Trends in co-prescribed opioids and benzodiazepines, non-prescribed opioids and benzodiazepines, and schedule-I drugs in the United States, 2013 to 2019.

Concurrent opioid and benzodiazepine users are at increased risk of overdose death, compared to opioid-only users. The objective of this study was to understand recent time trends in opioid and benzodiazepine concurrent use, misuse, and schedule-I drug use, and how these differ by age, sex and geographic region. Commercial, United States medical insurance claims data and urine drug test results from 2013 to 2019 were used to study the outcomes of concurrent use (n = 756,258), schedule-I drug use (n = 746,672) and prescription misuse (n = 452,523). Drug use outcomes were studied at quarterly time points for each year. Data analysis included joinpoint regression models to estimate quarterly drug use rates, determined by positive urine tests for corresponding drug categories, and was conducted from November 2021 through January 2022. Concurrent use decreased from 19.3% to 9.8%, misuse generally decreased from 75.6% to 55.1%, and schedule-I use increased from 8.9% to 13.8%, from 2013 to 2019. Concurrent use decreased at greater rates after 2016, after the Centers for Disease Control and Food and Drug Administration guidelines against concurrent use were released, while schedule-I use increased, notably after the 2014 hydrocodone reschedule. This indicates a potential shift from prescription use to non-prescribed drug use, where most affected groups included males, younger individuals, and those residing in Northeastern regions. Study results support public health initiatives focused on policy that increases access to multimodal pain management and substance use disorder management programs-critical steps in preventing patients from seeking non-prescribed drugs for self- medicating due to pain or addiction.

Association of sleep duration and quality with serum testosterone concentrations among men and women: NHANES 2011-2016.

BACKGROUND: The association between testosterone concentrations and sleep duration is poorly understood. OBJECTIVE: To evaluate the association between sleep duration and quality with serum testosterone concentrations and its variation by sex and age. METHODS: Data were analyzed for 8748 men and women (≥20 years old) who participated in the cycles of the National Health and Nutrition Examination Survey 2011-2016, a cross-sectional study. Total testosterone (ng/dL) was measured and categorized (low, moderate, and high) based on established cut-offs for men and its tertile distribution among women. Sleep duration was classified as ≤6, 7-8, and ≥9 h. Sleep quality was classified as poor or good based on the frequency of trouble falling or staying asleep or sleeping too much. Weighted multivariable adjusted and multinomial logistic regression models were conducted to assess these associations. RESULTS: The association between sleep duration and testosterone concentrations, varied according to sex and age. Sleep deprivation (≤6 h) was associated with high testosterone (odds ratio = 3.62; 95% confidence interval: 1.37, 9.53) among young men (20-40 years old); meanwhile, middle-aged men (41-64 years old) who reported more sleep duration had low testosterone (odds ratio = 2.03; 95% confidence interval: 1.10, 3.73). A J-shaped association between sleep duration and low testosterone (odds ratio≤6 h  = 1.57; 95% confidence interval: 1.10, 2.27; odds ratio≥9  h  = 2.06; 95% confidence interval: 1.18, 3.59) was observed in women aged 41-64 years. We did not find any association with sleep quality. CONCLUSION: The association of sleep duration with serum testosterone concentrations varies with sex and age group. Prospective studies are warranted to confirm these sex and age group differences.

The Association Between Mental Well-Being and School Attendance Among Palestinian Adolescent Refugees in UNRWA Schools.

Adolescent refugees experience psychosocial stressors, including traumatic events, poverty, and loss of home and family. Exposure to conflict affects mental well-being in Palestinian adolescent refugees. Adolescent girls are among those vulnerable to post-traumatic stress associated with living in conflict zones, We assessed the association between reported mental well-being and school attendance among Palestinian adolescent refugees in UNRWA schools in Occupied Palestinian Territories, Jordan, Lebanon, and Syria. We also examined differences based on gender and place of residence, Palestinian adolescent refugees with certain mental well-being concerns were more likely to miss more days of school. Generally, females reported higher rates of loneliness and worry, but males were more likely to miss school. Gender-based differences were highest in Lebanon and least in the West Bank, More school-based and community-based mental well-being interventions are needed. Female-tailored programs are needed, especially in Palestinian refugee camps in Lebanon.

Association of total and free testosterone with cardiovascular disease in a nationally representative sample of white, black, and Mexican American men.

