Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Validity of mobile electronic data capture in clinical studies: a pilot study in a pediatric population.

BACKGROUND: Clinical studies in children are necessary yet conducting multiple visits at study centers remains challenging. The success of "care-at-home" initiatives and remote clinical trials suggests their potential to facilitate conduct of pediatric studies. This pilot aimed to study the feasibility of remotely collecting valid (i.e. complete and correct) saliva samples and clinical data utilizing mobile technology. METHODS: Single-center, prospective pilot study in children undergoing elective tonsillectomy at the University of Basel Children's Hospital. Data on pain scores and concomitant medication and saliva samples were collected by caregivers on two to four inpatient study days and on three consecutive study days at home. A tailored mobile application developed for this study supported data collection. The primary endpoint was the proportion of complete and correct caregiver-collected data (pain scale) and saliva samples in the at-home setting. Secondary endpoints included the proportion of complete and correct saliva samples in the inpatient setting, subjective feasibility for caregivers, and study cost. RESULTS: A total number of 23 children were included in the study of which 17 children, median age 6.0 years (IQR 5.0, 7.4), completed the study. During the at-home phase, 71.9% [CI = 64.4, 78.6] of all caregiver-collected pain assessments and 53.9% [CI = 44.2, 63.4] of all saliva samples were complete and correct. Overall, 64.7% [CI = 58.7, 70.4] of all data collected by caregivers at home was complete and correct. The predominant reason for incorrectness of data was adherence to the timing of predefined patient actions. Participating caregivers reported high levels of satisfaction and willingness to participate in similar trials in the future. Study costs for a potential sample size of 100 patients were calculated to be 20% lower for the at-home than for a traditional in-patient study setting. CONCLUSIONS: Mobile device supported studies conducted at home may provide a cost-effective approach to facilitate conduct of clinical studies in children. Given findings in this pilot study, data collection at home may focus on electronic data capture rather than biological sampling

Reliability of computerized eye-tracking reaction time tests in non-athletes, athletes, and individuals with traumatic brain injury

Background: Eye tracking technologies and methodologies have advanced significantly in recent years. Specifically, the use of eye tracking to quantitatively measure oculomotor and psychophysiological constructs is gaining momentum. Reaction time has been measured in a number of different ways from a simple response to a stimulus to more challenging choice or discrimination responses to stimuli. Traditionally, reaction time is measured from the beginning of a stimulus event to a response event and includes both visual and motor response times. Eye tracking technology can provide a more discrete measurement of reaction time to include visual components such as visual latencies and visual speed, and can identify if the person was looking at the target area when a stimulus is presented. The aim of this paper was to examine the reliability of the simple reaction time, choice reaction time, and discriminate reaction time tests measured using eye tracking technology. Additionally, we sought to establish performance norms and examine gender differences in reaction time in the general population. A final objective was to conduct a preliminary comparison of reaction time measures across different populations including non-athletes, athletes, and individuals that had sustained a traumatic brain injury. Methods: A sample of 125 participants were recruited to undertake test-retest reliability, analysed using Cronbach’s alpha and intraclass correlation coefficients. A different data set of 1893 individuals, including athletes (n = 635), non-athletes (n = 627) and people with traumatic brain injury (n = 631) were compared using MANOVA to explore group differences in reaction time. Results: Results demonstrated that overall, the tests had good test-retest reliability. No significant differences were found for gender. Significant differences were found between groups with athletes performing best overall. Reaction times of people with traumatic brain injury were overall much more variable, showing very large standard deviations, than those of the non-athletes and athletes. Conclusions: Future research should consider the accuracy of eye movements and various demographic variables within groups

The open abdomen in trauma and non-trauma patients : WSES guidelines

Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartment syndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangements and multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinical situations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source of infection or the necessity to re-explore (as a "planned second-look" laparotomy) or complete previously initiated damage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-trauma patients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuries or critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consuming and represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only be considered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as the patient can physiologically tolerate it. All precautions to minimize complications should be implemented.Peer reviewe

Strengthening nursing, midwifery and allied health professional leadership in the UK - a realist evaluation

