Phenome-wide association study identifies new clinical phenotypes associated with Staphylococcus aureus infections.

BACKGROUND: Phenome-Wide Association study (PheWAS) is a powerful tool designed to systematically screen clinical observations derived from medical records (phenotypes) for association with a variable of interest. Despite their usefulness, no systematic screening of phenotypes associated with Staphylococcus aureus infections (SAIs) has been done leaving potential novel risk factors or complications undiscovered. METHOD AND COHORTS: We tailored the PheWAS approach into a two-stage screening procedure to identify novel phenotypes correlating with SAIs. The first stage screened for co-occurrence of SAIs with other phenotypes within medical records. In the second stage, significant findings were examined for the correlations between their age of onset with that of SAIs. The PheWAS was implemented using the medical records of 754,401 patients from the Marshfield Clinic Health System. Any novel associations discovered were subsequently validated using datasets from TriNetX and All of Us, encompassing 109,884,571 and 118,538 patients respectively. RESULTS: Forty-one phenotypes met the significance criteria of a p-value < 3.64e-5 and odds ratios of > 5. Out of these, we classified 23 associations either as risk factors or as complications of SAIs. Three novel associations were discovered and classified either as a risk (long-term use of aspirin) or complications (iron deficiency anemia and anemia of chronic disease). All novel associations were replicated in the TriNetX cohort. In the All of Us cohort, anemia of chronic disease was replicated according to our significance criteria. CONCLUSIONS: The PheWAS of SAIs expands our understanding of SAIs interacting phenotypes. Additionally, the novel two-stage PheWAS approach developed in this study can be applied to examine other disease-disease interactions of interest. Due to the possibility of bias inherent in observational data, the findings of this study require further investigation.

Efficacy and safety of once-weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus-A systematic review and meta-analysis of randomized controlled trials.

Semaglutide is found to be efficient for weight loss in patients with overweight or obesity with diabetes mellitus (DM). With a wide range of adverse events reported, the efficacy and safety of once-weekly subcutaneous semaglutide in individuals without DM, with overweight or obesity, is unclear. We conducted a comprehensive meta-analysis of randomized studies on once-weekly semaglutide in this patient population. We identified nine studies with 11,641 patients in the semaglutide group and 10,479 in the placebo group. We observed that semaglutide resulted in significant benefits, including change in body weight (%): mean difference (MD) of -11.49% (p < 0.0001), change in absolute body weight: MD of -11.74 kg (p < 0.0001), and change in waist circumference: MD of -9.06 cm (p < 0.0001). Gastrointestinal side effects are predominant including nausea: odds ratio (OR) of 4.06 (p < 0.0001), vomiting: OR of 4.43 (p < 0.0001), diarrhea: OR of 2.10 (p < 0.0001), constipation: OR of 2.43 (p < 0.0001), gallbladder disorders: OR of 1.26 (p = 0.010), and cholelithiasis: OR of 2.06 (p = 0.04). Serious adverse events were not statistically significant: OR of 1.06 (p = 0.82). However, the percentage of participants discontinuing due to adverse events and gastrointestinal side effects was statistically significant: ORs of 2.22 (p < 0.0001) and 3.77 (p < 0.0001), respectively. This study shows that in patients with overweight or obesity without DM, once-weekly subcutaneous semaglutide can significantly decrease body weight without risk of serious adverse events when compared with a placebo. However, gastrointestinal side effects are predominant with semaglutide, which can result in medication discontinuation.

