George Tomlinson

BackgroundRealizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years.MethodsIn this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1–10 years old with documented haemoglobin SS or haemoglobin Sβ zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose …

Objective The objective of this study was to reduce the incidence of urinary tract infection (UTI) in women undergoing outpatient cystoscopy and/or urodynamic studies (UDS) at our centre by identifying and then altering modifiable risk factors through an analysis of incidence variability among physicians. Methods This was a quality improvement study involving adult women undergoing outpatient cystoscopy and/or UDS at an academic tertiary urogynecology practice. Prophylactic practices for cystoscopy/UDS were surveyed and division and physician‐specific UTI rates following cystoscopy/UDS were established. In consultation with key stakeholders, this delineated change concepts based on associations between prophylactic practices and UTI incidence, which were then implemented while monitoring counterbalance measures. Results Two “Plan‐Do‐Study‐Act‐Cycles” were conducted whereby 212 and 210 …

Background Co-Symptom Screening in Pediatrics Tool (co-SSPedi) is a dyadic (child-guardian) approach to symptom assessment. Objectives were to evaluate the reliability and validity of co-SSPedi for pediatric patients receiving cancer treatments. Methods This multicenter study included dyads of patients aged 4-18 years of age with cancer or undergoing hematopoietic cell transplant and their guardians. Two groups were enrolled. The more symptomatic group included those receiving active treatment for cancer or undergoing hematopoietic cell transplant where patients were in hospital or clinic for 4 consecutive days. The less symptomatic group included those receiving maintenance therapy for acute lymphoblastic leukemia or who had completed cancer treatments. At baseline, all dyads completed co-SSPedi, and guardians completed measures of mucositis, nausea …

IntroductionPatients with kidney failure with replacement therapy (KFRT) suffer premature cardiovascular (CV) mortality and events with few proven pharmacological interventions. Omega-3 polyunsaturated essential fatty acids (n-3 PUFAs) are associated with a reduced risk of CV events and death in non-dialysis patients and in patients with established CV disease but n-3 PUFAs have not been evaluated in the high risk KFRT patient population.Methods and analysisThis multicentre randomised, placebo controlled, parallel pragmatic clinical trial tests the hypothesis that oral supplementation with n-3 PUFA, when added to usual care, leads to a reduction in the rate of serious CV events in haemodialysis patients when compared with usual care plus matching placebo. A target sample size of 1100 KFRT patients will be recruited from 26 dialysis units in Canada and Australia and randomised to n-3 PUFA or matched …

Rationale: Outcomes for people with respiratory failure in the United States vary by patient race and ethnicity. Invasive ventilation is an important treatment initiated based on expert opinion. It is unknown whether the use of invasive ventilation varies by patient race and ethnicity. Objectives: To measure 1) the association between patient race and ethnicity and the use of invasive ventilation; and 2) the change in 28-day mortality mediated by any association. Methods: We performed a multicenter cohort study of nonintubated adults receiving oxygen within 24 hours of intensive care admission using the Medical Information Mart for Intensive Care IV (MIMIC-IV, 2008–2019) and Phillips eICU (eICU, 2014–2015) databases from the United States. We modeled the association between patient race and ethnicity (Asian, Black, Hispanic, White) and invasive ventilation rate using a Bayesian multistate model that adjusted for …

Aims Our aims were, in the setting of type 2 diabetes mellitus (T2DM) in pregnancy, to investigate the association of polycystic ovary syndrome (PCOS) with perinatal outcomes and to examine whether treatment with metformin had a differential effect in those with and without PCOS. Materials and Methods We performed a retrospective cohort study using the metformin in women with type 2 diabetes in pregnancy (MiTy) trial data. We examined differences in maternal and neonatal outcomes among MiTy participants with and without PCOS using linear and logistic regression to adjust for potential confounders. We additionally examined the relative difference in the effect of metformin treatment on pregnancy outcomes among MiTy participants with PCOS versus those without PCOS. Results Among women with T2DM in pregnancy, PCOS was significantly associated with higher excess gestational weight gain …

PurposeIntubation is a common procedure in acute hypoxemic respiratory failure (AHRF), with minimal evidence to guide decision-making. We conducted a survey of when to intubate patients with AHRF to measure the influence of clinical variables on intubation decision-making and quantify variability.MethodsWe developed an anonymous factorial vignette-based web survey to ask clinicians involved in the decision to intubate “Would you recommend intubation?” Respondents selected an ordinal recommendation from a 5-point scale ranging from “Definite no” to “Definite yes” for up to 10 randomly allocated vignettes. We disseminated the survey through clinical and academic societies, analyzed responses using Bayesian proportional odds modeling with clustering by individual, country, and region, and reported mean odds ratios (OR) with 95% credible intervals (CrI).ResultsBetween September 2023 and January 2024, 2,294 respondents entered 17,235 vignette responses in 74 countries [most common: Canada (29%), USA (26%), France (9%), Japan (8%), and Thailand (5%)]. Respondents were attending physicians (63%), nurses (13%), trainee physicians (9%), respiratory therapists (9%), other (6%). Lower oxygen saturation, higher inspired oxygen fraction, non-invasive ventilation compared to high-flow, tachypnea, neck muscle use, abdominal paradox, drowsiness, and inability to obey were associated with increased odds of intubation; diagnosis, vasopressors, and duration of symptoms were not. Within a country the odds of recommending intubation changed between clinicians by an average factor of 2.60, while changing between …

