27,811 research outputs found
Enhanced postoperative surveillance versus standard of care to reduce mortality among adult surgical patients in Africa (ASOS-2) : a cluster-randomised controlled trial
No full textFunding Information: R M Pearse reports grants from Edwards Lifesciences and Intersurgical; and personal fees from Edwards Lifesciences and GlaxoSmithKline, outside of the submitted work. R M Pearse also reports being a member of the editorial boards of the British Journal of Anaesthesia and the British Journal of Surgery. A B A Prempah was the recipient of the World Federation of Societies of Anaesthesiologists–International Anesthesia Research Society Clinical Research Fellow in Global Surgery and Anaesthesia in Africa. All other authors declare no competing interests. Funding Information: The ASOS-2 pilot and trial were partially supported by a grant (OPP#1161108) from the Bill & Melinda Gates Foundation, as a subaward from Praekelt. Researchers for the process evaluation were supported by a grant from the World Federation of Societies of Anaesthesiologists. Publisher Copyright: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licensePeer reviewe
Enhanced postoperative surveillance versus standard of care to reduce mortality among adult surgical patients in Africa (ASOS-2): a cluster-randomised controlled trial
No full textBackground: Risk of mortality following surgery in patients across Africa is twice as high as the global average. Most of these deaths occur on hospital wards after the surgery itself. We aimed to assess whether enhanced postoperative surveillance of adult surgical patients at high risk of postoperative morbidity or mortality in Africa could reduce 30-day in hospital mortality. Methods We did a two-arm, open-label, cluster-randomised trial of hospitals (clusters) across Africa. Hospitals were eligible if they provided surgery with an overnight postoperative admission. Hospitals were randomly assigned through minimisation in recruitment blocks (1:1) to provide patients with either a package of enhanced postoperative surveillance interventions (admitting the patient to higher care ward, increasing the frequency of postoperative nursing observations, assigning the patient to a bed in view of the nursing station, allowing family members to stay in the ward, and placing a postoperative surveillance guide at the bedside) for those at high risk (ie, with African Surgical Outcomes Study Surgical Risk Calculator scores ≥10) and usual care for patients at low risk (intervention group), or for all patients to receive usual postoperative care (control group). Health-care providers and participants were not masked, but data assessors were. The primary outcome was 30 day in-hospital mortality of patients at low and high risk, measured at the participant level. All analyses were done as allocated (by cluster) in all patients with available data. This trial is registered with ClinicalTrials.gov, number NCT03853824. Findings Between May 3, 2019, and July 27, 2020, 594 eligible hospitals indicated a desire to participate across 33 African countries; 332 (56%) were able to recruit participants and were included in analyses. We allocated 160 hospitals (13 275 patients) to provide enhanced postoperative surveillance and 172 hospitals (15 617 patients) to provide standard care. The mean age of participants was 37·1 years (SD 15·5) and 20 039 (69·4%) of 28 892 patients were women. 30-day in-hospital mortality occurred in 169 (1·3%) of 12 970 patients with mortality data in the intervention group and in 193 (1·3%) of 15 242 patients with mortality data in the control group (relative risk 0·96, 95% CI 0·69–1·33; p=0·79). 45 (0·2%) of 22 031 patients at low risk and 309 (5·6%) of 5500 patients at high risk died. No harms associated with either intervention were reported. Interpretation This intervention package did not decrease 30-day in-hospital mortality among surgical patients in Africa at high risk of postoperative morbidity or mortality. Further research is needed to develop interventions that prevent death from surgical complications in resource-limited hospitals across Africa. Funding Bill & Melinda Gates Foundation, the World Federation of the Societies of Anaesthesiologists
Outcomes after surgery for children in Africa (ASOS-Paeds): a 14-day prospective observational cohort study.
