Safety of ACEi and ARB in COVID-19 management: A retrospective analysis.

BACKGROUND & AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of coronavirus disease 2019 (COVID-19) depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection.Severe acute respiratory yndrome with coronavirus (SARS-CoV2) is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of COVID-19 depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection. MATERIALS & METHODOLOGY: This multicenter retrospective observational study enrolled 2935 COVID-19 patients admitted at six hospitals in Southern California, USA, between March 2020 and August 2021. Our primary outcome was the association of pre-hospital use of ACEi and ARB on in-hospital mortality in COVID-19 patients. First, relevant deidentified patient data were extracted using an SQL program from the electronic medical record. Then, a bivariate analysis of the relationship between ACEi and ARB use and different study variables using χ2 and t test was done. Finally, we did a backward selection Cox multivariate regression analysis using mortality as a dependent variable. RESULTS: Of the 2935 patients in the study, hypertension was present in 40.6%, and congestive heart failure in 13.8%. ACEi and ARB were used by 17.5% and 11.3% of patients, respectively, with 28.8% of patients on either medication. After adjusting for confounding variables in the multivariate analysis, the use of ACEi (HR: 1.226, 95% CI: 0.989-1.520) or ARB (HR: 0.923, 95% CI: 0.701-1.216) was not independently associated with increased mortality. CONCLUSION: Our results are consistent with the clinical guidelines and position statements per the International Society of Hypertension, that there is no indication to stop the use of ACEi/ARB in COVID-19 patients.

Associations Between Women's Perception of Their Husbands'/Partners' Social Support and Pap Screening in Pacific Islander Communities.

Pacific Islanders experience high rates of cervical cancer incidence and mortality. This cross-sectional study examined the extent to which Samoan, Chamorro, and Tongan women's perceived receipt of social support from their husbands or male partners was associated with rates of routine cancer screening- specifically Pap testing. A total of 585 Pacific Islander women who live in the United States completed a self-report survey. Women who reported having a Pap test within the past 3 years had significantly higher scores on support from their husbands/male partners. Furthermore, the relationship of emotional support and informational support with increased Pap testing was significantly stronger for Tongan women. The findings suggest that men play an important role in promoting women's cancer prevention behaviors in Pacific Islander and potentially other collectivistic populations. Incorporating social support messages into interventions may be a simple yet effective strategy to increase women's Pap testing.

CBPR-Informed Recruitment and Retention Adaptations in a Randomized Study of Pap Testing Among Pacific Islanders in Southern California.

BACKGROUND: Pacific Islanders (PIs) experience high cervical cancer rates in the United States. Stage of diagnosis is also later for PIs than non-Hispanic Whites. The Pap test is severely underutilized among PIs: only 71% of Asian American and Pacific Islander women age 25 years or older received a Pap test within the last 3 years (U.S. average, 82%). Community-based participatory research (CBPR) is increasingly seen as an essential approach in designing and conducting culturally relevant and appropriate studies that reduce cancer incidence and other health disparities among minority and other medically underserved populations. PURPOSE: The purpose of this article is to describe the lessons learned thus far regarding the identification, recruitment, and retention of PI community organizations and members into a CBPR-informed, randomized, community trial promoting Pap testing. METHODS: This 5-year study used CBPR to develop and test the efficacy of a social support intervention for Chamorro, Samoan, and Tongan women to increase Pap testing in southern California. Eligible women were between the ages of 21 and 65, and married or in a long-term relationship with a man for at least 5 years. Women and their husbands or significant others received a 2-hour, culturally tailored workshop that include a group activity, information on Pap testing, a video, and corresponding materials. Comparison participants received a brochure about Pap testing. Three waves of data are collected from all participants: pretest (before workshop or brochure), posttest 1 (immediately after workshop or brochure), and posttest 2 (6 months follow-up). RESULTS: Of the 76 organizations approached to participate in the study, 67 (88.2%) eventually agreed to participate. Thus far, 473 women and 419 men completed the study pretest, post-test, education, and 6-month follow-up. Only 242 women and 204 men of the eligible participants have completed the follow-up survey (63.5% of women and 60.5% of men retained after 6 months). LESSONS LEARNED: The main strategy to overcome initial recruitment challenges was study staff persistence, because they averaged five contacts with each church or clan leader before receiving confirmation that an educational session can be scheduled. Personal connections provided an introduction to the most appropriate church or clan leader. Other efforts for retention include creation of an online version of the survey, re-attending church services, and creating special events organized around clan activities. CONCLUSIONS: Although CBPR improves the cultural competence and relevance of study activities for ethnically diverse populations, selected past research shows that it does not ensure that such designs overcome all of the unique challenges in ethnically diverse communities. PI-specific organizational recruitment and individual retention is influenced by study issues and cultural factors in each community.

Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy.

PURPOSE: Trastuzumab resistance has been linked to activation of the phosphoinositol 3-kinase (PI3K) pathway. Phosphatase and tensin homolog (PTEN) is a dual phosphatase that counteracts the PI3K function; PTEN loss leads to activation of the Akt cascade and the downstream mammalian target of rapamycin (mTOR). Preclinical studies demonstrated that mTOR inhibition sensitized the response to trastuzumab in mice with HER2 overexpressing and PTEN-deficient breast xenografts. Our trial evaluated the safety and efficacy of the combination of everolimus and trastuzumab in women with HER2-overexpressing metastatic breast cancer (MBC) that progressed on trastuzumab-based therapy. PATIENTS AND METHODS: This represents a pooled analysis (n = 47), stemming from two trials that occurred concurrently in The University of Texas MD Anderson Cancer Center, Beth Israel Deaconess Medical Center, and Dana-Farber Cancer Institute. Patients with HER2-overexpressing MBC who had progressed on trastuzumab-based therapy received trastuzumab every 3 weeks in combination with daily everolimus. RESULTS: Among 47 patients, the combination of everolimus and trastuzumab provided partial responses in seven patients (15%) and persistent stable disease (lasting 6 months or longer) in nine patients (19%), resulting in a clinical benefit rate of 34%. The median progression-free survival (PFS) was 4.1 month. Fatigue, infection, and mucositis were the predominant nonhematologic toxicities. Trastuzumab did not have significant influence on the pharmacokinetic profile of everolimus. Patients with PTEN loss demonstrated decreased overall survival (P = .048). However, PFS was not affected by PTEN loss. CONCLUSION: Inhibition of mTOR results in clinical benefit and disease response in patients with trastuzumab-resistant HER2-overexpressing MBC.