Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African American and 44,365 Latin American) and data from UK Biobank (ncombined = 898,680). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviours in children and hundreds of medical outcomes, including HIV infection, heart disease and pain. This work furthers our biological understanding of TUD and establishes electronic health records as a source of phenotypic information for studying the genetics of TUD.

Phenotypic distinctions in depression and anxiety: a comparative analysis of comorbid and isolated cases.

BACKGROUND: Anxiety and depression are frequently comorbid yet phenotypically distinct. This study identifies differences in the clinically observable phenome across a wide variety of physical and mental disorders comparing patients with diagnoses of depression without anxiety, anxiety without depression, or both depression and anxiety. METHODS: Using electronic health records for 14 994 participants with depression and/or anxiety in the Mayo Clinic Biobank, a phenotype-based phenome-wide association study (Phe2WAS) was performed to test for differences between these groups across a broad range of clinical diagnoses observed in the electronic health record. Additional analyses were performed to determine the temporal sequencing of diagnoses. RESULTS: Compared to patients diagnosed only with anxiety, those diagnosed only with depression were more likely to have diagnoses of obesity (OR 1.75; p = 1 × 10-27), sleep apnea (OR 1.71; p = 1 × 10-22), and type II diabetes (OR 1.74; p = 9 × 10-18). Compared to those diagnosed only with depression, those diagnosed only with anxiety were more likely to have diagnoses of palpitations (OR 1.91; p = 2 × 10-25), benign skin neoplasms (OR 1.61; p = 2 × 10-17), and cardiac dysrhythmias (OR 1.45; p = 2 × 10-12). Patients with comorbid depression and anxiety were more likely to have diagnoses of other mental health disorders, substance use disorders, sleep problems, and gastroesophageal reflux relative to isolated depression. CONCLUSIONS: While depression and anxiety are closely related, this study suggests that phenotypic distinctions exist between depression and anxiety. Improving phenotypic characterization within the broad categories of depression and anxiety could improve the clinical assessment of depression and anxiety.

Multi-ancestry meta-analysis of tobacco use disorder prioritizes novel candidate risk genes and reveals associations with numerous health outcomes.

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviors, and although strides have been made using genome-wide association studies (GWAS) to identify risk variants, the majority of variants identified have been for nicotine consumption, rather than TUD. We leveraged five biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records, EHR) in 898,680 individuals (739,895 European, 114,420 African American, 44,365 Latin American). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviors in children, and hundreds of medical outcomes, including HIV infection, heart disease, and pain. This work furthers our biological understanding of TUD and establishes EHR as a source of phenotypic information for studying the genetics of TUD.

Longitudinal factors associated with increased alcohol consumption in adults during the COVID-19 pandemic.

Background: Alcohol is the most abused substance among adults in the United States. The COVID-19 pandemic impacted patterns of alcohol use, but data are conflicting, and previous studies are largely limited to cross-sectional analyses.Objective: This study aimed to longitudinally assess sociodemographic and psychological correlates of changes in three patterns of alcohol use (number of alcoholic drinks, drinking regularity, and binge drinking) during COVID-19.Methods: We studied changes in self-reported drinking behaviors in 222,195 Mayo Clinic patients over 21 years of age (58.1% female and 41.9% male) between April 1, 2019, and March 30, 2021. Logistic regression models were used to estimate associations between patient characteristics and change in alcohol consumption.Results: Sociodemographically younger age, White race, having a college degree, and living in a rural area were associated with increased alcohol use regularity (all p < .05). Younger age, male, White, high-school education or less, living in a more deprived neighborhood, smoking, and living in a rural area were associated with increases in number of alcohol drinks (all p ≤ .04) and binge drinking (all p ≤ .01). Increased anxiety scores were associated with increased number of drinks, while depression severity was associated with both increased drinking regularity and increased number of drinks (all p ≤ .02) independent of sociodemographic characteristics.Conclusion: Our study showed that both sociodemographic and psychological characteristics were associated with increased alcohol consumption patterns during the COVID-19 pandemic. Our study highlights specific target groups previously not described in the literature for alcohol interventions based on sociodemographic and psychological characteristics.

Detection of Cadmium and Lead in Kidney Stones. Associations with Patient Demographics, Stone Composition, and Smoking.

