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OBJECTIVES/SPECIFIC AIMS: The study investigated whether adults diagnosed with epilepsy or migraine (a neurological disorder with common features to epilepsy) are at increased risk for developing substance abuse disorders following diagnosis compared to (presumably healthy) adults with lower extremity fracture (LEF). METHODS/STUDY POPULATION: A retrospective cohort analysis was conducted using a subset of surveillance data of hospital admissions, emergency department visits and outpatient visits in South Carolina, USA from January 1, 2000 through December 31, 2011. Individuals aged 18 years or older were identified using the International Classification of Disease, 9th Revision Clinical modification (ICD-9) with a diagnosis of epilepsy (epilepsy-cohort 1; n = 78,547; 52.7% female, mean age [SD] 51.3 years [19.2]), migraine (migraine-cohort 2; n = 121,155; 81.5% female, mean age [SD] 40.0 years [14.5]), or LEF (control cohort; n = 73,911; 55.4% female, mean age [SD] 48.7 years [18.7]). Individuals with substance abuse or dependence diagnosis following epilepsy, migraine, or LEF were identified with ICD-9 codes. Cox proportional hazard regression analyses modelled the time to substance abuse diagnosis comparing epilepsy to LEF and comparing migraine to LEF. RESULTS/ANTICIPATED RESULTS: Adjusting for insurance payer, age and sex, adults with epilepsy are diagnosed with substance abuse disorders at 2.5 times the rate of those with LEF [HR 2.54 (2.43, 2.67)] and adults with migraine are diagnosed with substance abuse disorders at 1.10 times the rate of those with LEF [HR 1.10 (1.04, 1.16)]. An interaction between exposure and insurance payer was found with hazard ratios comparing epilepsy to LEF of 4.56, 3.60, and 1.94 within the commercial payer, uninsured and Medicaid strata, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Compared to adults with LEF, adults with epilepsy had a substantially higher hazard of subsequent substance abuse, while adults with migraine showed a small, but still significant, increased hazard of subsequent substance abuse.
Objectives: Caregivers of youth with heavy prenatal alcohol exposure report impaired communication, which can significantly impact quality of life. Using data collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), we examined whether cognitive variables predict communication ability of youth with histories of heavy prenatal alcohol exposure. Methods: Subjects (ages 10–16 years) comprised two groups: adolescents with heavy prenatal alcohol exposure (AE) and non-exposed controls (CON). Selected measures of executive function (NEPSY, Delis-Kaplan Executive Function System), working memory (CANTAB), and language were tested in the child, while parents completed communication ratings (Vineland Adaptive Behavior Scales – Second Edition). Separate multiple regression analyses determined which cognitive domains predicted communication ability. A final, global model of communication comprised the three cognitive models. Results: Spatial Working Memory and Inhibition significantly contributed to communication ability across groups. Twenty Questions performance related to communication ability in the CON group only while Word Generation performance related to communication ability in the AE group only. Effects remained significant in the global model, with the exception of Spatial Working Memory. Conclusions: Both groups displayed a relation between communication and Spatial Working Memory and Inhibition. Stronger communication ability related to stronger verbal fluency in the AE group and Twenty Questions performance in the CON group. These findings suggest that alcohol-exposed adolescents may rely more heavily on learned verbal storage or fluency for daily communication while non-exposed adolescents may rely more heavily on abstract thinking and verbal efficiency. Interventions aimed at aspects of executive function may be most effective at improving communication ability of these individuals. (JINS, 2018, 24, 1026–1037)
Similar patterns of parasite prevalence in animal communities may be driven by a range of different mechanisms. The influences of host heterogeneity and host–parasite interactions in host community assemblages are poorly understood. We sampled birds at 27 wetlands in South Africa to compare four hypotheses explaining how host community heterogeneity influences host specificity in avian haemosporidia communities: the host-neutral hypothesis, the super-spreader hypothesis, the host specialist hypothesis and the heterogeneity hypothesis. A total of 289 birds (29%) were infected with Plasmodium, Haemoproteus and/or Leucocytozoon lineages. Leucocytozoon was the most diverse and generalist parasite genus, and Plasmodium the most conservative. The host-neutral and host specialist hypotheses received the most support in explaining prevalence by lineage (Leucocytozoon) and genus (Plasmodium and Haemoproteus), respectively. We observed that haemosporidian prevalence was potentially amplified or reduced with variation in host and/or parasitic taxonomic levels of analysis. Our results show that Leucocytozoon host abundance and diversity was influential to parasite prevalence at varying taxonomic levels, particularly within heterogeneous host communities. Furthermore, we note that prevalent mechanisms of infection can potentially act as distinct roots for shaping communities of avian haemosporidia.
OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and increases risk for cirrhosis and liver cancer. Identifying modifiable risk factors for NAFLD could allow better targeting of prevention programs. Insulin resistance (IR) plays a significant role in the development and progression of NAFLD. IR is also an important precursor to the development of type 2 diabetes (T2DM). However, the development and duration of IR during young adulthood and its association with NAFLD and T2DM in midlife is unclear. To test whether trajectories of IR using homeostatic model assessment (HOMA-IR) change throughout early adulthood are associated with risk of prevalent NAFLD and T2DM among persons with NAFLD in midlife independent of current or baseline HOMA-IR. METHODS/STUDY POPULATION: Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18–30 years), underwent HOMA-IR measurement (≥8 h fasting and not pregnant) at baseline (1985–1986) and follow-up exam years 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010–2011), liver fat was assessed by noncontrast computed tomography (CT). NAFLD was defined as CT liver attenuation <51 Hounsfield Units after exclusion of other causes of liver fat (alcohol/hepatitis/medications). Latent mixture modeling was used to identify 25-year trajectories in HOMA-IR over time. Multivariable logistic regression models were used to assess associations between HOMA-IR trajectory groups and prevalent NAFLD with adjustment for baseline or Y25 HOMA-IR. RESULTS/ANTICIPATED RESULTS: Among 3060 participants, we identified 3 distinct trajectory groups for HOMA-IR for individuals free from diabetes in middle adulthood: qualitatively low-stable (46.7% of the cohort), moderate-increasing (42.0%), and high-increasing (11.3%) with a NAFLD prevalence at Y25 of: 8.3%, 33.4%, and 63.5%, respectively (p-trend<0.0001). After adjustment for confounders (baseline smoking status, alcohol use, body mass index, physical activity score, systolic blood pressure, antihypertensive medication use, and total/HDL cholesterol ratio) and baseline HOMA-IR, increasing HOMA-IR trajectories were associated with greater NAFLD prevalence compared with the low-stable trajectory group [odds ratio (95% CI): 5.8 (4.3–7.9) and 22.3 (14.2–34.9) for moderate and high, respectively]. These associations were attenuated, but remained significant, even after controlling for current Y25 HOMA-IR [OR=3.6 (2.6–5.0) for moderate and 5.9 (3.4–10.3) for high (referent: low)]. Among participants with NAFLD (n=511), high-increasing HOMA-IR trajectory was associated with greater prevalent [OR=6.5 (1.6–25.7)] and incident [OR=8.7 (2.2–34.4)] T2DM at Y25 independent of confounders and Y25 HOMA-IR (referent: low-stable). DISCUSSION/SIGNIFICANCE OF IMPACT: In this community-based sample of individuals free from diabetes at baseline, an increasing HOMA-IR trajectory through young adulthood was associated with greater NAFLD prevalence in midlife. Knowledge of changes in IR throughout adulthood provides new information on the risk of T2DM among persons with NAFLD in midlife independent of current level of IR. These findings highlight early identification of increasing IR as a potential target for primary prevention of T2DM in the setting of NAFLD.
To investigate an outbreak of Burkholderia cepacia complex and describe the measures that revealed the source.
