Self-reported Use Research Articles

#910 Pharmacometabolomics identified nonactivated metabolites of azathioprine and mycophenolate mofetil in urine of kidney transplant recipients

Abstract Background and Aims Metabolomics is employed frequently in clinical research with the aim of identifying disease-related mechanisms, biomarkers, and druggable targets. This technique is also used increasingly to obtain molecular evidence of chemical exposures, including dietary (e.g. caffeine, ethanol), lifestyle (e.g. tobacco smoke, illicit drugs), and medical exposures (e.g. therapeutic drugs). The latter opportunity recently led to the development of the subfield of ‘pharmacometabolomics’ that aims to yield insights into real-world patterns of drug metabolism, which may not always be in agreement with published (consensus) metabolic patterns. These insights are particularly relevant for drugs having narrow therapeutic windows, such as immunosuppressive drugs, and could contribute to more personalized evaluations of drug efficacy and safety. In this work, we applied pharmacometabolomics to study the real-world metabolism of the immunosuppressive drugs azathioprine and mycophenolate mofetil in kidney transplant recipients (KTR). In addition, we used the same data to obtain molecular evidence for the use of various prescribed, contraindicated, and illicit drugs. Method Untargeted ‘SWATH’ pharmacometabolomics was applied to 24-hour urine samples of 1258 kidney transplant recipients included in the TransplantLines Food and Nutrition Biobank and Cohort Study (NCT02811835) and the TransplantLines Biobank and Cohort Study (NCT03272841). Corresponding data were evaluated in order to assess whether observed metabolite profiles of azathioprine and mycophenolate mofetil are in agreement with consensus metabolic patterns. In addition, data were evaluated to validate self-reported drug use and to detect illicit (e.g. cocaine) and contraindicated drugs (e.g. NSAIDs after kidney transplantation). Results We unveiled disagreements between the consensus and real-world metabolism of both azathioprine and mycophenolate mofetil by discovering previously unreported drug metabolites. Importantly, our data suggest that considerable portions of these two prodrugs are not converted to their active forms. Based on several therapeutic drug classes, we furthermore demonstrated the capability of pharmacometabolomics to validate self-reported drug use, with both data sources being in good agreement (Cohen's kappa ≥0.90). Pharmacometabolomics also proved to be useful in the study of underreported exposures, as we identified cocaine and varying cocaine adulterants in the urine of 5 (0.4%) KTR. Moreover, we found NSAIDs in the urine of 49 (4%) KTR, for which the latter drugs are contraindicated. Conclusion Our work provides new insights into the metabolic fate of azathioprine and mycophenolate mofetil. Notably, we found the parent prodrugs as well as multiple nonactivated drug metabolites which warrant further investigations to rule out potential underdosing, as is associated with an increased risk of graft failure and morbidity. In addition, we could use the same data to obtain molecular evidence of prescribed, contraindicated, and illicit drugs, as are frequently studied using data retrieved through anamnesis and questionnaires. This application thus allows for reducing information bias in subsequent pharmacoepidemiological studies. Furthermore, it may have a signaling function for certain risky lifestyle habits and for inappropriate drug use.

Association of conventional cigarette smoking, heated tobacco product use, and dual use with hearing loss: A working population-based study.

