Approaches to estimate bidirectional causal effects using Mendelian randomization with application to body mass index and fasting glucose.

Mendelian randomization (MR) is an epidemiological framework using genetic variants as instrumental variables (IVs) to examine the causal effect of exposures on outcomes. Statistical methods based on unidirectional MR (UMR) are widely used to estimate the causal effects of exposures on outcomes in observational studies. To estimate the bidirectional causal effects between two phenotypes, investigators have naively applied UMR methods separately in each direction. However, bidirectional causal effects between two phenotypes create a feedback loop that biases the estimation when UMR methods are naively applied. To overcome this limitation, we proposed two novel approaches to estimate bidirectional causal effects using MR: BiRatio and BiLIML, which are extensions of the standard ratio, and limited information maximum likelihood (LIML) methods, respectively. We compared the performance of the two proposed methods with the naive application of UMR methods through extensive simulations of several scenarios involving varying numbers of strong and weak IVs. Our simulation results showed that when multiple strong IVs are used, the proposed methods provided accurate bidirectional causal effect estimation in terms of median absolute bias and relative median absolute bias. Furthermore, compared to the BiRatio method, the BiLIML method provided a more accurate estimation of causal effects when weak IVs were used. Therefore, based on our simulations, we concluded that the BiLIML should be used for bidirectional causal effect estimation. We applied the proposed methods to investigate the potential bidirectional relationship between obesity and diabetes using the data from the Multi-Ethnic Study of Atherosclerosis cohort. We used body mass index (BMI) and fasting glucose (FG) as measures of obesity and type 2 diabetes, respectively. Our results from the BiLIML method revealed the bidirectional causal relationship between BMI and FG in across all racial populations. Specifically, in the White/Caucasian population, a 1 kg/m2 increase in BMI increased FG by 0.70 mg/dL (95% confidence interval [CI]: 0.3517-1.0489; p = 8.43×10-5), and 1 mg/dL increase in FG increased BMI by 0.10 kg/m2 (95% CI: 0.0441-0.1640; p = 6.79×10-4). Our study provides novel findings and quantifies the effect sizes of the bidirectional causal relationship between BMI and FG. However, further studies are needed to understand the biological and functional mechanisms underlying the bidirectional pathway.

Secondhand tobacco smoke exposure in homes and vehicles in youth: disparities among racial, and sexual and gender minorities.

Background: Secondhand smoke exposure (SHSe) among youth is a serious public health concern, leading to an increased risk of conditions such as asthma and respiratory infections. However, there is little research on SHSe among vulnerable populations, such as racial and sexual minorities. Understanding the factors associated with youth SHSe in homes and vehicles is crucial to developing better protective policies. Methods: This study utilized 2020 data from the National Youth Tobacco Survey, a representative sample of middle- and high-school students in the US. The primary outcomes were youth SHSe at home and while riding in a vehicle. Multinomial regression models were used to assess factors associated with SHSe. Results: The data included 9,912 students enrolled in grades 6 through 12 in the United States who reported never using any form of tobacco. Non-Hispanic Black students living with someone who does not use any form of tobacco products were significantly more likely to experience moderate [OR = 2.1 (1.1-3.9), p = 0.03] and severe [OR = 5.1 (2.2-11.7), p < 0.001] secondhand smoke exposure (SHSe) in homes compared to their non-Hispanic White counterparts. Heterosexual female students had lower odds of reporting moderate SHSe in the home compared to heterosexual males [OR = 0.7 (0.6-0.99), p = 0.02], whereas bisexual females had two-fold increased odds of severe SHSe in homes [OR = 2.0 (1.2-3.4), p = 0.01]. Conclusion: Significant efforts are needed to develop targeted interventions to reduce SHSe in homes and vehicles, particularly in these vulnerable populations.

Awareness and interest in cannabis use for cancer management among cancer survivors.

BACKGROUND: We examined the awareness, interest, and information sources relating to cannabis use for cancer management (including management of cancer symptoms and treatment-related side effects) and determined factors associated with cancer survivors' awareness and interest in learning about cannabis use for cancer management. METHODS: This was a cross-sectional study of adult cancer survivors (N = 1886) receiving treatment at a comprehensive cancer center. Weighted prevalence and multivariable logistic regression analyses were conducted. RESULTS: Among cancer survivors, 88% were aware and 60% were interested in learning about cannabis use for cancer management. Common sources of information to learn about cannabis use for cancer management were cancer doctors/nurses (82%), other patients with cancer (27%), websites/blogs (26%), marijuana stores (20%), and family/friends (18%). The odds of being aware of cannabis use for cancer management was lower among male compared to female survivors (adjusted odds ratio [AOR]: 0.61; 95% confidence interval [CI]: 0.41-0.90), non-Hispanic Blacks compared to non-Hispanic Whites (AOR: 0.36; 95% CI: 0.21-0.62), and survivors who do not support the legalization of cannabis for medical use compared to those who do (AOR: 0.10; 95% CI: 0.04-0.23). On the other hand, the odds of being interested in cannabis use for cancer management was higher among non-Hispanic Blacks compared to non-Hispanic Whites (AOR: 1.65; 95% CI: 1.04-2.62), and among cancer survivors actively undergoing cancer treatment compared to patients on non-active treatment (AOR: 2.25; 95% CI: 1.74-2.91). CONCLUSION: Awareness of cannabis use for cancer management is high within the cancer survivor population. Results indicated health care providers are leading information source and should receive continued medical education on cannabis-specific guidelines. Similarly, tailored educational interventions are needed to guide survivors on the benefits and risks of cannabis use for cancer management.

