Exemplar Hospital initiation trial to Enhance Treatment Engagement (EXHIT ENTRE): protocol for CTN-0098B a randomized implementation study to support hospitals in caring for patients with opioid use disorder.

BACKGROUND: Hospitalizations involving opioid use disorder (OUD) are increasing. Medications for opioid use disorder (MOUD) reduce mortality and acute care utilization. Hospitalization is a reachable moment for initiating MOUD and arranging for ongoing MOUD engagement following hospital discharge. Despite existing quality metrics for MOUD initiation and engagement, few hospitals provide hospital based opioid treatment (HBOT). This protocol describes a cluster-randomized hybrid type-2 implementation study comparing low-intensity and high-intensity implementation support strategies to help community hospitals implement HBOT. METHODS: Four state implementation hubs with expertise in initiating HBOT programs will provide implementation support to 24 community hospitals (6 hospitals/hub) interested in starting HBOT. Community hospitals will be randomized to 24-months of either a low-intensity intervention (distribution of an HBOT best-practice manual, a lecture series based on the manual, referral to publicly available resources, and on-demand technical assistance) or a high-intensity intervention (the low-intensity intervention plus funding for a hospital HBOT champion and regular practice facilitation sessions with an expert hub). The primary efficacy outcome, adapted from the National Committee on Quality Assurance, is the proportion of patients engaged in MOUD 34-days following hospital discharge. Secondary and exploratory outcomes include acute care utilization, non-fatal overdose, death, MOUD engagement at various time points, hospital length of stay, and discharges against medical advice. Primary, secondary, and exploratory outcomes will be derived from state Medicaid data. Implementation outcomes, barriers, and facilitators are assessed via longitudinal surveys, qualitative interviews, practice facilitation contact logs, and HBOT sustainability metrics. We hypothesize that the proportion of patients receiving care at hospitals randomized to the high-intensity arm will have greater MOUD engagement following hospital discharge. DISCUSSION: Initiation of MOUD during hospitalization improves MOUD engagement post hospitalization. Few studies, however, have tested different implementation strategies on HBOT uptake, outcome, and sustainability and only one to date has tested implementation of a specific type of HBOT (addiction consultation services). This cluster-randomized study comparing different intensities of HBOT implementation support will inform hospitals and policymakers in identifying effective strategies for promoting HBOT dissemination and adoption in community hospitals. TRIAL REGISTRATION: NCT04921787.

Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial.

BACKGROUND: A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. METHODS: PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). FINDINGS: Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). INTERPRETATION: Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. FUNDING: Regeneron Pharmaceuticals and Bayer.

Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guérin Challenge Model for Assessment of Tuberculosis Immunity In Vivo.

BACKGROUND: A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development. METHODS: In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to 16 × 106 colony-forming units of Bacillus Calmette-Guérin (BCG). The primary endpoints were safety and BCG shedding as measured by quantitative polymerase chain reaction, colony-forming unit plating, and MGIT BACTEC culture. RESULTS: Doses up to 8 × 106 were safe, and there was evidence for increased BCG shedding with dose escalation. The MGIT time-to-positivity assay was the most consistent and precise measure of shedding. Power analyses indicated that 10% differences in MGIT time to positivity (area under the curve) could be detected in small cohorts (n = 30). Potential biomarkers of mycobacterial immunity were identified that correlated with shedding. Transcriptomic analysis uncovered dose- and time-dependent effects of BCG challenge and identified a putative transcriptional TB protective signature. Furthermore, we identified immunologic and transcriptomal differences that could represent an immune component underlying the observed higher rate of TB disease incidence in males. CONCLUSIONS: The safety, reactogenicity, and immunogenicity profiles indicate that this BCG human challenge model is feasible for assessing in vivo TB immunity and could facilitate the vaccine development process. CLINICAL TRIALS REGISTRATION: NCT01868464 (ClinicalTrials.gov).

Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): A stepped wedge hybrid type 1 effectiveness-implementation study.