Although conventional cigarette smoking has been linked to an increased risk of hearing loss, the association between heated tobacco products (HTPs) and hearing loss is unknown. The objective of this study was to investigate the association between cigarette and HTP use and hearing loss. This cross-sectional study examined the data of 7769 employees from five companies (Study I) and 34404 employees from a large company (Study II), all participants in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into five groups based on their self-reported tobacco use: never smokers, former smokers, exclusive cigarette smokers, exclusive users of HTPs, and those who used both cigarettes and HTPs. Hearing levels were measured using pure-tone audiometry at 1 and 4 kHz frequencies. Separate analyses were carried out for each study, and the results were then combined using fixed-effect models to pool the estimates. The analysis included 42173 participants, with a prevalence of 12.9% for exclusive cigarette smoking, 9.8% for exclusive HTP use, and 5.5% for dual use. The pooled adjusted odds ratios with 95% confidence intervals for unilateral hearing loss at 4 kHz were 1.21 (95% CI: 1.10-1.33) for former smokers, 1.83 (95% CI: 1.64-2.05) for exclusive cigarette smokers,1.46 (95% CI: 1.28-1.67) for exclusive HTP users, and 1.66 (95% CI: 1.41-1.96) for dual users, compared to never smokers. Additionally, the adjusted odds ratios for hearing loss at 4 kHz among exclusive cigarette smokers, exclusive HTP users, and dual users increased with the intensity of cigarette/HTP consumption (all p for trend <0.001). No significant associations were found between exclusive HTP use, dual use, and hearing loss at 1 kHz, apart from exclusive cigarette smoking. In this cross-sectional study, associations were found between exclusive cigarette smoking, exclusive HTP use, dual use, and hearing loss, particularly at 4 kHz. Further research is needed to confirm these findings.

Screening of substance use in pregnancy: A Danish cross-sectional study.

There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine among the general population of Danish pregnant women. In this anonymous, national, cross-sectional, descriptive study, pregnant women were invited when attending an ultrasound scan between November 2019 and December 2020 at nine Danish hospitals. Women submitted a urine sample and filled out a questionnaire. Urine samples were screened on-site with a qualitative urine dipstick for 15 substances including alcohol, nicotine, opioids, amphetamines, cannabis, and benzodiazepines. All screen-positive urine samples underwent secondary quantitative analyses with gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results were compared to questionnaire information to analyze the validity of self-reporting and to examine possible cross-reactions. A total of 1903 of 2154 invited pregnant women participated (88.3%). The prevalence of dipstick-positive urine samples was 25.0%. 44.0% of these were confirmed positive, resulting in a total confirmed prevalence of 10.8%. The prevalence of nicotine use was 10.1%-and for all other substances, <0.5%. Nicotine use was more prevalent among younger pregnant women, while other substance use appeared evenly distributed over age groups. Self-reporting of use of nicotine products was high (71.1%), but low for cannabis and alcohol intake (0% and 33.3%, respectively). Prescription medication explained almost all cases of oxycodone, methylphenidate, and benzodiazepine use. Substance use among pregnant women consisted mainly of nicotine. Dipstick screening involved risks of false negatives and false positives. Except for alcohol intake and cannabis use, dipstick analyses did not seem to provide further information than self-reporting. LC-MS/MS analyses remain gold standard, and future role of dipstick screenings should be discussed.

Effects of Recall and Selection Biases on Modeling Cancer Risk From Mobile Phone Use: Results From a Case-Control Simulation Study.

The largest case-control study (Interphone study) investigating glioma risk related to mobile phone use showed a J-shaped relationship with reduced relative risks for moderate use and a 40% increased relative risk among the 10% heaviest regular mobile phone users, using a categorical risk model based on deciles of lifetime duration of use among ever regular users. We conducted Monte Carlo simulations examining whether the reported estimates are compatible with an assumption of no effect of mobile phone use on glioma risk when the various forms of biases present in the Interphone study are accounted for. Four scenarios of sources of error in self-reported mobile phone use were considered, along with selection bias. Input parameters used for simulations were those obtained from Interphone validation studies on reporting accuracy and from using a nonresponse questionnaire. We found that the scenario simultaneously modeling systematic and random reporting errors produced a J-shaped relationship perfectly compatible with the observed relationship from the main Interphone study with a simulated spurious increased relative risk among heaviest users (odds ratio = 1.91) compared with never regular users. The main determinant for producing this J shape was higher reporting error variance in cases compared with controls, as observed in the validation studies. Selection bias contributed to the reduced risks as well. Some uncertainty remains, but the evidence from the present simulation study shifts the overall assessment to making it less likely that heavy mobile phone use is causally related to an increased glioma risk.

Concept-Focused and Procedure-Focused Instruction on the Algebra Performance of Grade 9 Students With and Without Mathematics Difficulty.

