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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 (

Background Transcatheter aortic valve replacement (TAVR) is a rapidly evolving treatment for severe aortic stenosis. However, uncertainties exist for optimal valve selection as there are few long-term studies comparing patient survival by valve type. Objective We hypothesized that self-expandable valves (SEV) would provide a survival advantage over balloon expandable valves (BEV), as self-expandable valves continue to expand and might better accommodate to the anatomy of the aortic valve over time. Methods We examined outcomes according to valve type from a rural tertiary referral center between 2012 and 2017. Results Out of 269 patients, 77 deaths (28.6%) occurred over the study period with six deaths by 1 month post-TAVR and 37 deaths by 1 year post-TAVR. The median observation time for survivors was 21.5 months. The probability of survival at 3 years was 60.7% and 61.9% for patients who underwent treatment with SEV and BEV, respectively. There was no statistically significant difference in overall patient survival with or without adjustment for factors such as age, sex, race, and aortic valve area. Additionally, in a secondary analysis restricted to those patients treated in later years (2015-2017) survival among patients with BEV appeared superior (HR=0.456, p=0.015). Conclusion Patients who underwent TAVR at a rural medical center with an SEV showed similar survival compared to those who received a BEV. Superior survival was observed among those who received a BEV versus SEV between 2015 and 2017.

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.

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.

BACKGROUND: World Health Organization (WHO) 2017 diagnostic criteria for hemoglobin levels in polycythemia vera (PV) were lowered from 185 g/L to 165 g/L for men and from 165 g/L to 160 g/L for women, but these cutoffs were not designed for screening. OBJECTIVES: The primary aim of this study was to assess the value of laboratory and clinical parameters in deciding whether to further pursue a diagnosis of PV. A secondary aim was to explore the diagnostic utility of bone marrow morphology. METHODS: We evaluated clinical and laboratory parameters that may be useful when considering further diagnostic work-up, emphasizing PV vs. secondary erythrocytosis (SE). We classified 200 patients with JAK2 V617F testing using WHO criteria. RESULTS: Patients with myeloproliferative neoplasms (MPN) were rarely under age 40 and uncommonly obese (BMI ≥ 30 kg/m(2)). Current smoking history favored SE, and these patients rarely had a platelet count ≥ 450 × 10(3)/uL. Laboratory parameters suggesting greater PV likelihood were: RBC > 6.8 × 10(6) for men or > 5.9 × 10(6) for women; low erythropoietin; and low MCV or low ferritin. Bone marrow morphology (available in 111 cases) was generally more cellular in PV vs. SE and assessed disease progression. CONCLUSIONS: Readily accessible clinical and laboratory data can assist in considering a PV workup, and a possible diagnostic algorithm is presented. These preliminary findings warrant larger studies to develop a more formal PV-risk scoring system with optimal cutoffs and weighting.

The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at 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 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%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. 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. This article is protected by copyright. All rights reserved.

Summary 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.

Children on Canadian farms are at high risk for fatal injury. Ongoing surveillance of these deaths is required to affirm recurrent patterns of injury, and to determine whether historical approaches to prevention have resulted in declines in the occurrence of these traumatic events. We analyzed epidemiological patterns and trends in the occurrence of fatal pediatric farm injuries over 23 years. Records of deaths were obtained from the Canadian Agricultural Injury Reporting system. To contrast more recent data with injury patterns described historically, cases were compared between two time periods. An intentional consensus process was used to finalize key patterns and their clinical or social importance. 374 fatal farm injuries to children in Canada were identified over the 23 years of study; 253 in period 1 and 121 in period 2. While machinery and non-machinery causes of death varied between the two study periods, mean annual rates of fatal injury (approximately 4 per 100,000 children) remained similar. Notably emergent types of injury in recent years included those caused by all-terrain vehicles, skid steer loaders, and drownings. Observed declines in the numbers of fatal farm injuries are most likely attributable to analogous declines in the number of registered farms in Canada. Our findings call into question the effectiveness of pediatric farm safety initiatives that primarily focus on education. Second, while CAIR fatality data are maintained, surveillance of hospitalized injuries has been disbanded and the fatality records require updating. Only by doing so will such surveillance findings provide comprehensive information to inform prevention.

