of experienced surgeons and gastroenterologists were nominated to develop the topics assigned and answer the questions addressed by the Steering Committee of the project. Each expert followed a precise analysis and grading of the studies selected for review. Statements and recommendations were discussed and voted at the Consensus Conference of the 6th World Society of Emergency Surgery held in Nijmegen (The Netherlands) in June 2019. Conclusions Complicated inflammatory bowel disease requires a multidisciplinary approach because of the complexity of this patient group and disease spectrum in the emergency setting, with the aim of obtaining safe surgery with good functional outcomes and a decreasing stoma rate where appropriate.Peer reviewe

Help-seeking pathways in early psychosis

INTRODUCTION: Understanding the help-seeking pathways of patients with a putative risk of developing psychosis helps improving development of specialised care services. This study aimed at obtaining information about: type of health professionals contacted by patients at putative risk for psychosis on their help-seeking pathways; number of contacts; type of symptoms leading to contacts with health professionals; interval between initial contact and referral to a specialised outpatient service. METHOD: The help-seeking pathways were assessed as part of a prospective study in 104 patients with suspected at-risk states for psychosis. RESULTS: The mean number of contacts prior to referral was 2.38. Patients with psychotic symptoms more often contacted mental health professionals, whereas patients with insidious and more unspecific features more frequently contacted general practitioners (GPs). CONCLUSIONS: GPs have been found to under-identify the insidious features of emerging psychosis (Simon et al. (2005) Br J Psychiatry 187:274–281). The fact that they were most often contacted by patients with exactly these features calls for focussed and specialised help for primary care physicians. Thus, delays along the help-seeking pathways may be shortened. This may be of particular relevance for patients with the deficit syndrome of schizophrenia

A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults

<p>Abstracts</p> <p>Background</p> <p>Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults.</p> <p>Methods/Design</p> <p>We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale.</p> <p>Discussion</p> <p>This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01478009">NCT01478009</a>.</p

A physiological time analysis of the duration of the gonotrophic cycle of Anopheles pseudopunctipennis and its implications for malaria transmission in Bolivia

<p>Abstract</p> <p>Background</p> <p>The length of the gonotrophic cycle varies the vectorial capacity of a mosquito vector and therefore its exact estimation is important in epidemiological modelling. Because the gonotrophic cycle length depends on temperature, its estimation can be satisfactorily computed by means of physiological time analysis.</p> <p>Methods</p> <p>A model of physiological time was developed and calibrated for <it>Anopheles pseudopunctipennis</it>, one of the main malaria vectors in South America, using data from laboratory temperature controlled experiments. The model was validated under varying temperatures and could predict the time elapsed from blood engorgement to oviposition according to the temperature.</p> <p>Results</p> <p>In laboratory experiments, a batch of <it>An. pseudopunctipennis </it>fed at the same time may lay eggs during several consecutive nights (2–3 at high temperature and > 10 at low temperature). The model took into account such pattern and was used to predict the range of the gonotrophic cycle duration of <it>An. pseudopunctipennis </it>in four characteristic sites of Bolivia. It showed that the predicted cycle duration for <it>An. pseudopunctipennis </it>exhibited a seasonal pattern, with higher variances where climatic conditions were less stable. Predicted mean values of the (minimum) duration ranged from 3.3 days up to > 10 days, depending on the season and the geographical location. The analysis of ovaries development stages of field collected biting mosquitoes indicated that the phase 1 of Beklemishev might be of significant duration for <it>An. pseudopunctipennis</it>. The gonotrophic cycle length of <it>An. pseudopunctipennis </it>correlates with malaria transmission patterns observed in Bolivia which depend on locations and seasons.</p> <p>Conclusion</p> <p>A new presentation of cycle length results taking into account the number of ovipositing nights and the proportion of mosquitoes laying eggs is suggested. The present approach using physiological time analysis might serve as an outline to other similar studies and allows the inclusion of temperature effects on the gonotrophic cycle in transmission models. However, to better explore the effects of temperature on malaria transmission, the others parameters of the vectorial capacity should be included in the analysis and modelled accordingly.</p

Mate Value and Self-Esteem: Evidence from Eight Cultural Groups

This paper explores self-perceived mate value (SPMV), and its association with self-esteem, in eight cultures. 1066 participants, from 8 cultural groups in 7 countries, rated themselves on 24 SPMVs and completed a measure of self-esteem. Consistent with evolutionary theory, women were more likely to emphasise their caring and passionate romantic nature. In line with previous cross-cultural research, characteristics indicating passion and romance and social attractiveness were stressed more by respondents from individualistic cultures, and those higher on self-expression (rather than survival) values; characteristics indicative of maturity and confidence were more likely to be mentioned by those from Traditional, rather than Secular, cultures. Contrary to gender role theory, societal equality had only limited interactions with sex and SPMV, with honesty of greater significance for male self-esteem in societies with unequal gender roles. These results point to the importance of cultural and environmental factors in influencing self-perceived mate qualities, and are discussed in relation to broader debates about the impact of gender role equality on sex differences in personality and mating strategies