Prevalence, reasons for use, perceived benefits, and awareness of health risks of cannabis use among cancer survivors - implications for policy and interventions.

BACKGROUND: There is increasing discourse on the use of cannabis as a palliative for cancer/cancer-treatment-related symptoms. We described the prevalent reasons for use, perceived benefits, and awareness of health risks from cannabis use for cancer management among cancer survivors. METHODS: Cross-sectional survey of adult (≥ 18 years) cancer survivors from 41 US states receiving treatment at a comprehensive cancer center. RESULTS: Of 1,886 cancer survivors included, 17.4% were current users, 30.5% were former users, and 52.2% were never users of cannabis. Among survivors who currently or formerly used cannabis after their cancer diagnosis (n = 510), the reasons for cannabis use in cancer management were; sleep disturbance (60%), pain (51%), stress (44%), nausea (34%), and mood disorder/depression (32%). Also, about a fifth (91/510) of survivors used cannabis to treat their cancer. Across the different symptoms assessed, over half of the survivors who reported a reason for using cannabis currently or after their cancer diagnosis perceived that cannabis was helpful to a great extent in improving their symptoms. However, of the 167 survivors who reported awareness of potential health risks from cannabis use, the awareness of adverse health risks associated with cannabis use was low: suicidal thoughts (5%), intense nausea and vomiting (6%), depression (11%), anxiety (14%), breathing problems (31%), and interaction with cancer drugs (35%). CONCLUSION: Prevalence of cannabis use among survivors was notable, with most reporting a great degree of symptomatic improvement for the specified reason for use. However, only a few were aware of the health risks of cannabis use during cancer management. IMPLICATIONS FOR CANCER SURVIVORS: With more cancer survivors using cannabis as a palliative in managing their cancer-related symptoms, future guidelines and policies on cannabis use in cancer management should incorporate cannabis-based interventions to minimize the inadvertent harm from cannabis use during cancer treatment among survivors.

Cannabis Use among Cancer Survivors: Use Pattern, Product Type, and Timing of Use.

Despite growing interest in the use of cannabis for the treatment of cancer-related symptoms, there are limited studies that have assessed the use pattern, type, and mode of delivery of cannabis products used by cancer survivors. This study describes the current state of the use pattern, product type, and mode of delivery of cannabis used by cancer survivors. This was a cross-sectional study of cancer survivors from 41 U.S. states who received treatment at the largest NCI-designated comprehensive cancer center. The weighted prevalence of the use patterns, product types, and modes of delivery of cannabis used by cancer survivors was estimated. A total of 1886 cancer survivors were included in the study, with 915 (48% [95% CI: 45-51]) reporting ever using cannabis. Of survivors who had ever used cannabis, 36% (95% CI: 33-40) were current users. Among survivors who reported cannabis use after diagnosis, 40% used cannabis during and after cancer treatment, 35% used cannabis during treatment, and 25% used cannabis after completing their cancer treatment. Additionally, 48% of survivors reported an increase in cannabis use since cancer diagnosis. The commonest types of cannabis products used by cancer survivors were dry leaf cannabis (71%), cannabidiol (CBD) oil (46%), and cannabis candy (40%). Moreover, cancer survivors frequently used baked goods (32%), creams and gels (21%), and tinctures (18%). Furthermore, among ever users, the predominant mode of use was cannabis inhalation/smoking (69%) compared to eating/drinking (59%). More so, the common mode of inhalation/smoking of cannabis products were rolled cannabis cigarettes (79%), pipes (36%), water pipes (34%), vaporizers or vapes (14%), and e-cigarette devices (14%). A substantial number of cancer survivors use cannabis during cancer treatment, with increased use following cancer diagnosis. The forms and modes of delivery of cannabis varied among survivors, with most survivors inhaling or smoking cannabis. There is a need to educate healthcare providers (HCPs) and survivors on current evidence of cannabis use and strengthen cannabis regulatory frameworks to optimize benefits and minimize adverse events from cannabis use during cancer treatment.

Change in Trust in US Government Health Agencies for Cancer Information in the COVID-19 Era.

This cross-sectional study assesses changes in levels of public trust in US government health agencies providing cancer information.