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.

PURPOSE The United States has no comprehensive national surveillance system for fatal or nonfatal child agricultural injuries. Thus, important knowledge gaps exist about recurrent injury patterns that could provide targeted focus for prevention efforts. The purpose of this study was to explore existing US public health data systems to determine their utility with respect to informing child agricultural injury surveillance and primary prevention. METHODS Public health data systems were selected if they: (1) were national in scope, (2) were active and ongoing, (3) included physical injuries, and (4) contained a "farm" location variable. Data systems explored included National Emergency Medical Services Information System, National Trauma Data Bank, National Electronic Injury Surveillance System-All Injury Program, and National Vital Statistics System-Multiple Cause File. FINDINGS Each data system contained substantial information per case with the number of fields ranging from 77 to 127. Beyond basic demographic information about the injured child, there were many injury descriptors, but few commonalities across systems. The most striking finding was the uniform absence of information on injury circumstances; that is, why and how the injury occurred, which is fundamental to planning and evaluating prevention initiatives. CONCLUSIONS Although these public health data systems captured many details regarding medical aspects of the injury, they included little information on circumstances leading to injury, thus limiting their utility for child agricultural injury surveillance and primary prevention initiatives. We recommend any child agricultural injury data collection tool formally incorporate a structured narrative so underlying circumstances leading to injury events are documented.

PURPOSE: To determine whether patterns of adolescent risk behavior in rural populations, and especially farm populations, are associated with negative indicators of adolescent health and well‐being, beyond an established association between risk‐taking and injury. METHODS: The study base was Cycle 7 (2014) of the Canadian Health Behaviour in School‐Aged Children study. Children aged 11‐16 years (n = 2,565; 2,533 weighted) who reported living or working on farms were matched within schools in a 1:1 ratio with other rural children. We related a scale describing engagement in multiple risk behavior to a series of indicators of adolescent health and well‐being. FINDINGS: Farm children, particularly male farm children, showed the highest levels of risk behavior. Multiple risk behavior was strongly and consistently associated with negative indicators of general health, mental health (life satisfaction, psychosomatic symptoms), and academic performance in all subpopulations. CONCLUSIONS: Adolescent risk behavior in rural populations, and especially farm populations, is common and associated with a variety of negative indicators of adolescent health and well‐being. We speculate that the origins of this risk‐taking lifestyle surround cultural definitions of self and identity, which have both protective and negative effects.

The US Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing safety database, can be used to differentiate brand versus generic safety signals. To explore the methods for identifying and analyzing brand versus generic adverse event (AE) reports. Public release FAERS data from January 2004 to March 2015 were analyzed using alendronate and carbamazepine as examples. Reports were classified as brand, generic, and authorized generic (AG). Disproportionality analyses compared reporting odds ratios (RORs) of selected known labeled serious adverse events stratifying by brand, generic, and AG. The homogeneity of these RORs was compared using the Breslow-Day test. The AG versus generic was the primary focus since the AG is identical to brand but marketed as a generic, therefore minimizing generic perception bias. Sensitivity analyses explored how methodological approach influenced results. Based on 17,521 US event reports involving alendronate and 3733 US event reports involving carbamazepine (immediate and extended release), no consistently significant differences were observed across RORs for the AGs versus generics. Similar results were obtained when comparing reporting patterns over all time and just after generic entry. The most restrictive approach for classifying AE reports yielded smaller report counts but similar results. Differentiation of FAERS reports as brand versus generic requires careful attention to risk of product misclassification, but the relative stability of findings across varying assumptions supports the utility of these approaches for potential signal detection.

Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics.Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected P0.01.A total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P0.01.Similar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study.

