Re-examining the effect of door-to-balloon delay on STEMI outcomes in the context of unmeasured confounders: a retrospective cohort study

Literature studying the door-to-balloon time-outcome relation in coronary intervention is limited by the potential of residual biases from unobserved confounders. This study re-examines the time-outcome relation with further consideration of the unobserved factors and reports the population average effect. Adults with ST-elevation myocardial infarction admitted to one of the six registry participating hospitals in Australia were included in this study. The exposure variable was patient-level door-to-balloon time. Primary outcomes assessed included in-hospital and 30 days mortality. 4343 patients fulfilled the study criteria. 38.0% (1651) experienced a door-to-balloon delay of >90 minutes. The absolute risk differences for in-hospital and 30-day deaths between the two exposure subgroups with balanced covariates were 2.81 (95% CI 1.04, 4.58) and 3.37 (95% CI 1.49, 5.26) per 100 population. When unmeasured factors were taken into consideration, the risk difference were 20.7 (95% CI −2.6, 44.0) and 22.6 (95% CI −1.7, 47.0) per 100 population. Despite further adjustment of the observed and unobserved factors, this study suggests a directionally consistent linkage between longer door-to-balloon delay and higher risk of adverse outcomes at the population level. Greater uncertainties were observed when unmeasured factors were taken into consideration

Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients

BACKGROUND: Molecular markers and the rich biological information they contain have great potential for cancer diagnosis, prognostication and therapy prediction. So far, however, they have not superseded routine histopathology and staging criteria, partly because the few studies performed on molecular subtyping have had little validation and limited clinical characterization. METHODS: We obtained gene expression and clinical data for 412 breast cancers obtained from population-based cohorts of patients from Stockholm and Uppsala, Sweden. Using the intrinsic set of approximately 500 genes derived in the Norway/Stanford breast cancer data, we validated the existence of five molecular subtypes – basal-like, ERBB2, luminal A/B and normal-like – and characterized these subtypes extensively with the use of conventional clinical variables. RESULTS: We found an overall 77.5% concordance between the centroid prediction of the Swedish cohort by using the Norway/Stanford signature and the k-means clustering performed internally within the Swedish cohort. The highest rate of discordant assignments occurred between the luminal A and luminal B subtypes and between the luminal B and ERBB2 subtypes. The subtypes varied significantly in terms of grade (p < 0.001), p53 mutation (p < 0.001) and genomic instability (p = 0.01), but surprisingly there was little difference in lymph-node metastasis (p = 0.31). Furthermore, current users of hormone-replacement therapy were strikingly over-represented in the normal-like subgroup (p < 0.001). Separate analyses of the patients who received endocrine therapy and those who did not receive any adjuvant therapy supported the previous hypothesis that the basal-like subtype responded to adjuvant treatment, whereas the ERBB2 and luminal B subtypes were poor responders. CONCLUSION: We found that the intrinsic molecular subtypes of breast cancer are broadly present in a diverse collection of patients from a population-based cohort in Sweden. The intrinsic gene set, originally selected to reveal stable tumor characteristics, was shown to have a strong correlation with progression-related properties such as grade, p53 mutation and genomic instability

Efficacy of Smartphone-Based Secondary Preventive Strategies in Coronary Artery Disease.

Background: Cardiac rehabilitation programs provide a comprehensive framework for the institution of secondary preventive measures. Smartphone technology can provide a platform for the delivery of such programs and is a promising alternative to hospital-based services. However, there is limited evidence to date supporting this approach. Accordingly, we performed a systematic review and meta-analysis examining smartphone-based secondary prevention programs to traditional cardiac rehabilitation in patients with established coronary artery disease to ascertain the feasibility and effectiveness of these interventions. Methods: A systematic search of PubMed, MEDLINE, EMBASE, and the Cochrane Library was conducted. A meta-analysis was performed using a random-effects model with the outcomes of interest being 6-minute walk test (6MWT) distance, systolic blood pressure, low-density lipoprotein (LDL) cholesterol, and body mass index (BMI). Results: A total of 8 studies with 1120 patients across 5 countries were included in the quantitative analysis. Follow-up ranged from 6 weeks to 12 months. Five studies examined all patients post acute coronary syndrome, 2 studies examined only patients undergoing percutaneous coronary intervention, and 1 study examined all patients with a diagnosis of coronary artery disease, independent of intervention. Exercise capacity, as measured by the 6MWT, was significantly greater in the smartphone group (20.10 meters, 95% confidence interval [CI] 7.44-33.97; P  .05). Conclusion: Publicly available smartphone-based cardiac rehabilitation programs are a convenient and easily disseminated intervention which show merit in exercise promotion in patients with established coronary artery disease. Further research is required to establish the clinical significance of recent findings favoring their use

Renin-angiotensin system inhibition and risk of infection and mortality in COVID-19: a systematic review and meta-analysis