Developing both conceptual and procedural knowledge is important for students' mathematics competence. This study examined whether Grade 9 general education mathematics teachers' self-reported use of concept-focused instruction (CFI) and procedure-focused instruction (PFI) were associated differently with ninth graders' algebra achievement after 2.5 years, depending on students' mathematics difficulty (MD) status. Data for this study were drawn from the High School Longitudinal Study for the years 2009-2010 and 2011-2012 (N = 19,104). Multiple regression analyses indicated that students with MD who participated in Grade 9 mathematics classrooms where teachers self-reported the use of less CFI and more PFI were more positively associated with having higher algebra achievement after 2.5 years. Conversely, students without MD in classrooms where mathematics teachers self-reported the use of more CFI and less PFI were positively associated with having higher algebra achievement after 2.5 years. However, this study's findings do not suggest that teachers should disregard CFI and provide only PFI when teaching students with MD. Because the data set did not include any variable to discover whether teachers provided sufficient support (i.e., evidence-based practices) for students with MD, who have more constraints in their cognitive skills compared to students without MD, to benefit from CFI, the findings of this study should be interpreted cautiously. Directions for future research and practical implications are discussed.

Development of a screener to assess athlete risk behavior of not using third-party tested nutritional supplements.

The aim of this cross-sectional study was to develop an algorithm to predict athletes use of third-party tested (TPT) supplements. Therefore, a nutritional supplement questionnaire was used with a section about self-reported TPT supplement use. Outcomes were randomly assigned to a training dataset to identify predictors using logistic regression models, or a cross-validation dataset. Training data were used to develop an algorithm with a score from 0 to 100 predicting use or non-use of TPT nutritional supplements. A total of n = 410 NCAA Division I student-athletes (age: 21.4 ± 1.6 years, 53% female, from >20 sports) were included. Then n = 320 were randomly selected, of which 34% (n = 109) of users consistently reported that all supplements they used were TPT. Analyses resulted in a 10-item algorithm associated with use or non-use of TPT. Risk quadrants provided the best fit for classifying low vs. high risk toward inconsistent TPT-use resulting in a cut-off ≥60% (χ2(4) = 61.26, P < 0.001), with reasonable AUC 0.78. There was a significant association for TPT use (yes/no) and risk behavior (low vs. high) defined from the algorithm (χ2(1)=58.6, P < 0.001). The algorithm had a high sensitivity, classifying 89% of non-TPT users correctly, while having a low specificity, classifying 49% of TPT-users correctly. This was confirmed by cross-validation (n = 34), reporting a high sensitivity (83%), despite a lower AUC (0.61). The algorithm classifies high-risk inconsistent TPT-users with reasonable accuracy, but lacks the specificity to classify consistent users at low risk. This approach should be useful in identifying athletes that would benefit from additional counseling.

Incident psychotic experiences following self-reported use of high-potency cannabis: Results from a longitudinal cohort study.

High-potency cannabis has been associated with increased risk of psychosis, but a lack of prospective data hinders understanding of causality in this relationship. This study aimed to combine prospective report of cannabis use with retrospective report of potency to infer the potency of cannabis used in adolescence and explore whether use of cannabis, and the use of high-potency cannabis, in adolescence is associated with incident psychotic experiences. Population-based birth cohort study. United Kingdom. n = 5570 participants who reported on any cannabis use (yes/no) age 16 and 18 years, and n = 1560 participants from this group who also retrospectively reported on cannabis potency. In questionnaires at ages 16 and 18, individuals self-reported lifetime cannabis use, and at age 24, participants reported the type of cannabis they most commonly used in the whole time since first using cannabis. Psychotic experiences were assessed at age 24 years using the semi-structured Psychosis-Like Symptom Interview, with incident defined as new-onset occurring between ages 19 and 24 years. Use of high-potency cannabis at age 16 or 18 was associated with twice the likelihood of experiencing incident psychotic experiences from age 19-24 (Odds Ratio 2.15, 95% Confidence Intervals 1.13-4.06). There was less evidence for an effect of any cannabis use on incident psychotic experiences (Odds Ratio 1.45, 95% Confidence Intervals 0.94-2.12). Use of high-potency cannabis appears to be associated with increased likelihood of psychotic experiences.