Background Operating farm tractors is dangerous for children. Recent studies document mismatches between children and physical requirements for operating tractors. The role of cognition has not been studied, because such research conducted in real-life situations places youth at risk. The objective of this study was to evaluate the feasibility and psychometric properties of a simulated virtual tractor environment to examine how children’s age and development impacts safe tractor operations. Methods Fifty-five male youth ages 10–17 living/working on farms with experience driving tractors tested the virtual environment and simulation modules. Six adult male farmers were recruited as a reference group to compare youth performance with adults. Results The simulation had adequate face validity with realism scores reported between “somewhat” and “quite” realistic. Internal reliability of the simulation was excellent, as demonstrated by highly significant intraclass correlations for key indicators of performance (speeds and hazard clearances). While there was some evidence for construct validity, as indicated by trends in performance across the age groups, findings were mixed. Conclusion Study findings support using simulation for assessing the abilities of children to safely operate tractors.

A majority of adults with persistently low serum alkaline phosphatase values carry a pathogenic or likely pathogenic variant in the ALPL gene and also have elevated alkaline phosphatase substrate values in serum and urine. These adults may fall within the spectrum of the adult form of hypophosphatasia. The primary objective of this study was to determine what proportion of adults with persistently low serum alkaline phosphatase values (hypophosphatasemia) harbor mutations in the ALPL gene or have elevated alkaline phosphatase (ALP) substrates. Some adults with persistent hypophosphatasemia share clinical and radiographic features with the adult form of hypophosphatasia (HPP). In HPP, ALPL mutations result in persistent hypophosphatasemia and ALP substrate accumulation in plasma (pyridoxal-5-phosphate (PLP)) and urine (phosphoethanolamine (PEA)). Biochemical analyses, including serum ALP activity, bone-specific ALP, plasma PLP, and urine PEA, were performed in adults with persistent hypophosphatasemia. Mutational analyses were performed using PCR and Sanger sequencing methods. Gene variants were classified as pathogenic (P), likely pathogenic (LP), variants of uncertain significance (VUS), likely benign (LB), and benign (B). P and LP variants were further grouped as “Positive ALPL variants” and LB and B grouped as “Negative ALPL variants.” Fifty subjects completed all mutational and biochemical analyses. Sixteen percent carried only Negative ALPL variants. Of the remaining 42 subjects, 67% were heterozygous for a P variant, 19% for an LP variant, and 14% for a VUS. Biochemical results were highly inter-correlated and consistent with the expected inverse relationship between ALP and its substrates. Subjects harboring Positive ALPL variants showed lower ALP and BSAP and higher PLP and PEA values compared with subjects harboring only Negative ALPL variants. Approximately half of all subjects harboring Positive ALPL variants or ALPL VUS showed elevations in plasma PLP, and three quarters showed elevations in urine PEA. Adults with persistent hypophosphatasemia frequently harbor ALPL mutations and have elevated ALP substrates. These adults may fall within the spectrum of the adult form of hypophosphatasia. Clinicians should take note of persistent hypophosphatasemia in their patients and be cautious in prescribing bisphosphonates when present.

tudy Objective Generic drugs contain identical active ingredients as their corresponding brand drugs and are pharmaceutically equivalent and bioequivalent, whereas authorized generic drugs contain both identical active and inactive ingredients as their corresponding brand drugs but are marketed as generics. The objective of this study was to compare generic-to-brand switchback rates between generic and authorized generic drugs. Design Retrospective cohort study. Data Source Claims and electronic health record data from a regional United States health care system. Patients The full cohort consisted of 5542 unique patients who received select branded drugs during the 6 months prior to their generic drug market availability (between 1999 and 2014), and then were switched to an authorized generic or generic drug within 30 months of generic drug entry; for these patients, 5929 unique patient-drug combinations (867 with authorized generic drugs and 5062 with generic drugs) were evaluated. Measurements and Main Results Ten drugs with authorized generics and generics marketed between 1999 and 2014 were evaluated. The date of the first generic prescription was considered the index date for each drug, and this date marked the beginning of follow-up to evaluate the occurrence of generic-to-brand switchback patterns over the subsequent 30 months. Switchback rates were compared between patients receiving authorized generics versus those receiving generics using multivariable Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson comorbidity score, pre-index drug use characteristics, and pre-index health care utilization. Among the 5542 unique patients who switched from brand-to-generic or brand-to–authorized generic, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for authorized generics compared with generics (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65–1.15). The likelihood of switchback was higher for alendronate (HR 1.64, 95% CI 1.20–2.23) and simvastatin (HR 1.81, 95% CI 1.30–2.54) and lower for amlodipine (HR 0.27, 95% CI 0.17–0.42) compared with the other drugs evaluated. Conclusion Overall switchback rates were similar between authorized generic and generic drug users, indirectly supporting similar efficacy and tolerability profiles for brand and generic drugs. Reasons for differences in switchback rates among specific products need to be further explored. This article is protected by copyright. All rights reserved.

