Cerebrospinal fluid galactomannan detection for the diagnosis of central nervous system aspergillosis: a diagnostic test accuracy systematic review and meta-analysis.

BACKGROUND: Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics. OBJECTIVES: To evaluate the diagnostic test characteristics of CSF galactomannan in CNS aspergillosis. METHODS: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, Web of Science, and Scopus, from inception to 24 February 2023. STUDY ELIGIBILITY CRITERIA: Prospective and retrospective studies with one-group and two-group designs using any galactomannan assay on CSF to diagnose CNS aspergillosis. PARTICIPANTS: Adult and/or pediatric CNS aspergillosis patients. TEST(S): Galactomannan testing on CSF specimens. REFERENCE STANDARD: European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) diagnostic criteria, or equivalent. ASSESSMENT OF RISK OF BIAS: QUADAS-2 assessment in duplicate. METHODS OF DATA SYNTHESIS: Bivariate restricted maximum-likelihood estimation random-effects meta-analysis, summarized using forest and summary receiver-operator characteristic plots; bivariate meta-regression models to investigate heterogeneity; and subgroup and sensitivity analyses to explore subgroup effects and methodologic choices (PROSPERO registration: CRD42022296331; funding: none). RESULTS: We included eight studies (n=342 participants). The summary estimates of CSF galactomannan sensitivity and specificity were 69.0% (95% CI: 57.2-78.7%) and 94.4% (95% CI: 82.8-98.3%), respectively. Using meta-regression, galactomannan cut-off (p=0.38), EORTC/MSGERC criteria version (p=0.48), or whether the reference standard was defined as both proven and probable or only proven aspergillosis (p=0.48) did not explain observed heterogeneity. No subgroup effects were demonstrated by analyzing the EORTC/MSGERC criteria reference standard used (e.g., 2002 versus 2008 definitions) or whether pediatric patients were included. Diagnostic sensitivity was improved using a galactomannan cut-off of 1.0, and by excluding high risk of bias and one-group design studies. DISCUSSION: CSF galactomannan is a highly specific but insensitive test for use as a component for CNS aspergillosis diagnosis. Few included studies, no prospective studies, and a high risk of bias are study limitations.

Evaluating in vivo effectiveness of sotrovimab for the treatment of Omicron subvariant BA.2 versus BA.1: a multicentre, retrospective cohort study.

BACKGROUND: In vitro data suggested reduced neutralizing capacity of sotrovimab, a monoclonal antibody, against Omicron BA.2 subvariant. However, limited in vivo data exist regarding clinical effectiveness of sotrovimab for coronavirus disease 2019 (COVID-19) due to Omicron BA.2. METHODS: A multicentre, retrospective cohort study was conducted at three Canadian academic tertiary centres. Electronic medical records were reviewed for patients ≥ 18 years with mild COVID-19 (sequencing-confirmed Omicron BA.1 or BA.2) treated with sotrovimab between February 1 to April 1, 2022. Thirty-day co-primary outcomes included hospitalization due to moderate or severe COVID-19; all-cause intensive care unit (ICU) admission, and all-cause mortality. Risk differences (BA.2 minus BA.1 group) for co-primary outcomes were adjusted with propensity score matching (e.g., age, sex, vaccination, immunocompromised status). RESULTS: Eighty-five patients were included (15 BA.2, 70 BA.1) with similar baseline characteristics between groups. Adjusted risk differences were non-statistically significant between groups for 30-day hospitalization (- 14.3%; 95% confidence interval (CI): - 32.6 to 4.0%), ICU admission (- 7.1%; 95%CI: - 20.6 to 6.3%), and mortality (- 7.1%; 95%CI: - 20.6 to 6.3%). CONCLUSIONS: No differences were demonstrated in hospitalization, ICU admission, or mortality rates within 30 days between sotrovimab-treated patients with BA.1 versus BA.2 infection. More real-world data may be helpful to properly assess sotrovimab's effectiveness against infections due to specific emerging COVID-19 variants.

More Than a Decade Since the Latest CONSORT Non-inferiority Trials Extension: Do Infectious Diseases Trials Do Enough?

More than a decade after the Consolidated Standards of Reporting Trials group released a reporting items checklist for non-inferiority randomized controlled trials, the infectious diseases literature continues to underreport these items. Trialists, journals, and peer reviewers should redouble their efforts to ensure infectious diseases studies meet these minimum reporting standards.

