Description: Objectives To explore patient, caregiver and physician perceptions and attitudes regarding the balance of benefit and risk in using antibacterial drugs developed through streamlined development processes. Design Semistructured focus groups and in-depth interviews were conducted to elicit perceptions and attitudes about the use of antibacterial drugs to treat multidrug-resistant infections. Participants were given background information about antibiotic resistance, streamlined drug development programmes and FDA drug approval processes. Audio recordings of focus groups/interviews were reviewed and quotes excerpted and categorised to identify key themes. Participants Two primary stakeholder groups were engaged: one comprising caregivers, healthy persons and patients who had recovered from or were at risk of resistant infection (N=67; 11 focus groups); and one comprising physicians who treat resistant infections (N=23). Results Responses from focus groups/interviews indicated widespread awareness among patients/caregivers and physicians of the seriousness of the problem of antibacterial resistance. Both groups were willing to accept a degree of uncertainty regarding the balance of risk and benefit in a new therapy where a serious unmet need exists, but also expressed a desire for rigorous monitoring and rapid, transparent reporting of safety/effectiveness data. Both groups wanted to ensure that 〉1 physician had input on whether to treat patients with antibiotics developed through a streamlined process. Some patients/caregivers unfamiliar with exigencies of critical care suggested a relatively large multidisciplinary team, while physicians believed individual expert consultations would be preferable. Both groups agreed that careful oversight and stewardship of antibacterial drugs are needed to ensure patient safety, preserve efficacy and prevent abuse. Conclusions Groups comprising patients/caregivers and physicians were aware of serious issues posed by resistant infections and the lack of effective antibacterial drug therapies and shared a consensus that streamlined development programmes represent a necessary response to the resistance crisis, but one that requires enhanced safeguards and risk communication.

Description: Introduction To interrupt malaria transmission, strategies must target the parasite reservoir in both humans and mosquitos. Testing of community members linked to an index case, termed reactive case detection (RACD), is commonly implemented in low transmission areas, though its impact may be limited by the sensitivity of current diagnostics. Indoor residual spraying (IRS) before malaria season is a cornerstone of vector control efforts. Despite their implementation in Namibia, a country approaching elimination, these methods have been met with recent plateaus in transmission reduction. This study evaluates the effectiveness and feasibility of two new targeted strategies, reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in Namibia. Methods and analysis This is an open-label cluster randomised controlled trial with 2 x 2 factorial design. The interventions include: rfMDA (presumptive treatment with artemether-lumefantrine (AL)) versus RACD (rapid diagnostic testing and treatment using AL) and RAVC (IRS with Acellic 300CS) versus no RAVC. Factorial design also enables comparison of the combined rfMDA+RAVC intervention to RACD. Participants living in 56 enumeration areas will be randomised to one of four arms: rfMDA, rfMDA+RAVC, RACD or RACD+RAVC. These interventions, triggered by index cases detected at health facilities, will be targeted to individuals residing within 500 m of an index. The primary outcome is cumulative incidence of locally acquired malaria detected at health facilities over 1 year. Secondary outcomes include seroprevalence, infection prevalence, intervention coverage, safety, acceptability, adherence, cost and cost-effectiveness. Ethics and dissemination Findings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with MoHSS and community leaders in Namibia. Trial registration number NCT02610400; Pre-results.

Description: Introduction Although randomised controlled trials have demonstrated that preoperative glucocorticoids may improve postoperative surrogate outcomes among patients undergoing major liver resection, evidence supporting improved patient-important outcomes is lacking. This superiority trial aims to evaluate the effect of administration of a bolus of the glucocorticoid methylprednisolone versus placebo during induction of anaesthesia on postoperative morbidity among adults undergoing elective major liver resection. Methods and analysis This will be a randomised, dual-arm, parallel-group, superiority trial. All consecutive adults presenting to a large Canadian tertiary care hospital who consent to undergo major liver resection will be included. Patients aged 〈18 years and those currently receiving systemic corticosteroid therapy will be excluded. We will randomly allocate participants to a preoperative 500 mg intravenous bolus of methylprednisolone versus placebo. Surgical team members and outcome assessors will be blinded to treatment allocation status. The primary outcome measure will be postoperative complications. Secondary outcome measures will include mortality, the incidence of several specific postoperative complications, and blood levels of select proinflammatory cytokines, acute-phase proteins, and laboratory liver enzymes or function tests on postoperative days 0, 1, 2 and 5. The incidence of postoperative complications and mortality will be compared using Fisher's exact test, while the above laboratory measures will be compared using mixed-effects models with a subject-specific random intercept. Ethics and dissemination This trial will evaluate the protective effect of a single preoperative dose of methylprednisolone on the hazard of postoperative complications. A report releasing study results will be submitted for publication in an appropriate journal, approximately 3 months after finishing the data collection. Trial registration number NCT01997658; Pre-results.

