The treatment landscape for advanced hepatocellular carcinoma (HCC) has recently changed and become relatively confusing. Head-to-head comparisons between most of the available agents have not been performed and are less likely to be examined in a prospective fashion in the future. Therefore, a network meta-analysis (NMA) is helpful to compare different agents from across different trials.OBJECTIVE To evaluate comparative effectiveness of different systemic treatments in advanced patients with HCC across lines of therapy.DATA SOURCES We searched various databases for abstracts and full-text articles published from database inception through March 2020.STUDY SELECTION We included phase 3 trials evaluating different vascular endothelial growth factor inhibitors (VEGFis), checkpoint inhibitors (CPIs), or their combinations in advanced HCC, in the first-line or refractory setting. DATA EXTRACTION AND SYNTHESISThe reporting of this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The overall effect was pooled using the random effects model. MAIN OUTCOMES AND MEASURES Outcomes of interest included overall (OS) and progression-free survival (PFS).FINDINGS Fourteen trials (8 in the first-line setting and 6 in the second-line setting) at low risk of bias were included. The 8 trials in the first-line setting encompassed a total of 6290 patients, with an age range of 18 to 89 years. The 5 trials included in the second-line analysis encompassed a total of 2653 patients, with an age range of 18 to 91 years. Network meta-analysis showed the combination of atezolizumab and bevacizumab was superior in patients with HCC treated in the first-line setting compared with lenvatinib (HR, 0.63; 95% CI, 0.44-0.89), sorafenib (HR, 0.58; 95% CI, 0.42-0.80), and nivolumab (HR, 0.68; 95% CI, 0.48-0.98). In the refractory setting, NMA showed that all studied drugs had PFS benefit compared with placebo. However, this only translated into OS benefit with regorafenib (HR, 0.62; 95% CI, 0.51-0.75) and cabozantinib (HR, 0.76; 95% CI, 0.63-0.92) compared with placebo. In the NMA of patients with α-fetoprotein (AFP) levels of 400 ng/mL or greater, regorafenib, cabozantinib, and ramucirumab showed PFS and OS benefit compared with placebo with no superiority of an active drug compared with any others.CONCLUSIONS AND RELEVANCE This systematic review and NMA of 14 trials found that atezolizumab and bevacizumab in combination is now considered the standard of care in the first-line setting in patients with advanced HCC. Regorafenib and cabozantinib are preferred options in refractory patients, with ramucirumab as an additional option in those with levels of AFP of 400 ng/mL or higher. Future trials should focus on other potential combinations and best treatment strategy in patients with prior VEGFi/CPI exposure.
Students demonstrated positive attitudes toward UR activities. The relationships between participation in UR activities and male gender, increased number of years spent at medical college and higher GPA were directly proportional.
There are limited numbers of studies which comprehensively explored the research publications authored by medical students. To descriptively analyze the student-authored research publications originating from Alfaisal University—College of Medicine (Riyadh, Saudi Arabia) over a 6-year period. All student-authored research publications were retrieved from PubMed® and the College’s publication database. Study inclusion criteria included: (1) at least one medical student author, (2) published and/or accepted in-press PubMed-indexed article from 10 September 2008 to 31 December 2014. Data was transferred to Microsoft Excel Software for descriptive statistical analysis of variable parameters. Seventy-three (n = 73) articles met the study inclusion criteria. They were published by 170 students; the majority were males (79.4 %) and clerkship students (65.9 %). There was a markedly steady increase in number of yearly publications from 1 publication in 2009 to 35 publications by the end of 2014. Fifty (68.5 %), twenty-nine (39.7 %) and thirty-seven (50.7 %) students were first, second and corresponding authors, respectively. The most frequent research areas were clinical science (43.8 %), basic science (23.3 %) and medical education (21.9 %). The most frequent research types were case reports (41.1 %), research articles (32.9 %) and correspondence letters (15.1 %). Fifty-seven (78.1 %) and sixteen (21.9 %) publications took place in local and abroad institutes, respectively. Most publications (71.2 %) had impact factors below 2. The mean ± SD of articles’ impact factors and citations were 3.9 ± 9.9 and 1.9 ± 4.1, respectively. Students demonstrated positive attitudes towards publishing and significantly contributed to the institution’s pool of research publications.
Most patients with coronavirus disease 2019 (COVID-19) have mild to moderate illness not requiring hospitalization. However, no study has detailed the evolution of symptoms in the first month of illness. At our institution, we conducted remote (telephone and video) visits for all adult outpatients diagnosed with COVID-19 within 24 h of a positive nasopharyngeal polymerase chain test for SARS-CoV-2. We repeated regular video visits at 7, 14, and 28 days after the positive test, retrospectively reviewed the prospective data collected in the remote visits, and constructed a week by week profile of clinical illness, through week 4 of illness. We reviewed the courses of 458 symptomatic patients diagnosed between March 12, 2020, and June 22, 2020, and characterized their weekly courses. Common initial symptoms included fever, headache, cough, and chest pain, which frequently persisted through week 3 or longer. Upper respiratory or gastrointestinal symptoms were much shorter lived, present primarily in week 1. Anosmia/ageusia peaked in weeks 2 to 3. Emergency department visits were frequent, with 128 visits in the 423 patients who were not hospitalized and 48 visits among the 35 outpatients (7.6%) who were eventually hospitalized (2 subsequently died). By the fourth week, 28.9% said their illness had completely resolved. After the 4-week follow up, 20 (4.7%) of the 423 nonhospitalized patients had further medical evaluation and management for subacute or chronic COVID-19 symptoms. Mild to moderate outpatient COVID-19 is a prolonged illness, with evolving symptoms commonly lasting into the fourth week of illness.
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