Quality of life and cost-effectiveness of convalescent plasma compared to standard care for hospitalized COVID-19 patients in the CONCOR-1 trial.

BACKGROUND: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings. METHODS: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population. RESULTS: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078. DISCUSSION: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19.

Follow-up blood cultures do not reduce mortality in hospitalized patients with Gram-negative bloodstream infection: a retrospective population-wide cohort study.

OBJECTIVES: The utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit but may be limited by single-centre designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. METHODS: Adult patients with GN-BSI hospitalized between April 2017 and December 2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay, and number of days alive and out of hospital at 30 and 90 days. RESULTS: Thirty-four thousand one hundred patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range, 10.0-29.7%; range, 0-66.1%) across 101 hospitals; this correlated with positivity and contamination rate. Eight hundred ninety (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully adjusted model, there was no association between FUBC and mortality (hazard ratio, 0.97; 95% CI, 0.90-1.04). Patients with FUBC had significantly longer length of stay (median, 11 vs. 7 days; adjusted risk ratio, 1.18; 95% CI, 1.16-1.21) and fewer number of days alive and out of hospital at 30 and 90 days. DISCUSSION: FUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC.

Sepsis policy, guidelines and standards in Canada: a jurisdictional scoping review protocol.

INTRODUCTION: To our knowledge, this study is the first to identify and describe current sepsis policies, clinical practice guidelines, and health professional training standards in Canada to inform evidence-based policy recommendations. METHODS AND ANALYSIS: This study will be designed and reported according to the Arksey and O'Malley framework for scoping reviews and the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews. EMBASE, CINAHL, Medline, Turning Research Into Practice and Policy Commons will be searched for policies, clinical practice guidelines and health professional training standards published or updated in 2010 onwards, and related to the identification, management or reporting of sepsis in Canada. Additional sources of evidence will be identified by searching the websites of Canadian organisations responsible for regulating the training of healthcare professionals and reporting health outcomes. All potentially eligible sources of evidence will be reviewed for inclusion, followed by data extraction, independently and in duplicate. The included policies will be collated and summarised to inform future evidence-based sepsis policy recommendations. ETHICS AND DISSEMINATION: The proposed study does not require ethics approval. The results of the study will be submitted for publication in a peer-reviewed journal and presented at local, national and international forums.

Can Decision Support Tools Improve Empiric Antibiotic Prescribing?

Decision Support Tools for Antibiotic PrescribingChoosing the right antibiotic is challenging. Unnecessarily broad-spectrum antibiotic treatment promotes antimicrobial resistance; inappropriately narrow-spectrum antibiotic use can lead to treatment failure. A cluster-randomized trial of a model-informed clinical decision support tool is proposed for guiding empiric antibiotic therapy for hospitalized patients with suspected infection.

Documenting the indication for antimicrobial prescribing: A retrospective observational study of long-term care homes.

BACKGROUND: Overuse of antimicrobials in residents of long-term care homes is common and can result in harm. Antimicrobial stewardship interventions are needed in the long-term care (LTC) homes setting to improve the appropriate use of antimicrobials. Previous literature has highlighted the importance of documenting antimicrobial indication as a strategy that contributes to improve antimicrobial use; however, there is a lack of evidence in LTC homes. This study examines the prevalence, clarity, and facility-level variability of antibiotic indication documentation in this setting. METHODS: This is an observational retrospective study of oral antibiotic prescriptions dispensed to 218 homes between January 1 2021 and December 31 2022 in Ontario, Canada. Indication was obtained from reviewing antibiotic prescription data. Clarity was determined by comparing documented indication to the National Antimicrobial Prescribing Survey (NAPS). Descriptive analysis was performed to examine the prevalence and clarity of indication documentation. Funnel plots were generated to examine variability in prevalence of indication documentation and clarity at the home level. RESULTS: Overall, 22.9% (7998/34,867) of prescriptions had an indication documented. The proportion of indications that were clear was 37% (2984/7998). The most common indications were for urinary (45%), skin and soft tissue (19.9%) and respiratory infections (15.0%). At the home level, the median prevalence of indication was 19.6% (interquartile range [IQR]: 10.8%-31.4%) and median prevalence of clear indications was 35.1% (IQR: 23.8%-42.9%). Funnel plots revealed substantial variability in indication prevalence with 46.3% of homes falling outside of 99% limits but minimal variability in indication clarity between homes with only 8.7% of homes outside of 99% control limits. CONCLUSIONS: There is an opportunity to increase both the prevalence and clarity of antibiotic prescriptions in LTC homes. Future work should focus on determining how best to support prescription indication documentation in this setting with consideration being given to prescription workflow and most common antibiotic prescription indications.