No full textBACKGROUND: Safe anaesthesia and surgery are a public health imperative. There are few data describing outcomes for children undergoing anaesthesia and surgery in Africa. We aimed to get robust epidemiological data to describe patient care and outcomes for children undergoing anaesthesia and surgery in hospitals in Africa. METHODS: This study was a 14-day, international, prospective, observational cohort study of children (aged <18 years) undergoing surgery in Africa. We recruited as many hospitals as possible across all levels of care (first, second, and third) providing surgical treatment. Each hospital recruited all eligible children for a 14-day period commencing on the date chosen by each participating hospital within the study recruitment period from Jan 15 to Dec 23, 2022. Data were collected prospectively for consecutive patients on paper case record forms. The primary outcome was in-hospital postoperative complications within 30 days of surgery and the secondary outcome was in-hospital mortality within 30 days after surgery. We also collected hospital-level data describing equipment, facilities, and protocols available. This study is registered with ClinicalTrials.gov, NCT05061407. FINDINGS: We recruited 8625 children from 249 hospitals in 31 African countries. The mean age was 6·1 (SD 4·9) years, with 5675 (66·0%) of 8600 children being male. Most children (6110 [71·2%] of 8579 patients) were from category 1 of the American Society of Anesthesiologists Physical Status score undergoing elective surgery (5325 [61·9%] of 8604 patients). Postoperative complications occurred in 1532 (18·0%) of 8515 children, predominated by infections (971 [11·4%] of 8538 children). Deaths occurred in 199 (2·3%) of 8596 patients, 169 (84·9%) of 199 patients following emergency surgeries. Deaths following postoperative complications occurred in 166 (10·8%) of 1530 complications. Operating rooms were reported as safe for anaesthesia and surgery for neonates (121 [54·3%] of 223 hospitals), infants (147 [65·9%] of 223 hospitals), and children younger than 6 years (188 [84·3%] of 223 hospitals). INTERPRETATION: Outcomes following anaesthesia and surgery for children in Africa are poor, with complication rates up to four-fold higher (18% vs 4·4-14%) and mortality rates 11-fold higher than high-income countries in a crude, unadjusted comparison (23·15 deaths vs 2·18 deaths per 1000 children). To improve surgical outcomes for children in Africa, we need health system strengthening, provision of safe environments for anaesthesia and surgery, and strategies to address the high rate of failure to rescue. FUNDING: Jan Pretorius Research Fund of the South African Society of Anaesthesiologists and Association of Anesthesiologists of Uganda
SINGLE-BOLUS TENECTEPLASE COMAPRED WITH FRONT-LOADED ALTEPLASE IN ACUTE MYOCARDIAL INFARCTION. THE ASSENT-2 DOUBLE-BLIND RANDOMISED TRIAL.
No full textDNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
No full textSingle Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be
associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose
polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p,0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03– 1.16), p = 2.761023) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03–1.21,
p = 4.861023). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/ 2 mutation carriers and should be more comprehensively studied
Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial.