BACKGROUND: Extended-release injectable naltrexone (XR-NTX) is an effective treatment for opioid use disorder (OUD), but initiation remains a barrier to implementation. Standard practice requires a 10- to 15-day inpatient admission prior to XR-NTX initiation and involves a methadone or buprenorphine taper followed by a 7- to 10-day washout, as recommended in the Prescribing Information for XR-NTX. A 5- to 7-day rapid induction approach was developed that utilizes low-dose oral naltrexone and non-opioid medications. METHODS: The CTN-0097 Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT) study was a hybrid type I effectiveness-implementation trial that compared the effectiveness of the standard procedure (SP) to the rapid procedure (RP) for XR-NTX initiation across six community inpatient addiction treatment units, and evaluated the implementation process. Sites were randomized to RP every 14 weeks in an optimized stepped wedge design. Participants (target recruitment = 450) received the procedure (SP or RP) that the site was implementing at time of admission. The hypothesis was RP will be non-inferior to SP on proportion of inpatients who receive XR-NTX, with a shorter admission time for RP. Superiority testing of RP was planned if the null hypothesis of inferiority of RP to SP was rejected. DISCUSSION: If RP for XR-NTX initiation is shown to be effective, the shorter inpatient stay could make XR-NTX more feasible and have an important public health impact expanding access to OUD pharmacotherapy. Further, a better understanding of facilitators and barriers to RP implementation can help with future translatability and uptake to other community programs. TRIAL REGISTRATION: NCT04762537 Registered February 21, 2021.

Peer-to-Peer Mentoring for African American Women With Lupus: A Feasibility Pilot.

OBJECTIVE: To examine the feasibility and potential benefits of peer mentoring to improve the disease self-management and quality of life of individuals with systemic lupus erythematosus (SLE). METHODS: Peer mentors were trained and paired with up to 3 mentees to receive self-management education and support by telephone over 12 weeks. This study took place at an academic teaching hospital in Charleston, South Carolina. Seven quads consisting of 1 peer mentor and 3 mentees were matched, based on factors such as age, area of residence, and marital and work status. Mentee outcomes of self-management, health-related quality of life, and disease activity were measured using validated tools at baseline, mid-intervention, and post-intervention. Descriptive statistics and effect sizes were calculated to determine clinically important (>0.3) changes from baseline. RESULTS: Mentees showed trends toward lower disease activity (P = 0.004) and improved health-related quality of life, in the form of decreased anxiety (P = 0.018) and decreased depression (P = 0.057). Other improvements in health-related quality of life were observed with effect sizes >0.3, but did not reach statistical significance. In addition, both mentees and mentors gave very high scores for perceived treatment credibility and service delivery. CONCLUSION: The intervention was well received. Training, the peer-mentoring program, and outcome measures were demonstrated to be feasible with modifications. This result provides preliminary support for the efficacy, acceptability, and perceived credibility of a peer-mentoring approach to improve disease self-management and health-related quality of life in African American women with SLE. Peer mentoring may augment current rheumatologic care.

Relationship between empowerment and wealth: trends and predictors in Kenya between 2003 and 2008-2009.

OBJECTIVES: This study aimed to examine the association between women's empowerment and wealth over time in Kenya. METHODS: Kenya Demographic and Health Surveys (DHS) for 2003 and 2008-2009 were used. Eligible women and men were either married or living with a partner. Two scales were used for empowerment: female participation in decision-making, and attitudes toward domestic violence against female partners. Hierarchical linear models were used based on theoretical blocks of covariates. RESULTS: In a sample of 9847 women and 3207 men, results showed empowerment increased over time. After adjustment, female partners' reporting greater empowerment on either scale remained significantly associated with increased wealth, (urban: ß = 0.04, p value < 0.05; ß = - 0.06, p value < 0.01) and (rural: ß = 0.04, p value < 0.01, ß = - 0.07, p value < 0.01). Based on male partners' responses, female partners' participation in decision-making was associated with increased wealth in rural regions (ß = 0.04, p value < 0.01), and agreement with domestic violence towards a female partner was significantly associated with a decrease in wealth in urban regions (ß = - 0.08, p value < 0.01). CONCLUSIONS: Women's empowerment has increased over time in Kenya and is associated with increased family wealth. The association varies by gender of respondent and rural/urban residence.

