Effect of perceived discrimination on depression and suicidal ideation during the COVID-19 pandemic: a large-scale, repeated-measures study in the All of Us Research Program

ObjectiveThe COVID-19 pandemic has coincided with an increase in depressive symptoms as well as a growing awareness of health disparities and discrimination against racial and ethnic minority communities in the United States. Here, we examine the mental health impact of perceived discrimination during the pandemic in a large and diverse cohort of the All of Us Research Program.MethodsUsing repeated assessments of 62,651 participants in May to July of 2020, we fitted mixed-effects models to assess the effect of perceived discrimination on moderate to severe depression (Patient Health Questionnaire (PHQ)-9 ≥ 10) and suicidal ideation (PHQ-9 item 9 > 0), and applied inverse probability weights to account for non-random probabilities of completing the voluntary survey.ResultsPerceived discrimination was associated with an increased odds of depression (adjusted odds ratio (aOR) [95% CI]: 1.21 [1.20 -1.22]) and suicidal ideation (1.17 [1.16-1.18]). For depression, the effects were larger in earlier phases of the pandemic (interaction p=8.2×10−5), which varied by main reason for discrimination and self-reported race. Among those who identified race or ancestry as a primary reason for discrimination, Asian and Black participants had 24% and 17% increase in the odds of depression in May of 2020 (1.24 [1.17-1.31] and 1.17 [1.12-1.22]), respectively, versus a 3% and 7% increase in July (1.03 [0.96-1.10] and 1.07 [1.02-1.12]).ConclusionIn this large and diverse sample, increased levels of perceived discrimination were associated with higher odds of depression, particularly during the early phase of the pandemic among participants self-identifying as Asian or Black.

742Analyzing the statistical pitfalls of treating mediators as confounders

Background Numerous studies indicated that infants born small-for-gestational-age (SGA) are at higher risk of overweight. However, the association between SGA and overweight may be due to overcontrolling for body size. This study aimed to analyze the effect of controlling for child’s weight and height in the association between SGA and overweight in children born preterm. Methods Data were obtained from the Preterm Infant Multicenter Growth Study (n = 1089). The association between SGA and overweight at 36 months corrected age (CA) was analyzed using logistic regression models: 1) crude, 2) adjusted for baseline covariates, 3) adjusted for baselines covariates with additional adjustments separately for child’s weight and height at 21 months CA. Marginal structural models (MSM) with stabilized inverse probability weights were used to estimate the direct effect of SGA on overweight. Results The crude and adjusted models yielded a null association (OR, 95% CI: 0.88, 0.26-2.96; 0.95, 0.28-3.29). Adjusting for later height reversed the effect (OR, 95% CI: 2.31, 0.52-10.26), and adjusting for later weight reversed the effect and provided a significant association (OR, 95% CI: 6.60, 1.10-37.14). The MSMs with height and weight considered as mediators indicated no direct effect of SGA on overweight (OR, 95% CI: 0.83, 0.14-5.01; 0.71, 0.18-2.81). Conclusions Overcontrolling for body size can falsely induce an association between SGA and overweight. Key messages Mediators should not be treated as confounders.

Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register

ObjectiveTo compare event and incidence rates of herpes zoster (HZ), also known as shingles, in patients with rheumatoid arthritis under treatment with conventional synthetic (cs), targeted synthetic (ts) or biologic (b) disease-modifying antirheumatic drugs (DMARDs).MethodsPatients were prospectively enrolled from 2007 until October 2020. Reported HZ events were assigned to ongoing treatments or those terminated within 1 month prior to the HZ event. Exposure-adjusted event rates (EAERs) of HZ were calculated per 1000 patient years (py) and adjusted HRs with 95% CIs computed. Inverse probability weights (IPW) were used to adjust for confounding by indication.ResultsData of 13 991 patients (62 958 py) were analysed, with 559 HZ events reported in 533 patients. The EAER of HZ was highest for tsDMARDs (21.5, 95% CI 16.4 to 27.9), followed by B cell targeted therapy (10.3, 95% CI 8.0 to 13.0), monoclonal antitumour necrosis factor (anti-TNF) antibodies (9.3, 95% CI 7.7 to 11.2), interleukin 6 inhibitors (8.8, 95% CI 6.9 to 11.0), soluble TNF receptor fusion protein (8.6, 95% CI 6.8 to 10.8), T cell costimulation modulator (8.4, 95% CI 5.9 to 11.8) and csDMARDs (7.1, 95% CI 6.0 to 8.3). Adjusted for age, sex and glucocorticoids and weighted with IPW, tsDMARDs (HR 3.66, 95% CI 2.38 to 5.63), monoclonal anti-TNF antibodies (HR 1.63, 95% CI 1.17 to 2.28) and B cell targeted therapy (HR 1.57, 95% CI 1.03 to 2.40) showed a significantly higher risk compared with csDMARDs.ConclusionOur results provide evidence for a 3.6-fold increased risk of HZ associated with tsDMARDs and an increased risk of HZ under bDMARDs compared with csDMARDs.

Risks of Opportunistic Infections in People Living with HIV with Cancers Treated with Chemotherapy

Introduction We ascertained incidence of OIs in people living with HIV (PLHIV) with cancer undergoing chemotherapy with non-HIV comparators. Methods We identified 2,106 PLHIV and 2,981 uninfected Veterans with cancer who received at least one dose of chemotherapy between 1996 and 2017 from the Veterans Aging Cohort Study. We ascertained incident OIs within six months of chemotherapy amongst zoster, cytomegalovirus, tuberculosis, Candida esophagitis, Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, Cryptococcosis, atypical Mycobacterium infection, Salmonella bacteremia, histoplasmosis, coccidioidomycosis, or progressive multifocal leukoencephalopathy. We used Poisson methods to calculate OI incidence rates by HIV status, stratifying for hematological and non-hematological tumors. We compared OI rates by HIV status, using inverse probability weights of HIV status, further adjusting for PCP prophylaxis. Results We confirmed 106 OIs in 101 persons. Adjusted OI incidence rate ratios (IRR) indicated higher risk in PLHIV for all cancers (IRR 4·8; 95% confidence interval [CI]: 2·8-8·2), hematological cancers (IRR 8·2; 95% CI 2·4-27·3), and non-hematological cancers (IRR 3·9; 95% CI: 2·1-7·2). IRRs were not significantly higher in those with CD4>200 cells/mm 3 and viral load < 500 copies/mL (IRR 1·8; 95% CI: 0·9-3·2). All PCP cases (n=11) occurred in PLHIV, with two microbiologically unconfirmed cases among 1,467 PLHIV with non-hematological cancers, no PCP prophylaxis and CD4 counts >200/mm 3. Conclusions Veterans with HIV undergoing chemotherapy had higher rates of OIs than uninfected Veterans, particularly those with hematological cancers, but not in PLHIV with HIV controlled disease. Our study does not support systematic PCP prophylaxis in solid tumors in PLHIV with HIV controlled disease.

Advanced Placement Course Credit and Undergraduate Student Success in Gateway Science Courses

Approximately two million students take Advanced Placement (AP) examinations annually. However, departmental policies that allow students to replace introductory courses with AP credit greatly vary within and across universities, even across relatively similar universities. This study examines the impact of AP credit policies on subsequent course success in Biology, Chemistry, and Physics at six large public research universities (N = 48,230 students). Examining average treatment effects for students skipping college courses using inverse-probability weights with regression adjustment, we found that students who skipped actually performed similarly well or better in subsequent courses than students who did not skip, even in contexts where lower AP scores were accepted. We also discovered wide variation in percentage of students who chose to skip when meeting their local policies. Therefore, to reduce unnecessary coursework that is burdensome for both students and universities, we suggest that departments consider modifying AP credit policies and that advisors consider encouraging students to skip when they have eligible AP scores.

Adolescent Vision Health During the Outbreak of COVID-19: Association Between Digital Screen Use and Myopia Progression

The coronavirus (COVID-19) pandemic has impacted education systems globally, making digital devices common arrangements for adolescent learning. However, vision consequences of such behavioral changes are not well-understood. This study investigates the association between duration of daily digital screen engagement and myopic progression among 3,831 Chinese adolescents during the COVID-19 pandemic. Study subjects report an average of 2.70 (SD = 1.77), 3.88 (SD = 2.23), 3.58 (SD = 2.30), and 3.42 (SD = 2.49) hours of television, computer, and smartphone for digital learning use at home, respectively. Researchers analyzed the association between digital screen use and myopic symptoms using statistical tools, and find that every 1 h increase in daily digital screen use is associated with 1.26 OR [Odds Ratio] (95% CI [Confidence Interval: 1.21–1.31, p < 0.001]) higher risks of myopic progression. Using computers (OR = 1.813, 95% CI = 1.05–3.12, p = 0.032) and using smartphones (OR = 2.02, 95% CI = 1.19–3.43, p = 0.009) are shown to be associated with higher risks of myopic progression than television use. Results from additional sensitivity tests that included inverse probability weights which accounted for heterogeneous user profile across different device type categories confirm that these findings are robust. In conclusion, this study finds that daily digital screen use is positively associated with prevalence of myopic progression and holds serious vision health implications for adolescents.

Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study

(1) Background: There are limited data regarding the efficacy of convalescent plasma (CP) in critically ill patients admitted to the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). We aimed to determine whether CP is associated with better clinical outcome among these patients. (2) Methods: A retrospective single-center study including adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to the ICU for acute respiratory failure. The primary outcome was time to clinical improvement, within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale. (3) Results: Overall, 110 COVID-19 patients were admitted. Thirty-two patients (29%) received CP; among them, 62.5% received at least one CP with high neutralizing antibody titers (≥1:160). Clinical improvement occurred within 28 days in 14 patients (43.7%) of the CP group vs. 48 patients (61.5%) in the non-CP group (hazard ratio (HR): 0.75 (95% CI: 0.41–1.37), p = 0.35). After adjusting for potential confounding factors, CP was not independently associated with time to clinical improvement (HR: 0.53 (95% CI: 0.23–1.22), p = 0.14). Additionally, the average treatment effects of CP, calculated using the inverse probability weights (IPW), was not associated with the primary outcome (−0.14 days (95% CI: −3.19–2.91 days), p = 0.93). Hospital mortality did not differ between CP and non-CP groups (31.2% vs. 19.2%, p = 0.17, respectively). Comparing CP with high neutralizing antibody titers to the other group yielded the same findings. (4) Conclusions: In this study of life-threatening COVID-19 patients, CP was not associated with time to clinical improvement within 28 days, or hospital mortality.

No Efficacy of the Combination of Lopinavir/Ritonavir Plus Hydroxychloroquine Versus Standard of Care in Patients Hospitalized With COVID-19: A Non-Randomized Comparison

Objectives: No specific treatment has been approved for COVID-19. Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) have been used with poor results, and a trial showed advantages of combined antiviral therapy vs. single antivirals. The aim of the study was to assess the effectiveness of the combination of antivirals (LPV/r and HCQ) or their single use in COVID-19 hospitalized patients vs. standard of care (SoC).Methods: Patients ≥18 years with SARS-CoV-2 infection, defined as positive RT-PCR from nasal/oropharyngeal (NP/OP) swab or positive serology, admitted at L. Spallanzani Institute (Italy) were included.Primary endpoint: time to invasive ventilation/death. Secondary endpoint: time to two consecutive negative SARS-CoV-2 PCRs in NP/OP swabs. In order to control for measured confounders, a marginal Cox regression model with inverse probability weights was used.Results: A total of 590 patients were included in the analysis: 36.3% female, 64 years (IQR 51–76), and 91% with pneumonia. Cumulative probability of invasive ventilation/death at 14 days was 21.2% (95% CI 17.6, 24.7), without difference between SOC, LPV/r, hydroxychloroquine, HCQ + LPV/r, and SoC. The risk of invasive ventilation/death in the groups appeared to vary by baseline ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Overall cumulative probability of confirmed negative nasopharyngeal swabs at 14 days was 44.4% (95% CI 38.9, 49.9), without difference between groups.Conclusion: In this retrospective analysis, we found no difference in the rate of invasive ventilation/death or viral shedding by different strategies, as in randomized trials performed to date. Moreover, even the combination HCQ + LPV/r did not show advantages vs. SoC.

Surveillance as Determinant of Long-Term Survival in Non-Transplanted Hepatocellular Carcinoma Patients

Purpose: We aimed at assessing the impact of surveillance on long-term survival in HCC patients. Methods: From the ITA.LI.CA database, we selected 1028 cases with long (≥5 years, LS group) and 2721 controls with short-term survival (<5 years, SS group). The association between surveillance and LS was adjusted for confounders by multivariable logistic regression analysis. Survival of surveilled patients was presented both as observed and corrected for the lead-time bias, and the comparison of survival between surveillance and no surveillance groups was also performed after balancing the baseline characteristics with inverse probability weights (IPW). Results: LS patients were more frequently diagnosed under surveillance (p < 0.0001), and had more favorable baseline characteristics. Surveillance was an independent predictor of LS (OR = 1.413, 95% CI 1.195–1.671; p < 0.0001). The observed and the lead-time corrected survival of surveilled patients were significantly longer compared to the survival of not surveilled patients (p < 0.0001 and p = 0.0008, respectively). In IPW adjusted populations, no survival differences were demonstrated between the two groups (p = 0.30). Conclusions: Surveillance, increasing early-stage diagnosis and applicability of curative treatments, is a fundamental determinant of long-term survival in HCC patients. A wide implementation of surveillance programs should be pursued in order to improve HCC patients’ prognosis.