Recent Cannabis Use and Accelerometer-Measured Physical Activity and Sedentary Behavior Among Young-to-Midlife Adults: An Analysis of the National Health and Nutrition Examination Survey from 2011 to 2014.

Introduction: Cannabis use has been associated with reduced physical activity and increased sedentary behavior in adolescents. In adults, however, there is no conclusive evidence of such an association, and existing studies have primarily relied on self-reported activity measures. As cannabis use increases globally, a deeper understanding of its relationship with activity levels may inform clinical counseling and guidelines. This study investigated the association between recent cannabis use and accelerometer-measured activity. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. We included adults in the United States who responded to a cannabis questionnaire and had at least 4 days of activity data from an ActiGraph GT3X+ accelerometer, which comprised participants from 18 to 59 years. The primary exposure was any self-reported cannabis use in the past 30 days. The primary outcome was daily sedentary time and secondary outcomes were daily light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Analyses were performed with multivariable quasi-Poisson regression models. Results: Of 4666 included adults, 658 (14.1%) reported recent cannabis use. After covariate adjustment, recent cannabis use was not associated with daily sedentary time (adjusted incidence rate ratio [aIRR] 0.99, 95% confidence interval [CI]: 0.98-1.01) or daily MVPA time (aIRR 1.01, 95% CI: 0.98-1.04). Daily LPA time was 4% greater with recent cannabis use (aIRR 1.04, 95% CI: 1.01-1.06). Conclusion: Recent cannabis use in young to midlife adults was not associated with accelerometer-measured sedentary or MVPA time, but it was associated with a marginal increase in LPA time of unclear clinical significance. Our findings provide evidence against existing concerns that cannabis use independently promotes sedentary behavior and decreases physical activity. Future prospective studies are needed to determine if these findings generalize to specific populations using cannabis including chronic pain patients.

Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of 4 regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case analysis, and multiple imputation in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the United Kingdom. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with complete-case analysis or multiple imputation. We showed that RC methods resulted in more accurate estimation of the relationship between mobile phone use and health outcomes by combining self-reported data with objective operator-recorded data available for a subset of participants.

In flux: Associations of substance use with instability in housing, employment, and income among young adults experiencing homelessness.

Young adults experiencing homelessness (YAEH) are faced with instabilities in many areas of their lives, including their living situation, employment, and income. Little is known about how the experience of instability in these different domains might be associated with substance use. Leveraging data collected on 276 YAEH in Los Angeles County, regression analyses examine associations between three distinct types of instability (housing, employment, income) and participants' self-reported alcohol use, alcohol consequences, non-cannabis drug use, and substance use symptoms. Results indicated that recent instability in income, employment, and secure housing for those with access to it (but not housing in general or non-secure housing) were significantly associated with greater alcohol/drug use or substance use symptoms. Depression was also found to moderate the association between employment instability and alcohol use. Our findings suggest that efforts to reduce instability in income, employment, and secure housing may have positive benefits for substance using YAEH, especially those with depressive symptoms.

Psychologically Traumatic Birth: Associations with Increased Drinking and Delayed Risk of Alcohol Harm in Mothers