No full textBACKGROUND: High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. METHODS: We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK-based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. FINDINGS: Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45-116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants' systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2-5; n=420) in the GTN group versus 3 (2-5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97-1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2-5]; n=544, in the GTN group vs 3 [2-5]; n=558, in the sham group; 1·04 [0·84-1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. INTERPRETATION: Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultra-acute prehospital setting. FUNDING: British Heart Foundation
Police Investigators’ Perceptions of the Challenges Associated With Interviewing Adult Sexual Assault Complainants
No full textAlthough police organizations have devoted considerable effort to training investigators in evidence-based witness interviewing techniques, there is some suggestion that current practices do not meet the multifaceted requirements of sexual assault cases. Here, we assessed the specific challenges inherent in conducting interviews with adult sexual assault complainants, by conducting in-depth interviews with 21 experienced investigators from both Australia and New Zealand. The challenges that investigators identified fell into three broad themes: meeting the evidential needs of sexual assault investigations, establishing credibility, and managing complainant vulnerabilities. We discuss how the investigative interview process might be modified in line with these challenges.No Full Tex
Challenges and Experiences in Multicenter Prehospital Stroke Research: Narrative Data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial-2 (RIGHT-2)
No full textBackground: Ambulance services are increasingly research active and the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is the largest United Kingdom (UK) ambulance-based randomized controlled trial in stroke. We explore the complexities and challenges encountered during RIGHT-2. Methods: Five hundred and sixteen of 1487 paramedics from eight UK ambulance services serving 54 comprehensive or primary stroke care centers screened and consented 1149 patients presenting within 4 h of FAST-positive stroke and with systolic blood pressure >120 mmHg; participants were randomized to treatment with transdermal glyceryl trinitrate versus sham patch in the ambulance. Key findings: Working with multiple ambulance services demanded flexibility in the trial protocol to overcome variation in operating procedures to ensure deliverability. Many paramedics are novice researchers, and research concepts and practices are emerging including consent strategies in emergency stroke care. Regional variation in hospital participation and hours/days of operation presented paramedics with additional considerations prior to patient recruitment. The working hours of hospital research staff often do not reflect the 24/7 nature of ambulance work, which challenged deliverability until trial processes became fully embedded. Management of investigational medicinal product between ambulance stations, in-transit when on ambulance vehicles and on handover at hospital, necessitated an in-depth review to maintain accountability. Conclusion: RIGHT-2 demonstrated that although there are significant practical challenges to conducting multicenter ambulance-based research in a time-dependent environment, careful planning and management facilitated delivery. Lessons learned here will help inform the design and conduct of future ambulance-based trials
Child Sexual Abuse Material Online: The Perspective of Online Investigators on Training and Support
No full textThe development of online technologies in recent decades has led to the proliferation of the distribution, consumption, and sale of child sexual abuse material (CSAM) online. This trend has arguably also contributed to the sexual abuse of children offline. In this context, many organizations, including financial institutions and police agencies, have invested human, financial, and technological resources to address this problem. Combining statistics on recent crime trends with data collected from online police investigators suggests the critical need for this phenomenon to be taken more seriously on a global scale. Using data obtained from interviews conducted with online CSAM police investigators across several Australian police agencies, this study presents a detailed view of what is needed to best support police work in this domain. The most frequent responses obtained from investigators grouped around three dimensions: (1) knowledge and skills related to the tools used during investigations, such as computers, information technology, the Internet, and legislations; (2) knowledge related to offenders, how they operate, and how investigators should interact with them virtually; and (3) mental health wellbeing of investigators.No Full Tex
'Elasticity' in the processing of criminal evidence: The role of investigators' need for closure
No full textCriminal investigators have to balance the motivation to accurately examine their cases (accuracy goal), with the motivation to quickly achieve results and reach conclusions (closure goal). Previous research has shown that investigators are more skeptical towards evidence that disconfirms their prior belief about a case, and more so concerning witness evidence than technical evidence (i.e., an ‘elasticity’ effect; Ask, Rebelius & Granhag, 2008). We hypothesize that it is not the inconsistency with a prior belief, but rather with a closure goal, that makes investigators more skeptical towards exonerating evidence. Hence, investigators who initially believe a target person to be innocent, and subsequently receives a piece of evidence, should judge inconsistent (i.e., incriminating) evidence as more reliable than consistent (i.e., exonerating) evidence. The hypothesis was tested in an experiment following a 2 (Type of evidence: DNA vs. witness) × 2 (Consistency: consistent vs. inconsistent) × 2 (Need for closure: high vs. low) factorial design. Police trainees read background information about a homicide case and about a seemingly innocent person who was questioned by the police, and judged the probability of him being the offender. Later they received consistent or inconsistent evidence and were asked to assess the reliability of the additional evidence. Preliminary results show that, consistent with the hypothesis, participants who received inconsistent (vs. consistent) evidence rated the evidence as more reliable. The effect was stronger in the witness than in the DNA group, indicating a ‘reversed’ elasticity effect, and was more pronounced among persons high in need for closure
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