A 629-bed, tertiary-care, pediatric hospital in Houston, Texas.
Pediatric patients without cystic fibrosis (CF) hospitalized in the pediatric and cardiovascular intensive care units.
We investigated an outbreak of B. cepacia complex from February through July 2016. Isolates were evaluated for molecular relatedness with repetitive extragenic palindromic polymerase chain reaction (rep-PCR); specific species identification and genotyping were performed at an independent laboratory. The investigation included a detailed review of all cases, direct observation of clinical practices, and respiratory surveillance cultures. Environmental and product cultures were performed at an accredited reference environmental microbiology laboratory.
Overall, 18 respiratory tract cultures, 5 blood cultures, 4 urine cultures, and 3 stool cultures were positive in 24 patients. Among the 24 patients, 17 had symptomatic infections and 7 were colonized. The median age of the patients was 22.5 months (range, 2–148 months). Rep-PCR typing showed that 21 of 24 cases represented the same strain, which was identified as a novel species within the B. cepacia complex. Product cultures of liquid docusate were positive with an identical strain of B. cepacia complex. Local and state health departments, as well as the CDC and FDA, were notified, prompting a multistate investigation.
Our investigation revealed an outbreak of a unique strain of B. cepacia complex isolated in clinical specimens from non-CF pediatric patients and from liquid docusate. This resulted in a national alert and voluntary recall by the manufacturer.
Based on archival and other materials from Rostov-on-Don, a major industrial center in southern Russia, Jeffrey W.Jones examines the different representations of collaboration apparent in Soviet society during and after the war. Jones analyzes several different levels of discourse: inner party deliberations and reports on the subject, depictions of collaborators and their actions in the local party press, questions and comments of workers and others at public meetings as recorded by party officials, and Cold War and post-Cold War era memoirs and interviews. These sources overlap to a significant degree but deal with the complex issue of collaboration in nuanced ways, stressing different themes and asking different questions. The evidence reveals a subtle divide in the perception and representation of this issue between party leaders and the population at large while also showing that the party's public assurances of cossack loyalty contrasted with a widely shared assumption of cossack disloyalty.
We aimed to obtain a better understanding of how different aspects of patient functioning affect key cost and caregiver outcomes in Alzheimer's disease (AD).
Baseline data from a prospective observational study of community-living AD patients (GERAS) were used. Functioning was assessed using the Alzheimer's Disease Cooperative Study – Activities of Daily Living Scale. Generalized linear models were conducted to analyze the relationship between scores for total activities of daily living (ADL), basic ADL (BADL), instrumental ADL (IADL), ADL subdomains (confirmed through factor analysis) and individual ADL questions, and total societal costs, patient healthcare and social care costs, total and supervision caregiver time, and caregiver burden.
Four distinct ADL subdomains were confirmed: basic activities, domestic/household activities, communication, and outside activities. Higher total societal costs were associated with impairments in all aspects of ADL, including all subdomains; patient costs were associated with total ADL and BADL, and basic activities subdomain scores. Both total and supervision caregiver hours were associated with total ADL and IADL scores, and domestic/household and outside activities subdomain scores (greater hours associated with greater functional impairments). There was no association between caregiver burden and BADL or basic activities subdomain scores. The relationship between total ADL, IADL, and the outside activities subdomain and outcomes differed between patients with mild and moderate-to-severe AD.
Identification of ADL subdomains may lead to a better understanding of the association between patient function and costs and caregiver outcomes at different stages of AD, in particular the outside activities subdomain within mild AD.
We consider Markov chain Monte Carlo algorithms which combine Gibbs updates with Metropolis-Hastings updates, resulting in a conditional Metropolis-Hastings sampler (CMH sampler). We develop conditions under which the CMH sampler will be geometrically or uniformly ergodic. We illustrate our results by analysing a CMH sampler used for drawing Bayesian inferences about the entire sample path of a diffusion process, based only upon discrete observations.