Challenges and opportunities in shared care for international patients treated with cellular therapy for nonmalignant disease.

As cellular therapies gradually become the mainstay of treatment for several nonmalignant diseases, there appears to be varied accessibility to these therapies globally. Despite considerable burden of nonmalignant conditions, such as sickle cell disease, thalassemia, and aplastic anemia in populations of low-middle-income countries, the utilization of cellular therapies remain sparse because of lack of resources. Globally, the frequency of hematopoietic stem cell transplant (HSCT) has increased disproportionately in countries with higher gross national income (GNI) per capita, governmental healthcare expenditures, and a high human development index. This leads to a large subset of international patients seeking care in the United States. This review summarizes the unique set of challenges that often arise when offering sophisticated therapies such as HSCT to international patients constituting of cross-cultural, logistical, financial, and medical challenges and the opportunities that are available to bridge the gap.

Mild to moderate COVID-19 illness in adult outpatients: Characteristics, symptoms, and outcomes in the first 4 weeks of illness.

ABSTRACT: 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.

Post-Marketing Analysis of Peripheral Neuropathy Burden with New-Generation Proteasome Inhibitors Using the FDA Adverse Event Reporting System

Proteasome inhibitors (PIs) are an integral component of multiple myeloma therapies. Peripheral neuropathy (PN) is a well-knownconsequence of PIs, most frequently reported with earlier generations such as bortezomib (BTZ). There is a paucity of data highlighting the risk of developing PN with the new-generation PIs carfilzomib (CFZ) and ixazomib (IZB). This study evaluated reports of PN encountered with all three PIs using the Food and Drug Administration Adverse Event (AE) Reporting System (FAERS). Signal disproportionality analysis was reported using the reporting odds ratio (ROR) with 95% confidence interval (CI). PN was reported in a total of 2.1%, 5.0%, and 10.9% of AEs with CFZ, IZB, and BTZ, respectively. The ROR (95% CI) for PN secondary to BTZ, CFZ, and IZB was 34.10 (32.76-35.49), 6.37 (5.50-7.37), and 14.97 (13.63-16.44), respectively. Compared to BTZ, CFZ and IZB have lower rates of reported PN, with RORs of 0.19 (0.16-0.22) and 0.48 (0.43-0.54), respectively.

Systemic Therapy and Sequencing Options in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-analysis.

Importance: 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 Synthesis: The 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.

Radial artery access is under-utilized in women undergoing PCI despite potential benefits: Mayo Clinic PCI Registry.

BACKGROUND: Women may benefit from radial artery access (RAA) for percutaneous coronary interventions (PCI) due to a higher risk of bleeding compared to men; however, RAA may be underutilized in women. We sought to determine the frequency and predictors of RAA use in patients undergoing PCI. METHODS: We studied 21,123 (29.0% female) participants in the Mayo Clinic PCI Registry from January 1, 2006-December 31, 2016. Data were analyzed as a cohort and by time tertiles. Frequency of RAA versus femoral access and bleeding events were recorded. Logistic regression was used to identify predictors of RAA. RESULTS: In the overall cohort, women compared to men were older (69.6 ± 12.6 vs. 65.6 ± 11.9; p < .001), more likely to present with acute coronary syndrome (82.0% in women vs. 80.0% in men; p = .0008) and had more comorbidities. RAA increased from tertile one (3.5% for women vs. 4.0% for men; p = .3) through tertile three (46.8% for women vs. 50.3% for men; p = .01), but remained lower in women. In multivariable analysis, female sex is associated with 22% less RAA use (OR 0.78, 95% CI 0.72-0.84; p < .0001). Women compared to men experienced more bleeding (6.3 vs. 3.0%; p < .0001) but bleeding was less likely in RAA (OR 0.45, 95% CI 0.36-0.56; p < .0001). CONCLUSION: Women undergoing PCI are less likely to receive RAA compared to men despite having a higher risk of bleeding. This trend persists despite increase in RAA use. Given the potential benefit of RAA in women, sex should be considered in patient selection for RAA.

Epidemiology of Primary Ophthalmic Inpatient Admissions in the United States.

PURPOSE: To determine the national estimates, demographics, and costs of inpatient eye care in the United States (US). DESIGN: Retrospective cross-sectional study. METHODS: National Inpatient Sample (NIS), a representative sample of all US community hospitals, was used to analyze inpatient admissions with a primary ophthalmic diagnosis from 2001 to 2014. National estimates of the most prevalent diagnoses were determined, and descriptive statistics were calculated for demographics and costs. RESULTS: From 2001 to 2014, there were an estimated 671 324 inpatient admissions (male patients, 51.6%; mean [standard deviation] age, 44.5 [27.3] years) in the US owing to an ophthalmic disorder-an annual rate of 16 per 100 000 population. The Mid-Atlantic region had the highest rate. Most admissions were owing to nontraumatic disorders (75.3%), classified as emergencies (41.8%), and covered by public insurance (48.9%). The median length of stay was 2 days and mortality was 0.2%. The total inflation-adjusted cost over the 14-year period was $5.9 billion. The most prevalent diagnosis was orbital cellulitis (14.5%), followed by orbital floor fracture (9.6%) and eyelid abscess (6.0%). Most diagnoses were infectious (28.0%) and the majority were attributed to external disease (24.3%). A total of 31.1% of all patients had an ophthalmic procedure, pars plana vitrectomy (4.8%) being the most common one. CONCLUSION: There were around 48 000 ophthalmic inpatient admissions in the US costing $421 million every year. Orbital pathology, namely infection and trauma, was the leading cause of admissions. Implementing interventions to decrease the incidence of these conditions may significantly reduce the burden of inpatient ophthalmic care.

Perceived influential factors toward participation in undergraduate research activities among medical students at Alfaisal University-College of Medicine: A Saudi Arabian perspective.

AIMS: (1) To explore correlations between medical students' participation in undergraduate research (UR) activities and their characteristics, and (2) to explore students' perceived influential factors toward participation in UR activities at Alfaisal University-College of Medicine, Saudi Arabia. METHODS: An online, anonymous, cross-sectional, self-rating survey was administered. Chi-square test was used to correlate between participation in UR activities and students' characteristics (age, academic year and grade point average [GPA]). Two-tailed Mann-Whitney U-test was used to compare the mean 5-point Likert scale responses between students with and without previous UR activities. RESULTS: About 218 students participated in the survey (n = 218/350; response rate: 62.3%). The top three influential factors to undertake UR activities were "facilitate entry into competitive residency programs," (88.1%) "improve curriculum vitae" (81.2%) and "publish in peer-reviewed journals" (79.8%). Percentage of participation in previous UR activities significantly differed by gender (p < 0.03825), academic year (p < 0.000003) and GPA (p < 0.02627). Students who had previous UR activities were more positively influenced to participate in future UR activities than those who did not (p < 0.0488). CONCLUSION: 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.

The Student-Authored Biomedical Publications at Alfaisal University, Saudi Arabia: a 6-year descriptive analysis.

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.