Methodological and Reporting Quality of Noninferiority Randomized Controlled Trials Comparing Antiretroviral Therapies: A Systematic Review.

BACKGROUND: It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year. METHODS: We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P < .05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded. RESULTS: We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double-blinded (28.1% vs 10.3%; P = .03) and to describe missing data handling (78.5% vs 59.0%; P = .02). The overall risk of bias was low in 96 of 160 studies (60.0%). CONCLUSIONS: ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence.

An allergist's approach to food poisoning.

Foodborne illnesses represent a significant global health concern. These preventable diseases lead to substantial mortality and morbidity worldwide. Substantial overlap with food allergy exists with similar clinical presentations and symptom onset. Knowledge of the typically implicated microorganisms and toxins can help properly identify these diseases. A thorough history is essential to differentiate between these 2 disorders. The types of food implicated may be similar including milk, egg, fish, and shellfish. The timing of symptom onset may overlap and lead to misdiagnosis of disorders such as food protein-induced enterocolitis syndrome. Classically, histamine-related food poisoning is also typically confused with true food allergy and may be seen as related to fish and cheese. Knowledge of epidemiology, patterns, and etiology of allergic conditions and foodborne illness may help the allergist differentiate among these common diseases.

Staphylococcus aureus bacteremia mortality across country income groups: A secondary analysis of a systematic review.

OBJECTIVES: Staphylococcus aureus bacteremia (SAB) is a common infection worldwide. We compared SAB mortality in low- and middle-income countries (LMIC) versus high-income countries (HIC) in a meta-analysis. METHODS: We searched MEDLINE, Embase, and Cochrane Database of Systematic Reviews from 1991-2021 and included observational, single-country studies on patients with positive blood cultures for S. aureus. The main outcome was the proportion of patients with SAB who died in the hospital. A generalized linear mixed random-effects model was used to pool estimates, and a meta-regression was used to adjust for study-level characteristics. RESULTS: A total of 332 studies involving 517,671 patients in 39 countries were included. No study was conducted in a low-income country. Only 33 (10%) studies were performed in middle-income countries (MIC), which described 6,216 patients. The pooled in-hospital mortality was 32.4% (95% confidence interval [CI] 27.2%-38.2%, T2 = 0.3063) in MIC and 22.3% (95% CI 20.1%-24.6%, T2 = 0.3257) in HIC. In a meta-regression model, MIC had higher in-hospital mortality (adjusted odds ratio 1.37, 95% CI 1.11-1.71; P = 0.0042) than HIC. CONCLUSION: In SAB studies, LMIC are poorly represented. In-hospital mortality was significantly higher in MIC than in HIC. Research should be conducted in LMIC to characterize differences in care processes driving the mortality gap.

What Is the Optimal Follow-up Length for Mortality in Staphylococcus aureus Bacteremia? Observations From a Systematic Review of Attributable Mortality.

Background: Deaths following Staphylococcus aureus bacteremia (SAB) may be related or unrelated to the infection. In SAB therapeutics research, the length of follow-up should be optimized to capture most attributable deaths and minimize nonattributable deaths. We performed a secondary analysis of a systematic review to describe attributable mortality in SAB over time. Methods: We systematically searched Medline, Embase, and Cochrane Database of Systematic Reviews from 1 January 1991 to 7 May 2021 for human observational studies of SAB. To be included in this secondary analysis, the study must have reported attributable mortality. Two reviewers extracted study data and assessed risk of bias independently. Pooling of study estimates was not performed due to heterogeneity in the definition of attributable deaths. Results: Twenty-four observational cohort studies were included. The median proportion of all-cause deaths that were attributable to SAB was 77% (interquartile range [IQR], 72%-89%) at 1 month and 62% (IQR, 58%-75%) at 3 months. At 1 year, this proportion was 57% in 1 study. In 2 studies that described the rate of increase in mortality over time, 2-week follow-up captured 68 of 79 (86%) and 48 of 57 (84%) attributable deaths that occurred by 3 months. By comparison, 1-month follow-up captured 54 of 57 (95%) and 56 of 60 (93%) attributable deaths that occurred by 3 months in 2 studies. Conclusions: The proportion of deaths that are attributable to SAB decreases as follow-up lengthens. Follow-up duration between 1 and 3 months seems optimal if evaluating processes of care that impact SAB mortality. Clinical Trials Registration: PROSPERO CRD42021253891.

How Generalizable Are Randomized Controlled Trials (RCTs) in Staphylococcus aureus Bacteremia? A Description of the Mortality Gap Between RCTs and Observational Studies.

In Staphylococcus aureus bacteremia, mortality rates in randomized controlled trials (RCTs) are consistently lower than observational studies. Stringent eligibility criteria and omission of early deaths in RCTs contribute to this mortality gap. Clinicians should acknowledge the possibility of a lower treatment effect when applying RCT results to bedside care.

Staphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis.

BACKGROUND: Precise estimates of mortality in Staphylococcus aureus bacteraemia (SAB) are important to convey prognosis and guide the design of interventional studies. OBJECTIVES: We performed a systematic review and meta-analysis to estimate all-cause mortality in SAB and explore mortality change over time. DATA SOURCES: The MEDLINE and Embase databases, as well as the Cochrane Database of Systematic Reviews, were searched from January 1, 1991 to May 7, 2021. STUDY ELIGIBILITY CRITERIA: Human observational studies on patients with S. aureus bloodstream infection were included. PARTICIPANTS: The study analyzed data of patients with a positive blood culture for S. aureus. METHODS: Two independent reviewers extracted study data and assessed risk of bias using the Newcastle-Ottawa Scale. A generalized, linear, mixed random effects model was used to pool estimates. RESULTS: A total of 341 studies were included, describing a total of 536,791 patients. From 2011 onward, the estimated mortality was 10.4% (95% CI, 9.0%-12.1%) at 7 days, 13.3% (95% CI, 11.1%-15.8%) at 2 weeks, 18.1% (95% CI, 16.3%-20.0%) at 1 month, 27.0% (95% CI, 21.5%-33.3%) at 3 months, and 30.2% (95% CI, 22.4%-39.3%) at 1 year. In a meta-regression model of 1-month mortality, methicillin-resistant S. aureus had a higher mortality rate (adjusted OR (aOR): 1.04; 95% CI, 1.02-1.06 per 10% increase in methicillin-resistant S. aureus proportion). Compared with prior to 2001, more recent time periods had a lower mortality rate (aOR: 0.88; 95% CI, 0.75-1.03 for 2001-2010; aOR: 0.82; 95% CI, 0.69-0.97 for 2011 onward). CONCLUSIONS: SAB mortality has decreased over the last 3 decades. However, more than one in four patients will die within 3 months, and continuous improvement in care remains necessary.

Secondary Analysis of a Systematic Review: Are Antifungal Noninferiority Trials at Risk of Eroding Effectiveness Because of Biocreep?

Noninferiority randomized controlled trial (RCT) effectiveness may erode when results favor the active control over time and when a decreasingly effective control arm is used in serial trials. We analyzed 32 antifungal noninferiority RCTs (NI-RCTs) for these scenarios in this secondary analysis of a systematic review. Our exploratory analysis suggests that the erosion risk in the effectiveness of antifungal noninferiority trials is uncommon. Findings are limited by small sample size and overall risk of bias.

Methodological and reporting quality of non-inferiority randomized controlled trials comparing antifungal therapies: a systematic review.

BACKGROUND: Detailed reporting is essential in non-inferiority randomized controlled trials (NI-RCTs) to assess evidence quality, as these trials inform standards of care. OBJECTIVES: The primary objective was to evaluate the methodological and reporting quality of antifungal NI-RCTs. DATA SOURCES: Medline, EMBASE, the Cochrane CENTRAL and the United States Federal Drug Administration (FDA) drugs database were searched to 9 September 2020. STUDY ELIGIBILITY CRITERIA: NI-RCTs differing by antifungal formulation, type, dose, administration and/or duration were included. Articles were independently assessed in duplicate using quality indicators developed by the Consolidated Standards of Reporting Trials (CONSORT) group. PARTICIPANTS: Patients enrolled in antifungal trials for prophylactic and therapeutic use. METHODS: The Cochrane RoB 2.0 tool was used to assess risk of bias. Descriptive statistics were used; all statistical tests were two sided. RESULTS: Of 32 included studies, 22 (68.7%) did not justify the NIM. Handling of missing data was not described in 20 (62.5%). Intention-to-treat (ITT) and per-protocol (PP) analyses were both reported in 12/32 (37.5%) studies. Eleven of 32 studies (34.3%) reported potentially misleading conclusions. Industry-financed studies were more likely to report only the ITT analysis (n = 14/27, 51.9%). Methodological and reporting quality was unaffected by publication year; risk of bias from missing data changed over time. Overall risk of bias across included studies was moderate to high, with high risk in randomization process (n = 8/32, 25%), missing outcome data (n = 5/32, 15.6%), and selection of reported result (n = 9/32, 28.1%). CONCLUSIONS: Justification of the non-inferiority margin, reporting of ITT and PP analyses, missing data handling description, and ensuring conclusions are consistent with reported data is necessary to improve CONSORT adherence. Small sample size and overall risk of bias are study limitations. (Systematic Review Registration Number PROSPERO CRD42020219497).

Confidence interval of risk difference by different statistical methods and its impact on the study conclusion in antibiotic non-inferiority trials.

BACKGROUND: Numerous statistical methods can be used to calculate the confidence interval (CI) of risk differences. There is consensus in previous literature that the Wald method should be discouraged. We compared five statistical methods for estimating the CI of risk difference in terms of CI width and study conclusion in antibiotic non-inferiority trials. METHODS: In a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, reported risk differences for the primary outcome, and described the number of successes and/or failures as well as patients in each arm. For each study, we re-calculated the risk difference CI using the Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and skewness-corrected asymptotic score (SCAS) methods. The CIs by different statistical methods were compared in terms of CI width and conclusion on non-inferiority. A wider CI was considered to be more conservative. RESULTS: The analysis included 224 comparisons from 213 studies. The statistical method used to calculate CI was not reported in 134 (59.8%) cases. The median (interquartile range IQR) for CI width by Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and SCAS methods was 13.0% (10.8%, 17.4%), 13.3% (10.9%, 18.5%), 13.6% (11.1%, 18.9%), 13.6% (11.1% and 19.0%), and 13.4% (11.1%, 18.9%), respectively. In 216 comparisons that reported a non-inferiority margin, the conclusion on non-inferiority was the same across the five statistical methods in 211 (97.7%) cases. The differences in CI width were more in trials with a sample size of 100 or less in each group and treatment success rate above 90%. Of the 18 trials in this subgroup with a specified non-inferiority margin, non-inferiority was shown in 17 (94.4%), 16 (88.9%), 14 (77.8%), 14 (77.8%), and 15 (83.3%) cases based on CI by Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and SCAS methods, respectively. CONCLUSIONS: The statistical method used to calculate CI was not reported in the majority of antibiotic non-inferiority trials. Different statistical methods for CI resulted in different conclusions on non-inferiority in 2.3% cases. The differences in CI widths were highest in trials with a sample size of 100 or less in each group and a treatment success rate above 90%. TRIAL REGISTRATION: PROSPERO CRD42020165040 . April 28, 2020.

Intention-to-treat analysis may be more conservative than per protocol analysis in antibiotic non-inferiority trials: a systematic review.

BACKGROUND: In non-inferiority trials, there is a concern that intention-to-treat (ITT) analysis, by including participants who did not receive the planned interventions, may bias towards making the treatment and control arms look similar and lead to mistaken claims of non-inferiority. In contrast, per protocol (PP) analysis is viewed as less likely to make this mistake and therefore preferable in non-inferiority trials. In a systematic review of antibiotic non-inferiority trials, we compared ITT and PP analyses to determine which analysis was more conservative. METHODS: In a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, used absolute risk reduction (ARR) as the main outcome and reported both ITT and PP analyses. All estimates and confidence intervals (CIs) were oriented so that a negative ARR favored the control arm, and a positive ARR favored the treatment arm. We compared ITT to PP analyses results. The more conservative analysis between ITT and PP analyses was defined as the one having a more negative lower CI limit. RESULTS: The analysis included 164 comparisons from 154 studies. In terms of the ARR, ITT analysis yielded the more conservative point estimate and lower CI limit in 83 (50.6%) and 92 (56.1%) comparisons respectively. The lower CI limits in ITT analysis favored the control arm more than in PP analysis (median of - 7.5% vs. -6.9%, p = 0.0402). CIs were slightly wider in ITT analyses than in PP analyses (median of 13.3% vs. 12.4%, p < 0.0001). The median success rate was 89% (interquartile range IQR 82 to 93%) in the PP population and 44% (IQR 23 to 60%) in the patients who were included in the ITT population but excluded from the PP population (p < 0.0001). CONCLUSIONS: Contrary to common belief, ITT analysis was more conservative than PP analysis in the majority of antibiotic non-inferiority trials. The lower treatment success rate in the ITT analysis led to a larger variance and wider CI, resulting in a more conservative lower CI limit. ITT analysis should be mandatory and considered as either the primary or co-primary analysis for non-inferiority trials. TRIAL REGISTRATION: PROSPERO registration number CRD42020165040 .

The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. METHODS: Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2-) MBC; pooled overall estimates for incidence were calculated using random effects models. RESULTS: 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0-34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5-40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9-36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10-0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09-0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03-0.08) for patients with HR+/HER2- MBC. CONCLUSION: There is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

Methodological and Reporting Quality of Noninferiority Randomized Controlled Trials Comparing Antibiotic Therapies: A Systematic Review.

BACKGROUND: Antibiotic noninferiority randomized controlled trials (RCTs) are used for approval of new antibiotics and making changes to antibiotic prescribing in clinical practice. We conducted a systematic review to assess the methodological and reporting quality of antibiotic noninferiority RCTs. METHODS: We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews, and the Food and Drug Administration drug database from inception until November 22, 2019, for noninferiority RCTs comparing different systemic antibiotic therapies. Comparisons between antibiotic types, doses, administration routes, or durations were included. Methodological and reporting quality indicators were based on the Consolidated Standards of Reporting Trials reporting guidelines. Two independent reviewers extracted the data. RESULTS: The systematic review included 227 studies. Of these, 135 (59.5%) studies were supported by pharmaceutical industry. Only 83 (36.6%) studies provided a justification for the noninferiority margin. Reporting of both intention-to-treat (ITT) and per-protocol (PP) analyses were done in 165 (72.7%) studies. The conclusion was misleading in 34 (15.0%) studies. The studies funded by pharmaceutical industry were less likely to be stopped early because of logistical reasons (3.0% vs 19.1%; odds ratio [OR] = 0.13; 95% confidence interval [CI], .04-.37) and to show inconclusive results (11.1% vs 42.9%; OR = 0.17; 95% CI, .08-.33). The quality of studies decreased over time with respect to blinding, early stopping, reporting of ITT with PP analysis, and having misleading conclusions. CONCLUSIONS: There is room for improvement in the methodology and reporting of antibiotic noninferiority trials. Quality can be improved across the entire spectrum from investigators, funding agencies, as well as during the peer-review process.There is room for improvement in the methodology and reporting of antibiotic noninferiority trials including justification of noninferiority margin, reporting of intention-to-treat analysis with per-protocol analysis, and having conclusions that are concordant with study results.Clinical Trials Registration PROSPERO registration number CRD42020165040.

Proposed framework for a national set of reporting measures in Canada in response to the COVID-19 pandemic.

An effective strategy to control the ongoing coronavirus disease 2019 (COVID-19) pandemic takes into account inputs from many domains, including community epidemiology, surveillance and testing, contact tracing capacity, support for vulnerable populations, and health care system strain. Provincial and federal governments currently lack a universal approach to presenting relevant pandemic data from these domains to the general public in a way that engages them in decision making and promotes adherence to policies. We propose a framework to analyze COVID-19 pandemic data on an ongoing basis using inputs from these five domains, which can be scaled to the local public health unit, provincial, or national level. Data analysis was qualitative and semi-quantitative because there was a paucity of publicly available data on surveillance and testing, contact tracing, and health care system strain, which limited our ability to perform internal and external validation of our model. We urge the federal government to mandate a core set of reporting items across local, provincial, and federal jurisdictions that may then be used to perform validation and implementation of our proposed framework.

Une stratégie efficace pour contrôler la pandémie continue de maladie à coronavirus 2019 (COVID-19) tient compte de l'apport de divers domaines, soit l'épidémiologie communautaire, la surveillance et le dépistage, la capacité de traçage des contacts, le soutien de populations vulnérables et la souche du système de santé. À l'heure actuelle, les gouvernements provinciaux et fédéral ne proposent pas de démarche universelle pour présenter des données pertinentes sur ces domaines de la pandémie au grand public, de manière à le faire participer aux prises de décision et à promouvoir l'adhésion aux politiques. Les auteurs proposent un outil pour procéder à l'analyse des données sur la pandémie de COVID-19 à partir des données de ces cinq domaines, qui peut être adapté pour les unités sanitaires locales, provinciales ou nationale. L'analyse des données était qualitative et semi-quantitative en raison du peu de données publiques sur la surveillance et le dépistage, le traçage des contacts et la souche du système de santé, qui ont limité notre capacité de procéder à une validation interne et externe de notre modèle par l'analyse quantitative. Les auteurs exhortent le gouvernement fédéral à mandater un ensemble d'éléments à signaler dans les régions sociosanitaires locales, provinciales et fédérale qui peuvent ensuite utilisés pour valider mettre en œuvre le cadre proposé.

Novel Antibiotics May Be Noninferior but Are They Becoming Less Effective?: a Systematic Review.

Novel antibiotics approved by noninferiority trials may become less effective over time in two scenarios: (i) the treatment effect in studies of novel antibiotics may be consistently worse than studies of older antibiotics; (ii) when a decreasingly effective control arm is used in a series of noninferiority trials. Our systematic review of 175 noninferiority antibiotic trials found these scenarios to be rare.

Quality of adverse event reporting in phase III randomized controlled trials of breast and colorectal cancer: A systematic review.

BACKGROUND: Clinical trial reports often emphasize efficacy over harms, leading to misinterpretation of the risk-to-benefit ratio of new therapies. Clear and sufficiently detailed reporting of methods and results is especially important in the abstracts of trial reports, as readers often base their assessment of a trial on such information. In this study, we evaluated the quality of adverse event (AE) reporting and abstract quality in phase III randomized controlled trials (RCTs) of systemic therapies in breast and colorectal cancer. METHODS: Medline, EMBASE, Cochrane Database of RCTs, and Cochrane Database of Systematic Reviews were searched from November 2005 to September 2018. Phase III RCTs evaluating systemic therapies in breast or colorectal cancer were included. Each article was independently reviewed by two investigators using a standardized data extraction form based on guidelines developed by the Consolidated Standards of Reporting Trials (CONSORT) group. Descriptive statistics, bivariate analysis, and multivariable linear regression were used to analyze data. All statistical tests were two-sided. RESULTS: Of 166 RCTs identified, 99.4% reported harms in the manuscript body, and 59.6% reported harms in the abstract. Reporting was restricted to severe harms in 15.6% of RCTs. Statistical comparison of AE rates went unreported in 59.0% of studies. Information regarding AEs leading to dose reductions, treatment discontinuations, or study withdrawals went unreported in 59.3%, 18.7%, and 86.8% of studies, respectively. Recently published RCTs (P = .009) and those sponsored at least partially by for-profit companies (P = .003) had higher abstract quality scores. CONCLUSIONS: Breast and colorectal cancer phase III RCTs inadequately report CONSORT-compliant AE data. Improved guideline adherence and abstract reporting is required to properly weigh benefits and harms of new oncologic therapies. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42019140673.

Recurrent multidrug-resistant Salmonella enterica serovar Typhimurium bacteremia in a returned traveller.

This case report describes a 68-year-old male with recurrent multidrug-resistant Salmonella enterica serovar Typhimurium bacteremia acquired during travel abroad. He experienced a recurrence of bacteremia without a clear source and was successfully treated with 10 weeks of intravenous ertapenem. Post hoc genome sequencing revealed an isolate bearing class A, C, and D extended-spectrum ß-lactamases (ESBLs). A review of English- and French-language literature since 2000 revealed eight publications that discussed recurrent S. enterica serovar Typhimurium bacteremia. Patients with multidrug-resistant S. enterica serovar Typhimurium should be monitored frequently for recrudescence, even in the absence of risk factors.

Le présent rapport décrit le cas d'un homme de 68 ans atteint d'une bactériémie à Salmonella enterica sérovar Typhimurium multirésistante contractée lors d'un voyage à l'étranger. Un traitement à l'ertapénem par voie intraveineuse pendant dix semaines a guéri cette récidive de la bactériémie, dont la source n'a pu être décelée. Le séquençage génétique de l'isolat clinique effectué a posteriori a révélé des bêta-lactamases à spectre élargi de classe A, C et D. Grâce à une analyse bibliographique des publications en anglais et en français après 2000, huit publications sur la bactériémie récurrente à S. enterica sérovar Typhimurium ont été recensées. Les patients atteints d'une bactériémie à S. enterica sérovar Typhimurium multirésistante devraient faire l'objet d'une surveillance fréquente pour écarter les recrudescences, même en l'absence de facteurs de risque.