The Efficacy and Safety of Sacubitril/Valsartan Compared to Valsartan in Patients with Heart Failure and Mildly Reduced and Preserved Ejection Fractions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Sacubitril/valsartan improves heart failure (HF) outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, randomized controlled trials (RCTs) in patients with heart failure and mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) have shown inconsistent results. We conducted this meta-analysis to comprehensively evaluate the efficacy and safety of sacubitril/valsartan compared to valsartan within this specific patient population. Methods: We searched the MEDLINE database and ClinicalTrials.gov and identified four RCTs that could be included in our analysis, with 3375 patients in the sacubitril/valsartan group and 3362 in the valsartan group. Results: Our study shows that, in patients with HFmrEF and HFpEF, sacubitril/valsartan was superior to valsartan in some of the key HF outcomes, such as the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), with a small but significant mean difference of 1.13 (95% confidence interval or CI of 0.15 to 2.11, p-value 0.024), an improvement in the New York Heart Association (NYHA) class (odds ratio or OR of 1.32, 95% CI 1.11 to 1.58, p-value 0.002), and the composite outcome of hospitalizations for HF and cardiovascular death, with a relative risk (RR) of 0.86 (95% CI 0.75 to 0.99, p-value 0.04). However, there was no additional benefit with sacubitril/valsartan compared to valsartan for the outcomes of cardiovascular death and all-cause mortality. In terms of side effects, sacubitril/valsartan was associated with a higher risk of hypotension when compared to valsartan (OR 1.67, 95% CI 1.27 to 2.19, p-value < 0.0001), but did not show an increased risk of hyperkalemia or worsening renal function. Conclusions: In individuals with HFmrEF or HFpEF, sacubitril/valsartan can result in improvements in the HF outcomes of the KCCQ CSS, the NYHA class, and the composite outcome of hospitalization for HF and cardiovascular death when compared to valsartan. While there was a higher risk of hypotension with sacubitril/valsartan compared to valsartan, there was no corresponding increase in the risk of hyperkalemia or worsening renal function.

Early development and adaptive functioning in children with Bardet-Biedl syndrome.

This study had two aims. Aim one investigated achievement of 10 developmental milestones in children with Bardet-Biedl syndrome (BBS). Aim one data were derived from retrospective responses by caregivers of individuals with BBS who are enrolled in the Clinical Registry Investigating Bardet-Biedl syndrome (CRIBBS). CRIBBS is a natural history registry acquiring serial observations. Aim two investigated early adaptive skills using the Adaptive Behavior Assessment System (ABAS-II 0-5) completed by caregivers of children with BBS aged from 0 to 5. There were 652 individuals with milestone information (with some variability based on availability of information for specific milestones), and 101 individuals (including 95 among the 652) with ABAS-II information. Results revealed wide-ranging delays in adaptive skills, particularly in the domain of Self-Care. Expressive language appears to be the most frequently delayed developmental milestone. We found a difference by BBS genotype wherein individuals with BBS1 had higher adaptive/developmental scores than individuals with BBS10. Age also carried a significant association with adaptive skills diverging farther from a normative trajectory as children with BBS progress through early childhood.

Medically Attended Suicidality in Youth Who Live on Farms.

Suicides are increasing in U.S. youth, particularly in rural areas. The influence of farming, however, is unclear, as suicide rates are higher in individual adult farm workers, but lower in farming-reliant counties. Early recognition of suicidality (suicidal ideation, intent, or attempt) is a key element of prevention, but there are no prior studies comparing suicidality in farm vs. non-farm youth. The purpose of this study was to examine associations between farm/rural residence and suicidality. Medical records were reused from an existing cohort of child and adolescent patients under surveillance for agricultural injuries in a Wisconsin healthcare system. The sample included 2,010 youth who lived on farms and 51,900 youth who did not live on farms (57% rural). The outcome was medically attended suicidality in 2017-2022 per a composite of diagnoses for suicidal ideation, attempt, or intentional self-harm that presented to ambulatory, emergency, or inpatient care settings. Suicidality was observed in 0.8% of farm, 1.8% of non-farm rural, and 1.6% of non-farm non-rural youth. After covariate adjustment, farm youth had significantly lower odds of suicidality (adjusted odds ratio [aOR] [95% confidence interval; CI] = 0.55 [0.33, 0.91], P = .019), while non-farm rural youth had significantly greater odds of suicidality (aOR [CI] = 1.21 [1.05, 1.40], P = .007), relative to non-farm non-rural youth. Children and adolescents who live on farms are about half as likely to (medically) present for suicidality as compared to their non-farm counterparts, both rural and non-rural. Future research should identify causal suicide protection factors in farm youth.

Race, Rurality, and Suicidality in Children and Adolescents.