Rural-Urban Differences in Trends in the Wealth Index in Kenya: 1993-2009.

BACKGROUND: The aim of this study was to construct a wealth index that could be compared over time in order to understand the trends in wealth in Kenya and determine predictors of change in wealth index. METHODS: Data were from the Demographic and Health Survey program collected in Kenya between 1993 and 2009. Variable categories were collapsed to match and factor analysis was performed on the 4-year pooled data to generate a harmonized wealth index. Possible predictors of wealth were selected from household variables available for all 4 years. Household sampling weights and stratification by rural/urban was used. RESULTS: Overall, wealth increased in Kenya between 1993 and 2008; however, when stratified, no significant increase existed in urban areas and a significant increase was identified in rural areas specifically between 2003 and 2008. The strongest predictor was education, with more than a standard deviation difference for secondary or higher levels of education over those with no education. The association of gender of the head of household and whether the head of household had a partner differed between rural and urban areas, with household heads who were women and those who had a partner having more wealth in urban areas but less wealth in rural areas. CONCLUSION: Wealth in Kenya increased over time, specifically in rural regions. Differences were identified in predictors of wealth by urban/rural residence, educational level, and gender of the head of household and should be taken into account when planning interventions to target those in disproportionately low wealth brackets.

Randomized Controlled Trial of Technology-Assisted Case Management in Low Income Adults with Type 2 Diabetes.

OBJECTIVE: To assess the efficacy of technology-assisted case management (TACM) with medication titration by nurses using guideline-based algorithms, under physician supervision in improving glycemic control in low-income rural adults with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: Adults (aged ≥18 years) from the southeastern United States with hemoglobin A1c [HbA1c] ≥8% were randomized to TACM or usual care. Evidence-based guidelines were used to develop medication titration algorithms in conjunction with clinic physicians. Participants were given a telehealth device that uploaded blood glucose and blood pressure readings daily to a central server. A nurse case manager was trained on the algorithms and authorized to titrate medications every 2 weeks based on the algorithm under the supervision of an internist and an endocrinologist. Participants were assessed at baseline, 3 months, and 6 months. The primary outcome was HbA1c at 6-months postrandomization in the intent-to-treat (ITT) population. RESULTS: One hundred thirteen participants were randomized to either TACM intervention or usual care. Based on ITT population after multiple imputation, the analysis of covariance with baseline HbA1c as covariate showed that HbA1c at 6 months for TACM was significantly lower compared to the usual care group (-0. 99, P = 0.024). Moreover, longitudinal mixed effects analysis suggested that the rate of decline in HbA1c over time for TACM was significantly faster compared to the usual care group (-0.16, P = 0.038). Results based on per-protocol population were similar. CONCLUSIONS: Technology-assisted case management by a nurse with medication titration under physician supervision is efficacious in improving glycemic control in low-income rural adults with poorly controlled type 2 diabetes.

Telephone-Delivered Behavioral Skills Intervention for African American Adults with Type 2 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Diabetes disproportionately affects African Americans and is associated with poorer outcomes. Self-management is important for glycemic control; however, evidence in African Americans is limited. OBJECTIVE: To assess the efficacy of a combined telephone-delivered education and behavioral skills intervention (TBSI) in reducing hemoglobin A1c (HbA1c) levels in African Americans with type 2 diabetes, using a factorial design. DESIGN: This is a four-year randomized clinical trial, using a 2 x 2 factorial design.: Participants: African American adults ≥18 years) with poorly controlled type 2 diabetes (HbA1c ≥9%) were randomly assigned to one of four groups: 1) knowledge only, 2) skills only, 3) combined knowledge and skills (TBSI), or 4) control group. INTERVENTION: All participants received 12 telephone-delivered 30-min intervention sessions specific to their assigned group. Participants were assessed at baseline and 3, 6, and 12 months. MAIN MEASURE: The primary outcome was HbA1c at 12 months post-randomization in the intent-to-treat (ITT) population. KEY RESULTS: Two hundred fifty-five participants were randomly assigned to the four groups. Based on the ITT population after multiple imputation, the analysis of covariance with baseline HbA1c as the covariate showed that HbA1c at 12 months for the intervention groups did not differ significantly from that of the control group (knowledge: 0.49, p = 0.123; skills: 0.23, p = 0.456; combined: 0.48, p = 0.105). Absolute change from baseline at 12 months for all treatment arms was 0.6. Longitudinal mixed effects analysis showed that, on average, there was a significant decline in HbA1c over time for all treatment groups (-0.07, p < 0.001). However, the rates of decline for the intervention groups were not significantly different from that of the control group (knowledge: 0.06, p = 0.052; skills: 0.02, p = 0.448; combined: 0.05, p = 0.062). Results from per-protocol populations were similar. CONCLUSIONS: For African Americans with poorly controlled type 2 diabetes, combined education and skills training did not achieve greater reductions in glycemic control (i.e., HbA1c levels) at 12 months compared to the control group, education alone, or skills training alone. This trial is registered with ClinicalTrials.gov, identifier no. NCT00929838.

