International Prospective Cohort Study Research Articles

Duodenal Adenomas and Cancer in MUTYH-associated Polyposis: An International Cohort Study

Duodenal Adenomas and Cancer in MUTYH-associated Polyposis: An International Cohort Study

Training a Fit-For-Purpose Rural Health Workforce for Low- and Middle-Income Countries (LMICs): How Do Drivers and Enablers of Rural Practice Intention Differ Between Learners From LMICs and High Income Countries?

Equity in health outcomes for rural and remote populations in low- and middle-income countries (LMICs) is limited by a range of socio-economic, cultural and environmental determinants of health. Health professional education that is sensitive to local population needs and that attends to all elements of the rural pathway is vital to increase the proportion of the health workforce that practices in underserved rural and remote areas. The Training for Health Equity Network (THEnet) is a community-of-practice of 13 health professional education institutions with a focus on delivering socially accountable education to produce a fit-for-purpose health workforce. The THEnet Graduate Outcome Study is an international prospective cohort study with more than 6,000 learners from nine health professional schools in seven countries (including four LMICs; the Philippines, Sudan, South Africa and Nepal). Surveys of learners are administered at entry to and exit from medical school, and at years 1, 4, 7, and 10 thereafter. The association of learners' intention to practice in rural and other underserved areas, and a range of individual and institutional level variables at two time points—entry to and exit from the medical program, are examined and compared between country income settings. These findings are then triangulated with a sociocultural exploration of the structural relationships between educational and health service delivery ministries in each setting, status of postgraduate training for primary care, and current policy settings. This analysis confirmed the association of rural background with intention to practice in rural areas at both entry and exit. Intention to work abroad was greater for learners at entry, with a significant shift to an intention to work in-country for learners with entry and exit data. Learners at exit were more likely to intend a career in generalist disciplines than those at entry however lack of health policy and unclear career pathways limits the effectiveness of educational strategies in LMICs. This multi-national study of learners from medical schools with a social accountability mandate confirms that it is possible to produce a health workforce with a strong intent to practice in rural areas through attention to all aspects of the rural pathway.

Developing and validating subjective and objective risk-assessment measures for predicting mortality after major surgery: An international prospective cohort study

Preoperative risk prediction is important for guiding clinical decision-making and resource allocation. Clinicians frequently rely solely on their own clinical judgement for risk prediction rather than objective measures. We aimed to compare the accuracy of freely available objective surgical risk tools with subjective clinical assessment in predicting 30-day mortality. We conducted a prospective observational study in 274 hospitals in the United Kingdom (UK), Australia, and New Zealand. For 1 week in 2017, prospective risk, surgical, and outcome data were collected on all adults aged 18 years and over undergoing surgery requiring at least a 1-night stay in hospital. Recruitment bias was avoided through an ethical waiver to patient consent; a mixture of rural, urban, district, and university hospitals participated. We compared subjective assessment with 3 previously published, open-access objective risk tools for predicting 30-day mortality: the Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality (P-POSSUM), Surgical Risk Scale (SRS), and Surgical Outcome Risk Tool (SORT). We then developed a logistic regression model combining subjective assessment and the best objective tool and compared its performance to each constituent method alone. We included 22,631 patients in the study: 52.8% were female, median age was 62 years (interquartile range [IQR] 46 to 73 years), median postoperative length of stay was 3 days (IQR 1 to 6), and inpatient 30-day mortality was 1.4%. Clinicians used subjective assessment alone in 88.7% of cases. All methods overpredicted risk, but visual inspection of plots showed the SORT to have the best calibration. The SORT demonstrated the best discrimination of the objective tools (SORT Area Under Receiver Operating Characteristic curve [AUROC] = 0.90, 95% confidence interval [CI]: 0.88-0.92; P-POSSUM = 0.89, 95% CI 0.88-0.91; SRS = 0.85, 95% CI 0.82-0.87). Subjective assessment demonstrated good discrimination (AUROC = 0.89, 95% CI: 0.86-0.91) that was not different from the SORT (p = 0.309). Combining subjective assessment and the SORT improved discrimination (bootstrap optimism-corrected AUROC = 0.92, 95% CI: 0.90-0.94) and demonstrated continuous Net Reclassification Improvement (NRI = 0.13, 95% CI: 0.06-0.20, p < 0.001) compared with subjective assessment alone. Decision-curve analysis (DCA) confirmed the superiority of the SORT over other previously published models, and the SORT-clinical judgement model again performed best overall. Our study is limited by the low mortality rate, by the lack of blinding in the 'subjective' risk assessments, and because we only compared the performance of clinical risk scores as opposed to other prediction tools such as exercise testing or frailty assessment. In this study, we observed that the combination of subjective assessment with a parsimonious risk model improved perioperative risk estimation. This may be of value in helping clinicians allocate finite resources such as critical care and to support patient involvement in clinical decision-making.