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 st...

Background Farm environments are especially hazardous for young people. While much is known about acute physical causes of traumatic farm injury, little is known about social factors that may underlie their aetiology. Objectives In a nationally representative sample of young Canadians aged 11–15 years, we described and compared farm and non-farm adolescents in terms of the qualities of their social environments, engagement in overt multiple risk-taking as well as how such exposures relate aetiologically to their reported injury experiences. Methods Cross-sectional analysis of survey reports from the 2014 (Cycle 7) Canadian Health Behaviour in School-Aged Children study was conducted. Children (n=2567; 2534 weighted) who reported living or working on farms were matched within schools in a 1:1 ratio with children not living or working on farms. Scales examining quality of social environments and overt risk-taking were compared between the two groups, stratified by gender. We then related the occurrence of any serious injury to these social exposures in direct and interactive models. Results Farm and non-farm children reported social environments that were quite similar, with the exception of overt multiple risk-taking, which was demonstrably higher in farm children of both genders. Engagement in overt risk-taking, but not the other social environmental factors, was strongly and consistently associated with risks for serious injury in farm as well as non-farm children, particularly among males. Conclusions Study findings highlight the strength of associations between overt multiple risk-taking and injury among farm children. This appears to be a normative aspect of adolescent farm culture.

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.

INTRODUCTION: Several different types of drugs acting on the central nervous system (CNS) have previously been associated with an increased risk of suicide and suicidal ideation (broadly referred to as suicide). However, a differential association between brand vs. generic CNS drugs and suicide has not been reported. OBJECTIVES: This study compares suicide adverse event rates for brand vs. generic CNS drugs using multiple sources of data. METHODS: Selected examples of CNS drugs (sertraline, gabapentin, zolpidem, and methylphenidate) were evaluated via the FDA Adverse Event Reporting System (FAERS) for a hypothesis generating study, and then via administrative claims and electronic health record (EHR) data for a more rigorous retrospective cohort study. Disproportionality analyses with reporting odds ratios (ROR) and 95% confidence intervals (CIs) were used in the FAERS analyses to quantify the association between each drug and reported suicide. For the cohort studies, Cox proportional hazards models were used, controlling for demographic and clinical characteristics as well as the background risk of suicide in the insured population. RESULTS: The FAERS analyses found significantly lower suicide reporting rates for brands compared with generics for all four studied products (Breslow-Day P

Objective: To use urine drug testing (UDT) results and other covariates to develop a model for the assessment of opioid medication prescription adherence. Design: Retrospective study. Setting: The Pain Management Clinic at one center of a large, private, multispecialty healthcare system (consisting of 52 regional centers) in northcentral and western Wisconsin. Participants: Seven hundred thirty-three Pain Management Clinic patients with an opioid prescription and UDT between June 1, 2007 and May 17, 2010. UDT results were available for 2,615 individual drug screens from 2,364 urine samples. Intervention: Patient characteristics, drug dosage, quantitative urine creatinine and drug/analyte levels, and reported adherence/nonadherence were abstracted from the electronic medical record. Main outcome measures: Adherence was categorized for all UDT results using an objective set of criteria. Drug adherence was modeled excluding samples for clinically observed adherence issues, detection of illicit substances, diagnosed addictive disorders, and/or metabolic reasons. Results: Considerable variability was observed for primary urine analytes, even among those prescribed the same dose and believed to be adherent and free of confounding medical issues. For all medications evaluated, only urine creatinine contributed significantly (p < 0.0001) to predictive models of adherence based on dose alone. Simulated underuse and review of identified overuse and underuse suggest that this model could provide useful adherence information. Conclusion: Predictive models based on urine analyte levels and clinical covariates, particularly urine creatinine, may be clinically useful for assessing opioid adherence. Future work should evaluate whether genetics or other factors can improve predictive accuracy of these models.