Weibull mixture regression for marginal inference in zero-heavy continuous outcomes.

Continuous outcomes with preponderance of zero values are ubiquitous in data that arise from biomedical studies, for example studies of addictive disorders. This is known to lead to violation of standard assumptions in parametric inference and enhances the risk of misleading conclusions unless managed properly. Two-part models are commonly used to deal with this problem. However, standard two-part models have limitations with respect to obtaining parameter estimates that have marginal interpretation of covariate effects which are important in many biomedical applications. Recently marginalized two-part models are proposed but their development is limited to log-normal and log-skew-normal distributions. Thus, in this paper, we propose a finite mixture approach, with Weibull mixture regression as a special case, to deal with the problem. We use extensive simulation study to assess the performance of the proposed model in finite samples and to make comparisons with other family of models via statistical information and mean squared error criteria. We demonstrate its application on real data from a randomized controlled trial of addictive disorders. Our results show that a two-component Weibull mixture model is preferred for modeling zero-heavy continuous data when the non-zero part are simulated from Weibull or similar distributions such as Gamma or truncated Gauss.

Prenatal vitamin D and enamel hypoplasia in human primary maxillary central incisors: a pilot study.

BACKGROUND: Enamel hypoplasia (EH) increases risk for dental caries and also is associated with vitamin D deficiencies. This pilot study evaluates the feasibility to determine the association of human maternal circulating vitamin D concentrations during pregnancy and EH in infant's teeth that develop in utero. METHODS: A pilot population of 37 children whose mothers participated in a RCT of vitamin D supplementation during pregnancy was evaluated. Major outcome was EH and major exposure was maternal monthly serum circulating 25(OH)D concentrations during pregnancy. EH was assessed using the Enamel Defect Index and digital images made by a ProScope High Resolution™ handheld digital USB microscope at 50x magnification. RESULTS: During initial 8 weeks of study, 29/37 children had evaluable data with mean age of 3.6 ± 0.9 years; 48% male; and 45% White, 31% Hispanic, and 24% Black. EH was identified in 13 (45%) of the children. Maternal mean 25(OH)D concentrations were generally lower for those children with EH. CONCLUSIONS: Preliminary results suggest follow-up of children of mothers in a vitamin D supplementation RCT during pregnancy provides an important approach to study the etiology of EH in the primary teeth. Further study is needed to discern thresholds and timing of maternal serum 25(OH)D concentrations during pregnancy associated with absence of EH in teeth that develop in utero. Potential dental public health implications for prevention of early childhood caries via sound tooth structure as related to maternal vitamin D sufficiency during pregnancy need to be determined.

Meaning of Illness and Cardiovascular Risk Factors in Patients With Type 2 Diabetes.