Purpose: This paper aims to share the findings of a realist evaluation study that set out to identify how to strengthen nursing, midwifery and allied health professions (NMAHP) leadership across all health-care contexts in the UK conducted between 2018 and 2019. The collaborative research team were from the Universities of Bangor, Ulster, the University of the West of Scotland and Canterbury Christ Church University. Design/methodology/approach: Realist evaluation and appreciative inquiry were used across three phases of the study. Phase 1 analysed the literature to generate tentative programme theories about what works, tested out in Phase 2 through a national social media Twitter chat and sense-making workshops to help refine the theories in Phase 3. Cross-cutting themes were synthesised into a leadership framework identifying the strategies that work for practitioners in a range of settings and professions based on the context, mechanism and output configuration of realist evaluation. Stakeholders contributed to the ongoing interrogation, analysis and synthesis of project outcomes. Findings: Five guiding lights of leadership, a metaphor for principles, were generated that enable and strengthen leadership across a range of contexts. – “The Light Between Us as interactions in our relationships”, “Seeing People’s Inner Light”, “Kindling the Spark of light and keeping it glowing”, “Lighting up the known and the yet to be known” and “Constellations of connected stars”. Research limitations/implications: This study has illuminated the a-theoretical nature of the relationships between contexts, mechanisms and outcomes in the existing leadership literature. There is more scope to develop the tentative programme theories developed in this study with NMAHP leaders in a variety of different contexts. The outcomes of leadership research mostly focussed on staff outcomes and intermediate outcomes that are then linked to ultimate outcomes in both staff and patients (supplemental). More consideration needs to be given to the impact of leadership on patients, carers and their families. Practical implications: The study has developed additional important resources to enable NMAHP leaders to demonstrate their leadership impact in a range of contexts through the leadership impact self-assessment framework which can be used for 360 feedback in the workplace using the appreciative assessment and reflection tool. Social implications: Whilst policymakers note the increasing importance of leadership in facilitating the culture change needed to support health and care systems to adopt sustainable change at pace, there is still a prevailing focus on traditional approaches to individual leadership development as opposed to collective leadership across teams, services and systems. If this paper fails to understand how to transform leadership policy and education, then it will be impossible to support the workforce to adapt and flex to the increasingly complex contexts they are working in. This will serve to undermine system integration for health and social care if the capacity and capability for transformation are not attended to. Whilst there are ambitious global plans (WHO, 2015) to enable integrated services to be driven by citizen needs, there is still a considerable void in understanding how to authentically engage with people to ensure the transformation is driven by their needs as opposed to what the authors think they need. There is, therefore, a need for systems leaders with the full skillset required to enable integrated services across place-based systems, particularly clinicians who are able to break down barriers and silo working across boundaries through the credibility, leadership and facilitation expertise they provide. Originality/value: The realist evaluation with additional synthesis from key stakeholders has provided new knowledge about the principles of effective NMAHP leadership in health and social care, presented in such a way that facilitates the use of the five guiding lights to inform further practice, education, research and policy development

What's the Weight? Estimating Controlled Outcome Differences in Complex Surveys for Health Disparities Research

A basic descriptive question in statistics often asks whether there are differences in mean outcomes between groups based on levels of a discrete covariate (e.g., racial disparities in health outcomes). However, when this categorical covariate of interest is correlated with other factors related to the outcome, direct comparisons may lead to biased estimates and invalid inferential conclusions without appropriate adjustment. Propensity score methods are broadly employed with observational data as a tool to achieve covariate balance, but how to implement them in complex surveys is less studied - in particular, when the survey weights depend on the group variable under comparison. In this work, we focus on a specific example when sample selection depends on race. We propose identification formulas to properly estimate the average controlled difference (ACD) in outcomes between Black and White individuals, with appropriate weighting for covariate imbalance across the two racial groups and generalizability. Via extensive simulation, we show that our proposed methods outperform traditional analytic approaches in terms of bias, mean squared error, and coverage. We are motivated by the interplay between race and social determinants of health when estimating racial differences in telomere length using data from the National Health and Nutrition Examination Survey. We build a propensity for race to properly adjust for other social determinants while characterizing the controlled effect of race on telomere length. We find that evidence of racial differences in telomere length between Black and White individuals attenuates after accounting for confounding by socioeconomic factors and after utilizing appropriate propensity score and survey weighting techniques. Software to implement these methods can be found in the R package svycdiff at https://github.com/salernos/svycdiff

Evolutionary dynamics of the clade 2.3.4.4B H5N8 high-pathogenicity avian influenza outbreaks in coastal seabirds and other species in southern Africa from 2017 to 2019

From late 2017 to early 2018, clade 2.3.4.4B H5N8 highly pathogenic avian influenza (HPAI) viruses caused mass die-offs of thousands of coastal seabirds along the southern coastline of South Africa. Terns (Laridae) especially were affected, but high mortalities in critically endangered and threatened species like African Penguins (Spheniscus demersus) caused international concern and, exactly a year later, the disease recurred at a key African Penguin breeding site on Halifax Island, Namibia. Twenty-five clade 2.3.4.4B H5N8 HPAI viruses from coastal seabirds and a Jackal Buzzard (Buteo rufofuscus) were isolated and/or sequenced in this study. Phylogenetic analyses of the full viral genomes and time to the most recent common ancestor (tMRCA) analyses of the HA, NA, PB1 and PA genes determined that the South African coastal seabird viruses formed a monophyletic group nested within the South African genotype 4 viruses. This sub-lineage likely originated from a single introduction by terrestrial birds around October 2017. Only the HA and NA sequences were available for the Namibian penguin viruses, but the phylogenetic data confirmed that the South African coastal seabird viruses from 2017 to 2018 were the source and the most closely related South African virus was found in a gull. tMRCA analyses furthermore determined that the progenitors of the five genotypes implicated in the earlier 2017 South African outbreaks in wild birds and poultry were dated at between 2 and 4 months prior to the index cases. tMRCA and phylogenetic data also showed that the novel genotype 6 virus introduced to South Africa in 2018, and later also detected in Nigeria and Poland in 2019, most likely arose in late 2017 in West, Central or East Africa. We propose that it continued to circulate there, and that an unidentified reservoir was the source of both the South African outbreaks in early 2018 and in Nigeria in mid-2019.NRF-DSI SARChI.http://wileyonlinelibrary.com/journal/tbedhj2022Production Animal Studie

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation