Evaluation of Two-Assay Serological Testing Strategies for Anti-HCV Screening in Italian Populations: A Dual Screening Approach.

(1) Background: Hepatitis C virus (HCV) screening mostly uses a one-assay anti-HCV testing approach, which has a higher probability of false-positive results in populations with low HCV prevalence. (2) Methods: In this investigation, 17,926 participants were screened for HCV, and the reactives were tested using a two-assay anti-HCV approach: Elecsys ElectroChemiLuminescence (ECL) and a ChemiLuminescence ImmunoAssay (CLIA), respectively. A recombinant immunoblot assay (RIBA) was performed to confirm anti-HCV positivity. Statistical analysis was performed. (3) Results: A total of 350 specimens were reactive in the ECL screening, of which CLIA retesting showed that 292 (83.4%) were anti-HCV reactive (283 positives, 9 indeterminate, none negative by RIBA), but 58 (16.6%) were not anti-HCV reactive (15 positive, 12 indeterminate, 31 negatives by RIBA). The two-assay strategy significantly improved the positive predictive value (PPV: 95.00%) with χ2: 7.59 (p < 0.01) compared to the PPV assessed by one assay (PPV: 90.6%) with χ2: 34.51 (p < 0.001). The ROC curve defined a sensibility and specificity for the dual approach of 99.66% and 100.00%. (4) Conclusions: Compared with a one-assay testing strategy, the two-assay testing strategy may significantly reduce false positives in anti-HCV testing and identify inactive HCV infection in low seroprevalence populations.

Landiolol for the prevention of postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Although the evidence suggests that beta blockers prevent POAF, they often cause hypotension. Landiolol, an ultra-short-acting ß1 blocker, may prevent POAF, without adverse hemodynamic consequences. SOURCE: We searched MEDLINE, CENTRAL, Embase, and trial registries between January 1970 and March 2022. We included randomized controlled trials (RCTs) that evaluated the effect of landiolol for the prevention of POAF after cardiac surgery. Two reviewers independently assessed eligibility, extracted data, and assessed risk of bias using the Risk of Bias 2.0 tool. We pooled data using random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess certainty of evidence. PRINCIPAL FINDINGS: Nine RCTs including 868 participants met the eligibility criteria. Patients randomized to landiolol (56/460) had less POAF compared with controls (133/408) with a relative risk (RR) of 0.40 (95% confidence interval [CI], 0.30 to 0.54; I2 = 0%;) and an absolute risk of 12.2% vs 32.6% (absolute risk difference, 20.4%; 95% CI, 15.0 to 25.0). Landiolol resulted in a shorter hospital length-of-stay (LOS) (268 patients; mean difference, -2.32 days; 95% CI, -4.02 to -0.57; I2 = 0%). We found no significant difference in bradycardia (RR, 1.11; 95% CI, 0.48 to 2.56; I2 = 0%). No hypotension was reported with landiolol. We judged the certainty of evidence as moderate for POAF (because of indirectness as outcomes were not clearly defined) and low for LOS (because of imprecision and concern of reporting bias). CONCLUSION: In patients undergoing cardiac surgery, landiolol likely reduces POAF and may reduce LOS. A definitive large RCT is needed to confirm these findings. STUDY REGISTRATION: PROSPERO (CRD42021262703); registered 25 July 2021.

RéSUMé: OBJECTIF: La fibrillation auriculaire postopératoire (FAPO) est une complication fréquente après une chirurgie cardiaque. Bien que les données probantes suggèrent que les bêta-bloqueurs préviennent la FAPO, ces agents provoquent souvent une hypotension. Le landiolol, un ß1-bloqueur à action ultra-courte, pourrait prévenir la FAPO sans conséquences hémodynamiques indésirables. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, CENTRAL et Embase, et dans les registres d'études publiées entre janvier 1970 et mars 2022. Nous avons inclus les études randomisées contrôlées (ERC) évaluant l'effet du landiolol pour la prévention de la FAPO après une chirurgie cardiaque. Deux personnes ont indépendamment révisé l'éligibilité, extrait les données et évalué le risque de biais à l'aide de l'outil Risque de biais 2.0. Nous avons regroupé les données à l'aide de modèles à effets aléatoires. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Neuf ERC incluant 868 personnes remplissaient les critères d'éligibilité. Les patient·es randomisé·es dans le groupe landiolol (56/460) présentaient moins de FAPO que les témoins (133/408), avec un risque relatif (RR) de 0,40 (intervalle de confiance [IC] à 95 %, 0,30 à 0,54; I2 = 0 %) et un risque absolu de 12,2 % vs 32,6 % (différence de risque absolue, 20,4 %; IC 95 % 95 %, 15,0 à 25,0). Le landiolol a entraîné une durée de séjour hospitalier plus courte (268 patient·es; différence moyenne, −2,32 jours; IC 95 %, −4,02 à −0,57; I2 = 0 %). Nous n'avons trouvé aucune différence significative en matière de bradycardie (RR, 1,11; IC 95 %, 0,48 à 2,56; I2 = 0 %). Aucune hypotension n'a été rapportée avec le landiolol. Nous avons jugé que la certitude des données probantes était modérée pour la FAPO (en raison du caractère indirect car les critères d'évaluation n'étaient pas clairement définis) et faible pour la durée de séjour hospitalier (en raison de l'imprécision et de questionnements concernant le biais de déclaration). CONCLUSION: Chez les patient·es bénéficiant d'une chirurgie cardiaque, le landiolol réduit probablement la FAPO et peut réduire la durée de séjour hospitalier. Une ERC définitive à grande échelle est nécessaire pour confirmer ces résultats. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262703); enregistrée le 25 juillet 2021.

Healthcare Costs and Healthcare Utilization Outcomes of Vitamin D3 Supplementation at 5000 IU Daily during a 10.9 Month Observation Period within a Pragmatic Randomized Clinical Trial.

Vitamin D insufficiency has been linked to multiple conditions including bone disease, respiratory disease, cardiovascular disease, diabetes, and cancer. Observational studies indicate lower healthcare costs and healthcare utilization with sufficient vitamin D levels. The secondary aims of our previously published pragmatic clinical trial of vitamin D3 supplementation were comparisons of healthcare costs and healthcare utilization. Comparisons were made between the vitamin D3 at 5000 IU supplementation group and a non-supplemented control group. Costs of care between the groups differed but were not statistically significant. Vitamin D3 supplementation reduced healthcare utilization in four major categories: hospitalizations for any reason (rate difference: -0.19 per 1000 person-days, 95%-CI: -0.21 to -0.17 per 1000 person-days, p < 0.0001); ICU admissions for any reason (rate difference: -0.06 per 1000 person-days, 95%-CI: -0.08 to -0.04 per 1000 person-days, p < 0.0001); emergency room visits for any reason (rate difference: -0.26 per 1000 person-days, 95%-CI: -0.46 to -0.05 per 1000 person-days, p = 0.0131; and hospitalizations due to COVID-19 (rate difference: -8.47 × 10-3 per 1000 person-days, 95%-CI: -0.02 to -1.05 × 10-3 per 1000 person-days, p = 0.0253). Appropriately powered studies of longer duration are recommended for replication of these utilization findings and analysis of cost differences.

Remote and semi-automated methods to conduct a decentralized randomized clinical trial.

Introduction: Designing and conducting clinical trials is challenging for some institutions and researchers due to associated time and personnel requirements. We conducted recruitment, screening, informed consent, study product distribution, and data collection remotely. Our objective is to describe how to conduct a randomized clinical trial using remote and automated methods. Methods: A randomized clinical trial in healthcare workers is used as a model. A random group of workers were invited to participate in the study through email. Following an automated process, interested individuals scheduled consent/screening interviews. Enrollees received study product by mail and surveys via email. Adherence to study product and safety were monitored with survey data review and via real-time safety alerts to study staff. Results: A staff of 10 remotely screened 406 subjects and enrolled 299 over a 3-month period. Adherence to study product was 87%, and survey data completeness was 98.5% over 9 months. Participants and study staff scored the System Usability Scale 93.8% and 90%, respectively. The automated and remote methods allowed the study maintenance period to be managed by a small study team of two members, while safety monitoring was conducted by three to four team members. Conception of the trial to study completion was 21 months. Conclusions: The remote and automated methods produced efficient subject recruitment with excellent study product adherence and data completeness. These methods can improve efficiency without sacrificing safety or quality. We share our XML file for researchers to use as a template for learning purposes or designing their own clinical trials.

Noninferiority margins exceed superiority effect estimates for mortality in cardiovascular trials in high-impact journals.

