Clinical trial results in context: comparison of baseline characteristics and outcomes of 38,510 RECOVERY trial participants versus a reference population of 346,271 people hospitalised with COVID-19 in England.

BACKGROUND: Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects, is enhanced by understanding how the trial population may differ from the populations it aims to represent. METHODS: We compared baseline characteristics and mortality of RECOVERY participants recruited in England (n = 38,510) with a reference population hospitalised with COVID-19 in England (n = 346,271) from March 2020 to November 2021. We used linked hospitalisation and mortality data for both cohorts to extract demographics, comorbidity/frailty scores, and crude and age- and sex-adjusted 28-day all-cause mortality. RESULTS: Demographics of RECOVERY participants were broadly similar to the reference population, but RECOVERY participants were younger (mean age [standard deviation]: RECOVERY 62.6 [15.3] vs reference 65.7 [18.5] years) and less frequently female (37% vs 45%). Comorbidity and frailty scores were lower in RECOVERY, but differences were attenuated after age stratification. Age- and sex-adjusted 28-day mortality declined over time but was similar between cohorts across the study period (RECOVERY 23.7% [95% confidence interval: 23.3-24.1%]; vs reference 24.8% [24.6-25.0%]), except during the first pandemic wave in the UK (March-May 2020) when adjusted mortality was lower in RECOVERY. CONCLUSIONS: Adjusted 28-day mortality in RECOVERY was similar to a nationwide reference population of patients admitted with COVID-19 in England during the same period but varied substantially over time in both cohorts. Therefore, the absolute effect estimates from RECOVERY were broadly applicable to the target population at the time but should be interpreted in the light of current mortality estimates. TRIAL REGISTRATION: ISRCTN50189673- Feb. 04, 2020, NCT04381936- May 11, 2020.

Improving risk models for patients having emergency bowel cancer surgery using linked electronic health records: a national cohort study.

BACKGROUND: Life-saving emergency major resection of colorectal cancer (CRC) is a high-risk procedure. Accurate prediction of postoperative mortality for patients undergoing this procedure is essential for both healthcare performance monitoring and preoperative risk assessment. Risk-adjustment models for CRC patients often include patient and tumour characteristics, widely available in cancer registries and audits. The authors investigated to what extent inclusion of additional physiological and surgical measures, available through linkage or additional data collection, improves accuracy of risk models. METHODS: Linked, routinely-collected data on patients undergoing emergency CRC surgery in England between December 2016 and November 2019 were used to develop a risk model for 90-day mortality. Backwards selection identified a 'selected model' of physiological and surgical measures in addition to patient and tumour characteristics. Model performance was assessed compared to a 'basic model' including only patient and tumour characteristics. Missing data was multiply imputed. RESULTS: Eight hundred forty-six of 10 578 (8.0%) patients died within 90 days of surgery. The selected model included seven preoperative physiological and surgical measures (pulse rate, systolic blood pressure, breathlessness, sodium, urea, albumin, and predicted peritoneal soiling), in addition to the 10 patient and tumour characteristics in the basic model (calendar year of surgery, age, sex, ASA grade, TNM T stage, TNM N stage, TNM M stage, cancer site, number of comorbidities, and emergency admission). The selected model had considerably better discrimination compared to the basic model (C-statistic: 0.824 versus 0.783, respectively). CONCLUSION: Linkage of disease-specific and treatment-specific datasets allowed the inclusion of physiological and surgical measures in a risk model alongside patient and tumour characteristics, which improves the accuracy of the prediction of the mortality risk for CRC patients having emergency surgery. This improvement will allow more accurate performance monitoring of healthcare providers and enhance clinical care planning.