Description: Objectives Some medical patients are at greater risk of adverse outcomes than others and may benefit from higher observation hospital units. We constructed and validated a model predicting adverse hospital outcome for patients. Study results may be used to admit patients into planned tiered care units. Adverse outcome comprised death or cardiac arrest during the first 30 days of hospitalisation, or transfer to intensive care within the first 48 h of admission. Setting The study took place at two tertiary teaching hospitals and two community hospitals in Winnipeg, Manitoba, Canada. Participants We analysed data from 4883 consecutive admissions at a tertiary teaching hospital to construct the Early Prediction of Adverse Hospital Outcome for Medical Patients (ALERT) model using logistic regression. Robustness of the model was assessed through validation performed across four hospitals over two time periods, including 65 640 consecutive admissions. Outcome Receiver-operating characteristic curves (ROC) and sensitivity and specificity analyses were used to assess the usefulness of the model. Results 9.3% of admitted patients experienced adverse outcomes. The final model included gender, age, Charlson Comorbidity Index, Activities of Daily Living Score, Glasgow Coma Score, systolic blood pressure, respiratory rate, heart rate and white cell count. The model was discriminative (ROC=0.83) in predicting adverse outcome. ALERT accurately predicted 75% of the adverse outcomes (sensitivity) and 75% of the non-adverse outcomes (specificity). Applying the same model to each validation hospital and time period produced similar accuracy and discrimination to that in the development hospital. Conclusions Used during initial assessment of patients admitted to general medical wards, the ALERT scale may complement other assessment measures to better screen patients. Those considered as higher risk by the ALERT scale may then be provided more effective care from action such as planned tiered care units.

Description: Objective Administrative health data are important for health services and outcomes research. We optimised and validated in intensive care unit (ICU) patients an International Classification of Disease (ICD)-coded case definition for sepsis, and compared this with an existing definition. We also assessed the definition's performance in non-ICU (ward) patients. Setting and participants All adults (aged ≥18 years) admitted to a multisystem ICU with general medicosurgical ICU care from one of three tertiary care centres in the Calgary region in Alberta, Canada, between 1 January 2009 and 31 December 2012 were included. Research design Patient medical records were randomly selected and linked to the discharge abstract database. In ICU patients, we validated the Canadian Institute for Health Information (CIHI) ICD-10-CA (Canadian Revision)-coded definition for sepsis and severe sepsis against a reference standard medical chart review, and optimised this algorithm through examination of other conditions apparent in sepsis. Measures Sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results Sepsis was present in 604 of 1001 ICU patients (60.4%). The CIHI ICD-10-CA-coded definition for sepsis had Sn (46.4%), Sp (98.7%), PPV (98.2%) and NPV (54.7%); and for severe sepsis had Sn (47.2%), Sp (97.5%), PPV (95.3%) and NPV (63.2%). The optimised ICD-coded algorithm for sepsis increased Sn by 25.5% and NPV by 11.9% with slightly lowered Sp (85.4%) and PPV (88.2%). For severe sepsis both Sn (65.1%) and NPV (70.1%) increased, while Sp (88.2%) and PPV (85.6%) decreased slightly. Conclusions This study demonstrates that sepsis is highly undercoded in administrative data, thus under-ascertaining the true incidence of sepsis. The optimised ICD-coded definition has a higher validity with higher Sn and should be preferentially considered if used for surveillance purposes.

Description: Introduction To improve surgical safety, health systems must identify preventable adverse outcomes and measure changes in these outcomes in response to quality improvement initiatives. This requires understanding of the scope and limitations of available population-level data. To derive literature-based summary estimates of benchmarks of care, we will systematically review and meta-analyse rates of postoperative complications associated with several common and/or high-risk operations performed in five high-income countries (HICs). Methods and analysis An electronic search of PubMed, Embase, Web of Science, Cochrane Central, the NHS Economic Evaluations Database and Health Technology Assessment database will be performed to identify studies reviewing national surgical complication rates between 2000 and 2016. Two reviewers will screen titles and abstracts and full texts of potentially relevant studies to determine eligibility for inclusion in the systematic review. We will include English-language publications using data from health databases in the USA, Canada, the UK, Australia and New Zealand. We will include studies of patients who underwent hip or knee arthoplasty, appendectomy, cholecystectomy, oesophagectomy, abdominal aortic aneurysm repair, aortic valve replacement or coronary artery bypass graft. Outcomes will include mortality, length of hospital stay, pulmonary embolism, pneumonia, sepsis or septic shock, reoperation, surgical site infection, wound dehiscence/disruption, blood transfusion, bile duct injury, stroke and myocardial infarction. We will calculate summary estimates of cumulative incidence, incidence rate, prevalence and occurrence rate of complications using DerSimonian and Laird random effects models. Heterogeneity in these estimates will be examined using subgroup analyses and meta-regression. We will correlate findings within contemporary clinical databases. Ethics and dissemination This study of secondary data does not require ethics approval. It will be presented internationally and published in the peer-reviewed literature. Results will inform a future quality improvement tool and provide benchmarks of surgical complication rates within HICs. Trial registration International Prospective Register of Systematic Reviews (PROSPERO). Registration number CRD42016037519.