Burden of respiratory syncytial virus infection in community-dwelling older adults in Europe (RESCEU): an international prospective cohort study.

Respiratory syncytial virus (RSV) infection in older adults is recognised as an important health issue. We aimed to assess the community burden of RSV in Europe in older adults aged ≥60 years. This international, prospective, observational cohort study is part of work by the REspiratory Syncytial virus Consortium in EUrope (RESCEU). Participants were recruited through general practitioners' (GPs) offices before two independent RSV seasons. Participants reported weekly about symptoms of acute respiratory tract infection (ARTI) during one RSV season. ARTI patients were tested for RSV during home visits and completed a daily symptom diary. RSV illness included PCR-confirmed ARTI and those showing seroconversion over the season. RSV ARTI was based on PCR alone (ClinicalTrials.gov, NCT03621930). We recruited 1040 participants (527 in season 2017-2018 and 513 in season 2018-2019) with a median age of 75 years (range 60-100 years). Of these, 1023 (99%) lived independently at home at baseline. RSV illness incidence was 22 out of 527 (4.2%) and 37 out of 513 (7.2%) in the respective seasons. RSV illness did not affect frailty or cardiopulmonary status during the course of the study. No patients were hospitalised or died from RSV illness. In the 36 patients with PCR confirmed RSV ARTI, symptom duration averaged 19 days, while a doctor's visit took place in 11 out of 36 cases (31%). RSV ARTI could not be differentiated clinically from all other ARTIs based on symptoms. This European study showed that RSV is prevalent in community-dwelling older adults and rarely causes severe disease. This suggests that watchful waiting, using a continuity of care approach to identify those who do need more intensive care, is often justified when RSV is suspected in family practice.

A Deep Learning Approach Validates Genetic Risk Factors for Late Toxicity After Prostate Cancer Radiotherapy in a REQUITE Multi-National Cohort.

Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors.Methods: The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity.Results: One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint.Conclusion: Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning.

ICU-acquired pneumonia in immunosuppressed patients with acute hypoxemic respiratory failure: A post-hoc analysis of a prospective international cohort study.

Intensive Care Units (ICU) acquired Pneumonia (ICU-AP) is one of the most frequent nosocomial infections in critically ill patients. Our aim was to determine the effects of having an ICU-AP in immunosuppressed patients with acute hypoxemic respiratory failure. Post-hoc analysis of a multinational, prospective cohort study in 16 countries. ICU. Immunosuppressed patients with acute hypoxemic respiratory failure. None. The original cohort had 1611 and in this post-hoc analysis a total of 1512 patients with available data on hospital mortality and occurrence of ICU-AP were included. ICU-AP occurred in 158 patients (10.4%). Hospital mortality was higher in patients with ICU-AP (14.8% vs. 7.1% p<0.001). After adjustment for confounders and centre effect, use of vasopressors (Odds Ratio (OR) 2.22; 95%CI 1.46-3.39) and invasive mechanical ventilation at day 1 (OR 2.12 vs. high flow oxygen; 95%CI 1.07-4.20) were associated with increased risk of ICU-AP while female gender (OR 0.63; 95%CI 0.43-94) and chronic kidney disease (OR 0.43; 95%CI 0.22-0.88) were associated with decreased risk of ICU-AP. After adjustment for confounders and centre effect, ICU-AP was independently associated with mortality (Hazard Ratio 1.48; 95%CI 14.-1.91; P=0.003). The attributable mortality of ICU-AP has been repetitively questioned in immunosuppressed patients with acute respiratory failure. This manuscript found that ICU-AP represents an independent risk factor for hospital mortality.