Fluid Optimisation in Emergency Laparotomy (FLO-ELA) Trial: study protocol for a multi-centre randomised trial of cardiac output-guided fluid therapy compared to usual care in patients undergoing major emergency gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in patients undergoing major emergency gastrointestinal surgery are a major burden on healthcare systems. Optimal management of perioperative intravenous fluids may reduce mortality rates and improve outcomes from surgery. Previous small trials of cardiac-output guided haemodynamic therapy algorithms in patients undergoing gastrointestinal surgery have suggested this intervention results in reduced complications and a modest reduction in mortality. However, this existing evidence is based mainly on elective (planned) surgery, with little evaluation in the emergency setting. There are fundamental clinical and pathophysiological differences between the planned and emergency surgical setting which may influence the effects of this intervention. A large definitive trial in emergency surgery is needed to confirm or refute the potential benefits observed in elective surgery and to inform widespread clinical practice. METHODS: The FLO-ELA trial is a multi-centre, parallel-group, open, randomised controlled trial. 3138 patients aged 50 and over undergoing major emergency gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intra-venous fluid, or usual care without cardiac output monitoring. The trial intervention will be carried out during surgery and for up to 6 h postoperatively. The trial is funded through an efficient design call by the National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) programme and uses existing routinely collected datasets for the majority of data collection. The primary outcome is the number of days alive and out of hospital within 90 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation. Participant recruitment started in September 2017 with a 1-year internal pilot phase and is ongoing at the time of publication. DISCUSSION: This will be the largest contemporary randomised trial examining the effectiveness of perioperative cardiac output-guided haemodynamic therapy in patients undergoing major emergency gastrointestinal surgery. The multi-centre design and broad inclusion criteria support the external validity of the trial. Although the clinical teams delivering the trial interventions will not be blinded, significant trial outcome measures are objective and not subject to detection bias. TRIAL REGISTRATION: ISRCTN 14729158. Registered on 02 May 2017.

Implementation and Evaluation of an Acute Care Multicomponent Intervention for Dementia-Related Behavioral Expressions.

Despite the high prevalence and negative outcomes associated with poorly managed dementia-related behavioral expressions (BE) during hospitalization, evidence-based interventions for BE management in acute care environments are lacking. To address this gap, we designed, implemented, and evaluated feasibility, utility, and exploratory nurse and patient outcomes associated with a low-cost, nurse-led multicomponent decision support intervention-the Personalized Approach and Targeted Interventions (PROACTIVE) Treatment Approach-which was implemented as a quality improvement program and evaluated with a historical matched comparison group. The intervention was feasibly implemented and improved nurse-sensitive outcomes (stress, confidence), practices (use of nonpharmacological approaches) for BE management, and perceived utility of intervention resources. Patients receiving the PROACTIVE Treatment Approach (N = 40) had higher rates of acetaminophen use, and shorter lengths of stay (N = 40). More rigorous evaluation is needed to better determine optimal implementation strategies and intervention impact. [Journal of Gerontological Nursing, 47(9), 21-30.].

Older patients undergoing emergency laparotomy: observations from the National Emergency Laparotomy Audit (NELA) years 1-4.

BACKGROUND: older patients aged ≥65 years constitute the majority of the National Emergency Laparotomy Audit (NELA) population. To better understand this group and inform future service changes, this paper aims to describe patient characteristics, outcomes and process measures across age cohorts and temporally in the 4-year period (2014-2017) since NELA was established. METHODS: patient-level data were populated from the NELA data set years 1-4 and linked with Office of National Statistics mortality data. Descriptive data were compared between groups delineated by age, NELA year and geriatrician review. Primary outcomes were 30- and 90-day mortality, length of stay (LOS) and discharge to care-home accommodation. RESULTS: in total, 93,415 NELA patients were included in the analysis. The median age was 67 years. Patients aged ≥65 years had higher 30-day (15.3 versus 4.9%, P < 0.001) and 90-day mortality (20.4 versus 7.2%, P < 0.001) rates, longer LOS (median 15.2 versus 11.3 days, P < 0.001) and greater likelihood of discharge to care-home accommodation compared with younger patients (6.7 versus 1.9%, P < 0.001). Mortality rate reduction over time was greater in older compared with younger patients. The proportion of older NELA patients seen by a geriatrician post-operatively increased over years 1-4 (8.5 to 16.5%, P < 0.001). Post-operative geriatrician review was associated with reduced mortality (30-day odds ratio [OR] 0.38, confidence interval [CI] 0.35-0.42, P < 0.001; 90-day OR 0.6, CI 0.56-0.65, P < 0.001). CONCLUSIONS: older NELA patients have poorer post-operative outcomes. The greatest reduction in mortality rates over time were observed in the oldest cohorts. This may be due to several interventions including increased perioperative geriatrician input.

Problematizing the DSM-5 criteria for opioid use disorder: A qualitative analysis.