Abstract Background Experience of trauma is a risk factor for increased alcohol use. Childbirth can be psychologically traumatic but there is minimal research investigating whether psychological birth trauma (PBT) is a risk factor for increased maternal drinking or what factors are associated with alcohol use in mothers who have and who have not experienced PBT. Method An online observational survey of mothers with (n = 291) and without (n = 230) experience of PBT. Participants self-reported alcohol use and completed measures of alcohol harm, drinking motives, trauma (general and birth related) and mental health. Free text options were included to complement quantitative data. Results Irrespective of PBT status, stronger endorsement of negative reinforcement drinking motives (e.g. coping) predicted higher alcohol use and hazardous drinking. However, children’s age influenced this relationship. In mothers with a history of PBT, negative reinforcement drinking motives predicted weekly alcohol use and alcohol harm as their children grew older. In mothers without PBT, positive reinforcement drinking motives predicted greater weekly alcohol use as children grew older, but negative drinking motives predicted reduced drinking. Multiple aspects of the parental role influenced drinking (e.g. coping-based motives) and non-drinking (e.g. child well-being motives) behaviour. Changes in motives from pre-motherhood to motherhood focused around a shift from positive to negative reinforcement drinking motives. Mothers with PBT reported mental health symptoms as both a reason to drink and not to drink alcohol. Conclusion This study provides novel evidence on maternal alcohol use, and how PBT may influence drinking behaviour in mothers. Importantly, PBT may be a type of trauma which is associated with a delayed risk for maladaptive alcohol use and risk of alcohol harm. This evidence can facilitate more research aimed at understanding this important public health issue and can inform alcohol interventions tailored to the needs of mothers which consider the long-lasting impact of birth experience.

Ask how they did it: untangling the relationships between task-specific strategy use, everyday strategy use, and associative memory

ABSTRACT Objective Past research has shown that self-reported everyday strategy use and task-specific strategy use are related to associative memory performance in aging. Understudied is the relationship between these types of strategy use, whether they predict associative memory performance, and how this may differ across genders. Method A sample of older adults (N = 566, 53% female, ages 60–80) completed this online study. Study measures included 1. Multifactorial Memory Questionnaire (MMQ) Strategy Use subscale, a self-report measure of everyday strategy use, 2. Face-Name Task (FNT), a measure of associative memory, and 3. self-initiated number and types of strategies used on the FNT. Analyses examined the interrelationships among all study measures and their relative contributions to FNT performance while accounting for intraindividual factors. Results Participants who reported using more strategies on the FNT performed better than those who used fewer or no strategies; those who reported using at least three strategies and relating FNT to past experience performed best. Women outperformed men on the FNT but did not differ in task-specific strategy use. Participants who reported using no strategies on the FNT had lower MMQ Strategy Use scores. A multiple regression analysis indicated that female gender and using at least two task strategies were significant predictors of greater FNT performance. Conclusions The results indicate that task-specific strategy use relates more to associative memory performance than to everyday strategy use, but neither accounts for the female advantage in FNT performance. Findings encourage querying task-specific strategy use to contextualize age-related associative memory decline.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. We enrolled 343 816 adults aged ≥30years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend<0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend<0.001). Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

Patients presenting to the ED with nonfatal drug overdose: Self-reported history of overdose and naloxone use

BackgroundIn the context of polysubstance use and fentanyl detection in non-opioid drugs supplies (e.g., cocaine, methamphetamine), it is important to re-evaluate and expand our understanding of which populations are at high risk for fatal drug overdoses. The primary objective of this pilot study was to gather data from the ED to characterize the population presenting with drug overdose, including demographics, drug use patterns and comorbidities, to inform upstream overdose prevention efforts. MethodsA consecutive sample of ED patients undergoing treatment for non-fatal overdose were prospectively recruited for study participation at the time of ED visit. Participants reported history of substance use over the past six months, recent and lifetime overdose, and naloxone receipt and administration history. ResultsA total of 76 eligible participants were enrolled over the course of seven months. Participants reported high rates of opioid (56%), stimulant (56%), and cannabis use (59%). Self-reported polysubstance use, defined as self-reported use of more than one substance, was 83%. Of enrolled participants, 64% reported at least one overdose and 39% reported three or more lifetime overdoses prior to their index overdose ED visit. Participants with no self-reported intentional opioid use (n = 32) in the past six months had fentanyl positive urine drug screen 84% of the time versus 89% in the overall study population (n = 74). Participants who did not report opioid use in the past six months were less likely to possess (34% vs. 55%) or to know how to acquire (50% vs. 74%) naloxone compared to participants with self-reported history of opioid use. ConclusionThis study demonstrated high rates of fentanyl exposure on toxicology testing at time of overdose across all participants including study participants without self-reported intentional opioid use. Data gathered in the ED at time of overdose can be used to inform upstream naloxone distribution and public health initiatives.

