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Objective A substantial proportion of patients with rheumatic heart disease (RHD) have tricuspid regurgitation (TR). This study aimed to identify the impact of functional TR on clinical outcomes and predictors of progression in a large population of patients with RHD.Methods A total of 645 patients with RHD were enrolled, mean age of 47±12 years, 85% female. Functional TR was graded as absent, mild, moderate or severe. TR progression was defined either as worsening of TR degree from baseline to the last follow-up echocardiogram or severe TR at baseline that required surgery or died. Incidence of TR progression was estimated accounting for competing risks.Results Functional TR was absent in 3.4%, mild in 83.7%, moderate in 8.5% and severe in 4.3%. Moderate and severe functional TR was associated with adverse outcome (HR 1.91 (95% CI 1.15 to 3.2) for moderate, and 2.30 (95% CI 1.28 to 4.13) for severe TR, after adjustment for other prognostic variables. Event-free survival rate at 3-year follow-up was 91%, 72% and 62% in patients with no or mild, moderate and severe TR, respectively. During mean follow-up of 4.1 years, TR progression occurred in 83 patients (13%) with an overall incidence of 3.7 events (95% CI 2.9 to 4.5) per 100 patient-years. In the Cox model, age (HR 1.71, 95% CI 1.34 to 2.17), New York Heart Association functional class III/IV (HR 2.57, 95% CI 1.54 to 4.30), right atrial area (HR 1.52, 95% CI 1.10 to 2.10) and right ventricular (RV) dysfunction (HR 2.02, 95% CI 1.07 to 3.84) were predictors of TR progression. By considering competing risk, the effect of RV dysfunction on TR progression risk was attenuated.Conclusions In patients with RHD, functional TR was frequent and associated with adverse outcomes. TR may progress over time, mainly related to right-sided cardiac chambers remodelling.

Abstract Coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has impacted the lives and wellbeing of many people. This globally widespread disease poses a significant public health concern that urges to discover an effective treatment. This review paper discusses the effectiveness of repurposed drugs used to treat COVID-19 and potential novel therapies for COVID-19. Among the various repurposed drugs, remdesivir is the only agent approved by the Food and Drug Administration (FDA) to treat COVID-19. On the other hand, several drugs have been listed in the Emergency Use Authorization (EUA) by the FDA to treat COVID-19, including casirivimab and imdevimab, baricitinib (in combination with remdesivir), bamlanivimab, tocilizumab, and IL-6 inhibitors. In addition, in vitro and clinical studies have suggested cepharanthine, sotrovimab, and XAV-19 as potential treatments to manage COVID-19. Due to inadequate understanding of COVID-19 and the rapid mutation of SARS-CoV-2, COVID-19 remains a threat to global public health, with vaccination considered the most effective method to decrease COVID-19 transmission currently. Nevertheless, with the intense efforts of clinical researchers globally, more promising treatments for COVID-19 will be established in the future.

Abstract Background New York City (NYC) emergency departments (EDs) experienced a surge of patients because of coronavirus disease 2019 (COVID‐19) in March 2020. NYC Health and Hospitals established rapid medical screening exams (MSE) and each hospital designated areas to perform their MSE. Five of the 11 hospitals created a forward treatment area (FTA) external to the ED to disposition patients before entering who presented with COVID‐like symptoms. Three hospitals used paper‐based, and 2 used an electronic medical record (EMR)‐based MSE. This study evaluated the effectiveness of safely discharging patients home from the FTA while also evaluating the efficiency of using paper‐based versus EMR‐based MSEs. Methods Charts were reviewed using standardized data extraction templates. Patients discharged from the FTA were contacted by phone, and a structured interview captured additional data regarding subsequent clinical courses. Chi‐square tests were used to compare proportions of patients hospitalized, as well as proportions of patients with vital signs recorded. Mortality rates were compared with Fisher exact test. A logistic regression model with fixed effects to account for clustering at hospitals was used to compare the odds of being sent to the ED for further evaluation based on vital signs and adjusted for age and sex Results Across 5 EDs, 3335 patients were evaluated in their FTAs from March 17, 2020, to April 27, 2020. A total of 970 (29.1%) patients were referred for further evaluation into the ED, of which 203 (20.9%) were hospitalized and 19 (2.0%) died. Of 2302 patients discharged from the FTA, 182 (7.9%) returned to the ED within 7 days, resulting in 42 (1.8%) hospitalizations and 7 (0.3%) deaths. Facilities using EMR‐MSE discharged more patients from their FTA (81.9% vs 65.3%, P

Category: Ankle Introduction/Purpose: The modified Broström’s procedure has been widely accepted as the operative treatment of choice for treating lateral ankle instability in patients that have failed nonoperative management. However, the predisposing risk factors for failure of operative treatment, which has important implications for patient selection, is unknown. The purpose of this study is to thus identify independent risk factors for failure of an index Broström’s procedure. Methods: A retrospective single institutional study of 123 modified Broström’s procedures, average age 40 years, was performed with a minimum of 2 year follow-up. An electronic query based on Current Procedural Terminology codes was initially performed followed by a manual review of the operative report. Patients with any concurrent osteotomy, arthrodesis, or arthroplasty procedures were excluded. Foot and Ankle Ability Measure (FAAM) and Short Form Survey 12 (SF-12) were obtained both preoperatively and postoperatively. Cormorbidities and relevant demographic information were manually obtained. Treatment success was defined as a postoperative FAAM Sport score increase by greater than 9 points, an established minimal clinical difference established in the literature. A linear regression controlling demographic factors and baseline scores was utilized to predict scores at last follow-up. Results: At last follow-up, 31.4% did not demonstrate a self reported clinical improvement in the FAAM Sport scores with 2% (3/123) of the entire cohort requiring reoperation. A higher preoperative physical SF-12 score was associated with a reduction in the postoperative physical SF-12 score (p=0.035) while higher body mass index (p=0.010) was associated lower mental component SF-12 scores at follow-up. Interestingly, higher age is associated with higher 2-year PCS score. Furthermore, the occurrence of a complication was associated with lower ADL (p

Background There is a high incidence of serious mental illness (SMI) and antipsychotic use in the respiratory high dependence unit (HDU) compared with the general population. However, there is a paucity of data in the extant literature evaluating the relationships between respiratory failure and antipsychotics. Aims To investigate the relationship between antipsychotics and respiratory failure in people admitted to a respiratory HDU, and to gain a better understanding of the potential impact of antipsychotic medications on respiratory outcomes. Method Medical, demographic and clinical outcome data were collected for a consecutive sample of 638 individuals admitted to a respiratory HDU between the dates 1 January 2018 and 29 May 2021 at a large quaternary hospital. Results Multivariate models controlling for confounders found that antipsychotic medications increased risk of admission for type 2 respiratory failure and chronic obstructive pulmonary disease exacerbation without hypercapnia by 3.7 and 11.45 times, respectively. For people admitted with type 2 respiratory failure, antipsychotic use increased the risk of requiring non-invasive ventilation by 4.9 times. Those prescribed an antipsychotic were more likely to be readmitted within 30 days. Over 30% of individuals were prescribed antipsychotics for an unlicensed indication. Conclusions Poor respiratory outcomes may be a previously unknown adverse drug reaction of antipsychotics. Modifications to clinical care and clinical pathways for those with SMI prescribed antipsychotic medications, including optimising their chronic health and deprescribing where appropriate, should be prioritised.

Coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has impacted the lives and wellbeing of many people. This globally widespread disease poses a significant public health concern that urges to discover an effective treatment. This review paper discusses the effectiveness of repurposed drugs used to treat COVID-19 and potential novel therapies for COVID-19. Among the various repurposed drugs, remdesivir is the only agent approved by the Food and Drug Administration (FDA) to treat COVID-19. On the other hand, several drugs have been listed in the Emergency Use Authorization (EUA) by the FDA to treat COVID-19, including casirivimab and imdevimab, baricitinib (in combination with remdesivir), bamlanivimab, tocilizumab, and IL-6 inhibitors. In addition, in vitro and clinical studies have suggested cepharanthine, sotrovimab, and XAV-19 as potential treatments to manage COVID-19. Due to inadequate understanding of COVID-19 and the rapid mutation of SARS-CoV-2, COVID-19 remains a threat to global public health, with vaccination considered the most effective method to decrease COVID-19 transmission currently. Nevertheless, with the intense efforts of clinical researchers globally, more promising treatments for COVID-19 will be established in the future. [ABSTRACT FROM AUTHOR]

Classification is a vexing problem in folkloristics. Although broad genre classifications such as “ballad”, “folktale”, “legend”, “proverb”, and “riddle” are well established and widely accepted, these formal classifications are coarse and dolittle more than provide a first level sort on materials for collections that can easily include tens, if not hundreds, of thousands of records.

An expanded GGGGCC hexanucleotide in C9ORF72 (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It has been proposed that expanded transcripts adopt G-quadruplex (G-Q) structures and associate with proteins, but whether this occurs and contributes to disease is unknown. Here we show first that the protein that predominantly associates with GGGGCC repeat RNA in vitro is the splicing factor hnRNP H, and that this interaction is linked to G-Q formation. We then show that G-Q RNA foci are more abundant in C9 ALS patient fibroblasts and astrocytes compared to those without the expansion, and more frequently colocalize with hnRNP H. Importantly, we demonstrate dysregulated splicing of multiple known hnRNP H-target transcripts in C9 patient brains, which correlates with elevated insoluble hnRNP H/G-Q aggregates. Together, our data implicate C9 expansion-mediated sequestration of hnRNP H as a significant contributor to neurodegeneration in C9 ALS/FTD.