Background: There is a relative paucity of research examining the sport-specific injury epidemiology of high school and collegiate volleyball athletes. Moreover, differences in study methodology frequently limit our ability to compare and contrast injury data collected from selected populations. Hypothesis: There are differences between the injury patterns characteristic of high school and collegiate female volleyball athletes. Study Design: Retrospective clinical review. Level of Evidence: Level 3. Methods: We statistically analyzed injury incidence and outcome data collected over a 4-year interval (2005-2006 to 2008-2009) by 2 similar injury surveillance systems, the National Collegiate Athletic Association’s Injury Surveillance System (NCAA ISS) and the High School Reporting Injuries Online (HS RIO). We compared diagnoses, anatomic distribution of injuries, mechanisms of injury, and time lost from training or competition between high school and collegiate volleyball athletes. Results: The overall volleyball-related injury rate was significantly greater among collegiate athletes than among high school athletes during both competition (injury rate ratio, 2.9; 95% CI, 2.5-3.4) and practice (injury rate ratio, 3.5; 95% CI, 3.1-3.9). Collegiate athletes had a higher rate of ankle sprain, knee injury, and shoulder injury. Concussions represented a relatively high percentage of injuries in both populations (5.0% of total NCAA ISS injuries vs 4.8% of total HS RIO injuries, respectively). Conclusion: The data suggest that although similar, there were distinct differences between the injury patterns of the 2 populations. Compared with high school volleyball players, collegiate athletes have a higher rate of acute time loss injury as well as overuse time loss injury (particularly patellar tendinosis). Concussions represented a significant and worrisome component of the injury pattern for both study populations. Clinical Relevance: The injury data suggest that important differences exist in the injury patterns of female high school compared with collegiate volleyball athletes. Consideration of the specific injury patterns may be helpful in future prevention efforts.

Bioinformatics approaches to examine gene-gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge-driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty-three SNP-SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)–rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell-to-cell adhesion signaling, cell-cell junction organization, and cell-cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP-SNP models, which included signal transduction and PI3K-Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology-driven method, applicable for any genome-wide association study dataset.

Knowledge concerning frost–thaw profiles is important in the design of pavements for low-volume roads located in seasonal frost areas. In addition, because these roads are highly susceptible to damage during the spring thaw–weakened period, this knowledge is helpful in making decisions about seasonal load restriction (SLR) policies. Direct measurement of frost depth is expensive and usually limited in scope. Therefore, several highway agencies have expressed the need for a prediction model to help them in estimating frost–thaw profiles beneath roadways. A report from the U.S. Army Corps of Engineers New England Division examined frost prediction models. One of the equations in that report was Model 158, which was similar to the modified Berggren equation. Model 158 uses air temperature indexes as well as pavement material properties to integrate heat flow into the calculation of maximum seasonal frost depth. That model has been modified slightly and programmed in an Excel spreadsheet to predict frost and thaw depths on a daily basis. This paper presents an overview of the modified Model 158 and compares predictions obtained from that model with measured frost–thaw profiles obtained at several test sites located in northern New England during a period of five freeze–thaw seasons. Results suggest that the model shows much promise although it generally tended to slightly underpredict maximum frost depths. In tracking the thaw process for SLR posting, the model tended to be conservative in estimating end-of-thaw dates (especially during rapid thawing events); in many instances, estimated end-of-thaw dates fell after measured dates.

SummaryWhat is known and objective Some public scepticism exists about generics in terms of whether brand and generic drugs produce identical outcomes. This study explores whether adverse event (AE) reporting patterns are similar between brand and generic drugs, using authorized generics (AGs) as a control for possible generic drug perception biases. Methods Events reported to the FDA Adverse Event Reporting System from the years 2004-2015 were analysed. Drugs were classified as brand, AG or generic based on drug and manufacturer names. Reports were included if amlodipine, losartan, metoprolol extended release (ER) or simvastatin were listed as primary or secondary suspect drugs. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting labelled AEs compared to reporting these AEs with all other drugs. The Breslow-Day test compared RORs across brand, AG and generic. Interrupted time series analysis evaluated the impact of generic entry on reporting trends. Results and discussion Generics accounted for significant percentages of total U.S. reports, but AGs accounted for smaller percentages of reports, including for amlodipine (14.26%), losartan (1.48%), metoprolol ER (0.35%) and simvastatin (0.70%). Whereas the RORs were significantly different for multiple brand vs generic comparisons, the AG vs generic comparisons yielded fewer statistically significant findings. Namely, only the ROR for AG differed from generic for amlodipine with peripheral oedema (P