Use of melatonin supplements and risk of type 2 diabetes and cardiovascular diseases in the USA: insights from three prospective cohort studies

Use of melatonin supplements has been increasing substantially in both children and adults in the USA; however, their long-term cardiometabolic effects remain unclear. We aimed to assess the associations between regular use of melatonin supplements and the risk of developing type 2 diabetes or cardiovascular disease in adults. In this study, we included individuals from three US cohorts: the Nurses' Health Study (women only), the Health Professionals Follow-up Study (men only), and the Nurses' Health Study II (women only). Women aged 25-55 years and men aged 45-75 years at baseline, who had no diagnosis of cancer at baseline, and who responded to the question about melatonin supplement use (yes or no) were included. We excluded baseline prevalent cardiovascular disease and baseline prevalent type 2 diabetes for the main analyses. The main outcomes were cardiovascular disease and type 2 diabetes incidence. In secondary analyses, we stratified by duration of rotating night shift work in the Nurses' Health Study and Nurses' Health Study II to examine whether the associations with melatonin supplement use differed by rotating night shift work. For the cardiovascular disease analysis, we included 67 202 women from the Nurses' Health Study (follow-up 1998-2019, mean age at baseline: 63·6 years [SD 7·1]), 26 629 men from the Health Professionals Follow-up Study (1998-2020, 62·9 years [8·8], and 65 241 women from the Nurses' Health Study II (2003-19, 48·2 years [4·7]). Follow-up for incident type 2 diabetes was from 1998 to June 30, 2021, for the Nurses' Health Study; 2003 to Jan 31, 2023, for the Nurses' Health Study II; and from 1998 to Jan 31, 2020, for the Health Professionals' Follow-up Study. Melatonin supplement use in the study cohorts doubled over recent decades from less than 2% in 1998-2007 to 4% or higher in 2014-15 (4·0% in men and 5·3% in women). We documented 16 917 incident cardiovascular disease events during 2 609 068 person-years of follow-up and 12 730 incident cases of type 2 diabetes during 2 701 830 person-years of follow-up. In a pooled analysis of the three cohorts, comparing users with non-users of melatonin supplements, the pooled multivariable-adjusted hazard ratios were 0·94 (95% CI 0·83-1·06, p=0·32) for cardiovascular disease and 0·98 (0·86-1·12, p=0·80) for type 2 diabetes. In secondary analyses, melatonin supplement use appeared to attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease (pinteraction=0·013) among the female nurses. With up to 23 years of follow-up of three large prospective cohorts of middle-aged and older men and women, self-reported melatonin supplement use was not associated with risk of type 2 diabetes or cardiovascular disease. Further research is warranted to assess if melatonin supplement use could mitigate the potential risks of type 2 diabetes and cardiovascular disease associated with rotating night shift work. US National Institutes of Health.

Physicians’ intentions to use digital tools – a comparative survey, before and after the COVID-19 pandemic, in Southern Sweden

Objectives To describe changes in Swedish primary care physicians’ use of, attitudes and intentions toward digital tools in patient care between 2019 and 2022. Design A survey using a validated questionnaire measuring physician’s intentions to use digital tools based on the theory of planned behavior. Setting Sample of primary health care centers in southern Sweden. Subjects Primary care physicians. Main outcome measures Self-reported use and intentions to use, digital tools including digital consultations by text or video, chronic disease monitoring and artificial intelligence (AI) and the associations between attitudes, subjective norms, perceived behavioral control and behavioral intentions to use digital tools, in 2019 compared to 2022. Results In both 2019 (n = 198) and 2022 (n = 93), physicians reported high intentions to use digital tools. Self-reported use of video was slightly higher in 2022 (p = .03). No other changes were seen in the self-reported use or behavioral intentions to use digital tools. Conclusion The slow adoption of patient-related digital tools in Swedish primary health care does not seem to be explained by a low intention to use them among physicians. Future research on implementation of digital tools should include a focus on contextual factors such as organizational, technical and cultural barriers.