INTRODUCTION: Suicide is among the leading causes of death in U.S. youth. Rural residency is a risk factor, but suicide variability by race/ethnicity is more nuanced. Early detection of suicidal ideation and intent are key components of prevention, but to the authors' knowledge, few prior studies have examined how rurality and race interact on youth suicidality. This study examined suicidality between White non-Hispanic versus non-White or Hispanic youth, as well as those who lived in rural versus non-rural areas. METHODS: Cross-sectional analyses were conducted using data from youth age 5-17 years who had complete capture of their medical care in a Wisconsin healthcare system. Suicidality was extracted from medical records by screening for diagnoses indicative of suicidal attempt or ideation between 2017 and 2022. Race/ethnicity and rural residence were extracted from administrative records. Analyses were done in 2023. RESULTS: The sample included 27,392 rural and 20,370 non-rural youth, with suicidality observed in 2% of participants. There was a significant interaction between rural residence and race/ethnicity (p=0.015). Non-White or Hispanic youth in rural areas had the highest risk of suicidality at 75 (CI: 57, 97) per 10,000. Non-White or Hispanic youth in non-rural areas had the lowest risk of suicidality at 38 (CI: 28, 52) per 10,000. CONCLUSIONS: Racial/ethnic minority youth who lived in rural areas were more likely to experience suicidality as compared to their non-rural counterparts. Larger prospective studies are needed to identify causal elements of the rural environment that may hasten racial disparities in youth suicidality.

Modeling longitudinal oral health status and pneumonia risk: secondary data analyses of an integrated dental-medical cohort.

BACKGROUND: Mounting evidence indicates potential associations between poor oral health status (OHS) and increased pneumonia risk. Relative pneumonia risk was assessed in the context of longitudinally documented OHS. METHODS: Electronic medical/dental patient data captured from 2007 through 2019 were retrieved from the integrated health records of Marshfield Clinic Health Systems. Participant eligibility initiated with an assessment of OHS, stratified into the best, moderate, or worst OHS groups, with the additional criterion of 'no pneumonia diagnosis in the past 90 days'. Pneumonia incidence was longitudinally monitored for up to 1 year from each qualifying dental visit. Models were assessed, with and without adjustment for prior pneumonia incidence, adjusted for smoking and subjected to confounding mitigation attributable to known pneumonia risk factors by applying propensity score analysis. Time-to-event analysis and proportional hazard modeling were applied to investigate relative pneumonia risk over time among the OHS groups. RESULTS: Modeling identified associations between any incident pneumonia subtype and 'number of missing teeth' (p < 0.001) and 'clinically assessed periodontal status' (p < 0.01), which remained significant following adjustment for prior pneumonia incidence and smoking. The hazard ratio (HR) for 'any incident pneumonia' in the best OHS group for 'number of missing teeth' was 0.65, 95% confidence interval (CI) [0.54 - 0.79] (unadjusted) and 0.744, 95% CI [0.61 - 0.91] (adjusted). The HR for 'any incident pneumonia' in the best 'clinically assessed periodontal status' group was 0.72, 95% CI [0.58 - 0.90] (unadjusted) and 0.78, 95% CI [0.62 - 0.97] (adjusted). CONCLUSION/CLINICAL RELEVANCE: Poor OHS increased pneumonia risk. Proactive attention of medical providers to patient OHS and health literacy surrounding oral-systemic disease association is vital, especially in high-risk populations.

Mental health of agricultural adolescents and adults: Preliminary results of a five-year study.