The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis

BackgroundAlpha-mannosidosis is a lysosomal storage disorder caused by reduced enzymatic activity of alpha-mannosidase. SPARKLE is an alpha-mannosidosis registry intended to obtain long-term safety and effectiveness data on the use of velmanase alfa during routine clinical care in patients with alpha-mannosidosis. It is a post-approval commitment to European marketing authorization for Velmanase alfa (Lamzede®), the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild to moderate alpha-mannosidosis. In addition, SPARKLE will expand the current understanding of alpha-mannosidosis by collecting data on the clinical manifestations, progression, and natural history of the disease in treated and untreated patients, respectively.ResultsThe SPARKLE registry is designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis, starting patient enrollment in 2020. Patients will be followed for up to 15 years. Safety and effectiveness as post-authorization outcomes under routine clinical care in patients with treatment will be evaluated. The primary safety outcomes are the rate of adverse events (anti-velmanase alfa-immunoglobulin G antibody development, infusion-related reactions, and hypersensitivity). Secondary safety outcomes include the evaluation of medical events, change in vital signs, laboratory tests, physical examination, and electrocardiogram results. The primary effectiveness outcome is a global treatment response rate, evaluated as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality-of-life effectiveness outcomes; secondary effectiveness outcomes are to characterize the population of patients with alpha-mannosidosis with regard to clinical manifestation, progression, and natural history of the disease. Any patient in the European Union with a diagnosis of alpha-mannosidosis who is willing to participate will likely be eligible for inclusion in the registry. Publications to disseminate scientific insights from the registry are planned.ConclusionThis study will provide real-world data on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and increase the understanding of the natural course, clinical manifestations, and progression of this ultra-rare disease.

International prospective cohort study of microvascular angina - Rationale and design.

BackgroundPatients with signs and symptoms of myocardial ischemia and non-obstructive coronary artery disease (CAD) frequently have coronary functional abnormalities, including coronary microvascular dysfunction. Those with the latter are grouped under the term “microvascular angina” (MVA). Although diagnostic criteria exist for MVA, as recently proposed by our COVADIS (COronary VAsomotor Disorders International Study) group and the condition has been increasingly recognized in clinical practice, the clinical characteristics and long-term prognosis of MVA patients in the current era remain to be fully elucidated.AimsIn the present study, we aimed to prospectively assess the clinical characteristics and long-term prognosis of MVA subjects in the current era in an international, multicenter, observational, and prospective registry study.MethodsA total of 15 medical centers across 7 countries (USA, UK, Germany, Spain, Italy, Australia, and Japan) enrolled subjects fulfilling the COVADIS diagnostic criteria for MVA as follows; (1) signs and/or symptoms of myocardial ischemia, (2) absence of obstructive CAD, and (3) objective evidence of myocardial ischemia and/or coronary microvascular dysfunction. The primary endpoint was the composite of major cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to heart failure or unstable angina. Between July 2015 and December 2018, a total of 706 subjects with MVA (M/F 256/450, 61.1 ± 11.8 [SD] yrs.) were registered. Subjects will be followed for at least 1 year.SummaryThe present study will provide important information regarding the clinical characteristics, management, and long-term prognosis of MVA patients in the current era.

Open abdomen management for severe peritonitis in elderly. Results from the prospective International Register of Open Abdomen (IROA): Cohort study.

Analyzing the data of the International Register of Open Abdomen (IROA), the feasibility of open abdomen treatment has been demonstrated at every age. This new analysis on the IROA database investigates the risk factors for mortality in elderly patients treated with open abdomen for intra-abdominal infection. Data were derived from the IROA, a prospective observational international cohort study that enrolled patients treated with open abdomen worldwide. A univariate analysis of potential risk factors was performed. Inclusion criteria were patients older than 65 years and treated with open abdomen for intra-abdominal infection. End point was overall mortality, calculated within 30 days after open abdomen management, after 1-month and 1-year follow-up. A total of 116 patients was analyzed with mean age of 76 ± 7 years. Definitive closure was achieved in 93 patients (93/116, 80.2%) for a mean open abdomen duration of 5.0 ± 5.0 days. Complicated patients were 101 (101/116, 87.1%) for a total of 201 complications. Overall, 62 out of 116 patients (53.4%) died: 23 patients (23/62, 37.1%) during open abdomen management, 29 patients (46.8%) within 30 days after abdominal closure, 9 patients (14.5%) after 1-month follow-up, and 1 patient (1.6%) after 1-year follow-up. Age did not affect mortality (75 ± 6 years in alive patients versus 77 ± 7 years in dead patients, p = 0.773). Definitive abdominal closure was the most important factor to prevent mortality. This study confirmed that age alone cannot be considered a determinant for death, even in elderly patients managed with open abdomen for severe intra-abdominal infection.

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer

Background: Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy.Aims: The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC.Methods: PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels. Main outcome: adherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as “percent of standard chemotherapy dose delivered.” Secondary outcomes: rate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations. Analysis: chemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients. Sample size: based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval.Discussion: PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836.

Study protocol for the international Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS): understanding lupus and the role of type I interferon gene signature

IntroductionThe Systemic Lupus Erythematosus (SLE) Prospective Observational Cohort Study (SPOCS) aims to describe the disease course of SLE and its association with type I interferon gene signature (IFNGS) status.Methods and...

BODY-Q patient-reported outcomes measure (PROM) to assess sleeve gastrectomy vs. Roux-en-Y gastric bypass: eating behavior, eating-related distress, and eating-related symptoms.