Predictors of stool deoxyribonucleic acid test use in the United States: Implications for outreach to under-resourced populations

ObjectiveAlthough colorectal cancer screening (CRCS) is a public health priority, uptake is suboptimal in under-resourced groups. Noninvasive modalities, including stool deoxyribonucleic acid (sDNA) testing, may mitigate economic, geographic, cultural, or impairment-related barriers to CRCS. We assessed use of sDNA testing and other CRCS modalities in U.S. residents, comparing subgroups defined by several social determinants of health (SDOH). MethodsA nationally representative sample of community-dwelling respondents aged 50–75 years self-reported use of CRCS modalities in the 2020 Behavioral Risk Factor Surveillance System Survey. Statistical analyses assessed up-to-date screening status and choice of modality in the recommended screening interval. ResultsOf 179,833 sampled respondents, 60.8% reported colonoscopy, 5.7% sDNA testing, 5.5% another modality. The rate of up-to-date screening was 72.0% overall and negatively associated with Hispanic ethnicity (63.6%), lower educational and annual income levels (e.g., <high school, 63.7%, <$20,000, 67.2%), and cost-related difficulty accessing physician care (57.4%; all p < 0.001) but not with Black non-Hispanic race/ethnicity (74.6%) or sensory, cognitive, or physical impairments (73.1%–73.9%). Choice of sDNA instead of colonoscopy was made by 8.5% overall and was more common in the same SDOH groups (Hispanic ethnicity, 17.7%; <high school, 17.4%; <$20,000, 16.8%; cost-related difficulty accessing care, 12.0%); Black non-Hispanic race/ethnicity (11.6%); and impairments (sensory, 12.0%; other cognitive or physical, 12.9%). ConclusionsUnder-resourced persons were more likely than better-resourced persons to access sDNA testing, possibly offsetting screening barriers in some groups. Findings suggest opportunities to increase CRCS with heightened communication about sDNA testing to those who may experience difficulty accessing other modalities.

Prevalence, awareness, and control of hypertension in Greece before and after the COVID-19 pandemic: May Measurement Month survey 2019–2022

ObjectiveThe COVID-19 pandemic had an adverse impact on several cardiovascular risk factors. This study investigated the prevalence, awareness and treatment of hypertension in Greece before and after the pandemic. Data were collected in the context of the May Measurement Month (MMM) global survey initiated by the International Society of Hypertension. MethodsAdult volunteers (age ≥ 18 years) were recruited through opportunistic screening in public areas across cities in Greece in 2019 and 2022. Medical history and triplicate sitting blood pressure (BP) measurements were taken using validated automated upper-arm cuff devices. The data were uploaded to the international MMM cloud platform. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic ≥90 mm Hg and/or self-reported use of drugs for hypertension. The same threshold was used to define uncontrolled BP in treated individuals. ResultsData from 12,080 adults were collected (5,727/6,353 in MMM 2019/2022; men 46/49%, p < 0.01; mean age 52.7 ± 16.6/54.8 ± 16.2, p < 0.001; smokers, 24.7/30.5, p < 0.001; diabetics 12/11.5%, p = NS; cardiovascular disease 5/5.8%, p = NS). The prevalence of hypertension was 41.6/42.6% (MMM 2019/2022, p = NS), with 21.3/27.5% of individuals with hypertension being unaware of their condition (p < 0.001), 5.6/2.4% aware untreated (p < 0.001), 24.8/22.1% treated uncontrolled (p < 0.05), and 48.3/47.8% treated controlled (p = NS). ConclusionIn Greece, the COVID-19 pandemic did not appear to affect the prevalence and control of hypertension; however, the rate of undiagnosed hypertension was higher after the pandemic. National strategies need to be implemented for the early detection and optimal management of hypertension in the general population in Greece.