State‐of‐the‐art biostatistics methods allow for the simultaneous modeling of several correlated non‐fatal disease processes over time, but there is no clear guidance on the optimal analysis in most settings. An example occurs in diabetes, where it is not known with certainty how microvascular complications of the eyes, kidneys, and nerves co‐develop over time. In this article, we propose and contrast two general model frameworks for studying complications (sequential state and parallel trajectory frameworks) and review multivariate methods for their analysis, focusing on multistate and joint modeling. We illustrate these methods in a tutorial format using the long‐term follow‐up from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study public data repository. A formal comparison of prediction error and discrimination is included. Multistate models are …

Following publication of the original article [1], the authors identified errors in the Additional file 1. The Figures on pages 15, 16 of the Additional file 1 (S2 and S3) have been corrected and some minor corrections to the table of contents were made. The correct Additional file 1 file is included in this article.

Objective: This study sought to determine if a presacral nerve (PSN) block affects early postoperative pain, opioid use, and rates of urinary retention after laparoscopic hysterectomy. Materials and Methods: Patients who had elective total laparoscopic hysterectomy (TLH) without histories of chronic pain or opioid use were assigned randomly to either a PSN block of 10 mL of 0.5% bupivacaine or a sham block of 10 mL normal saline post surgery. The primary outcome was pain assessed on a visual analogue scale (VAS) at 3 hours postoperatively and secondary outcomes included pain at 1, 2, and 3 hours, and opioid use post surgery. Participant recruitment was halted due to cancellation of elective surgeries during the COVID-19 pandemic, and, therefore, the data of the patients who were already recruited, was analyzed as an interim analysis for a pilot study design. Results: Thirty-four patients were recruited …

Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a longitudinal Phase I/II trial of hydroxyurea in children with SCA from Angola, Democratic Republic of Congo, Kenya, and Uganda. After enrollment, children had a two‐month pre‐treatment screening period followed by 6 months of fixed‐dose hydroxyurea (15–20 mg/kg/day), 18 months of dose escalation, and then stable dosing at maximum tolerated dose (MTD). Characteristics associated with transfusions were analyzed with univariate and multivariable models. Transfusion incidence rate ratios …

Aims: We evaluated attainment of the hemoglobin A1c (HbA1c) target of ≤7.0%, its temporal trends, and associated factors among adults with type 1 diabetes in Ontario, Canada, using administrative data. Methods: We conducted a retrospective cohort study, including Ontarians with type 1 diabetes ≥18 years old with ≥1 HbA1c test between April 1, 2012 (fiscal year 2013), and March 31, 2023. Generalized estimating equations were used to determine probabilities of meeting the HbA1c target, as well as associations between fiscal year and individual-, physician-, and system-level factors on odds of meeting the target. Results: Among 28,827 adults with type 1 diabetes [14,385 (49.9%) female, 17,998 (62.4%) pump users], with median age at index of 25 years [interquartile range (IQR) 18–37] and median diabetes duration of 12 years [6–18], there were 474,714 HbA1c tests [median 2/individual/year (IQR: 1–3 …

Rationale Intravenous sedation is an important tool for managing invasively ventilated patients, yet excess sedation is harmful, and dosing could be influenced by implicit bias. Objective To measure the association between sex, race and ethnicity, and sedation practices. Methods We performed a retrospective cohort study of adults receiving invasive ventilation for 24 hours or more using the MIMIC-IV (2008-2019) database from Boston, USA. We used a repeated-measures design (4-hour time intervals) to study the association between patient sex (female, male) or race and ethnicity (Asian, Black, Hispanic, White) and sedation outcomes. Sedation outcomes included sedative use (propofol, benzodiazepine, dexmedetomidine) and minimum sedation score. We divided sedative use into five categories: no sedative given, then lowest, second, third, and highest quartiles of sedative dose. We used multilevel Bayesian proportional odds modeling to adjust for baseline and time-varying covariates and reported posterior odds ratios with 95% credible intervals [CrI]. Results We studied 6,764 patients: 43% female; 3.5% Asian, 12% Black, 4.5% Hispanic and 80% white. We analyzed 116,519 4-hour intervals. Benzodiazepines were administered to 2,334 (36%) patients. Black patients received benzodiazepines less often and at lower doses than White patients (OR 0.66, CrI 0.49 to 0.92). Propofol was administered to 3,865 (57%) patients. Female patients received propofol less often and at lower doses than male patients (OR 0.72, CrI 0.61 to 0.86). Dexmedetomidine was administered to 1,439 (21%) patients, and use was largely similar across sex or …