OBJECTIVES: To determine, in a sample of noninferiority trials, the noninferiority margins (NIMs) and their relation to effect estimates in superiority trials, the rationale being that in general NIMs should be no larger than effects declared important in superiority trials. STUDY DESIGN AND SETTING: To identify cardiovascular trials published in high-impact journals with a statistically significant primary outcome involving mortality, we systematically searched PubMed, Embase, and MEDLINE databases (January 2015-July 2020). We documented the NIMs and determined the proportion of trials with NIMs larger than the median effect estimates across superiority trials. RESULTS: From 1,477 screened titles, 65 (39 noninferiority, 26 superiority) trials proved eligible. The NIMs ranged from risk difference of 0.54-10%. The effect estimate across superiority trials was a median risk difference of 2.1% (interquartile range 1.5-4.9); the NIM was larger than 2.1% in 28 (71.8%) noninferiority trials and larger than 1.5%, which was the lower bound of the interquartile range in 32 (82.1%) noninferiority trials. CONCLUSION: The very wide range of noninferiority margins and the proportion above a threshold that most would consider an important mortality reduction suggest that clinicians and guideline panels should focus on study results, paying little attention to authors' noninferiority margins.

A Simple Admission Order-set Improves Adherence to Canadian Guidelines for Hospitalized Patients With Severe Ulcerative Colitis.

Background: Individuals hospitalized with severe ulcerative colitis represent a complex group of patients. Variation exists in the quality of care of admitted patients with inflammatory bowel disease. We hypothesized that implementation of a standardized admission order set could result in improved adherence to current best practice guidelines (Toronto Consensus Statements) for the management of this patient population. Methods: A retrospective cohort study of patients admitted with severe ulcerative colitis to a Montreal tertiary center was conducted. Two cohorts were defined based on pre- and post-implementation of a standardized order set. Adherence to 11 quality indicators was assessed before and after implementation of the intervention. These included: Clostridioides difficile and stool cultures testing, ordering an abdominal X-ray and CRP, organizing a flexible sigmoidoscopy, documenting latent tuberculosis, initiating thromboprophylaxis, use of intravenous steroids, prescribing infliximab if refractory to steroids, limiting narcotics, and surgical consultation if refractory to medical therapy. Results: Adherence to 6 of the 11 quality indicators was improved in the post-intervention cohort. Significant increases were noted in adherence to C difficile testing (75.5% versus 91.9%, P < 0.05), CRP testing (71.4% versus 94.6%, P < 0.01), testing for latent tuberculosis (38.1% versus 84.6%, P < 0.01), thromboprophylaxis (28.6% versus 94.6%, P < 0.01), adequate corticosteroids prescription (72.9% versus 94.6%, P < 0.01), and limitation of narcotics prescribed (68.8% versus 38.9%, P < 0.01). Conclusions: Implementation of a standardized order set, focused on pre-defined quality indicators for hospitalized patients with severe UC, was associated with meaningful improvements to most quality indicators defined by the Toronto Consensus Statements.

Bleeding in women with venous thromboembolism during pregnancy: A systematic review of the literature.

Objectives: Venous thromboembolism (VTE) represents an important cause of maternal morbidity and mortality. Estimates of bleeding associated with therapeutic-dose anticoagulation are variable. We describe the frequency of bleeding in pregnant women receiving therapeutic anticoagulation for VTE by means of a systematic review of the literature. Data Sources: Medical Literature Analysis and Retrieval System, Embase, Scopus, Web of Science, and ClinicalTrials.gov were searched. Databases were searched from inception to February 27, 2022. There was no language or geographic location restriction. Methods of Study Selection: The search yielded 2773 articles with 2212 unique citations. Studies were included if they described pregnant women treated for an acute VTE with therapeutic-dose anticoagulation and a defined bleeding outcome was reported. Tabulation Integration and Results: Five studies met inclusion criteria. Included studies were judged to have a serious to critical risk of bias using the Risk of Bias in Nonrandomized Studies of Intervention tool. The rate of bleeding, as defined by respective studies, ranged between 2.9% and 30.0%. Two studies included control groups, one of which found no significant difference in the risk of bleeding between groups, while the other found a significantly increased bleeding risk associated with therapeutic anticoagulation. Conclusion: Among pregnant women anticoagulated for VTE, the reported bleeding risk is variable. The ability to draw definite conclusions is limited by the scarcity and low quality of the studies, the small number of included patients, and the heterogeneity of bleeding definitions used. Large-scale studies with standardized bleeding definitions are required to provide acute bleeding estimates and optimize the care of these patients. Systematic Review Registration: PROSPERO, CRD42021276771.

