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ImportanceMelanoma accounts for most of the deaths due to skin cancer. In the past decade, effective US Food and Drug Administration (FDA)–approved therapies for melanoma have emerged.ObjectiveTo review changes in the long-term melanoma mortality rate (MMR) trends in the US and determine whether they have any temporal association with the FDA approval of new agents.Design, Setting, and ParticipantsThis cross-sectional study used population data from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed the age-adjusted MMR trends in adult patients (aged ≥18 years) from 1975 to 2019 in the US population. The timeline of the FDA approvals for melanoma treatment was also reviewed. Data were analyzed from March 15 to August 15, 2022.ExposuresOutcomes were assessed in association with FDA approval of drugs for the treatment of melanoma.Main Outcomes and MeasuresMortality rates are from the SEER database, reported per 100 000 population and age-adjusted to the 2000 US standard population. The annual percent change (APC) has been used to report long-term trends.ResultsAfter the introduction of newer treatments in 2011 (most after 2013), a significant reduction in MMR was seen from 2013 to 2017 in the US for the first time in the past 40 years. Rates increased from 1975 to 1988 (APC, 1.65% [95% CI, 1.30%-2.00%]; P < .001). No statistically significant change in MMR was seen from 1988 to 2013 (APC, 0.01% [95% CI, −1.10% to 0.12%]; P = .85). The MMR decreased significantly from 2013 to 2017 (APC, −6.28% [95% CI, −8.52% to −3.97%]; P < .001).Conclusions and RelevanceThese findings suggest a benefit associated with the availability of effective therapies in the past decade and further suggest that the use of new pharmacological therapies is associated with decreased MMR in the US population. These data are very encouraging and support the continued development of such therapies. Additionally, the accessibility of these treatments and the associated health care costs need to be addressed.

Background: Left ventricular thrombus (LVT) may develop in systolic heart failure or after acute myocardial infarction. The current recommendations support the use of vitamin K antagonists (VKAs) for the treatment of LVT. Limited data exist regarding the use of direct oral anticoagulants (DOACs) in patients with LVT. This meta-analysis aims to investigate the efficacy and safety of DOACs versus VKAs for LVT. Methods: We performed a comprehensive literature search using PubMed, Embase, and Cochrane Library databases through November 2020 for all studies that evaluated the efficacy and safety of DOACs versus VKAs in patients with LVT. The primary outcomes were LVT resolution, overall thromboembolic events, and thromboembolic stroke. The secondary outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence intervals (CIs) were obtained by the Mantel–Haenszel method within a random-effects model. Heterogeneity was assessed by I 2 statistic. Results: A total of 11 studies including 2153 patients with LVT on anticoagulation (570 on DOACs vs. 1583 on VKAs) were included. LVT resolution was significantly higher in DOACs compared with VKAs [RR: 1.18 (95% CI: 1.04–1.35); P = 0.01, I 2 = 25%]. However, no significant difference existed between DOACs and VKAs regarding overall thromboembolic events [RR: 1.10 (95% CI: 0.75–1.62); P = 0.61, I 2 = 0%] and thromboembolic stroke [RR: 0.63 (95% CI: 0.39–1.02); P = 0.06, I 2 = 0%]. Major bleeding [RR: 1.00 (95% CI: 0.66–1.51); P = 0.99, I 2 = 4%] and all-cause mortality [RR: 0.84 (95% CI: 0.50–1.43); P = 0.53, I 2 = 0%] were similar between the 2 groups. Conclusions: DOACs seem to be more efficacious in achieving LVT resolution compared with VKAs. However, there was no significant difference between the 2 groups in thromboembolic events, major bleeding, and all-cause mortality. Randomized controlled trials are needed to confirm our findings.

Background: Recent clinical trials have investigated the use of fluvoxamine in preventing clinical deterioration in nonhospitalized patients with acute COVID-19 infection via stimulation of sigma-1 receptors, which regulates cytokine production and functional inhibition of acid sphingomyelinase activity, which may prevent infection of epithelial cells with SARS-CoV-2. However, the role of fluvoxamine is currently unclear because of a paucity of studies, particularly because the drug is being repurposed as an immunomodulatory and antiviral agent.Study Question: Aim of our meta-analysis was to investigate the efficacy of fluvoxamine in nonhospitalized patients with acute COVID-19 infection.Data Source: Comprehensive literature search of PubMed, Embase, Cochrane Library databases, and Web of Science was performed from inception to February 10, 2022, for studies comparing fluvoxamine versus placebo for outpatient management of COVID-19.Study Design: The primary outcome of interest was rate of hospitalization. The secondary outcomes were rates of patients requiring mechanical ventilation and mortality. The random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). A P value ,0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I 2 index.Results: Three studies (2 randomized controlled trials and one prospective cohort trial) involving 1762 patients were included in the meta-analysis. In patients who received fluvoxamine compared with placebo, there was no significant difference in rates of hospitalization (RR 0.26, 95% CI, 0.04-1.73, P 5 0.16, I 2 5 62%), mechanical ventilation (RR 0.73, 95% CI, 0.45-1.19, P 5 0.21, I 2 5 0%), and mortality (RR 0.67, 95% CI, 0.37-1.22, P 5 0.19, I 2 5 0%).Conclusion: Current evidence does not indicate a significant effect of fluvoxamine on the rates of hospitalization, mechanical ventilation, and mortality of patients with COVID-19 infection.

Introduction: Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS). The use of IPVD has been shown to improve the partial pressure of oxygen in arterial blood (PaO2), reduce fraction of inspired oxygen (FiO2) requirements, and ultimately increase PaO2/FiO2 (P/F) ratios in ARDS patients. However, the role of IPVD in COVID-19 ARDS is still unclear. Therefore, we performed this meta-analysis to evaluate the role of IPVD in COVID-19 patients. Methods: Comprehensive literature search of PubMed, Embase, Web of Science and Cochrane Library databases from inception through April 22, 2022 was performed for all published studies that utilized IPVD in COVID-19 ARDS patients. The single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm meta-analysis. Primary outcomes for the 1-arm and 2-arm meta-analyzes were change in pre- and post-IPVD P/F ratios and mortality, respectively. Secondary outcomes for the 1-arm meta-analysis were change in pre- and post-IPVD positive end-expiratory pressure (PEEP) and lung compliance, and for the 2-arm meta-analysis the secondary outcomes were need for endotracheal intubation and hospital length of stay (LOS). Results: 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. The pre-IPVD P/F ratios were significantly lower compared to post-IPVD, but there was no significant difference between pre- and post-IPVD PEEP and lung compliance. The mortality rates, need for endotracheal intubation, and hospital LOS were similar between the IPVD and standard therapy groups. Conclusion: Although IPVD may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. However, randomized controlled trials are warranted to validate our findings.