BACKGROUND: This paper includes the voices of people who are members of a peer-led drug user group (SNAP) in Canada who are receiving heroin-assisted treatment (HAT) outside of a clinical trial. Drawing from critical drug studies, we problematize the criteria for severe opioid use disorder (OUD) from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, by exploring SNAP members' experiences in relation to heroin-assisted treatment, and examining how SNAP participants' narratives challenge conventional notions of what constitutes severe opioid use disorder. METHOD: Drawing on critical analysis and research guidelines developed by drug user unions and organizations, and critical methodological frameworks on ethical community-based-and-responsive research for social justice, in this paper we focus on semi-structured interviews conducted with 36 SNAP members at the Vancouver Area Network of Drug Users site in the Downtown Eastside of Vancouver, Canada. We included opened ended questions about experiences prior to receiving HAT, experiences while receiving HAT, experiences of drug use and cessation, and future hopes. RESULTS: Although SNAP participants were diagnosed as suffering from OUD, the DSM-5 criteria for OUD fails to encompass their diverse experiences of opioid use. Nor does the DSM diagnosis capture the complexities of their lived experience. The DSM OUD constructs an idea of addiction and the addicted person based on a list of symptoms thought to be associated with extended use of opioids. The problem with this is that many of these "symptoms" of drug use are, in the case of SNAP participants, tied to contextual issues of living in the DTES, experiencing structural vulnerability, and being the target of punitive drug policies and laws. CONCLUSION: To label someone as having a severe disorder shifts the focus from political and social issues, including the lived experiences of people who use heroin. The DSM-5 de-contextualizes drug use. How addiction and heroin are constituted has political implications that will determine what types of services and programs will be set up. Treating a disorder, or a person with a disorder, requires a much different approach than understanding heroin use as a habit. SNAP, and their allies, are rupturing conventional ideas about heroin and taken for granted assumptions about people who use heroin.

Hospital-level evaluation of the effect of a national quality improvement programme: time-series analysis of registry data.

BACKGROUND AND OBJECTIVES: A clinical trial in 93 National Health Service hospitals evaluated a quality improvement programme for emergency abdominal surgery, designed to improve mortality by improving the patient care pathway. Large variation was observed in implementation approaches, and the main trial result showed no mortality reduction. Our objective therefore was to evaluate whether trial participation led to care pathway implementation and to study the relationship between care pathway implementation and use of six recommended implementation strategies. METHODS: We performed a hospital-level time-series analysis using data from the Enhanced Peri-Operative Care for High-risk patients trial. Care pathway implementation was defined as achievement of >80% median reliability in 10 measured care processes. Mean monthly process performance was plotted on run charts. Process improvement was defined as an observed run chart signal, using probability-based 'shift' and 'runs' rules. A new median performance level was calculated after an observed signal. RESULTS: Of 93 participating hospitals, 80 provided sufficient data for analysis, generating 800 process measure charts from 20 305 patient admissions over 27 months. No hospital reliably implemented all 10 processes. Overall, only 279 of the 800 processes were improved (3 (2-5) per hospital) and 14/80 hospitals improved more than six processes. Mortality risk documented (57/80 (71%)), lactate measurement (42/80 (53%)) and cardiac output guided fluid therapy (32/80 (40%)) were most frequently improved. Consultant-led decision making (14/80 (18%)), consultant review before surgery (17/80 (21%)) and time to surgery (14/80 (18%)) were least frequently improved. In hospitals using ≥5 implementation strategies, 9/30 (30%) hospitals improved ≥6 care processes compared with 0/11 hospitals using ≤2 implementation strategies. CONCLUSION: Only a small number of hospitals improved more than half of the measured care processes, more often when at least five of six implementation strategies were used. In a longer term project, this understanding may have allowed us to adapt the intervention to be effective in more hospitals.

Feasibility of collecting and assessing patient-reported outcomes for emergency admissions: laparotomy for gastrointestinal conditions.