Post-operative changes in eating behavior, eating-related distress and eating-related symptoms play an important role in the lives of bariatric surgery patients. However, there are no studies that assess these outcomes using a specifically designed patient-reported outcome measure (PROM) for patients undergoing bariatric surgery. We use our newly developed and validated scales as part of the well-established BODY-Q PROMs to compare laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass patients (LRYGB). We analyzed data from an international multi-center prospective cohort study of patients over 18 who underwent bariatric surgery. We used multivariable linear regression models to assess the difference between LRYGB and LSG for the new BODY-Q scales, which include eating behavior, eating-related distress and eating-related symptoms. All analyses were corrected for significant confounding variables. Out of 1420 patients, 920 underwent LRYGB and 500 underwent LSG. The LRYGB group had a higher percentage total weight loss (p < 0.001). There was no significant difference in eating behavior (e.g., stop eating before feeling full, avoiding unhealthy snacks, etc.) or eating-related distress (e.g., feeling ashamed or out of control after eating). Patients who underwent LSG scored significantly better on the post-prandial eating-related symptoms scale (e.g., vomiting, reflux; p < 0.001). Symptoms more prevalent in the LRYGB patients were related to dumping syndrome whereas symptoms more prevalent in LSG patients were related to reflux. Patients who underwent LRYGB had a significantly better weight loss after surgery, but they scored worse on post-prandial symptoms in comparison to LSG patients. This information may be relevant for patients in the pre-operative counseling setting, as it may influence their decision for surgical procedure selection.

Differences in responses to English and Korean versions of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD)

BackgroundThe purpose of this study was to identify differences in caregiver responses to Korean-language and English-language versions of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD) questionnaire.MethodsPatient data were acquired from the Cerebral Palsy Hip Outcomes Project database, which was established to run a large international multicenter prospective cohort study of the outcomes of hip interventions in cerebral palsy. Thirty-three children whose caregivers had completed the Korean version of CPCHILD were matched by propensity scoring with 33 children whose parents completed the English version. Matching was performed on the basis of 12 covariates: age, gender, gross motor function classification system level, migration percentage of right and hip, seizure status, feeding method, tracheostomy status, pelvic obliquity, spinal deformity, parental report of hip pain and contracture interfering with care.ResultsThere were no significant differences in CPCHILD scores for section 4 (Communication and Social Interaction), and section 5 (Health) between two groups. Korean-language CPCHILD scores were significantly lower than English-language CPCHILD scores for section 1 (Personal Care/Activities of Daily Living), section 2 (Positioning, Transferring and Mobility), section 3 (Comfort and Emotions) and section 6 (Overall Quality of Life) as well as in terms of total score.ConclusionsCultural influences, and the community or social environment may impact the caregivers’ perception of the health-related quality of life of their children. Therefore, physicians should consider these differences when interpreting the study outcomes across different countries.

An Inflammatory Composite Score Predicts Mycobacterial Immune Reconstitution Inflammatory Syndrome in People with Advanced HIV: A Prospective International Cohort Study.

Immune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART) with severe lymphopenia. Easily accessible tools that reliably predict emergence and elucidate pathogenesis of IRIS are needed to facilitate improved clinical management. Plasma levels of biomarkers were measured before ART initiation in a large multinational cohort of ART-naive PWH with severe immunosuppression (CD4+ count <100 cells/mm3) in United States, Kenya, and Thailand. We performed a series of multiparametric analyses of inflammatory and clinical biomarkers and developed a composite score merging relevant biomarkers for use in a prediction model. We identified a distinct baseline inflammatory profile and changes in inflammatory networks among biomarkers in participants who subsequently developed mycobacterial or viral IRIS. We also developed a composite score incorporating biomarkers associated with IRIS (interleukin-6 [IL-6], IL-10, IL-27, sCD14, interferon-γ, tumor necrosis factor-α, hyaluronic acid, D-dimer, body mass index, and hemoglobin) that accurately predicted mycobacterial IRIS and death in this cohort. Systemic inflammatory profiles in PWH with severe immunosuppression are predictive of IRIS. Composite scores for the prediction of mycobacterial IRIS and death could be useful for risk stratification in PWH and lymphopenia initiating ART. NCT00286767.

Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study establishing diagnostic criteria and prognostic importance

BackgroundWe aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS. MethodsThis was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery. ResultsOf 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin <70 g L−1, transfusion of ≥1 unit of red blood cells, or that was judged to be the cause of death. Bleeding independently associated with mortality after noncardiac surgery occurred in 17.3% of patients (2782). Death occurred in 5.8% of patients with BIMS (161/2782), 1.3% (39/3028) who met bleeding screening criteria but not BIMS criteria, and 1.1% (115/10 269) without bleeding. BIMS was associated with mortality (adjusted hazard ratio: 1.87; 95% confidence interval: 1.42–2.47). We estimated the proportion of 30-day postoperative deaths potentially attributable to BIMS to be 20.1–31.9%. ConclusionsBleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin <70 g L−1, blood transfusion, or that is judged to be the cause of death, is common and may account for a quarter of deaths after noncardiac surgery. Clinical trial registrationNCT00512109.

Fast track rehabilitation after reversed total shoulder arthroplasty: a protocol for an international multicentre prospective cohort study

IntroductionThe use of reversed total shoulder arthroplasty (rTSA) has increased because of an increasing number of indications for this procedure and by ageing of the population. Usual postoperative care consists...

Tracheal intubation in traumatic brain injury: a multicentre prospective observational study

BackgroundWe aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. MethodsData from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. ResultsIn the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79–1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65–1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. ConclusionThe benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. Clinical trial registrationNCT02210221.

Preoperative prediction of Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study

BackgroundDiagnostic criteria for Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS) have been defined as bleeding that leads to a postoperative haemoglobin <70 g L−1, leads to blood transfusion, or is judged to be the direct cause of death. Preoperative prediction guides for BIMS can facilitate informed consent and planning of perioperative care. MethodsIn a prospective cohort study of 16 079 participants aged ≥45 yr having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011, 17.3% (2782) experienced BIMS. An electronic risk calculator for BIMS was developed and internally validated by logistic regression with bootstrapping, and further simplified to a risk index. Decision curve analysis assessed the potential utility of each prediction guide compared with a strategy of identifying risk of BIMS based on preoperative haemoglobin <120 g L−1. ResultsWith information about the type of surgery, preoperative haemoglobin, age, sex, functional status, kidney function, history of high-risk coronary artery disease, and active cancer, the risk calculator accurately predicted BIMS (bias-corrected C-statistic, 0.84; 95% confidence interval, 0.837–0.852). A simplified index based on preoperative haemoglobin <120 g L−1, open surgery, and high-risk surgery also predicted BIMS, but less accurately (C-statistic, 0.787; 95% confidence interval, 0.779–0.796). Both prediction guides could improve decision making compared with knowledge of haemoglobin <120 g L−1 alone. ConclusionsBIMS, defined as bleeding that leads to a postoperative haemoglobin <70 g L−1, leads to blood transfusion, or that is judged to be the direct cause of death, can be predicted by a simple risk index before surgery. Clinical trial registrationNCT00512109.

Risks to healthcare workers following tracheal intubation of patients with COVID-19: a prospective international multicentre cohort study.

SummaryHealthcare workers involved in aerosol‐generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID‐19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID‐19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self‐reporting. The primary endpoint was the incidence of laboratory‐confirmed COVID‐19 diagnosis or new symptoms requiring self‐isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure‐related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow‐up of 32 (18–48 [0–116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID‐19 subsequently reported a COVID‐19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID‐19 transmission.

An International Prospective Cohort Study To Validate 2 Prediction Rules for Infections Caused by Third-generation Cephalosporin-resistant Enterobacterales.

BackgroundThe possibility of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric inappropriate treatment (IAT) and unnecessary carbapenem use (UCU). Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally validate 2 previously derived prediction rules for community-onset (CO) and hospital-onset (HO) suspected bloodstream infections.MethodsIn 33 hospitals in 13 countries we prospectively enrolled 200 patients per hospital in whom blood cultures were obtained and intravenous antibiotics with coverage for Enterobacterales were empirically started. Cases were defined as 3GC-R-BSI or 3GC-R gram-negative infection (3GC-R-GNI) (analysis 2); all other outcomes served as a comparator. Model discrimination and calibration were assessed. Impact on carbapenem use was assessed at several cutoff points.Results4650 CO infection episodes were included and the prevalence of 3GC-R-BSI was 2.1% (n = 97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398 of 4553 non–3GC-R-BSI patients (8.7%). Model calibration was good, and the AUC was .79 (95% CI, .75–.83) for 3GC-R-BSI. The prediction rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal. IAT and UCU in all 3GC-R-GNIs (analysis 2) improved at similar percentages. 1683 HO infection episodes were included and the prevalence of 3GC-R-BSI was 4.9% (n = 83). Here model calibration was insufficient.ConclusionsA prediction rule for CO 3GC-R infection was validated in an international cohort and could improve empirical antibiotic use. Validation of the HO rule yielded suboptimal performance.