R package regmedint: extension of regression-based causal mediation analysis with effect measure modification by covariates

This is the supplementary document of R package regmedint that implements the extension of the regression-based causal mediation analysis first proposed by Valeri and VanderWeele (2013, 2015). It supports including effect measure modification by covariates (treatment-covariate and mediator-covariate product terms in mediator and outcome regression models), and also accommodates the original SAS macro and PROC CAUSALMED procedure in SAS when there is no effect measure modification.

The Associations between Poor Antibiotic and Antimicrobial Resistance Knowledge and Inappropriate Antibiotic Use in the General Population Are Modified by Age

Objectives: Understanding factors influencing inappropriate antibiotic use can guide the design of interventions to improve antibiotic practices and reduce antimicrobial resistance (AMR). Methods: A nationally representative cross-sectional survey (N = 2004) was conducted between November 2020 and January 2021. Knowledge of antibiotic use and AMR using the World Health Organization’s Multi-Country AMR Survey questionnaire, and antibiotic practices were examined. Multivariable logistic regression was performed to identify factors associated with inappropriate antibiotic use and examine effect measure modifications. Results: After adjusting for potential confounding, poor knowledge of antibiotic use was associated with a 3× increased odds of inappropriate antibiotic use in adults aged ≥50 years (aOR 3.11, 95% CI [2.24–4.32]), 5x increased odds in those aged 35–49 years (aOR 4.88, 95% CI [3.32–7.16]), and 7× increased odds in those aged 21–34 years (aOR 6.58, 95% CI [4.19–10.33]). While there was no statistically significant association in adults aged ≥50 years, poor knowledge of AMR increased the odds of inappropriate antibiotic use by 4 times in adults aged 35–49 years (aOR 3.73, 95% CI [1.53–9.11]) and 5 times in those aged 21–34 years (aOR 4.90, 95% CI [1.84–13.02]). Conclusions: Targeted educational interventions for specific age groups are needed in conjunction with empowering the public with knowledge of antibiotic use and AMR.

Elevated De Ritis Ratio Is Associated With Poor Prognosis in COVID-19: A Systematic Review and Meta-Analysis

Objective: This meta-analysis aims to assess whether elevated De Ritis ratio is associated with poor prognosis in patients with coronavirus 2019 (COVID-19).Methods: A systematic literature search was performed using PubMed, Embase, and EuropePMC databases up until September 17, 2021. De Ritis ratio is also known as Aspartate aminotransferase/alanine transaminase (AST/ALT) ratio. The main outcome was poor prognosis, a composite of mortality, severity, the need for ICU care, and intubation. The effect measure was odds ratios (ORs) and mean differences. We generated sensitivity and specificity, negative and positive likelihood ratio (NLR and PLR), diagnostic odds ratio (DOR), and area under curve (AUC).Results: There were eight studies with 4,606 patients. De Ritis ratio was elevated in 44% of the patients. Patients with poor prognosis have higher De Ritis ratio [mean difference 0.41 (0.31, 0.50), p < 0.001; I2: 81.0%] and subgroup analysis showed that non-survivors also have higher De Ritis Ratio [mean difference 0.47 (0.46, 0.48), p < 0.001; I2: 0%]. Elevated De Ritis ratio was associated with poor prognosis [OR 3.28 (2.39, 4.52), p < 0.001; I2: 35.8%]. It has a sensitivity of 55% (36–73), specificity of 71% (52–85), PLR 1.9, NLR.63, DOR of 3 (2–4), and AUC of.67 (0.63–0.71). The posterior probability of poor prognosis was 38% if De Ritis is elevated, while 17% if De Ritis is not elevated.Conclusion: Elevated De Ritis ratio is associated with poor prognosis in patients with COVID-19.Systematic Review Registration: PROSPERO ID: CRD42020216634.

Examining Optimism, Psychosocial Risks, and Cardiovascular Health Using Life's Simple 7 Metrics in the Multi-Ethnic Study of Atherosclerosis and the Jackson Heart Study

Background: Optimism has been shown to be positively associated with better cardiovascular health (CVH). However, there is a dearth of prospective studies showing the benefits of optimism on CVH, especially in the presence of adversities, i.e., psychosocial risks. This study examines the prospective relationship between optimism and CVH outcomes based on the Life's Simple 7 (LS7) metrics and whether multilevel psychosocial risks modify the aforementioned relationship.Methods: We examined self-reported optimism and CVH using harmonized data from two U.S. cohorts: Multi-Ethnic Study of Atherosclerosis (MESA) and Jackson Heart Study (JHS). Modified Poisson regression models were used to estimate the relationship between optimism and CVH using LS7 among MESA participants (N = 3,520) and to examine the relationship of interest based on four biological LS7 metrics (body mass index, blood pressure, cholesterol, and blood glucose) among JHS and MESA participants (N = 5,541). For all CVH outcomes, we assessed for effect measure modification by psychosocial risk.Results: Among MESA participants, the adjusted risk ratio (aRR) for ideal or intermediate CVH using LS7 comparing participants who reported high or medium optimism to those with the lowest level of optimism was 1.10 [95% Confidence Interval (CI): 1.04–1.16] and 1.05 (95% CI: 0.99–1.11), respectively. Among MESA and JHS participants, the corresponding aRRs for having all ideal or intermediate (vs. no poor) metrics based on the four biological LS7 metrics were 1.05 (0.98–1.12) and 1.04 (0.97–1.11), respectively. The corresponding aRRs for having lower cardiovascular risk (0–1 poor metrics) based on the four biological LS7 metrics were 1.01 (0.98–1.03) and 1.01 (0.98–1.03), respectively. There was some evidence of effect modification by neighborhood deprivation for the LS7 outcome and by chronic stress for the ideal or intermediate (no poor) metrics outcome based on the four biological LS7 metrics.Conclusion: Our findings suggest that greater optimism is positively associated with better CVH based on certain LS7 outcomes among a racially/ethnically diverse study population. This relationship may be effect measure modified by specific psychosocial risks. Optimism shows further promise as a potential area for intervention on CVH. However, additional prospective and intervention studies are needed.

Cost-effectiveness Analysis of Pre- Versus Post-operative Radiotherapy for Patients With Oral Cancer

Background: Treatment for resectable oral cavity cancer (OCC) often includes combinations of surgery and radiotherapy (RT), but there is no conclusive information on by which order these measures are best administered. The aim of this study was to assess cost-effectiveness of two alternative treatment regimens for patients with OCC, reflecting pre-and post-operative RT.Methods: The study was performed on data from the ARTSCAN 2 randomised, controlled trial, which compares pre-operative accelerated RT with post-operative conventionally fractionated RT. Two-hundred-fifty patients were randomised and 240 were eligible for treatment outcomes. Costs were retrieved from the hospital’s economic systems and national registries. The incremental cost-effectiveness ratio (ICER) was calculated, and a sensitivity analysis was performed. Overall survival (OS) was used as effect measure in the analysis.Results: Two-hundred-nine patients completed the treatment and had retrievable data on costs. There was no statistically significant difference in OS between the treatment modalities (log-rank p=0.23). OS at three years was 67% and 74% for pre- and post-operative RT, respectively. Mean direct costs per patient were € 65 958 for pre-operative RT and € 53 172 for post-operative RT, while indirect costs were € 75 874 and € 73 184, respectively. All projected results indicated that post-operative RT was cost-effective in comparison to pre-operative RT.Conclusions: Post-operative RT for patients with resectable OCC is cost-effective compared to pre-operative RT.

Association between the dispositional optimism and depression in young people: a systematic review and meta-analysis

The objective of this study was to perform a meta-analysis of publications that reported the association between dispositional optimism and depression during youth, analyzing if the strength of this relationship varied according to potential factors. Systematic searches were carried out in APA PsycNet, Virtual Health Library, Embase, Web of Science, PubMed Central, and Scopus to collect English, Portuguese, or Spanish studies from 2009 onwards. Two reviewers selected the eligible articles, assessed the quality of each study, and extracted the data. For the synthesis of the results, a meta-analytic approach was used. We identified 4077 publications in the initial searches and 22 in the supplementary searches, from which 31 studies remained for analysis once the eligibility criteria were applied. The results showed a statistically significant negative association between dispositional optimism and depression in the young population, age being a factor that modifies the effect measure between these variables. This meta-analysis provides a consistent and robust synthesis on the interaction effect between dispositional optimism and depression in the young population. Based on these findings, early clinical admissions may effectively improve optimistic tendencies in young people, which could help them prevent depressive symptoms or episodes.