Background: Work-related stressors common to agriculture have been associated with adverse mental health outcomes among adult farmers and ranchers. However, the mental health status of agricultural youth is unknown, despite farm and ranch youth being exposed to the same occupational hazards as their adult counterparts. The objective of this study was to estimate the prevalence of symptoms of depression and anxiety among farm adults and their adolescent child and examine the correlation between symptoms of mental health conditions and financial indicators described in the Family Stress Model (FSM). Methods: Farm families were recruited to participate in online surveys by mail, email, and social media. One adolescent and at least one adult from each family were invited to complete on online survey. Where available, validated instruments were used to collect mental health, stress, family dynamics, and household financial variables. Descriptive statistics were used to describe sample demographics and prevalence of symptoms of depression and anxiety. Pearson correlations describe associations between variables within the Family Stress Model. Results: Farm families (N = 122) completed the online survey. The mean age of farm parents was 41.4 years (SD = 4.4) and the mean age of farm adolescents was 15.4 (1.2). A majority of farm parents and farm adolescents were male, 58.2% and 70.5%, respectively. The sample was primarily white, non-Hispanic. In this sample of farm parents and adolescents alike, 60% met the criteria for at least mild depression, based on the Patient Health Questionnaire-9 (PHQ-9) and Patient Health Questionnaire-A (PHQ-A). Similarly, among adolescents, 45.1% met the criteria for Generalized Anxiety Disorder (GAD), as did 54.9% of adults. As a measure of economic hardship, per capita income by itself showed relatively low correlations, even with other economic measures (r = 0.11 with negative financial events, r = 0.20 with financial needs, r = 0.17 with financial situation, and r = 0.27 with debt). Parent depressed mood was in turn highly associated with adolescent depression (r = 0.83), social anxiety (r = 0.54), and generalized anxiety (r = 0.69). Conclusions: The results show a strong association between parent and adolescent mental health and parental depressed mood and debt. There is not a clear association between economic stress and mental health in this sample, but further work is needed to be done at a population level. Preliminary results are promising for application of the full Family Stress Model as we continue to accrue farm families into the study cohort.

COVID-19 vaccine coverage disparities in rural and farm children.

BACKGROUND: The risks of severe outcomes associated with SARS-CoV-2 (COVID-19) are elevated in unvaccinated individuals. It remains crucial to understand patterns of COVID-19 vaccination, particularly in younger and remote populations where coverage often lags. This study examined disparities in COVID-19 vaccine coverage in farm children and adolescents. METHODS: A cross-sectional analysis was conducted in patients of the Marshfield Clinic Health System (MCHS) in Wisconsin. The sample included children/adolescents age 5-17 years who were eligible for COVID-19 vaccine initiation for ≥ 90 days (as of September 30, 2022), stratified by those who lived vs did not live on a farm. Outcomes included COVID-19 vaccine initiation, series completion, and booster receipt. Multivariable regression was used to examine associations between COVID-19 vaccination and farm, as well as rural and non-rural, residence. RESULTS: There were 47,104 individuals (5% farm residents) in the sample. Overall, 33% of participants initiated and 31% completed the COVID-19 vaccine series. After adjustment, farm residence was associated with significantly lower odds of COVID-19 vaccine initiation (aOR [95% CI] = 0.68 [0.61, 0.75], p < 0.001), series completion (aOR = 0.67 [0.60, 0.75], p < 0.001), and booster receipt (aOR = 0.73 [0.61, 0.88], p = 0.001). Secondary analyses found COVID-19 vaccine coverage was lowest in young children who lived on dairy farms. CONCLUSIONS: COVID-19 vaccine coverage is low in north-central Wisconsin children and adolescents. Those who live on farms have significantly lower likelihood of COVID-19 vaccine initiation, series completion, and booster receipt compared to non-farm counterparts. Farm families are an underserved group and require more effective public health interventions designed to prevent COVID-19.

Hydrochlorothiazide use, sun exposure, and risk of keratinocyte cancer.

BACKGROUND: Keratinocyte cancer (KC) rates are increasing in the U.S., particularly in older age groups. Use of hydrochlorothiazide (HCTZ), due to its photosensitizing properties, and high sun exposure are two known NMSC risk factors, but their synergistic effects are undetermined. The purpose of this study was to examine the development of NMSC between adults who did and did not use HCTZ, as well as those with high and low sun exposure. METHODS: A retrospective case-control sample was assembled from adult patients in north-central Wisconsin (USA). Duration of HCTZ use and occupational sun exposure were extracted from electronic health records, along with a linked survey of lifetime sun exposure. RESULTS: There were 333 cases and 666 controls in the analytical sample. A significant main effect was observed for HCTZ duration in the full sample. Under low sun exposure, the odds of NMSC was 14% greater for each additional year of HCTZ use (aOR = 1.14 [1.11, 1.18], p < 0.001). In a sensitivity analysis of participants age 70 years and over, there was a borderline significant (p = 0.086) HCTZ use by high sun exposure interaction, suggesting modestly increased HCTZ risk in older, high sun exposure adults. CONCLUSIONS: Consistent with prior studies, longer duration of HCTZ use was a predictor of NMSC in north-central Wisconsin adults. NMSC may be accelerated in HCTZ users with outdoor lifestyles, but future studies should attempt to further disaggregate specific effects of sun exposure time, HCTZ duration, and age on NMSC development.