IntroductionIndividuals with sickle cell disease (SCD) and central venous catheters (CVC) are at high risk for venous thromboembolism (VTE). Minimal data exist regarding the use of anticoagulation as thromboprophylaxis of VTE in this demographic, and as a result, clinical equipoise exists. Prophylactic dose rivaroxaban, a direct oral anticoagulant, is efficacious and safe as thromboprophylaxis in other demographics, and may be an optimal agent in SCD with CVC. Prior to conducting a full clinical trial to assess rivaroxaban as thromboprophylaxis in SCD with CVC, a pilot study is needed to gauge its feasibility.Methods and analysisTHromboprophylaxis In Sickle Cell Disease pilot trial is an investigator-initiated, multicentre, double-blinded, randomised controlled trial (RCT) assessing if it is feasible and safe to conduct an adequately powered RCT comparing rivaroxaban to matching placebo as thromboprophylaxis …

IntroductionOlder adults with metastatic prostate cancer (mPC) experience high symptom burden associated with treatment. Frailty may exacerbate treatment toxicity. The aim of this study was to explore short-term treatment toxicity in patients with metastatic prostate cancer.Materials and MethodsOlder adults with metastatic prostate cancer starting chemotherapy, androgen-receptor-axis targeted therapies, or radium-223 participated in a prospective, multicentre, observational study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment System for one treatment cycle via internet or telephone. The most common moderate-to-severe symptoms (score≥4), their duration, and the proportion of participants who experienced improvements in symptom severity (score<4) after reporting moderate-to-severe symptoms at baseline were determined using descriptive statistics. Once-weekly …

Introduction Patients with kidney failure with replacement therapy (KFRT) suffer premature cardiovascular (CV) mortality and events with few proven pharmacological interventions. Omega-3 polyunsaturated essential fatty acids (n-3 PUFAs) are associated with a reduced risk of CV events and death in non-dialysis patients and in patients with established CV disease but n-3 PUFAs have not been evaluated in the high risk KFRT patient population.Methods and analysis This multicentre randomised, placebo controlled, parallel pragmatic clinical trial tests the hypothesis that oral supplementation with n-3 PUFA, when added to usual care, leads to a reduction in the rate of serious CV events in haemodialysis patients when compared with usual care plus matching placebo. A target sample size of 1100 KFRT patients will be recruited from 26 dialysis units in Canada and Australia and randomised to n-3 PUFA or matched …

BackgroundSedation management has a major impact on outcomes in mechanically ventilated patients, but sedation strategies do not generally consider the differential effects of different sedatives on respiration and respiratory pattern. A systematic review was undertaken to quantitatively summarize the known effects of different classes of drugs used for sedation on respiratory pattern during both spontaneous breathing and assisted mechanical ventilation.MethodsThis was a systematic review and meta-analysis conducted using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials up to June 2020 to retrieve studies that measured respiratory parameters before and after the administration of opioids, benzodiazepines, intravenous and inhaled anaesthetic agents, and other hypnotic agents (PROSPERO #CRD42020190017). A random-effects …

IntroductionDifferences between health outcomes, participation/adoption, and cost-effectiveness of home-based (HOME) interventions and supervised group-based training (GROUP) in men with prostate cancer (PC) on androgen deprivation therapy (ADT) are currently unknown. The objective of this study was to assess the clinical efficacy, adherence, and cost-effectiveness of HOME versus GROUP in men on ADT for PC.Materials and MethodsThis was a multicentre, 2-arm non-inferiority randomized controlled trial and companion cost-effectiveness analysis. Men with PC on ADT were recruited from August 2016 to March 2020 from four Canadian centres and randomized 1:1 to GROUP or HOME. All study participants engaged in aerobic and resistance training four to five days weekly for six months. Fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F)] and functional endurance [6-min walk test …

INTRODUCTION AND OBJECTIVEBladder cancer (BCa) and its treatments have significant impacts on patient quality of life (QOL) and decision-making. To facilitate comparative effectiveness research, a BCa specific tool to measure both quality of life and utilities is required. We previously created and validated the Bladder Utility Symptom Scale (BUSS)-Psychometric (P), a 10-item multiple-choice questionnaire to measure QOL in all phases of BCa care. Our objective was to create two distinct algorithms to calculate utilities from BUSS-P responses.METHODSWe conducted in-person interviews with 200 BCa patients and 200 members of the general public. Purposeful sampling was used to ensure proportionate numbers of non-muscle invasive (NMIBC), muscle invasive (MIBC) and metastatic BCa patients. The general public sample was recruited proportionate to national age, sex, and income distributions. Each …

Comparing manual versus multi-model pulse oximeter measurements for temperature and respiratory rate in malnourished children Comparing manual versus multi-model pulse oximeter measurements for temperature and respiratory rate in malnourished children Acta Paediatr. 2024 Mar 26. doi: 10.1111/apa.17216. Online ahead of print. Authors Nancy M Dale 1 2 3 4 , Youssouf Djidita Hagre 5 , Laurent Dcbtanne 6 , George Tomlinson 7 8 , Susan Shepherd 6 , Stanley Zlotkin 1 2 9 , Christopher Parshuram 2 3 10 Affiliations 1 Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada. 2 Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Ontario, Canada. 3 Center for Safety Research, Toronto, Ontario, Canada. 4 Tampere Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University and Tampere …