Are Patients with Coronavirus Disease 2019 and Obesity at a Higher Risk of Hospital and Intensive Care Unit Admissions? A Systematic Review and Meta-analysis

BACKGROUND: Obesity, common condition among patients with COVID-19, contributes to illness severity during hospitalization. To date, knowledge on the prevalence, risk of hospital and intensive care units (ICU) admissions and mortality is limited. Therefore, systematic review and meta-analysis were conducted using a PRISMA guideline. PURPOSE: The study aimed to address the prevalence, risk of hospital and ICU admissions and mortality among patients with COVID-19 and obesity. METHODS: The Newcastle–Ottawa scale was used to assess the quality of a study. Primary outcomes were the prevalence and risk of hospitalization, and secondary outcomes were the risk of ICU admissions and mortality risk. Mantel–Haenszel with random effects was applied, and the effect measure was odds ratio (OR) with 95% confidence interval (CI). RESULTS: Nine studies were included in the systematic review, and only four studies for meta-analysis. Among 29,776 patients with COVID-19, obesity was identified as the second-highest comorbidity. The prevalence rates of obesity and severe obesity among patients with COVID-19 were 26.1% and 15.5%, respectively. Obesity resulted in significantly increased risk of hospital admission (OR = 1.99, 95% CI = 1.12–3.53, p = 0.02) and ICU admission (OR = 1.77, 95% = CI 1.52–2.06, p < 0.00001). Severe obesity had a significantly increased risk of ICU admission (OR = 1.79, 95% CI = 1.42–2.25, p < 0.00001). The mortality rate of patients with COVID-19 and obesity was about 30.5% (438/1,434), and 19.7% (2,777/14,095) of them recovered from COVID-19. CONCLUSION: Obesity poses as nearly twice the risk of hospital and ICU admissions, and severe obesity contributes to almost twice the risk of ICU admissions.

Effect of Statins on Helicobacter pylori Eradication Rate: A Systematic Review and Meta-Analysis

Statins have been used as adjuvants to standard treatment in order to increase the eradication rates<i></i>of<i> Helicobacter pylori</i> infection. This study aimed to summarize the results of the efficacy of adding statins to standard treatments used for the eradication<i></i>of<i> H. pylori</i> infection. We conducted a systematic search using a comprehensive combination of keywords in PubMed/MEDLINE, Web of Science, and Scopus to retrieve relevant studies from 1990 to 2020. The estimate of pooled relative risk (RR), as the effect measure, was calculated using random effects meta-analyses in Stata 14. We finally included 5 studies (all of them were randomized controlled trials). The meta-analysis of all studies showed that the pooled RR (95% confidence interval) was 1.03 (0.64–1.68) in the random effects model, which was not statistically significant. In other words, based on our meta-analysis, the addition of statins as an adjuvant therapy to the standard treatment regimens does not increase the rate of <i>H. pylori</i> eradication. However, further evidence is needed to confirm this result as the number of available studies was small.

The Efficacy of Low-dose Aspirin in Pregnancy Among Women in Malaria-endemic Countries

BackgroundLow dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia. MethodsThis is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence proportion ratios (PRs) for LDA by malaria for outcomes, and regression modelling to evaluate effect measure modification. We evaluated hemoglobin in late pregnancy based on malaria infection in early pregnancy.Results1,446 women were analyzed, with a malaria prevalence of 63% in the DRC site, 38% in the Kenya site, and 6% in the Zambia site. Preterm birth occurred in 83 (LDA) and 90 (placebo) women, (PR 0.92, 95% CI 0.70, 1.22), without interaction between LDA and malaria (p=0.75). Perinatal mortality occurred in 41 (LDA) and 43 (placebo) pregnancies, (PR 0.95, 95% CI 0.63, 1.44), with an interaction between malaria and LDA (p=0.014). Hemoglobin was similar by malaria and LDA status.ConclusionsMalaria in early pregnancy did not modify the effects of LDA on preterm birth, but modified the effect of LDA on perinatal mortality. This effect measure modification deserves continued study as LDA is used in malaria endemic regions.