INTRODUCTION: Audit of emergency surgery is usually limited to immediate clinical outcomes relating to outcomes during the acute hospital episode with little attempt to capture patients' views of their longer-term outcomes. Our aim was to determine the response rate to patient-reported outcome measures (PROMs) for patients who underwent an emergency laparotomy for gastrointestinal conditions, identify response bias and explore the feasibility of comparing outcomes with their prior health based on their recalled view collected during their admission. METHODS: Patients undergoing emergency laparotomy in 11 hospitals were recruited to complete a retrospective questionnaire containing the EQ-5D-3L and Gastrointestinal Quality of Life Index (GIQLI). Response rate for 3-month mailed follow-up questionnaire and potential response biases were assessed. Patients' outcomes were compared with their baseline using χ2 and paired t-test to assess for differences. RESULTS: Of 255 patients contacted at 3 months, 190 (74.1%) responded. Responders were more likely to be older, female and more affluent. Patients' health improved significantly as regards the GIQLI (93.3 vs 97.9; p=0.048) and the subscale on symptoms (51.9 vs 59.6; p<0.001). No significant change in subscales on emotion or physical aspects or for overall health status (EQ-5D: 0.58 vs 0.64; p=0.06). According to the social subscale, patients had deteriorated (11.0 vs 9.8; p<0.0006). Differences in change scores by patient characteristics were slight, suggesting minimal response bias. CONCLUSION: This approach offers the opportunity for assessing the impact of treatment, from the patient's perspective and the potential to evaluate emergency laparotomy care using PROMs.

Chemical and Non-Chemical Options for Managing Twospotted Spider Mite, Western Tarnished Plant Bug and Other Arthropod Pests in Strawberries.

California strawberries have two major arthropod pests-the twospotted spider mite, Tetranychus urticae and the western tarnished plant bug, Lygus hesperus, which result in significant losses to the yield and quality of marketable berries. Other important insect pests that are frequently seen in strawberry include the greenhouse whitefly, Trialeurodes vaporariorum and the western flower thrips, Frankliniella occidentalis that cause varying levels of damage depending on the level of infestation. Chemical pesticides play a major role in managing these pests but not without the associated risk of pesticide resistance and environmental safety. Two field studies were conducted in commercial strawberry fields in Santa Maria, one of the strawberry growing areas in California Central Coast, to determine the efficacy of chemical, botanical and microbial pesticides in the integrated pest management (IPM) of strawberry. Chemical, botanical and microbial pesticides were evaluated against T. urticae in a small plot study in 2013 and against L. hesperus and other insect pests in a large plot study in 2015 in commercial strawberry fields. Bug vacuums were also used in the 2015 study. Results demonstrated that non-chemical alternatives can play an important role in strawberry IPM.

Telling our stories: heroin-assisted treatment and SNAP activism in the Downtown Eastside of Vancouver.

BACKGROUND: This article highlights the experiences of a peer-run group, SALOME/NAOMI Association of Patients (SNAP), that meets weekly in the Downtown Eastside of Vancouver, British Columbia, Canada. SNAP is a unique independent peer- run drug user group that formed in 2011 following Canada's first heroin-assisted treatment trial (HAT), North America Opiate Medication Initiative (NAOMI). SNAP's members are now made up of former research participants who participated in two heroin-assisted trials in Vancouver. This article highlights SNAP members' experiences as research subjects in Canada's second clinical trial conducted in Vancouver, Study to Assess Longer-term Opioid Medication Effectiveness (SALOME), that began recruitment of research participants in 2011. METHODS: This paper draws on one brainstorming session, three focus groups, and field notes, with the SALOME/NAOMI Association of Patients (SNAP) in late 2013 about their experiences as research subjects in Canada's second clinical trial, SALOME in the DTES of Vancouver, and fieldwork from a 6-year period (March 2011 to February 2017) with SNAP members. SNAP's research draws on research principles developed by drug user groups and critical methodological frameworks on community-based research for social justice. RESULTS: The results illuminate how participating in the SALOME clinical trial impacted the lives of SNAP members. In addition, the findings reveal how SNAP member's advocacy for HAT impacts the group in positive ways. Seven major themes emerged from the analysis of the brainstorming and focus groups: life prior to SALOME, the clinic setting and routine, stability, 6-month transition, support, exiting the trial and ethics, and collective action, including their participation in a constitutional challenge in the Supreme Court of BC to continue receiving HAT once the SALOME trial ended. CONCLUSIONS: HAT benefits SNAP members. They argue that permanent HAT programs should be established in Canada because they are an effective harm reduction initiative, one that also reduces opioid overdose deaths.

Audio and video recording system for routine documentation of fluoroscopic procedures.