BACKGROUND: Kidney stones are a highly prevalent disease worldwide. Additionally, both environmental and occupational exposure to Pb and Cd continue to be prevalent globally and can result in renal toxicity. The objective of this study was to examine the potential presence of Pb and Cd in kidney stones, and to assess for correlation with demographic factors including smoking, gender, age, and kidney stone matrix composition. METHODS: Patient kidney stones (n = 96) were analyzed using Fourier transform infrared spectroscopy to identify the stone constituents. Cd and Pb concentrations (µg/g) were determined by inductively coupled plasma mass spectrometry. Cd and Pb concentrations were correlated using bivariable and multivariable statistical analysis with demographic factors (age, gender, smoking status), and kidney stone composition. RESULTS: Kidney stone Cd (median 0.092 µg/g, range 0.014 to 2.46) and Pb concentrations (median 0.95 µg/g, range 0.060 to 15.4) were moderately correlated (r = 0.56, P < 0.0001). Cd concentrations were positively associated with patient history of smoking, patient age, and calcium oxalate monohydrate levels while negatively associated with struvite and uric acid/uric acid dihydrate. Pb concentrations were positively associated with females and apatite levels while negatively associated with uric acid/uric acid dihydrate. After holding constant other stone type composition levels, smoking status, and age, both Pb and Cd were positively associated with apatite and negatively associated with uric acid/uric acid dihydrate, struvite, and calcium carbonate. CONCLUSIONS: Cd and Pb kidney stone concentrations are associated with specific kidney stone types. Cd and Pb kidney stone concentrations are both associated with smoking.

Assessment of gadolinium and iodine concentrations in kidney stones and correlation with contrast agent exposure, stone matrix composition, and patient demographic factors.

BACKGROUND: Gadolinium-based contrast agents (GBCAs) and Iodinated contrast media are widely utilized to increase medical imaging sensitivity. With predominant renal elimination, the potential for the incorporation of contrast agent derived gadolinium and iodine into kidney stones remains largely uncharacterized. The study objective was to measure gadolinium and iodine concentrations within kidney stones. Observed elemental concentrations were correlated with prior contrast agent administration, kidney stone composition, age, gender, and smoking status. METHODS: Kidney stones from 96 patients were analyzed by Fourier Transform Infrared Spectroscopy to determine stone composition. Residual kidney stone material was digested and analyzed by Inductively Coupled Plasma Mass Spectrometry to determine gadolinium and iodine concentrations. Univariable and multivariable lognormal linear regression were performed to study the relationship between kidney stone element concentrations and contrast agent administration, kidney stone composition, age, gender, and smoking status. RESULTS: Median iodine and gadolinium stone concentrations were 6.4 (range 0.6-3997) and 0.1 (range ≤0.013-113.5) µg/g respectively. Elevated gadolinium was strongly associated with GBCA history with a hazard rate of 2.20 (95 % CI 1.14-3.25 P < 0.001). Gadolinium was positively associated with smoking, as well as stones comprised of apatite and calcium oxalate. Iodine concentrations were negatively associated with uric acid stones. CONCLUSION: Gadolinium, but not iodine, concentrations in kidney stones was strongly correlated with contrast exposure history. Stone matrix composition and demographic factors, particularly smoking, can influence observed kidney stone elemental concentrations. Additional studies are needed to determine if exposure to gadolinium and iodine promote the formation of stone matrix and/or reflect exposure history.

Longitudinal Correlates of Increased Alcohol Use Among Adolescents and Young Adults During the COVID-19 Pandemic.

AIMS: The objective of this study is to longitudinally assess sociodemographic and psychological correlates of increased alcohol use during the coronavirus disease of 2019 (COVID-19) period among adolescents and young adults. METHODS: Pre-COVID period is defined as the 1-year period on or before 31 March 2020, and during-COVID period is defined as the period from 1st April 2020 to 30 March 2021. Univariable logistic regression models are used to evaluate the association of demographic characteristics, Area Deprivation Index (ADI), rurality, changes in Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale severity, and the risk of increased alcohol consumption (binge drinking, number of drinks and drinking regularity) from pre-COVID to during-COVID period. RESULTS AND CONCLUSION: Our study found that worsened anxiety symptoms, older age, being in college and current cigarette smoking status were associated with increased alcohol use among youth during the pandemic year. Socioeconomic position (measured by ADI) and rural status were not found to be associated with increased alcohol use among adolescents and young adults.

Prevention of external auditory canal exostosis in the Colorado whitewater community.