Authorized generics are identical in formulation to brand drugs, manufactured by the brand company but marketed as a generic. Generics, marketed by generic manufacturers, are required to demonstrate pharmaceutical and bioequivalence to the brand drug, but repetition of clinical trials is not required. This retrospective cohort study compared outcomes for generics and authorized generics, which serves as a generic vs. brand proxy that minimizes bias against generics. For the seven drugs studied between 1999 and 2014, 5,234 unique patients were on brand drugs prior to generic entry and 4,900 (93.6%) switched to a generic. During the 12 months following the brand-to-generic switch, patients using generics vs. authorized generics were similar in terms of outpatient visits, urgent care visits, hospitalizations, and medication discontinuation. The likelihood of emergency department (ED) visits was slightly higher for authorized generics compared with generics. These data suggest that generics were clinically no worse than their proxy brand comparators.

The United States has no comprehensive national surveillance system for fatal or nonfatal child agricultural injuries. Thus, important knowledge gaps exist about recurrent injury patterns that could provide targeted focus for prevention efforts. The purpose of this study was to explore existing US public health data systems to determine their utility with respect to informing child agricultural injury surveillance and primary prevention.Public health data systems were selected if they: (1) were national in scope, (2) were active and ongoing, (3) included physical injuries, and (4) contained a "farm" location variable. Data systems explored included National Emergency Medical Services Information System, National Trauma Data Bank, National Electronic Injury Surveillance System-All Injury Program, and National Vital Statistics System-Multiple Cause File.Each data system contained substantial information per case with the number of fields ranging from 77 to 127. Beyond basic demographic information about the injured child, there were many injury descriptors, but few commonalities across systems. The most striking finding was the uniform absence of information on injury circumstances; that is, why and how the injury occurred, which is fundamental to planning and evaluating prevention initiatives.Although these public health data systems captured many details regarding medical aspects of the injury, they included little information on circumstances leading to injury, thus limiting their utility for child agricultural injury surveillance and primary prevention initiatives. We recommend any child agricultural injury data collection tool formally incorporate a structured narrative so underlying circumstances leading to injury events are documented.

Childhood agricultural injuries are an important public health problem. Pediatricians are a trusted source of expertise in children's health and safety and could serve as a sphere of influence to augment child agricultural injury prevention efforts. The purpose of this pilot study was to begin to explore the perspectives of pediatricians in a large rural health clinic about addressing child agricultural injury prevention within their practice.Structured interviews were conducted with nine pediatricians who maintain a clinical practice of at least 2 days a week and care for newborns through adolescents. Detailed interviewer notes were reviewed and summarized.Rural pediatricians readily acknowledge substantial numbers of farm children in their practice. In general, these providers: (1) recognize farming environments as a safety risk and see agricultural injury prevention as an important topic to be addressed with their patients, (2) are comfortable discussing the topic, but seldom actually initiate such conversations, and (3) doubt farm parents would be receptive to integrating agricultural injury prevention into a rural pediatric practice.While rural pediatricians recognize child safety risks in farm environments, they are reluctant to actually initiate this conversation with parents. Future research should explore both pediatricians' hesitancy to discuss agricultural injury prevention and farm parents' readiness for integrating the topic into pediatric primary care visits. Such would help to assess the viability of pediatricians as a sphere of influence for augmenting child agricultural injury prevention efforts.

To determine whether patterns of adolescent risk behavior in rural populations, and especially farm populations, are associated with negative indicators of adolescent health and well-being, beyond an established association between risk-taking and injury.The study base was Cycle 7 (2014) of the Canadian Health Behaviour in School-Aged Children study. Children aged 11-16 years (n = 2,565; 2,533 weighted) who reported living or working on farms were matched within schools in a 1:1 ratio with other rural children. We related a scale describing engagement in multiple risk behavior to a series of indicators of adolescent health and well-being.Farm children, particularly male farm children, showed the highest levels of risk behavior. Multiple risk behavior was strongly and consistently associated with negative indicators of general health, mental health (life satisfaction, psychosomatic symptoms), and academic performance in all subpopulations.Adolescent risk behavior in rural populations, and especially farm populations, is common and associated with a variety of negative indicators of adolescent health and well-being. We speculate that the origins of this risk-taking lifestyle surround cultural definitions of self and identity, which have both protective and negative effects.

A serum alkaline phosphatase value below the age-adjusted lower limits of normal (hypophosphatasemia) is uncommonly encountered in clinical practice. The electronic and paper medical records of 885,165 patients treated between 2002 and 2012 at a large, rural, multispecialty health clinic were interrogated to estimate the prevalence and characterize the clinical and radiographic findings of adults whose serum alkaline phosphatase was almost always low (persistent hypophosphatasemia). We hypothesized that some of these patients might harbor previously unrecognized hypophosphatasia, a rare, inherited condition of impaired mineralization of bones and teeth. Persistent hypophosphatasemia (serum alkaline phosphatase ≤ 30 IU/L) was found in 1 of 1544 adult patients. These adult patients had more crystalline arthritis, orthopedic surgery, chondrocalcinosis, calcific periarthritis, enthesopathy, and diffuse idiopathic skeletal hyperostosis than a general adult patient population. A gender effect was observed. The clinical and radiographic findings of adult patients with persistent hypophosphatasemia resemble those of the adult form of hypophosphatasia. Clinicians should take notice of persistent hypophosphatasemia, consider the diagnosis of hypophosphatasia, and be cautious when considering potent anti-remodeling therapy in these adults. This population warrants further evaluation.

Unfavorable economic and environmental conditions have fueled the development of mental health resources and services for farmers. However, it is unclear who farmers want mental health information from (senders) and how they want mental health information delivered (channels). A self-administered questionnaire was used to determine the preferred senders of mental health information and the preferred channels of mental health information. Farmers were most receptive to receiving mental health information from medical providers, spouses/family members, and friends. Among the channels of information, respondents were interested in receiving mental health information from farm newspapers/magazines and one-on-one in person. Our findings have pragmatic implications for agricultural safety and health and public health organizations working to disseminate mental health information to farmers. Receptiveness to specific senders and channels of information among farmers should inform resource dispersion and future intervention.

Although prior studies showed mean aortic valve pressure gradient (mAoVpg) dramatically drops in patients with severe aortic stenosis following Transcatheter Aortic Valve Replacement (TAVR) with different valve types; it is not well known if this drop in mAoVpg is sustained through the years after

There are few studies comparing paravalvular leak (PVL) rates by valve types in patients with severe aortic stenosis following Transcatheter Aortic Valve Repair (TAVR); and none over the years. We hypothesized that self-expandable valves (SEV) were associated with a lower PVL over the years than

Effects of childhood overweight may persist into adulthood. We assessed the effect of childhood overweight on cardiovascular disease high risk factor levels in the same participants as adults, after controlling for adult body mass index (BMI) status.A subset of participants in an observational study (Heartwatch) were contacted approximately 26-27 years after initial enrollment to participate in a follow-up study on the long-term effects of childhood overweight. During follow-up, BMI, waist:hip circumference (WHC), blood pressure (BP), serum lipids, and ankle brachial index (ABI) were measured; additional BMI measures throughout childhood were obtained as available from the electronic medical record. Primary outcomes were ABI and serum low density lipoprotein (LDL).The 1982 Heartwatch study was conducted with children participants living in Marshfield, Wisconsin; follow-up included original participants who were re-contacted and agreed to be enrolled.Participants were a stratified random sample of eligible participants in the original 1982 Heartwatch study. Of the original 3106 participants, 647 adult participants completed follow-up exams.Among males with 1982 BMI ≥ 85(th) percentile, adult BMI, WHC, (both P ≤ 0.001), ABI (P = 0.001), total cholesterol (P = 0.01), LDL (P = 0.003) and BP (P0.02) were higher in 2008-2009 as compared to males with 1982 BMI85(th) percentile. Among females, BMI, BP and WHC (all P0.001) were higher in 2008-2009. BMI in 1982 and 2008-2009 were correlated [r = 0.56 (males); 0.58 (females), P0.001]. 2008-2009 BMI was more strongly correlated with 2008-2009 measures of ABI (r = 0.16, P = 0.006, males) and high LDL [r = 0.18, P = 0.002 (males); r = 0.11, P = 0.046 (females)]. 1982 BMI was not independently associated with ABI or LDL after adjusting for adult BMI.In a cohort studying childhood and adult overweight, childhood BMI was associated with health outcomes relating to cardiovascular disease in adulthood. However, childhood BMI was not independently related to LDL-C or ABI levels in adulthood after accounting for adult BMI. Longitudinal measurements of BMI and other health risk factors were not found to improve accuracy of models for high cardiovascular disease risk factor levels.