PURPOSE: The purpose of this study was to examine the relationship between meaning of illness and cardiovascular disease risk factors in patients with type 2 diabetes. METHODS: The sample population was recruited from primary care clinics in the southeastern United States. The meaning of illness was assessed by a validated questionnaire with 5 subscales. The primary outcomes were cardiovascular disease (CVD) risk factors, assessed by A1C, systolic and diastolic blood pressure (SBP and DBP, respectively), and low-density lipoprotein cholesterol (LDL-C). Multivariate linear regression models investigated associations between the clinical outcomes and the 5 MIQ factors, controlling for possible confounders. RESULTS: The sample comprised 302 black and white participants of whom more than half were elderly (65+ years) and the vast majority were male (98%). Systolic blood pressure was positively associated with non-anticipated vulnerability. Diastolic blood pressure was negatively associated with degree of stress/change in commitments and positively associated with challenge/motivation/hope and non-anticipated vulnerability. Low-density lipoprotein cholesterol was significantly and negatively associated with degree of stress/change in commitments. CONCLUSIONS: Meaning of illness had a significant effect on measured outcomes of CVD risk. The specific factor included in the overarching concept of meaning of illness differed in its influence, with more positive views of stress/commitments associated with lower blood pressure and LDL but more positive views of the challenge/hope/motivation and negative views of non-anticipated vulnerability associated with diabetes associated with higher systolic and diastolic blood pressure.

Health locus of control and cardiovascular risk factors in veterans with type 2 diabetes.

Perceptions of control impact outcomes in veterans with chronic disease. The purpose of this study was to examine the association between control orientation and clinical and quality of life (QOL) outcomes in male veterans with type 2 diabetes (T2DM). Cross-sectional study of 283 male veterans from a primary care clinic in the southeastern US. Health locus of control (LOC) was the main predictor and assessed using the Multidimensional Health LOC Scale. Clinical outcomes were glycosylated hemoglobin A1c (HbA1c), systolic and diastolic blood pressure, and low-density lipoprotein cholesterol (LDL-C). Physical (PCS) and mental (MCS) health component scores for QOL were assessed using the Veterans RAND 12-Item Health Survey. Unadjusted and adjusted multivariate analyses were performed to assess associations between LOC and outcomes. Unadjusted analyses showed internal LOC associated with HbA1c (ß = 0.036; 95% CI 0.001, 0.071), external LOC:powerful others inversely associated with LDL-C (ß = -0.794; 95% CI -1.483, -0.104), and external LOC:chance inversely associated with MCS QOL (ß = -0.418; 95% CI -0.859, -0.173). These associations remained significant when adjusting for relevant covariates. Adjusted analyses also demonstrated a significant relationship between external LOC:chance and PCS QOL (ß = 0.308; 95% CI 0.002, 0.614). In this sample of male veterans with T2DM, internal LOC was significantly associated with glycemic control, and external was significantly associated with QOL and LDL-C, when adjusting for relevant covariates. Assessments of control orientation should be performed to understand the perceptions of patients, thus better equipping physicians with information to maximize care opportunities for veterans with T2DM.

Meaning of illness and quality of life in patients with type 2 diabetes.

BACKGROUND: Investigations into personal factors influencing quality of life are important for those developing strategies to support patients with diabetes. This study aimed to investigate the influence of meaning of illness on quality of life in patients with type 2 diabetes. METHODS: Veterans from primary care clinics in the southeastern United States completed a questionnaire including questions from the validated 5-scale Meaning of Illness Questionnaire (MIQ). Unadjusted and adjusted linear regression models investigated the physical and mental components of quality of life with the 5 MIQ factors. RESULTS: The sample comprised 302 Black and White veterans. The physical component of quality of life (PCS) was positively associated with type of stress/attitude of harm (ß = 2.43, CI: 0.94 to 3.93) and challenge/motivation/hope (ß = 3.02, CI: 0.40 to 5.64) after adjustment, whereas the mental component of quality of life (MCS) was positively associated with the degree of stress/change in commitment (ß = 2.58, CI: 0.78 to 4.38), and negatively associated with challenge/motivation/hope (ß = -2.55, CI: -4.99 to -0.11). CONCLUSION: Attitudes of challenge, motivation and hope had opposite effects on mental and physical components of quality of life in this sample of veterans. Additionally, whereas, the type of stress and attitude towards harm or loss was associated with the physical component, the degree of stress and change in commitments was associated with the mental component. This suggests addressing the meaning of an illness may be complex but is an important consideration in improving both physical and mental components of quality of life in patients with type 2 diabetes.