CONTEXT: External auditory canal exostoses (EACE) are bony formations that develop insidiously in the auditory meatus from chronic exposure to cold water and, in severe cases, require surgery. This condition has been understudied in the whitewater kayakers and not yet studied in the riverboarding population. Precautions such as earplugs are thought to prevent the formation of EACE because they mechanically block cold water from contacting the sensitive skin in the external auditory canal; however, earplugs are not commonly utilized by athletes. Inquiring about hobbies and the use of protective equipment can be done during osteopathic physicians' preventive care visits. OBJECTIVES: This article aims to determine the prevalence of EACE in Colorado whitewater athletes and their attitudes about wearing ear protection before and after an educational intervention directed at increasing awareness and prevention of EACE. METHODS: In July 2020, participants of this cross-sectional study completed a 10-min survey that collected demographics, whitewater experience, and perceptions of EACE, followed by an educational intervention. Participant ears were photographed utilizing a digital otoscope to assess EACE, and severity ratings were categorized into one of four occlusion levels: none (0%), mild (<25%), moderate (25-75%), or severe (>75%). Spearman correlation coefficients and Wilcoxon signed-rank tests were utilized to assess changes in attitudes before and after the educational intervention. RESULTS: Eighty-one participants (mean [SD] age = 36.3 [12.6] years, 25.9% female) completed the study: 74 kayakers and seven riverboarders. After the intervention, 60.5% (49/81) (p<0.001) reported greater understanding of EACE and 75.0% (60/80) were more likely to wear ear protection (p<0.001). Most (58.0%, 47/81) never wore ear protection. Of the 61 (75.0%) participants with at least one ear severity rating, most (55.7%, 34/61) had moderate EACE, 29.5% (18/61) had no to mild EACE, and 14.8% (9/61) had severe EACE (p<0.001). Impaired hearing was the biggest barrier to utilizing ear protection (51.6%, 33/64). CONCLUSIONS: Our results suggested that the educational intervention improved understanding of EACE and may increase utilization of ear protection in this population. Such prevention efforts may lead to better health of whitewater paddlers by reducing the incidence of EACE. Encouraging osteopathic physicians to inquire about hobbies and protective equipment during primary care preventive visits is essential to help keep athletes in the river doing what they love for longer, contributing to a healthier and happier whole person.

Dental Students' Knowledge and Attitudes about Human Papillomavirus Prevention.

The purpose of the current study was to assess knowledge and attitudes about human papillomavirus (HPV) and HPV vaccination for oropharyngeal cancer (OPC) prevention in first-year through fourth-year dental students. METHODS: In this cross-sectional quantitative study, surveys assessed knowledge and attitudes about HPV, HPV-related OPC, and HPV vaccination of incoming first-year dental students (D1), outgoing first- and second-year dental students (D1-D2), and outgoing third- and fourth-year dental students (D3-D4). After completing a 40-item pre-training knowledge and attitude assessment survey, a one-time, one-hour national HPV training session was conducted. An 8-item attitudinal post-survey was completed after training. RESULTS: Of 173 participants (75.9% response rate), over 85% did not know that the rate of HPV is not highest among women in their 30s, and only 11% to 28% knew that smoking-associated OPC is more deadly than HPV-associated OPC. While participants overall expressed willingness to administer the HPV vaccine, the willingness of dental students to do so in their future practice tapered off progressively through dental school year categories (p < 0.001). Among outgoing D1-D4 students, the one-hour HPV training increased participants' self-perceived ability to describe the burden of HPV disease, discuss the importance of HPV vaccination for cancer prevention, and provide needed HPV vaccination information to parents (all p ≤ 0.004). CONCLUSIONS: Understanding deficits in dental student knowledge and attitudes across the 4 years of dental school may help dental educators better understand the timing and content needed for effective HPV training in the dental school curriculum to reduce HPV-associated OPC prevalence.

Effect of a required online graded curriculum in the clerkship years on medical student national standardized examination performance.

CONTEXT: Many medical schools have a distributed model for clinical clerkship education, challenging our ability to determine student gaps during clinical education. With the graduating class of 2017, A.T. Still University's School of Osteopathic Medicine in Arizona (ATSU-SOMA) began requiring additional online curricula for all clerkship courses. OBJECTIVES: To determine whether third year and fourth year students receiving ATSU-SOMA's online curricula during core clerkships performed better overall on national standardized examinations than students from previous years who had not received the curricula, and whether scores from online coursework correlated with outcomes on standardized examinations as possible early predictors of success. METHODS: This retrospective cohort study analyzed existing data (demographics and assessments) from ATSU-SOMA classes of 2017-2020 (curriculum group) and 2014-2016 (precurriculum group). The effect of the curriculum on national standardized examinations (Comprehensive Osteopathic Medical Achievement Test [COMAT] and Comprehensive Osteopathic Medical Licensing Examination of the United States [COMLEX-USA]) was estimated using augmented inverse probability weighting (AIPW). Correlations between assignment scores and national standardized examinations were estimated using linear regression models. RESULTS: The curriculum group had 405 students with a mean (standard deviation [SD]) age of 25.7 (±3.1) years. Two hundred and fifteen (53.1%) students in the curriculum group were female and 190 (46.9%) were male. The precurriculum group had 308 students (mean ± SD age, 26.4 ± 4.2 years; 157 [51.0%] male; 151 [49.0%] female). The online curriculum group had higher COMAT clinical subject exam scores in obstetrics and gynecology, osteopathic principles and practice (OPP), psychiatry, and surgery (all p≤0.04), as well as higher COMLEX-USA Level 2-Cognitive Evaluation (CE) family medicine and OPP subscores (both p≤0.03). The curriculum group had a 9.4 point increase in mean total COMLEX-USA Level 2-CE score (p=0.08). No effect was found for the curriculum overall on COMAT mean or COMLEX-USA Level 2-Performance Evaluation scores (all p≥0.11). Total coursework scores in each core clerkship, excluding pediatrics, were correlated with COMAT mean score (all adjusted p≤0.03). Mean scores for five of the seven assignment types in core clerkships, excluding evidence based medicine types, were positively correlated with COMAT mean scores (all adjusted p≤0.049). All assignment types correlated with COMLEX-USA Level 2-CE total score (all adjusted p≤0.04), except interprofessional education (IPE). CONCLUSIONS: Results from this study of 713 students from ATSU-SOMA suggested that our online curriculum supplemented clinic based learning during clerkship courses and improved student outcomes on national standardized examinations.

Does posttreatment thymoquinone reverse high-dose atorvastatin-induced hepatic oxidative injury in rats?

Atorvastatin (ATO) was commonly used to lower blood cholesterol, but it caused harmful effects to organs, including the liver. Thymoquinone (TQ), a prominent constituent of Nigella sativa, has antioxidant, antiinflammatory, antiapoptotic, antimicrobial, and anticancer activity. The current study investigated the mechanism of ATO-induced hepatotoxicity, whether posttreatment TQ could reverse ATO-induced hepatic injury, and the mechanism of action of TQ as a hepatoprotective agent. Forty adult male Sprague Dawley rats were divided into four equal groups: control, TQ-treated, ATO-treated, and combined ATO/TQ-treated. Rats were treated for 8 weeks and 10 days and euthanized by cervical dislocation 3 days after the last treatment. Blood samples and livers were tested for liver enzymes, oxidative stress, and apoptosis markers and used for histopathological and ultrastructural examination. The ATO-treated group showed an increase in liver enzymes, decreases in reduced glutathione and catalase, and increases in the malondialdehyde lipid peroxidation marker, protein carbonylation, and caspase 3 activity. Posttreatment TQ in the ATO/TQ-treated group seemed to reverse these changes. Histopathological and ultrastructural examination supported these data. Results from the current study suggested that posttreatment TQ may reverse oxidative stress injury in rat liver produced by ATO, suggesting a potential clinical application of using TQ to prevent ATO-induced hepatic injury.

Relationship between hypothermia and blood loss in adult patients undergoing open lumbar spine surgery.

CONTEXT: Intraoperative blood loss during open lumbar spine surgery is associated with adverse events and is a contributor to higher medical costs. Intraoperative hypothermia has been shown to increase blood loss and postoperative allogeneic blood transfusion rates in other realms of orthopedic surgery, but it has not been studied extensively in patients undergoing spine surgery. OBJECTIVE: To determine whether a clinically relevant association exists between intraoperative core body temperature and blood loss or transfusion rates in adult patients undergoing open lumbar spine surgery. METHODS: In this retrospective medical record review, the surgical records of 174 adult patients who underwent open, nonmicroscopically assisted lumbar spine surgery performed by a single surgeon at a single institution were evaluated. Maximum, minimum, and average temperature, hypothermic temperature, and temperature range parameters were compared with intraoperative, total, and net blood loss and blood transfusion parameters. Additional patient demographic and perioperative characteristics were compared with blood loss and transfusion parameters to determine potential confounders. Analysis of variance, Spearman rank correlation, and generalized multiple linear regression analysis were performed to test for an association between temperature and blood loss or allogeneic transfusion rates. Statistical significance was set at P≤.05. RESULTS: After implementation of exclusion criteria, 160 patient records and 168 surgical procedures were included in the analysis. For patients whose temperature decreased to a hypothermic level at some point during the procedure, hypothermic maximum temperature was protective against blood loss on bivariate analysis (P≤.02), but this finding lost significance after multivariate regression analysis (P>.09). Temperature range was associated with increased blood loss on bivariate analyses (P<.001) but also lost significance after adjusting for covariates in regression analysis (P≥.65). Surgery type (P≤.001) and operative time (P≤.001) were the most robust predictors of increased blood loss (P=.005) and were significantly associated with temperature (P<.001). CONCLUSION: No effect was found on perioperative blood loss from any temperature parameter or hypothermia in adult patients who underwent lumbar spine surgery once covariates were controlled for with multivariate analysis. One possible interpretation of these results is that the effect of temperature on blood loss can be explained by its strong relationship to the confounders of operative time and surgery type.