The temporal evolution of a low serum alkaline phosphatase value may relate to its cause. Precipitous lowering of serum alkaline phosphatase below the lower range of normal is uncommon and may indicate severe physiologic stress and increased short-term mortality.The differential diagnosis of a low serum alkaline phosphatase (ALP) value (hypophosphatasemia) is wide ranging, anecdotal, and unfamiliar. The temporal evolution of hypophosphatasemia may relate to its cause. The purpose of this study is to report conditions and circumstances associated with precipitous lowering of serum ALP below the lower range of normal.Marshfield Clinic IRB approved use of their electronic medical record to search for subjects with at least two serum ALP values ≤ 40 U/L (normal 40-125 U/L). When the temporal evolution of the qualifying ALP values indicated a precipitous lowering from usually normal serum ALP values, the subject was deemed to have acute hypophosphatasemia. Thirty years of laboratory data and 10 years of clinical narrative were analyzed. Associated diagnoses, clinical circumstances, and short-term mortality were recorded.A total of 458,767 subjects had 2,584,051 serum ALP values, and 5,190 (1.1 %) subjects had at least two serum values ≤ 40 U/L. A detailed review of 1,276 subjects selected on the basis of their lowest ALP value and age identified 190 subjects with acute hypophosphatasemia. Acute hypophosphatasemia was recorded during periods of major trauma/surgery, multisystem failure, acute anemia, blood product transfusions (often massive), apheresis, hypomagnesemia, and acute caloric restriction. Twenty-eight subjects (15 %) died within 35 days of their nadir serum ALP.Acute hypophosphatasemia is associated with profound illness or physiologic stress and followed by increased short-term mortality. The temporal evolution of hypophosphatasemia may relate to its cause.

Background Genetic studies require precise phenotype definitions, but electronic medical record (EMR) phenotype data are recorded inconsistently and in a variety of formats. Objective To present lessons learned about validation of EMR-based phenotypes from the Electronic Medical Records and Genomics (eMERGE) studies. Materials and methods The eMERGE network created and validated 13 EMR-derived phenotype algorithms. Network sites are Group Health, Marshfield Clinic, Mayo Clinic, Northwestern University, and Vanderbilt University. Results By validating EMR-derived phenotypes we learned that: (1) multisite validation improves phenotype algorithm accuracy; (2) targets for validation should be carefully considered and defined; (3) specifying time frames for review of variables eases validation time and improves accuracy; (4) using repeated measures requires defining the relevant time period and specifying the most meaningful value to be studied; (5) patient movement in and out of the health plan (transience) can result in incomplete or fragmented data; (6) the review scope should be defined carefully; (7) particular care is required in combining EMR and research data; (8) medication data can be assessed using claims, medications dispensed, or medications prescribed; (9) algorithm development and validation work best as an iterative process; and (10) validation by content experts or structured chart review can provide accurate results. Conclusions Despite the diverse structure of the five EMRs of the eMERGE sites, we developed, validated, and successfully deployed 13 electronic phenotype algorithms. Validation is a worthwhile process that not only measures phenotype performance but also strengthens phenotype algorithm definitions and enhances their inter-institutional sharing.