Kidney failure in Bardet-Biedl syndrome.

The aim of this study was to explore kidney failure (KF) in Bardet-Biedl syndrome (BBS), focusing on high-risk gene variants, demographics, and morbidity. We employed the Clinical Registry Investigating BBS (CRIBBS) to identify 44 (7.2%) individuals with KF out of 607 subjects. Molecularly confirmed BBS was identified in 37 KF subjects and 364 CRIBBS registrants. KF was concomitant with recessive causal variants in 12 genes, with BBS10 the most predominant causal gene (26.6%), while disease penetrance was highest in SDCCAG8 (100%). Two truncating variants were present in 67.6% of KF cases. KF incidence was increased in genes not belonging to the BBSome or chaperonin-like genes (p < 0.001), including TTC21B, a new candidate BBS gene. Median age of KF was 12.5 years, with the vast majority of KF occurring by 30 years (86.3%). Females were disproportionately affected (77.3%). Diverse uropathies were identified, but were not more common in the KF group (p = 0.672). Kidney failure was evident in 11 of 15 (73.3%) deaths outside infancy. We conclude that KF poses a significant risk for premature morbidity in BBS. Risk factors for KF include female sex, truncating variants, and genes other than BBSome/chaperonin-like genes highlighting the value of comprehensive genetic investigation.

Systematic review of studies examining contribution of oral health variables to risk prediction models for undiagnosed Type 2 diabetes and prediabetes.

OBJECTIVE: To conduct systematic review applying "preferred reporting items for systematic reviews and meta-analyses statement" and "prediction model risk of assessment bias tool" to studies examining the performance of predictive models incorporating oral health-related variables as candidate predictors for projecting undiagnosed diabetes mellitus (Type 2)/prediabetes risk. MATERIALS AND METHODS: Literature searches undertaken in PubMed, Web of Science, and Gray literature identified eligible studies published between January 1, 1980 and July 31, 2018. Systematically reviewed studies met inclusion criteria if studies applied multivariable regression modeling or informatics approaches to risk prediction for undiagnosed diabetes/prediabetes, and included dental/oral health-related variables modeled either independently, or in combination with other risk variables. RESULTS: Eligibility for systematic review was determined for seven of the 71 studies screened. Nineteen dental/oral health-related variables were examined across studies. "Periodontal pocket depth" and/or "missing teeth" were oral health variables consistently retained as predictive variables in models across all systematically reviewed studies. Strong performance metrics were reported for derived models by all systematically reviewed studies. The predictive power of independently modeled oral health variables was marginally amplified when modeled with point-of-care biological glycemic measures in dental settings. Meta-analysis was precluded due to high inter-study variability in study design and population diversity. CONCLUSIONS: Predictive modeling consistently supported "periodontal measures" and "missing teeth" as candidate variables for predicting undiagnosed diabetes/prediabetes. Validation of predictive risk modeling for undiagnosed diabetes/prediabetes across diverse populations will test the feasibility of translating such models into clinical practice settings as noninvasive screening tools for identifying at-risk individuals following demonstration of model validity within the defined population.

Regional surveillance of medically-attended farm-related injuries in children and adolescents.