Associations of total testosterone (T) and calculated free T with cardiovascular disease (CVD) remain poorly understood. Particularly how these associations vary according to race and ethnicity in a nationally representative sample of men. Data included 7058 men (≥20 years) from NHANES. CVD was defined as any reported diagnosis of heart failure (HF), coronary artery disease (CAD), myocardial infarction (MI), and stroke. Total T (ng/mL) was obtained among males who participated in the morning examination. Weighted multivariable-adjusted logistic regression models were conducted. We found associations of low T (OR = 1.57, 95% CI = 1.17-2.11), low calculated free T (OR = 1.53, 95% CI = 1.10-2.17), total T (Q1 vs Q5), and calculated free T (Q1 vs Q5) with CVD after adjusting for estradiol and SHBG. In disease specific analysis, low T increased prevalence of MI (OR = 1.72, 95% CI = 1.08-2.75) and HF (OR = 1.74, 95% CI = 1.08-2.82), but a continuous increment of total T reduced the prevalence of CAD. Similar inverse associations were identified among White and Mexican Americans, but not Blacks (OR = 0.93, 95% CI = 0.49-1.76). Low levels of T and calculated free T were associated with an increased prevalence of overall CVD and among White and Mexican Americans. Associations remained in the same direction with specific CVD outcomes in the overall population.

Joint association of statins and testosterone replacement therapy with cardiovascular disease among older men with prostate cancer: SEER-Medicare 2007-2015.

BACKGROUND: Use of statins and testosterone replacement therapy (TTh) have been independently linked with prostate cancer (PCa) and cardiovascular diseases (CVD). However, there is a research gap about the joint association of statins and TTh with CVD among PCa survivors and a matched cancer-free cohort. METHODS: In SEER-Medicare 2007-2015 (N = 35,990 men), we identified 17,995 PCa survivors, and 17,995 age- and index-matched cancer-free men. Pre-diagnostic prescription of statins and TTh was ascertained for this analysis and examined in two matched cohorts. Weighted multivariable-adjusted conditional logistic regression models were used to evaluate the independent and joint associations of statins and TTh with CVD. RESULTS: We found that independently statins (OR = 0.48, 95% CI: 0.44-0.53) and TTh (OR = 0.74, 95% CI: 0.0.61-0.90) were each inversely associated with CVD in the overall sample. TTh plus statins was inversely associated with CVD (OR = 0.50, 95% CI: 0.36-0.70, Pinteraction = 0.03). Similar associations were observed among the matched cancer-free cohort. Among PCa survivors, only statins (OR = 0.62, 95% CI: 0.56-0.68) and combination of TTh plus statins (OR = 0.63, 95% CI: 0.44-0.90) were inversely associated with CVD, but not the independent use of TTh. CONCLUSION: Pre-diagnostic use of statins and TTh, independent or in combination, were inversely associated with CVD in the overall and cancer-free populations, but among PCa survivors it was mainly use of statins, not TTh. Greater reduced effects on CVD were observed with statins or in combination with statins, but not with TTh. Future studies need to confirm these associations among older men with aggressive PCa.

High-sensitivity C-reactive protein is not independently associated with self-reported infertility in National Health and Nutrition Examination Survey 2015-2018 data.

Objective: To study the association between high-sensitivity C-reactive protein (hs-CRP) and infertility among reproductive-age women while controlling for obesity and other metabolic markers. Previous studies found a link between infertility and cardiovascular diseases (CVDs). C-reactive protein is a sensitive marker of CVDs, and its levels are affected by obesity. Design/Setting: We conducted a cross-sectional study using national data from 2015 through 2018. Patients: A total of 940 women aged 20-45 years who self-reported infertility, had hs-CRP values measured, and did not have CRP >10 mg/L, asthma, arthritis, bronchitis, thyroid disease, bilateral oophorectomy, hysterectomy, and who were not breastfeeding or pregnant, premenarchal at the time of study or had menarche after the age of 20. Interventions: N/A. Main outcome measures: Infertility status (ever reporting inability to conceive with 12 months of trying to become pregnant). Results: In comparison to noninfertile women, self-reported infertile women had higher mean of hs-CRP (3.11 mg/L vs. 2.40 mg/L) and higher percentage of moderate/high hs-CRP values (77.0% vs 58.8%). However, after adjusting for metabolic markers, there was a nonsignificant association between moderate/high hs-CRP and self-reported infertility in the multivariable logistic regression analysis. Odds ratio estimates of the association between hs-CRP and infertility increased over 40% after removing obesity measures and/or high-density lipoprotein from regression models. Conclusion: There was no association between hs-CRP and self-reported infertility after controlling for obesity measures and other risk factors for CVDs in a sample of U.S. women aged 20-45 years.

Low testosterone and high cholesterol levels in relation to all-cause, cardiovascular disease, and cancer mortality in White, Black, and Hispanic men: NHANES 1988-2015.