Because aviation and other reliable systems routinely record and analyze performance, the authors investigated the feasibility and utility of installing a system capable of recording image-guided procedures. An audio/video recording system adapted from those used in simulation laboratories was installed in a new pediatric interventional radiology suite. In this report, the authors describe the recording system as well as how it can be used to study radiation use during individual procedures. These results illustrate how routinely recording more than 300 procedures during the past 14 months and the detailed analysis of selected recordings can provide insights that lead to continual improvements in performance.

Performance of certified registered nurse anesthetists and anesthesiologists in a simulation-based skills assessment.

BACKGROUND: Anesthesiologists and certified registered nurse anesthetists (CRNAs) must acquire the skills to recognize and manage a variety of acute intraoperative emergencies. A simulation-based assessment provides a useful and efficient means to evaluate these skills. In this study, we evaluated and compared the performance of board-certified anesthesiologists and CRNAs managing a set of simulated intraoperative emergencies. METHODS: We enrolled 26 CRNAs and 35 board-certified anesthesiologists in a prospective, randomized, single-blinded study. These 61 specialists each managed 8 of 12 randomly selected, scripted, intraoperative simulation exercises. Participants were expected to recognize and initiate appropriate therapy for intraoperative events during a 5-min period. Two primary raters scored 488 simulation exercises (61 participants x 8 encounters). RESULTS: Anesthesiologists achieved a modestly higher mean overall score than CRNAs (66.6% +/- 11.7 [range = 41.7%-86.7%] vs 59.9% +/- 10.2 [range = 38.3%-80.4%] P < 0.01). There were no significant differences in performance between groups on individual encounters. The raters were consistent in their identification of key actions. The reliability of the eight-scenario assessment, with two raters for each scenario, was 0.80. CONCLUSION: Although anesthesiologists, on average, achieved a modestly higher overall score, there was marked and similar variability in both groups. This wide range suggests that certification in either discipline may not yield uniform acumen in management of simulated intraoperative emergencies. In both groups, there were practitioners who failed to diagnose and treat simulated emergencies. If this is reflective of clinical practice, it represents a patient safety concern. Simulation-based assessment provides a tool to determine the ability of practitioners to respond appropriately to clinical emergencies. If all practitioners could effectively manage these critical events, the standard of patient care and ultimately patient safety could be improved.

Transgene and mitochondrial DNA are indicators of efficient composting of transgenic pig carcasses.

Composting is an environmentally sound method for the disposal of on-farm livestock mortalities that generates material suitable for use as fertilizer; however, this method is not generally permitted for disposal of transgenic livestock mortalities during the research and development phase. This study has explored the application of the polymerase chain reaction (PCR) as a method for assessing the persistence of transgene and mitochondrial DNA markers during the composting of euthanized transgenic pig. There was at least a 10(7) fold reduction of genetic material to a level that not either transgene or mitochondrion markers were detectable. At the end of the composting period, only bone fragments that were completely demineralised and chalky were detected. Chemically the compost was similar to that from pig litter and poultry mortalities, except the copper content was lower. Based on these data, composting appears to be an appropriate method for the disposal of transgenic animals.

An evaluation of fluorescence polarization and lifetime discriminated polarization for high throughput screening of serine/threonine kinases.

We used two kinases, c-jun N terminal kinase (JNK-1) and protein kinase C (PKC), as model enzymes to evaluate the potential of fluorescence polarization (FP) for high-throughput screening and the susceptibility of these assays to compound interference. For JNK-1 the enzyme kinetics in the FP assay were consistent with those found in a [gamma-33P]ATP filter wash assay. Determined pIC(50)s for nonfluorescent JNK-1 inhibitors were also consistent with those found in the filter wash assay. In contrast, fluorescent compounds were found to interfere with the JNK-1 FP assay, appearing as false positives, defined by their lack of activity in the filter wash assay. We also developed a second assay using a different kinase, protein kinase C, which was used to test a 5000 compound diversity set. As for JNK-1, interference from fluorescent compounds caused a high false positive rate. The Molecular Devices Corporation 'FLARe' instrument is capable of discriminating between fluorophores on the basis of their fluorescence (excited state) lifetime, and may assist in reducing compound interference in fluorescent assays. In both model FP kinase assays described here some, although not complete, reduction in interference from fluorescent compounds was achieved by the use of FLARe.