As bispecific T-cell engagers (TCEs) gain traction in the oncology treatment landscape, cancer centres must develop robust clinical pathways to ensure their safe and efficient delivery. Given the limited experience of the Canadian medical oncology community with TCEs, collecting and publishing early clinical experiences with these novel agents will be essential to inform best practices and support their safe and effective adoption across the broader Canadian oncology community. The approval of tarlatamab, the first-in-class delta-like ligand 3 (DLL3)-targeted TCE for extensive-stage small cell lung cancer (ES-SCLC), underscores the importance of sharing early clinical experience with this agent, particularly given its unique safety profile, specific monitoring requirements, and use in a population that often has multiple comorbidities. Like other TCEs, tarlatamab is associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), adverse events (AEs) that necessitate the development of dedicated protocols by medical oncologists and multidisciplinary inpatient and outpatient clinical teams to ensure prompt recognition and management of these associated toxicities. By sharing insights into administration protocols, dose ramp-up procedures, post-cycle 1 monitoring, and AE management strategies implemented at their centres, early adopters of tarlatamab can help other institutions develop and refine their own protocols more efficiently. Lessons learned during the early implementation phase, including the roles of various healthcare providers and the transition from inpatient to outpatient care, should facilitate the smoother integration of tarlatamab and other TCEs for solid tumours into clinical pathways across Canada.
RATIONALE:Identifying patients who could be safely managed at home versus those needing hospitalisation was a particular concern during early COVID-19. Respiratory viruses remain a concern, including new COVID-19 variants, influenza and respiratory syncytial virus. We developed COVIDFree@Home, a mobile application and clinician dashboard for remote monitoring, to determine if remotely collected measures could predict low oxygen saturation in home-isolating patients with COVID-19. METHODS:We conducted a prospective cohort study of patients newly diagnosed with COVID-19 from three Toronto hospitals between 2020 and 2022. Participants used the COVIDFree@Home app daily to enter symptoms, temperature, heart rate and oxygen saturation at home, which clinicians monitored via an online dashboard. We analysed baseline characteristics and remote monitoring variables to identify predictors of oxygen saturation ≤92%. A random forest classifier was trained to predict low oxygen saturation in the following 2 days. A secondary objective was to identify factors predicting hospitalisation. RESULTS:Of 431 participants, 376 (87.2%) entered at least one measure. Of the 376, 49 (13%) experienced low oxygen saturation, and 19 (5.1%) were hospitalised. Baseline factors associated with low oxygen saturation included older age, obesity, pre-existing pulmonary disease and Alpha/Beta variant. The classifier predicted future low oxygen saturation with an area under the curve of 0.68 (sensitivity 57%, specificity 72%, positive predictive value 3%, negative predictive value 99%). Key predictive factors included cough, lower baseline oxygen saturation, severe fatigue, higher temperature and higher heart rate. Factors associated with hospitalisation included dyspnoea, fever, Alpha/Beta variant and comorbidities of hypertension, mental illness and diabetes. Patients with a runny nose or sore throat were less likely to be hospitalised. CONCLUSIONS:During the COVID-19 pandemic, remote monitoring along with knowledge of baseline characteristics could predict low oxygen saturation in the next 2 days in people with COVID-19. This approach may help identify individuals needing medical attention during future pandemics, though further model improvement is necessary. TRIAL REGISTRATION NUMBER:NCT04453774.
BACKGROUND:Pneumococcal infections are an important cause of morbidity and mortality, and a major contributor to the burden of antimicrobial resistance (AMR). Multiple factors affect AMR in pneumococci. METHODS:The Toronto Invasive Bacterial Diseases Network (TIBDN) conducted population-based surveillance for invasive pneumococcal disease (IPD) and hospitalization due to non-bacteremic pneumococcal pneumonia (NBPP) in Toronto/Peel Region, Ontario. Laboratories reported sterile site and respiratory isolates of Streptococcus pneumoniae. Patient data were collected by chart review and patient/physician interview. Population data were from Statistics Canada. Antimicrobial susceptibility testing was performed/interpreted per Clinical and Laboratory Standards Institute guidelines and/or by prediction from whole genome sequencing (WGS). Serotyping was performed by Quellung reaction or WGS. RESULTS:From 2014 to 2024, 3881 episodes of IPD and 887 of NBPP were identified. Resistance was most common to macrolides (31.4%, 1285/4086), tetracyclines (17.4%, 653/3756), penicillin (meningeal breakpoints: 17.2%, 749/4354), clindamycin (12.3%, 472/3823) and trimethoprim-sulfamethoxazole (12.6%, 495/3929); resistance to ceftriaxone (meningeal breakpoints) and levofloxacin was <1%. Resistance declined over time for ceftriaxone, fluoroquinolones, and erythromycin but increased for oral penicillin, tetracycline and trimethoprim-sulfamethoxazole. Non-susceptibility to ceftriaxone (meningeal breakpoints) increased. Non-susceptibility to ceftriaxone (OR 3.7, 95%CI 2.6-5.3) and resistance to erythromycin (OR 1.3, 95%CI 1.0-1.5) were more common in NBPP than IPD, and in hospital- versus community-acquired disease (ORs 2.0, 95%CI 1.3-3.0 and 1.9, 95%CI 1.4-2.5, respectively). Levofloxacin non-susceptibility was higher in long-term-care-acquired disease (OR 6.3, 95%CI 2.1-19). Recent antibiotic use was associated with increased resistance to the same antibiotic class. Ceftriaxone and erythromycin resistance were most common in 7-valent pneumococcal conjugate vaccine (PCV7) serotypes. Resistance to any antibiotic was not different in isolates of serotypes included in PCV20 versus PCV21. CONCLUSIONS:In our population, pneumococcal antimicrobial resistance has remained relatively stable, but changes differ by antibiotic class. Implementation of vaccination programs with PCV20 or PCV21 should reduce AMR by disease prevention.
OBJECTIVES:Observational studies suggest that acid suppression may worsen outcomes among patients infected with SARS-CoV-2. The objectives of this embedded substudy of a randomised controlled trial evaluating pantoprazole in mechanically ventilated patients were to (1) describe the clinical characteristics of critically ill patients with SARS-CoV-2, (2) compare clinical outcomes with a propensity-matched non-infected cohort and (3) assess whether pantoprazole's treatment effects differed by SARS-CoV-2 infection status. DESIGN:A pre-planned substudy of the re-evaluating the inhibition of stress erosions (REVISE) trial, including a propensity-matched analysis of infected and non-infected patients comparing the effect of pantoprazole between patients with and without SARS-CoV-2. SETTING:68 intensive care units (ICUs) in eight countries. PARTICIPANTS:From July 2019 to October 2023, 4821 eligible participants were enrolled in REVISE whether or not they had SARS-CoV-2 infection. PRIMARY AND SECONDARY OUTCOME MEASURES:Participants enrolled in REVISE with SARS-CoV-2 infection had additional data collection, including biomarkers, venous thromboembolism, SARS-CoV-2 therapies and tracheostomy timing. The primary outcomes were clinically important upper gastrointestinal bleeding and 90-day mortality. Secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, patient-important upper GI bleeding, renal replacement therapy, ICU and hospital mortality and duration of mechanical ventilation, ICU and hospital stay. RESULTS:Of the eligible trial cohort, 11.9% (540/4550) had SARS-CoV-2; 532 patients had additional SARS-CoV-2-specific data collection. Of these 532 patients, 87.8% received COVID-19-directed treatments-(dexamethasone 75.2%), 11.7% developed pulmonary embolism and 9.2% developed deep-vein thrombosis. After propensity matching, SARS-CoV-2 infection was not associated with clinically important upper gastrointestinal bleeding (adjusted HR 0.78, 95% CI 0.40 to 1.50) but was associated with significantly higher ICU, hospital and 90-day mortality, as well as longer duration of ventilation and ICU and hospital length of stay. The effect of pantoprazole on clinically important upper GI bleeding and 90-day mortality was consistent regardless of SARS-CoV-2 status. CONCLUSIONS:SARS-CoV-2 infection was associated with higher mortality and longer duration of mechanical ventilation, ICU and hospital stays, without an increased risk of clinically important upper gastrointestinal bleeding. Pantoprazole reduced clinically important upper gastrointestinal bleeding without adversely affecting other outcomes. TRIAL REGISTRATION NUMBER:REVISE trial (NCT03374800), SARS-CoV-2 cohort study (NCT05715567).
(1) Background: Genomic medicine—i.e., the use of laboratory-based biomarkers that measure the expression, function and regulation of genes and gene products to aid healthcare decision making is a rapidly emerging technology. Readiness to consider and adopt new testing programs effectively and avoid critical challenges requires health systems to harbor a number of key conditions that address infrastructural, as well operational and other needs. This assessment re-examines Canada’s state of readiness since a previously published 2023 assessment. (2) Methods: A mixed-methods approach of a review of the literature and key informant interviews with a purposive sample of experts was used. Health system readiness was assessed using a previously published set of conditions. (3) Results: This updated analysis of Canada’s state of readiness for genetic and genomic testing reveals Canada is only partially ready for a future of genomic medicine, although some progress has been made since 2023. The most established conditions were the use of appropriate service models and the integration of innovation and healthcare delivery functions. They suggest that Canada’s major healthcare regions are moving closer to a state of readiness for the consideration and adoption of new testing required for genomic medicine, although using different approaches and at different rates. These findings should be seen as generalizable to other regions internationally—health systems need to have functions that promote responsiveness and resilience, i.e., are able to recognize valuable innovation and quickly shift priorities and create conditions necessary to enable it.