Purpose: Due to numerous environmental hazards such as heavy machinery and large livestock, youth who live and work on farms are at high risk of injury, disability, and death. This study described a regional surveillance system for monitoring farm-related injuries in children and adolescents. As the risk of farm-related injuries are not exclusive to farm residents, trends in farm-related injuries over the previous 5 years were reported and compared between children/adolescents who did and did not live on farms in north-central Wisconsin. Methods: A retrospective cohort of child and adolescent patients of the Marshfield Clinic Health System was assembled. Incident farm-related injuries, including from agricultural work or other activities in a farm environment, were extracted from medical records from 2017 through 2021. Generalized linear models were created to compare age- and sex-adjusted farm-related injury rates by year. Results: There were 4,730 (5%) in-farm and 93,420 (95%) out-farm children and adolescents in the cohort. There were 65 incident farm-related injury cases in the in-farm group and 412 in the out-farm group. The annual incidence rate of farm-related injuries was higher in the in-farm group, but changes during the 5-year timeframe were not significant in either group. In the in-farm group, rates ranged from a high of 61.8 [95% confidence interval (CI): 38.3, 94.5] incident farm-related injuries per 10,000 children/adolescents in 2017 to a low of 28.2 (13.5, 51.9) injuries per 10,000 children/adolescents in 2018. In the out-farm group, rates ranged from 10.7 (8.3, 13.6) to 16.8 (13.7, 20.5) incident farm-related injuries per 10,000 children/adolescents per year between 2017 and 2021. The in-farm group had a higher proportion of injured males and heavy machinery injuries, while the out-farm group had more all-terrain vehicle injuries and pesticide poisonings. Conclusion: Farm residency remains hazardous for children and adolescents, as injury rates were three times higher in the in-farm group and remained stable over 5 years. All-terrain vehicle injuries were high in both groups, and should be a priority in rural safety interventions. With additional adaptations to other states, this surveillance model could be scaled across other healthcare systems.

Injuries and illnesses to children in commercial fishing in Alaska: A brief report.

BACKGROUND: Commercial fishing is the most hazardous occupation in the United States. While the epidemiology of adult injuries and fatalities are well documented, injuries to children (<18 years old) are not described. The purpose of this report was to describe the characteristics of nonfatal injuries to children involved in commercial fishing. METHODS: Nonfatal commercial fishing injuries to children were identified in the Alaska Fishermen's Fund. The Alaska Fishermen's Fund is an emergency fund payor of last resort. Data on nonfatal injuries to victims aged 17 or younger were analyzed. Descriptive statistics were used to characterize demographics and injury characteristics. RESULTS: Forty-four nonfatal child injury claims were made between 2012 and 2016. The mean age at the time of claim was 15.6 years (SD = 1.8) and 84% were male. The most common types of injuries among children were sprains and strains and the most commonly injured body parts were upper extremities and the trunk. Most injuries occurred in salmon fisheries. CONCLUSIONS: Children are participating in commercial fishing. Based on the results of this analysis, children are also experiencing occupational injuries. The results of this analysis underscore the need for additional safety and health information, guidance for supervisors, and intervention to prevent injuries to children participating in commercial fishing.

Bardet-Biedl syndrome: Weight patterns and genetics in a rare obesity syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare genetic disorder that severely inhibits primary cilia function. BBS is typified by obesity in adulthood, but pediatric weight patterns, and thus optimal periods of intervention, are poorly understood. OBJECTIVES: To examine body mass differences by age, gender, and genotype in children and adolescents with BBS. METHODS: We utilized the largest international registry of BBS phenotypes. Anthropometric and genetic data were obtained from medical records or participant/family interviews. Participants were stratified by age and sex categories. Genotype and obesity phenotype were investigated in a subset of participants with available data. RESULTS: Height and weight measurements were available for 552 unique individuals with BBS. The majority of birth weights were in the normal range, but rates of overweight or obesity rapidly increased in early childhood, exceeding 90% after age 5. Weight z-scores in groups >2 years were above 2.0, while height z-scores approached 1.0, but were close to 0.0 in adolescents. Relative to those with the BBS10 genotype, the BBS1 cohort had a lower BMI z-score in the 2-5 and 6-11 age groups, with similar BMI z-scores thereafter. Children with biallelic loss of function (LOF) genetic variants had significantly higher BMI z-scores compared to missense variants. CONCLUSION: Despite normal birth weight, most individuals with BBS experience rapid weight gain in early childhood, with high rates of overweight/obesity sustained through adolescence. Children with LOF variants are disproportionally affected. Our findings support the need for earlier recognition and initiation of weight management therapies in BBS.

A Contemporary Profile of the Mental Health of Girls from Farm and Non-Farm Environments.