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, enters human cells by binding of its viral protein to the aminopeptidase angiotensin-converting enzyme 2 (ACE2). This has led to speculation whether treatment with renin-angiotensin system (RAS) inhibitors was associated with an increased likelihood of a positive test for COVID-19 and risk of mortality. AIMS: We performed a systematic review and meta-analysis to investigate whether RAS inhibitors increased the likelihood of a positive test or death/severe illness in patients with COVID-19. METHODS: A systematic search of MEDLINE, PubMed and EMBASE was conducted for studies stratified by the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Pooled analysis was performed using a random-effects model. RESULTS: Seven trials of 73 122 patients were included. Overall, 16 624 (22.7%) patients had a positive COVID-19 test and 7892 (10.8%) were on a RAS inhibitor. RAS inhibitors were not associated with higher likelihood of a positive COVID-19 test result (odds ratio (OR) 0.97 (95% CI 0.97-1.05, P = 0.48) with low heterogeneity. This was comparable when stratifying by use of each medication class. The use of RAS inhibitors was also not associated with mortality or severe illness (OR 0.89, 95% CI 0.73-1.07, P = 0.21) with moderate heterogeneity. CONCLUSION: Use of ACEI or ARB was not associated with a heightened susceptibility for a positive diagnosis of COVID-19. Furthermore, they were not associated with increased illness severity or mortality due to COVID-19. Randomised controlled trials are needed to address definitively the potential benefits or harms of RAS inhibitors in patients with COVID-19

Factor Xa Inhibition for the Treatment of Venous Thromboembolism Associated With Cancer: A Meta-Analysis of the Randomised Controlled Trials

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients. Until recently, guidelines recommended the use of low-molecular weight heparin (LMWH) as standard of care for VTE in patients with cancer. Despite the proven efficacy of direct oral anticoagulants (DOACs) for treatment of VTE, there is equipoise supporting their use in cancer patients. METHODS: A systematic review of PubMed, Medline and EMBASE identified four randomised controlled trials (RCTs) in patients with cancer and VTE comparing a factor Xa inhibitor (FXaI) to LMWH. A meta-analysis was performed with a primary outcome of VTE recurrence and key secondary outcomes of major bleeding, clinically relevant non-major bleeding (CRNMB) and gastrointestinal (GI) bleeding. RESULTS: Four RCTs with 2,907 patients were included. 1,451 patients were randomised to FXaI and 1,456 to LMWH. VTE recurrence was lower in the FXaI group (RR 0.62, 95%CI 0.44-0.87; p=0.01; I2=24.90), with an absolute risk difference of -4% equating to a number needed to treat of 25 for prevention of recurrent VTE with FXaI. No significant difference in major bleeding was noted between groups (RR 1.33, 95%CI 0.84-2.11; p=0.23). Rates of GI bleeding (RR 1.87, 95%CI 1.06-3.29; p=0.03) and CRNMB (RR 1.57, 95%CI 1.11-2.23; p=0.01) were greater with FXaIs. CONCLUSION: In patients with cancer and VTE, the rate of VTE recurrence was significantly lower with FXaI than with LMWH without an increased risk of major bleeding. Our data supports the use of FXaIs as the standard of care for the treatment of VTE in this population

Transcatheter aortic valve replacement in patients with a history of cancer: Periprocedural and long-term outcomes

BACKGROUND: A history of cancer is incorporated into the surgical risk assessment of patients undergoing surgical aortic valve replacement through the Society for Thoracic Surgeons score. However, the prognostic significance of cancer in patients treated with transcatheter aortic valve replacement (TAVR) is unclear. As the cancer survivorship population increases, it is imperative to establish the efficacy and safety of TAVR in patients with severe symptomatic aortic stenosis (AS) and a history of malignancy. OBJECTIVES: The primary goal of this study was to assess the periprocedural outcomes and long-term mortality in patients with a history of cancer undergoing TAVR. METHODS: A systematic review of PubMed, MEDLINE, and EMBASE was conducted to identify studies reporting outcomes in patients with a history of malignancy undergoing TAVR. A meta-analysis was performed using a random-effects model with a primary outcome of all-cause mortality and cardiac mortality at the longest follow-up. On secondary analyses, procedural safety was assessed. RESULTS: A total of 13 observational studies with 10,916 patients were identified in the systematic review. Seven studies including 6,323 patients were included in the quantitative analysis. Short-term mortality (relative risk [RR] 0.61, 95%CI 0.36-1.01; p = .06) and long-term all-cause mortality (RR 1.24, 95%CI 0.95-1.63; p = .11) were not significantly different when comparing patients with and without a history of cancer. No significant difference in the rate of periprocedural complications including stroke, bleeding, acute kidney injury, and pacemaker implantation was noted. CONCLUSION: In patients with severe AS undergoing TAVR, a history of cancer was not associated with adverse short or long-term survival. Based on these findings, TAVR should be considered in all patients with severe symptomatic AS, irrespective of their history of malignancy