PURPOSE: The role of testosterone (T) deficiency (T ≤ 300 ng/dL) and hypercholesterolemia (total cholesterol ≥ 240 mg/dL) in the risk of all-cause cardiovascular diseases (CVD) and cancer mortality among a nationally representative sample of non-Hispanic White (NHW), non-Hispanic Black (NHB) and Hispanic men remains poorly understood. METHODS: Data included a full sample (NHANES 1988-1991, 1999-2004, 2011-2014) and subset sample (excluding 2011-2012, no estradiol and SHBG levels available) of 5379 and 3740 men, respectively. Participants were aged ≥ 20 y with serum T and cholesterol data (median follow-up 7.6 years). Weighted multivariable-adjusted Cox proportional hazards models were used in this study. RESULTS: In the overall population of full and subset samples, hypercholesterolemia was inversely associated with all-cause (HR = 0.76, 95% CI, 0.63-0.91) and cancer mortality (HR = 0.56, 95% CI, 0.34-0.90). Similar findings were observed among NHW men, but higher T levels increased the risk of CVD mortality in the subset sample (T3 vs T1, Ptrend = 0.02). Among NHB men in the full and subset samples, T deficiency increased the risk of CVD mortality, but T3 vs. T1 decreased it (Ptrend = 0.03), and hypercholesterolemia decreased cancer mortality. Among Hispanic men in the full and subset samples, T deficiency increased, and hypercholesterolemia decreased the risk of CVD mortality. CONCLUSION: Hypercholesterolemia was inversely associated with cancer mortality. However, higher levels of T were positively associated with CVD mortality among NHW and were inversely associated with CVD mortality among NHB and Hispanic men. Larger prospective studies are warranted to clarify the underlying relationship between T and cholesterol with mortality among racial and ethnic groups.

Obesity in Infertile Women, a Cross-Sectional Study of the United States Using NSFG 2011-2019.

Reproductive health can be affected by obesity through various mechanisms. Obesity-associated inflammatory markers and altered hormones can have direct and indirect impacts on female reproductive health. However, little is known about obesity prevalence and trend among infertile women and obesity association with infertility in reproductive-age women of the U.S. In a cross-sectional study, we sought to conduct a secondary analysis of National Survey of Family Growth (NSFG) data from 2011 to 2019. A total of 6,035 infertile and non-pregnant fecund women aged 20-44 years were included in a nationally representative sample of the U.S. The weighted prevalence of obesity (BMI ≥ 30) among infertile women was 41.63% for the period 2011-2019. Obese women had 62% higher odds of infertility (95% CI 1.24, 2.17) compared to non-obese women of reproductive age (20-44 years). However, there was no specific trend of obesity among infertile and non-pregnant fecund women aged 20-44 years in the U.S. from 2011 to 2019. Given the negative impact of obesity on female reproductive health and in light of our results, it is important to counsel obese infertile reproductive-age women of the U.S. about behavioral changes that include weight management. Future longitudinal studies are needed to evaluate the risk of infertility among obese women.

Trends in Urine Drug Testing Among Long-term Opioid Users, 2012-2018.

INTRODUCTION: Long-term opioid therapy increases the risk of opioid overdose death. Government agencies and medical societies, including the Center for Disease Control and Prevention and the American Society for Clinical Oncology, emphasized risk mitigation strategies, including urine drug testing, in published guidelines. Urine drug testing rates, time trends, and covariates among long-term opioid therapy users were examined to gauge guideline adherence. METHODS: Using Optum's De-identified Clinformatics DataMart, an incidence cohort (n=28,790) and prevalence cohort (n=621,449) were created to measure baseline and annual urine drug testing, respectively, from 2012 to 2018. Urine drug testing time trends were evaluated by demographics, pain conditions, and Elixhauser comorbidity index. A multivariable generalized estimating model was developed in 2020 to examine the factors associated with urine drug testing. RESULTS: Annual urine drug testing rates doubled from 25.6% in 2012 to 52.2% in 2018, whereas baseline urine drug testing also increased from 3.75% to 11.1%. Annual urine drug testing increased within each age group over time; however, older patients (OR=0.21, 95% CI=0.21, 0.22, aged >79 years) and patients with cancer (OR=0.82, 95% CI=0.80, 0.84) were less likely to receive urine drug testing. Patients residing in the South (OR=1.99, 95% CI=1.96, 2.01) and those with back pain (OR=2.04, 95% CI=2.02, 2.06) or with other chronic pain (OR=1.64, 95% CI=1.62, 1.66) were significantly more likely to be tested. Independent predictors of baseline urine drug testing were similar to predictors of annual urine drug testing. CONCLUSIONS: Despite increasing urine drug testing trends from 2012 to 2018, annual and baseline urine drug testing remained low in 2018, relative to numerous guideline recommendations. Findings suggest a need for research on better guideline implementation strategies and the effectiveness of urine drug testing on patient outcomes.