Background: The mental health of young people has become a public health priority in recent years. Many early symptoms of mental health disorders first appear during adolescence. The aim of this study was to develop a contemporary profile of the mental health of Canadian adolescent girls from farms and determine whether they differed from girls with non-farm backgrounds.Methods: Cross-sectional analyses of an established, school-based survey, the Health Behaviour in School-Aged Children (2014) were conducted. Study subjects were adolescent girls who reported living or working (n = 1,346) and not living or working (n = 13,158) on a farm and attending schools in rural, small, medium and large/metropolitan centers. Scales examining positive (prosocial behaviour, life satisfaction) and negative (psychological problems, overt risk-taking) mental health indicators were compared between the two groups of girls by grade and community size.Results: Both farm and non-farm girls in upper grades reported lower life satisfaction scores and higher scores for psychological problems and overt risking-taking compared to girls in lower grades. By community size, girls from farms in the most rural schools reported more positive mental health than non-farm girls, with the exception of overt risk-taking, where girls in grades 9-10 from the most rural backgrounds reported markedly higher levels of risk-taking, particularly girls from farms.Conclusions: This study identified differences in mental health of girls from farms as community size increases, with more positive indicators among girls in the most rural communities. However, across all community sizes, overt risk-taking was higher in girls from farms. Thus, it appears that agrarian culture and norms have both protective and negative effects on the mental health of girls from farms.

Depression, Anxiety and Stress Among Young Farmers and Ranchers: A Pilot Study.

Agriculture has been identified as a stressful industry and there is evidence that chronic stress may contribute to the development or progression of mental health disorders, specifically anxiety and depression. Young adult farmers and ranchers may be at increased risk of mental health disorders when compared to more experienced counterparts due to additional stressors. The objectives of this study were to identify the occupational stressors of young adult farmers and ranchers in the Midwest and estimate the prevalence of anxiety and depression among this population. An online survey consisting of reliable and valid instruments was used to identify the sources of stress and prevalence of anxiety and depression among the young farming and ranching population. The survey included items related to stress, anxiety, depression, general health, and farm/personal demographics. A total of 170 young farmers and ranchers responded to the survey. The mean age of the sample was 28.9 (SD 4.4) years. Approximately 71% of respondents met the criteria for Generalized Anxiety Disorder (GAD-7 score ≥ 5) and 53% met the criteria for Major Depressive Disorder (PHQ-9 score ≥ 5). Of seven presented stress domains, personal finances and time pressures were the sources of greatest concern. Personal finances, time pressures, economic conditions, and employee relations were associated with anxiety and depression. The burden of depression and anxiety is high among young adult farmers and ranchers. Stressors commonly affiliated with farming and ranching are associated with anxiety and depression. Additional research should further explore the burden of mental health disorders among the population and examine protective factors for mental illness and opportunities for interventions.

Sleep in Farm Adolescents.

PURPOSE: The objectives were to: (1) describe sleep timing and patterns among adolescents who live or work on farms; (2) compare these sleep characteristics to those of nonfarm adolescents; (3) explore whether the above sleep and farm versus nonfarm differences varied by age and gender. METHODS: Participants were aged 11-16 years and were abstracted from the 2014 Canadian Health Behaviour in School-aged Children study. Records from 2,160 farm adolescents were frequency matched (by school, gender, and grade) to records from 2,210 nonfarm adolescents. Participants self-reported their bedtimes and wake-up times on weekdays and weekends. FINDINGS: Among farm adolescents, average nightly sleep duration (hours:minutes) ranged from 08:34 among 14- to 16-year-old girls to 09:21 among 11- to 13-year-old girls. Approximately 24% to 32% of farm adolescents did not meet minimal sleep duration targets. For 11- to 13-year-olds, sleep characteristics did not differ according to farm status. However, for 14- to 16-year-olds, farm adolescents had shorter sleep durations than nonfarm adolescents (23 minutes for boys, P = .02; 20 minutes for girls, P = .06). Furthermore, a greater proportion of 14- to 16-year-old farm boys had sleep duration values less than the recommended 8 hours/night (27.7% vs 19.6%, P = .05). CONCLUSIONS: This study profiles the sleep experiences of 11- to 16-year-old farm adolescents. Almost 1 in 3 of these adolescents did not get adequate sleep. Older adolescents who lived or worked on a farm slept less than comparably aged nonfarm adolescents. This may reflect their participation in morning chores essential to the farm operation and may increase their injury risk.

Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals.

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived.