Quiz Ref ID Osteoarthritis is among the most prevalent chronic diseases,¹ and is a leading cause of disability worldwide.^1-3 Effective management of osteoarthritis requires long-term treatment strategies for symptoms (pain and limitations in physical function) and joint structure changes that lead to disability.⁴ Efficacy reviews of treatments for osteoarthritis typically emphasize short-term pain control and often do not consider long-term outcomes.^5,6 Thus, the aim of the present study was to systematically search, review, and quantitatively analyze long-term outcomes from randomized clinical trials (RCTs) of medications for knee osteoarthritis.

Depression rates in older people worldwide vary from 10% to 15% of community-dwelling older persons. There are two others problems related to depression in old age, namely the high incidence of falls and the so-called fear of falling (FOF), with a prevalence ranging from 20% to 85%; it was initially considered a post-fall syndrome, which later as a fall-independent event. Study aims to conduct a systematic review and meta-analysis to bridge the existing gap in literature about the association between depressive symptomatology, FOF, use of antidepressant therapy and falls, also identifying a possible effect of the study quality on the outcome. The selection of studies was carried out between May 20, 2020, and July 27, 2020 and only observational clinical trials, written in English, with participants aged more or equal to 60 years affected by diagnosis of depression or treatment for depression mentioned both as a clinical diagnosis in older patient, and as a predictor/consequence of falls were included. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for reporting systematic reviews and meta-analysis, and the protocol was recorded in the International Prospective Register of Systematic Reviews (PROSPERO). The screening process ultimately led to the inclusion of 18 articles. Many of the included studies showed that depressive symptoms caused the subsequent increase in the number of falls. Results from the meta-analysis had no highlighted association between depression and falls, in contrast to other review and meta-analysis works: our work includes a substantial number of studies, with a relatively recent publication date, including patients diagnosed with depression, clearly evaluating the association between depression and falls. Results all seem to confirm the hypothesis of an interdependent association between the presence of FOF and the risk of fall, despite the high percentage of cross-sectional studies prevents inferring on the direction of the association. Therapeutic interventions aimed at decrease rate of falls reducing depressive symptoms and FOF.

PURPOSE: To analyze the prevalence of homologous recombination deficiency (HRD) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the prevalence of HRD in PDAC from PubMed, Scopus, and Cochrane Library databases, and online cancer genomic data sets. The main outcome was pooled prevalence of somatic and germline mutations in the better characterized HRD genes ( BRCA1, BRCA2, PALB2, ATM, ATR, CHEK2, RAD51, and the FANC genes). The secondary outcomes were prevalence of germline mutations overall, and in sporadic and familial cases; prevalence of germline BRCA1/2 mutations in Ashkenazi Jewish (AJ); and prevalence of HRD based on other definitions (ie, alterations in other genes, genomic scars, and mutational signatures). Random-effects modeling with the Freeman-Tukey transformation was used for the analyses. PROSPERO registration number: (CRD42020190813). RESULTS: Sixty studies with 21,842 participants were included in the systematic review and 57 in the meta-analysis. Prevalence of germline and somatic mutations was BRCA1: 0.9%, BRCA2: 3.5%, PALB2: 0.2%, ATM: 2.2%, CHEK2: 0.3%, FANC: 0.5%, RAD51: 0.0%, and ATR: 0.1%. Prevalence of germline mutations was BRCA1: 0.9% (2.4% in AJ), BRCA2: 3.8% (8.2% in AJ), PALB2: 0.2%, ATM: 2%, CHEK2: 0.3%, and FANC: 0.4%. No significant differences between sporadic and familial cases were identified. HRD prevalence ranged between 14.5%-16.5% through targeted next-generation sequencing and 24%-44% through whole-genome or whole-exome sequencing allowing complementary genomic analysis, including genomic scars and other signatures (surrogate markers of HRD). CONCLUSION: Surrogate readouts of HRD identify a greater proportion of patients with HRD than analyses limited to gene-level approaches. There is a clear need to harmonize HRD definitions and to validate the optimal biomarker for treatment selection. Universal HRD screening including integrated somatic and germline analysis should be offered to all patients with PDAC.

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO₂/FiO₂ ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Background: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU.Methods: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with ‘do-not-intubate’ (DNI) orders.Results: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30–41%]. 26% [21–30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36–54%]. 23% [15–32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65–78%]. Oxygenation on admission was the main source of between-study heterogeneity.Conclusions: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance.Registration: PROSPERO,https://www.crd.york.ac.uk/prospero/, CRD42020224788, December 11, 2020.