Placement of an intrauterine device within 48 hours after second-trimester medical abortion: a randomized controlled trial

BackgroundInternational guidelines recommend placement of intrauterine devices immediately after second trimester medical abortion, but evidence concerning the optimal time for intrauterine device placement is lacking from clinical trials. ObjectiveWe aimed to investigate effectiveness, safety, and acceptability of intrauterine device placement within 48 hours, compared with placement at two to four weeks after second trimester medical abortion. We hypothesized that intrauterine device placement within 48 hours would be superior compared with placement at two to four weeks after the abortion, in terms of the proportion of intrauterine device use after six months, with maintained safety and acceptability. Study DesignIn this open-label, randomized, controlled, superiority trial, we recruited participants at eight abortion clinics in Sweden. Eligible participants were ≥18 years, requesting medical abortion with gestation ≥85 days and opting for use of a post abortion intrauterine device. Participants were randomized (1:1) to intrauterine device placement either within 48 hours of complete abortion (intervention) or after 2 to 4 weeks (control). Our primary outcome was self-reported use of an intrauterine device after 6 months. Secondary outcomes included expulsion rates, pain at placement, adverse events and complications, acceptability, and subsequent pregnancies and abortions. Differences in non-normal continuous variables were analyzed with the Mann-Whitney U-test and differences in dichotomous variables with the chi square or Fisher’s exact tests. A P value <.05 was considered statistically significant. Group differences are presented by modified intention-to-treat and per protocol analyses. ResultsBetween January 2019, and June 2022, we enrolled 179 participants, of whom 90 were assigned to intervention and 89 to control. Enrolment was prematurely stopped after an interim analysis exceeded a predefined intrauterine device expulsion rate of 20%. By modified intention-to-treat, use of intrauterine device after 6 months was 50.7% (34/67) in the intervention group compared to 71.6% (48/67) in the control group (proportion difference 20.9%; 95% confidence interval 4.4%-35.9%; P=.02). The intrauterine device expulsion rate was 30.1% (22/73) in the intervention group versus 2.9% (2/70; P <.001) in the control group. Other adverse events were rare and patient acceptability was high in both groups. ConclusionIntrauterine device placement within 48 hours after second trimester medical abortion was non-superior in terms of the proportion of intrauterine device use after 6 months when compared with placement after 2 to 4 weeks. Placement within 48 hours after second trimester abortion can be used in selected individuals after counselling on expulsion risk.

Public Perspectives on the Inclusion of Pregnant People in Clinical Trials [ID 2683498

INTRODUCTION: Pregnant people remain underrepresented in clinical trials despite extensive efforts to increase participation. The public’s perception about including pregnant people in research is limited, and no publications to date specifically include self-identified males. This research aims to elucidate the attitudes of reproductive-aged people in the United States regarding the inclusion of pregnant individuals in clinical trials. METHODS: An IRB-approved survey including five Likert-scale questions concerning the inclusion of pregnant patients in research was distributed via Facebook Marketing. Self-reported gender, race, ethnicity, education level, political affiliation, religion, relationship status, and contraceptive use and method were analyzed in bivariate analyses. Variables significant in the bivariate analyses were included in multivariable logistic regression models. RESULTS: Among 743 respondents, 405 (54.6%) agreed that pregnant people should be excluded from clinical trials and 392 (52.8%) agreed that the risks of including pregnant people in clinical trials outweigh the benefits. Females had lower odds of agreement (odds ratio [OR] 0.46 [95% CI, 0.33–0.65] and 0.39 [95% CI, 0.28–0.54], respectively). Most respondents (74.2%) agreed that pregnant people should obtain partner consent prior to participation; notably, males had 3.9 times greater odds of agreement (95% CI: 2.51–6.10). Paradoxically, 504 people (67.9%) agreed that including pregnant people in research is important for providing evidence-based medicine. CONCLUSION: Most participants agreed with excluding pregnant people from clinical research; however, self-identifying females were more likely than males to value the safe inclusion of pregnant people in clinical research to advance evidence-based obstetrical care. This juxtaposition highlights an important challenge to achieving equitable inclusion of pregnant people in clinical research and the importance of public perception in improving maternal and child health outcomes.