Meaning of illness and self-care in patients with type 2 diabetes.

PURPOSE: The purpose of this study was to assess the relationship between meaning of illness, diabetes knowledge, self-care understanding, and behaviors in a group of individuals with type 2 diabetes. METHODS: Patients diagnosed with type 2 diabetes completed questionnaires with measures for diabetes knowledge, self-care understanding, diet adherence, and control problems based on the validated Diabetes Care Profile, as well as a 5-factor Meaning of Illness Questionnaire (MIQ) measure. Linear regression investigated the associations between self-care outcomes and the 5 MIQ factors. RESULTS: After adjustment for possible confounders, both diabetes self-care understanding and diet adherence were negatively and significantly associated with little effect of illness. Control problems were negatively associated with degree of stress/change in commitments. Diabetes knowledge was not significantly associated with meaning of illness. CONCLUSION: Aspects of the meaning attributed to illness were significantly associated with self-care in patients with type 2 diabetes. Therefore, cognitive appraisals may explain variances observed in self-care understanding and behaviors. Based on these results, it is important to understand the negative effect that diabetes could have when promoting self-care understanding and diet adherence. In addition, it shows that helping patients address the stress and changing commitments that result from diabetes may help decrease the amount of diabetes control problems, even if there is little effect on diabetes understanding. Taking these differences into account may help in creating more personalized and effective self-care education plans.

Spatial environmental modeling of autoantibody outcomes among an African American population.

In this study of autoimmunity among a population of Gullah African Americans in South Carolina, the links between environmental exposures and autoimmunity (presence of antinuclear antibodies (ANA)) have been assessed. The study population included patients with systemic lupus erythematosus (n = 10), their first degree relatives (n = 61), and unrelated controls (n = 9) where 47.5% (n = 38) were ANA positive. This paper presents the methodology used to model ANA status as a function of individual environmental influences, both self-reported and measured, while controlling for known autoimmunity risk factors. We have examined variable dimension reduction and selection methods in our approach. Following the dimension reduction and selection methods, we fit logistic spatial Bayesian models to explore the relationship between our outcome of interest and environmental exposures adjusting for personal variables. Our analysis also includes a validation "strip" where we have interpolated information from a specific geographic area for a subset of the study population that lives in that vicinity. Our results demonstrate that residential proximity to exposure site is important in this form of analysis. The use of a validation strip network demonstrated that even with small sample numbers some significant exposure-outcome relationships can be detected.

The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids.

Incidence of sport-related traumatic brain injury and risk factors of severity: a population-based epidemiologic study.

PURPOSE: Few studies of sport-related traumatic brain injury (TBI) are population-based or rely on directly observed data on cause, demographic characteristics, and severity. This study addresses the epidemiology of sport-related TBI in a large population. METHODS: Data on all South Carolina hospital and emergency department encounters for TBI, 1998-2011, were analyzed. Annual incidence rate of sport-related TBI was calculated, and rates were compared across demographic groups. Sport-related TBI severity was modeled as a function of demographic and TBI characteristics using logistic regression. RESULTS: A total of 16,642 individuals with sport-related TBI yielded an average annual incidence rate of 31.5/100,000 population with a steady increase from 19.7 in 1998 to 45.6 in 2011. The most common mechanisms of sport-related TBI were kicked in football (38.1%), followed by fall injuries in sports (20.3%). Incidence rate was greatest in adolescents ages 12-18 (120.6/100,000/persons). Severe sport-related TBI was strongly associated with off-road vehicular sport (odds ratio [OR], 4.73; 95% confidence interval [95% CI], 2.92-7.67); repeated head trauma (OR, 4.36; 95% CI, 3.69-5.15); equestrian sport (OR, 2.73; 95% CI, 1.64-4.51); and falls during sport activities (OR, 2.72; 95% CI, 1.67-4.46). CONCLUSIONS: The high incidence of sport-related TBI in youth, potential for repetitive mild TBI, and its long-term consequences on learning warrants coordinated surveillance activities and population-based outcome studies.