Predictors of later COVID-19 test seeking.

Background: Delays in COVID-19 testing may increase the risk of secondary household and community transmission. Little is known about what patient characteristics and symptom profiles are associated with delays in test seeking. Methods: We conducted a retrospective cohort study of all symptomatic patients diagnosed with COVID-19 and assessed in a COVID Expansion to Outpatients (COVIDEO) virtual care program between March 2020 and June 2021. The primary outcome was later test seeking more than 3 days from symptom onset. Multivariable logistic regression was used to examine predictors of later testing including patient characteristics and symptoms (30 individual symptoms or 7 symptom clusters). Results: Of 5,363 COVIDEO patients, 4,607 were eligible and 2,155/4,607 (46.8%) underwent later testing. Older age was associated with increased odds of late testing (adjusted odds ratio [aOR] 1.007/year; 95% CI 1.00 to 1.01), as was history of recent travel (aOR 1.4; 95% CI 1.01 to 1.95). Health care workers had lower odds of late testing (aOR 0.50; 95% CI 0.39 to 0.62). Late testing was associated with symptoms in the cardiorespiratory (aOR 1.2; 95% CI 1.05, 1.36), gastrointestinal (aOR = 1.2; 95% CI 1.04, 1.4), neurological (aOR 1.1; 95% CI 1.003, 1.3) and psychiatric (aOR 1.3; 95% CI 1.1, 1.5) symptom clusters. Among individual symptoms, dyspnea, anosmia, dysgeusia, sputum, and anorexia were associated with late testing; pharyngitis, myalgia, and headache were associated with early testing. Conclusion: Certain patient characteristics and symptoms are associated with later testing, and warrant further efforts to encourage earlier testing to minimize transmission.

Historique: Les retards à effectuer les tests de dépistage de la COVID-19 peuvent accroître le risque de transmission secondaire dans la famille et la communauté. On ne sait pas vraiment quels sont les caractéristiques des patients et leurs profils de symptômes associés aux retards à se faire dépister. Méthodologie: Les chercheurs ont réalisé une étude de cohorte auprès de tous les patients symptomatiques ayant obtenu un diagnostic de COVID-19 évalués dans le cadre du programme de soins virtuels COVID Expansion to Outpatients (COVIDEO, ou expansion de la COVID aux patients ambulatoires) entre mars 2020 et juin 2021. Le résultat primaire était une demande de dépistage plus de trois jours après l'apparition des symptômes. Les chercheurs ont utilisé la régression logistique multivariable pour examiner les prédicteurs d'un dépistage tardif, y compris les caractéristiques et les symptômes des patients (30 symptômes individuels ou sept grappes de symptômes). Résultats: Des 5 363 patients ayant participé au programme COVIDEO, 4 607 étaient admissibles et 2 155 de ces 4 607 (46,8 %) se sont soumis à un dépistage tardif. Une plus grande probabilité de dépistage tardif était liée à un âge avancé (rapport de cotes corrigé [RCc] 1,007/année, IC à 95 %, 1,00 à 1,01), de même qu'à un voyage récent (RCc = 1,4, IC à 95 %, 1,01 à 1,95). Les travailleurs de la santé étaient moins susceptibles de se faire dépister tardivement (RCc = 0,50, IC à 95 %, 0,39 à 0,62). Le dépistage tardif était associé à des symptômes de la grappe cardiorespiratoire (RCc = 1,2, IC à 95 %, [1,05, 1,36]), gastrointestinale (RCc = 1,2, IC à 95 %, [1,04, 1,4]), neurologique (RCc = 1,1, IC à 95 %, [1,003, 1,3]) et psychiatrique (RCc = 1,3, IC à 95 %, [1,1, 1,5]). Parmi les symptômes individuels, la dyspnée, l'anosmie, la dysgueusie, les expectorations et l'anorexie étaient associées à un dépistage tardif, et la pharyngite, les myalgies et les céphalées, à un dépistage précoce. Conclusion: Certaines caractéristiques des patients et certains symptômes étaient associés à un dépistage tardif, ce qui justifie des efforts supplémentaires pour favoriser un dépistage plus rapide afin de limiter la transmission. Summary: This study of more than 4,000 patients with COVID-19 identified predictors of later test seeking, including older age, recent travel, non-health care worker occupation, cardiorespiratory, gastrointestinal, neurologic and psychiatric symptom clusters, and dyspnea, anosmia, dysgeusia, sputum, and anorexia.

Evaluating the impact of a SIMPlified LaYered consent process on recruitment of potential participants to the Staphylococcus aureus Network Adaptive Platform trial: study protocol for a multicentre pragmatic nested randomised clinical trial (SIMPLY-SNAP trial).

INTRODUCTION: Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity. METHODS AND ANALYSIS: SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06168474; www. CLINICALTRIALS: gov).

Association of delayed adequate antimicrobial treatment and organ dysfunction in pediatric bloodstream infections.

BACKGROUND: Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores. METHODS: We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment. RESULTS: Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8-20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference -0.07, 95% CI -0.92 to 0.79, p = 0.88). CONCLUSIONS: We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment. IMPACT: In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h. Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures. Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research.

Antibiotic treatment durations for pyogenic liver abscesses: A systematic review.

Background: We sought to systematically review the existing research on pyogenic liver abscesses to determine what data exist on antibiotic treatment durations. Methods: We conducted a systematic review and meta-analysis of contemporary medical literature from 2000 to 2020, searching for studies of pyogenic liver abscesses. The primary outcome of interest was mean antibiotic treatment duration, which we pooled by random-effects meta-analysis. Meta-regression was performed to examine characteristics influencing antibiotic durations. Results: Sixteen studies (of 3,933 patients) provided sufficient data on antibiotic durations for pooling in meta-analysis. Mean antibiotic durations were highly variable across studies, from 8.4 (SD 5.3) to 68.9 (SD 30.3) days. The pooled mean treatment duration was 32.7 days (95% CI 24.9 to 40.6), but heterogeneity was very high (I2 = 100%). In meta-regression, there was a non-significant trend towards decreased mean antibiotic treatment durations over later study years (-1.14 days/study year [95% CI -2.74 to 0.45], p = 0.16). Mean treatment duration was not associated with mean age of participants, percentage of infections caused by Klebsiella spp, percentage of patients with abscesses over 5 cm in diameter, percentage of patients with multiple abscesses, and percentage of patients receiving medical management. No randomized trials have compared treatment durations for pyogenic liver abscess, and no observational studies have reported outcomes according to treatment duration. Conclusions: Among studies reporting on antibiotic durations for pyogenic liver abscess, treatment practices are highly variable. This variability does not seem to be explained by differences in patient, pathogen, abscess, or management characteristics. Future RCTs are needed to guide optimal treatment duration for patients with this complex infection.

Historique: Les chercheurs ont procédé à l'analyse systématique des recherches sur les abcès hépatiques pyogènes afin de découvrir les données sur la durée de l'antibiothérapie. Méthodologie: Les chercheurs ont réalisé une analyse systématique et une méta-analyse des publications médicales parues entre 2000 et 2020 pour en extraire les études sur les abcès hépatiques pyogènes. Le résultat primaire était la durée moyenne de l'antibiothérapie, qu'ils ont regroupée par méta-analyse à effets aléatoires. Ils ont procédé à une méta-régression pour examiner les caractéristiques qui influent sur la durée de l'antibiothérapie. Résultats: Seize études (auprès de 3 933 patients) contenaient assez de données sur la durée de l'antibiothérapie pour être regroupées dans la méta-analyse. La durée moyenne de l'antibiothérapie était très variable d'une étude à l'autre, de 8,4±5,3 à 68,9±30,3 jours. La durée moyenne du traitement regroupé était de 32,7 jours (IC à 95 %, 24,9 à 40,6 jours), mais l'hétérogénéité était très élevée (I2 = 100 %). La méta-régression a révélé une tendance non significative vers une durée moins longue de l'antibiothérapie moyenne pendant les dernières années de l'étude (−1,14 jour par année d'étude, IC à 95 %, −2,74+0,45, p = 0,16). La durée moyenne du traitement n'était pas associée à l'âge moyen des participants, au pourcentage d'infections causées par les espèces de Klebsiella, au pourcentage de patients ayant un abcès de plus de cinq centimètres de diamètre, au pourcentage de patients ayant de multiples abcès et au pourcentage de patients recevant une prise en charge médicale. Aucune étude randomisée n'avait comparé la durée du traitement de l'abcès hépatique pyogène, et aucune étude observationnelle n'avait rendu compte des résultats cliniques en fonction de la durée du traitement. Conclusions: Dans les études sur la durée de l'antibiothérapie des abcès hépatiques pyogènes, les pratiques thérapeutiques sont très variables. Cette variabilité ne semble pas s'expliquer par les différences entre les patients, les agents pathogènes, les abcès ou les caractéristiques de prise en charge. Des études randomisées et contrôlées devront être réalisées pour obtenir des indications quant à la durée optimale du traitement chez les patients atteints de cette infection complexe.

A sepsis treatment algorithm to improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS): A prospective observational study.

BACKGROUND: Empiric antibiotic treatment selection should provide adequate coverage for potential pathogens while minimizing unnecessary broad-spectrum antibiotic use. We sought to pilot a sepsis treatment algorithm to individualize antibiotic recommendations, and thereby improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS). METHODS: In this observational study, the Early-IDEAS decision support algorithm was derived from previous Gram- negative and Gram-positive prediction rules and models along with local guidelines, and then applied to prospectively identified consecutive adults within 24 hours of suspected sepsis. The primary outcome was the proportion of patients for whom de-escalation of the primary antibiotic regimen was recommended by the algorithm. Secondary outcomes included: (1) proportion of patients for whom escalation was recommended; (2) number of recommended de-escalation steps along a pre-specified antibiotic cascade; and (3) adequacy of therapy in patients with culture-confirmed infection. RESULTS: We screened 578 patients, of whom 107 eligible patients were included. The Early-IDEAS treatment recommendation was informed by Gram-negative models in 76 (71%) patients, Gram-positive rules in 64 (59.8%), and local guidelines in 27 (25.2%). Antibiotic de-escalation was recommended in almost half of all patients (n = 52, 48.6%), with a median of 2 steps down the a priori antibiotic treatment cascade. No treatment change was recommended in 45 patients (42.1%), and escalation was recommended in 10 (9.3%). Among the 17 patients with positive blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage for the isolated pathogen in 12 patients (70.6%), (p = 1). Among the 25 patients with positive relevant, non-blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage in 20 (80%), (p = 1). CONCLUSION: An individualized decision support algorithm in early sepsis could lead to substantial antibiotic de-escalation without compromising adequate antibiotic coverage.

Patient predictors of pathogenic versus commensal Gram-positive bacilli organisms isolated from blood cultures.

Objective: Gram-positive bacilli represent a diverse species of bacteria that range from commensal flora to pathogens implicated in severe and life-threatening infection. Following the isolation of Gram-positive bacilli from blood cultures, the time to species identification may take upward of 24 hours, leaving clinicians to conjecture whether they may represent a contaminant (inadvertent inoculation of commensal flora) or pathogenic organism. In this study, we sought to identify patient variables that could help predict the isolation of contaminant versus pathogenic Gram-positive bacilli from blood cultures. Design: Retrospective cohort study. Settings: One quaternary academic medical center affiliated with the University of Toronto. Patients: Adult inpatients were admitted to hospital over a 5-year period (May 2014 to December 2019). Methods: A total of 260 unique Gram-positive bacilli blood culture results from adult inpatients were reviewed and analyzed in both a univariable and multivariable model. Results: Malignancy (aOR 2.78, 95% CI 1.33-5.91, p = 0.007), point increments in the Quick Sepsis Related Organ Failure Assessment score for sepsis (aOR 2.25, 95% CI 1.50-3.47, p < 0.001), peptic ulcer disease (aOR 5.63, 95% CI 1.43-21.0, p = 0.01), and the receipt of immunosuppression prior to a blood culture draw (aOR 3.80, 95% CI 1.86-8.01, p < 0.001) were associated with an increased likelihood of speciating pathogenic Gram-positive bacilli from blood cultures such as Clostridium species and Listeria monocytogenes. Conclusion: Such predictors can help supplement a clinician's assessment on determining when empirical therapy is indicated when faced with Gram-positive bacilli from blood cultures and may direct future stewardship interventions for responsible antimicrobial prescribing.

The impact of the COVID-19 pandemic on blood culture practices and bloodstream infections.

IMPORTANCE: Bacterial infections are a significant cause of morbidity and mortality worldwide. In the wake of the COVID-19 pandemic, previous studies have demonstrated pandemic-related shifts in the epidemiology of bacterial bloodstream infections (BSIs) in the general population and in specific hospital systems. Our study uses a large, comprehensive data set stratified by setting [community, long-term care (LTC), and hospital] to uniquely demonstrate how the effect of the COVID-19 pandemic on BSIs and testing practices varies by healthcare setting. We showed that, while the number of false-positive blood culture results generally increased during the pandemic, this effect did not apply to hospitalized patients. We also found that many infections were likely under-recognized in patients in the community and in LTC, demonstrating the importance of maintaining healthcare for these groups during crises. Last, we found a decrease in infections caused by certain pathogens in the community, suggesting some secondary benefits of pandemic-related public health measures.

Variability in changes in physician outpatient antibiotic prescribing from 2019 to 2021 during the COVID-19 pandemic in Ontario, Canada.

Objective: To evaluate inter-physician variability and predictors of changes in antibiotic prescribing before (2019) and during (2020/2021) the coronavirus disease 2019 (COVID-19) pandemic. Methods: We conducted a retrospective cohort analysis of physicians in Ontario, Canada prescribing oral antibiotics in the outpatient setting between January 1, 2019 and December 31, 2021 using the IQVIA Xponent data set. The primary outcome was the change in the number of antibiotic prescriptions between the prepandemic and pandemic period. Secondary outcomes were changes in the selection of broad-spectrum agents and long-duration (>7 d) antibiotic use. We used multivariable linear regression models to evaluate predictors of change. Results: There were 17,288 physicians included in the study with substantial inter-physician variability in changes in antibiotic prescribing (median change of -43.5 antibiotics per physician, interquartile range -136.5 to -5.0). In the multivariable model, later career stage (adjusted mean difference [aMD] -45.3, 95% confidence interval [CI] -52.9 to -37.8, p < .001), family medicine (aMD -46.0, 95% CI -62.5 to -29.4, p < .001), male patient sex (aMD -52.4, 95% CI -71.1 to -33.7, p < .001), low patient comorbidity (aMD -42.5, 95% CI -50.3 to -34.8, p < .001), and high prescribing to new patients (aMD -216.5, 95% CI -223.5 to -209.5, p < .001) were associated with decreases in antibiotic initiation. Family medicine and high prescribing to new patients were associated with a decrease in selection of broad-spectrum agents and prolonged antibiotic use. Conclusions: Antibiotic prescribing changed throughout the COVID-19 pandemic with overall decreases in antibiotic initiation, broad-spectrum agents, and prolonged antibiotic courses with inter-physician variability. These findings present opportunities for community antibiotic stewardship interventions.

Moving from intervention management to disease management: a qualitative study exploring a systems approach to health technology assessment in Canada.

OBJECTIVES: Health technology assessment (HTA) traditionally informs decision making for single health technologies, which could lead to ill-informed decisions, suboptimal care, and system inefficiencies. We explored opportunities for conceptualizing the decision space in HTA as a disease management question versus an intervention management question. METHODS: Semistructured interviews were conducted between April 2022 and October 2022 with purposefully selected individuals from national and provincial HTA agencies and related organizations in Canada. We conducted manual line by line coding of data informed by our interview guide and sensitizing concepts from the literature. One author coded the data, and findings were independently verified by a second author who coded a subset of transcripts. RESULTS: Twenty-four invitations were distributed, and eighteen individuals agreed to participate. A disease management approach to HTA was differentiated from traditional approaches as being disease-based, multi-interventional, and dynamic. There was general support for an explicit care pathway approach to HTA by informing discussions around patient choice and suboptimal care, creating a space where decision makers can collaborate on shared objectives, and in setting up a platform for open dialogue about managing high-cost and high-severity diseases. There are opportunities for a care pathway approach to be implemented that build on the strengths of the existing HTA system in Canada. CONCLUSIONS: A disease management approach may enhance the impact of HTA by supporting dynamic decision making that could better inform a proactive, resilient, and sustainable healthcare system in Canada.

Antibiotic prescribing guideline recommendations in COVID-19: a systematic survey.

Background: COVID-19 and antimicrobial resistance (AMR) are two intersecting public health crises. Antimicrobial overuse in patients with COVID-19 threatens to worsen AMR. Guidelines are fundamental in encouraging antimicrobial stewardship. We sought to assess the quality of antibiotic prescribing guidelines and recommendations in the context of COVID-19, and whether they incorporate principles of antimicrobial stewardship. Methods: We performed a systematic survey which included a search using the concepts "antibiotic/antimicrobial" up to November 15, 2022 of the eCOVID-19 living map of recommendations (RecMap) which aggregates guidelines across a range of international sources and all languages. Guidelines providing explicit recommendations regarding antibacterial use in COVID-19 were eligible for inclusion. Guideline and recommendation quality were assessed using the AGREE II and AGREE-REX instruments, respectively. We extracted guideline characteristics including panel representation and the presence or absence of explicit statements related to antimicrobial stewardship (i.e., judicious antibiotic use, antimicrobial resistance or adverse effects as a consequence of antibiotic use). We used logistic regression to evaluate the relationship between guideline characteristics including quality and incorporation of antimicrobial stewardship principles. Protocol registration (OSF): https://osf.io/4pgtc. Findings: Twenty-eight guidelines with 63 antibiotic prescribing recommendations were included. Recommendations focused on antibiotic initiation (n = 52, 83%) and less commonly antibiotic selection (n = 13, 21%), and duration of therapy (n = 15, 24%). Guideline and recommendation quality varied widely. Twenty (71%) guidelines incorporated at least one concept relating to antimicrobial stewardship. Including infectious diseases expertise on the guideline panel (OR 9.44, 97.5% CI: 1.09-81.59) and AGREE-REX score (OR 3.26, 97.5% CI: 1.14-9.31 per 10% increase in overall score) were associated with a higher odds of guidelines addressing antimicrobial stewardship. Interpretation: There is an opportunity to improve antibiotic prescribing guidelines in terms of both quality and incorporation of antimicrobial stewardship principles. These findings can help guideline developers better address antibiotic stewardship in future recommendations beyond COVID-19. Funding: This project was funded by Michael G. DeGroote Cochrane Canada and McMaster GRADE centres.

Identifying clusters of coexisting conditions and outcomes among adults admitted to hospital with community-acquired pneumonia: a multicentre cohort study.

BACKGROUND: Little is known about patterns of coexisting conditions and their influence on clinical care or outcomes in adults admitted to hospital for community-acquired pneumonia (CAP). We sought to evaluate how coexisting conditions cluster in this population to advance understanding of how multimorbidity affects CAP. METHODS: We studied 11 085 adults admitted to hospital with CAP at 7 hospitals in Ontario, Canada. Using cluster analysis, we identified patient subgroups based on clustering of comorbidities in the Charlson Comorbidity Index. We derived and replicated cluster analyses in independent cohorts (derivation sample 2010-2015, replication sample 2015-2017), then combined these into a total cohort for final cluster analyses. We described differences in medications, imaging and outcomes. RESULTS: Patients clustered into 7 subgroups. The low comorbidity subgroup (n = 3052, 27.5%) had no comorbidities. The DM-HF-Pulm subgroup had prevalent diabetes, heart failure and chronic lung disease (n = 1710, 15.4%). One disease category defined each remaining subgroup, as follows: pulmonary (n = 1621, 14.6%), diabetes (n = 1281, 11.6%), heart failure (n = 1370, 12.4%), dementia (n = 1038, 9.4%) and cancer (n = 1013, 9.1%). Corticosteroid use ranged from 11.5% to 64.9% in the dementia and pulmonary subgroups, respectively. Piperacillin-tazobactam use ranged from 9.1% to 28.0% in the pulmonary and cancer subgroups, respectively. The use of thoracic computed tomography ranged from 5.7% to 36.3% in the dementia and cancer subgroups, respectively. Adjusting for patient factors, the risk of in-hospital death was greater in the cancer (adjusted odds ratio [OR] 3.12, 95% confidence interval [CI] 2.44-3.99), dementia (adjusted OR 1.57, 95% CI 1.05-2.35), heart failure (adjusted OR 1.66, 95% CI 1.35-2.03) and DM-HF-Pulm subgroups (adjusted OR 1.35, 95% CI 1.12-1.61), and lower in the diabetes subgroup (adjusted OR 0.67, 95% CI 0.50-0.89), compared with the low comorbidity group. INTERPRETATION: Patients admitted to hospital with CAP cluster into clinically recognizable subgroups based on coexisting conditions. Clinical care and outcomes vary among these subgroups with little evidence to guide decision-making, highlighting opportunities for research to personalize care.

Are we enrolling the right patients? A scoping review of external validity and generalizability of clinical trials in bloodstream infections.

BACKGROUND: Having a representative population in randomized clinical trials (RCTs) improves external validity and generalizability of trial results. There are limited data examining differences between RCT-enrolled and real-world populations in bloodstream infections (BSI). OBJECTIVES: We conducted a scoping review aiming to review studies assessing generalizability of BSI RCT populations, to identify sub-groups that have been systematically under-represented and to explore approaches to improve external validity of future RCTs. SOURCES: MEDLINE, Embase, and Cochrane Library databases were searched for terms related to external validity or generalizability, BSI, and clinical trials in papers published up to 1 August 2023. Studies comparing enrolled versus nonenrolled patients, or papers discussing external validity or generalizability in the context of BSI RCTs were included. CONTENT: Sixteen papers were included in the final review. Five compared RCT-enrolled and nonenrolled participants from the same source population. There were significant differences between the two groups in all studies, with nonenrolled patients having a greater comorbidity burden and consistently worse outcomes including mortality. We identified several barriers to improving generalizability of RCT populations and outlined potential approaches to reduce these barriers, such as alternative/simplified consent processes, streamlining eligibility criteria and follow-up procedures, quota-based sampling techniques, and ensuring diversity in site and study team selection. IMPLICATIONS: Study cohorts in BSI RCTs are not representative of the general BSI patient population. As we increasingly adopt large pragmatic trials in infectious diseases, it is important to recognize the importance of maximizing generalizability to ensure that our research findings are of direct relevance to our patients.