Vitamin D3 Supplementation at 5000 IU Daily for the Prevention of Influenza-like Illness in Healthcare Workers: A Pragmatic Randomized Clinical Trial.

Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers. We conducted a prospective, controlled trial at a tertiary university hospital. A random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare system workers served as controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved. Incidence rates were compared between the vitamin D and control groups. Workers in the intervention group were included in the analysis if they completed at least 2 months of supplementation to ensure adequate vitamin D levels. The primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Between October 2020 and November 2021, 255 healthcare workers (age 47 ± 12 years, 199 women) completed at least two months of vitamin D3 supplementation. The control group consisted of 2827 workers. Vitamin D3 5000 IU supplementation was associated with a lower risk of ILI (incidence rate difference: -1.7 × 10-4/person-day, 95%-CI: -3.0 × 10-4 to -3.3 × 10-5/person-day, p = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: -1.3 × 10-4/person-day, 95%-CI -2.5 × 10-4 to -7.1 × 10-6/person-day, p = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: -4.2 × 10-5/person-day, 95%-CI: -10.0 × 10-5 to 1.5 × 10-5/person-day, p = 0.152). Daily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.

Delayed time to emergency hip surgery in patients taking oral anticoagulants.

INTRODUCTION: Surgical intervention within 48 h of admission in patients with acute hip fractures has been associated to lower morbidity and mortality. Patients anticoagulated with vitamin K antagonists (VKAs) have longer time to corrective surgery than those not anticoagulated. Sparse data exists on time to surgery (TTS) in patients taking direct oral anticoagulants (DOACs). The aim of this study is to establish TTS among non-anticoagulated and anticoagulated patients taking either VKA or DOAC. MATERIALS AND METHODS: We conducted a retrospective cohort study of consecutive patients admitted with acute hip fracture between July 1, 2016 and December 31, 2017. Patient-, anticoagulant- and surgery-related characteristics were collected. The primary outcome was TTS calculated from time of admission. Median TTS with interquartile range (IQR) was compared among 3 groups of patients: DOAC, VKA and No OAC. RESULTS: A total of 472 patients were included: 12.5% (59/472) were anticoagulated (28/472 on VKAs and 31/472 on DOACs). Median TTS was longer in the VKA group [64 h (IQR: 50-84)] and in the DOAC group [(61 h; IQR: 42 to 77)] versus the No OAC group [44 h (IQR: 28-63), p = 0.0006 and p = 0.003 respectively]. There was no significant difference in median TTS in the VKA group versus the DOAC group (p = 0.6396). CONCLUSION: Patients taking either VKA or DOAC have significant delays to emergency hip fracture surgery compared to those not anticoagulated. Future studies aimed at examining this relationship more closely are warranted. In the meantime, an action plan aimed at early identification and appropriate management of anticoagulation in this vulnerable group of patients is necessary.

Creation and validation of the PERFECT: a critical incident tool for evaluating change in the practices of health professionals.

RATIONALE: The critical incident technique provides a means to better understand the reasons behind clinicians' practices and changes in practice. No standardized tool exists to elicit information using this technique. OBJECTIVES: To create and validate a standardized tool that explores change and reasons for change in professional practice. METHOD: Item generation was based on expert consultation and a review of the clinical practice and knowledge translation literature. The draft tool was pilot-tested with a convenience sample of 10 rehabilitation clinicians to receive feedback on its content, clarity, optimal cueing, omissions and ease of recall of critical incidents. RESULTS: The tool was progressively refined and validated according to feedback from both the clinicians and expert reviewers. The final version of the tool includes 33 questions designed to elicit information on change and reasons for change in four areas: problem identification, assessment, treatment and referral practices. In addition, it elicits information on factors that facilitate or hinder change in practice. Cues are included when necessary to clarify questions and facilitate responses. Regarding ease of recall, all clinicians confirmed that beginning with a 6-month recall of practice change and working back to 1 year was a facilitator. All clinicians mentioned that the tool encouraged them to reflect about changes they made in their practice or lack thereof. CONCLUSION: The newly created standardized critical incident tool, named the PERFECT (Professional Evaluation & Reflection on Change Tool) provides an opportunity for widespread applicability to explore change, reasons for change, as well as facilitators and barriers to change in the practices of health professionals.