OBJECTIVES/SPECIFIC AIMS: In June 2016, the FDA cautioned against the use of SGLT-2 inhibitors because of increased risk of acute kidney injury (AKI) after 101 cases of AKI were reported between March 2013 and October 2015. This study seeks to determine risk of AKI associated with SGLT-2 inhibitors in a large cohort of type 2 diabetic patients. METHODS/STUDY POPULATION: Retrospective cohort study including SGLT-2 inhibitor users and nonusers in the Mount Sinai Chronic Kidney Disease Registry between January 2013 and September 2016. SGLT-2 inhibitor users and nonusers were type 2 diabetics with new SGLT-2 inhibitor prescription after January 2013 and an outpatient visit between 2013 and 2015, respectively. Subjects were propensity matched by nearest neighbor method based on demographics, comorbidities, laboratory values, medications, estimated glomerular filtration rate (eGFR), and length of follow-up. The primary end point was AKI (defined by KDIGO laboratory algorithm) occurring during the follow-up period. RESULTS/ANTICIPATED RESULTS: In total, 372 SGLT-2 inhibitor users [mean age 63 years; 205 (55%) men] and 372 [mean age 63; 194 (52%) men] nonusers were included in the primary analysis. Proportions of AKI events defined by KDIGO criteria in users and nonusers were 4.0% and 10.0%, respectively. Adjusted odds ratio for AKI was 1.00 (95% CI, 0.28–2.62). Median peak serum creatinine measurements during AKI events for user and nonuser groups were 1.60 (IQR 1.36–1.78) and 1.88 (IQR 1.55–2.44) (p=0.02), respectively. Sensitivity analyses yielded similar results. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that there is no evidence of increased odds of AKI in SGLT-2 inhibitor users compared with propensity-matched nonusers with type 2 diabetes.

OBJECTIVES/SPECIFIC AIMS: (1) Characterize the prevalence and initial pharmacological management of chronic pain syndromes during pregnancy in a women’s mental health program. (2) Describe the severity and qualitative characteristics of chronic pain during pregnancy and the acute postpartum period. (3) Compare obstetrical and neonatal outcomes between pregnant women with and without chronic pain syndromes. METHODS/STUDY POPULATION: A chart review was conducted to identify all pregnant women who presented for an initial evaluation to the Women’s Mental Health Program (WMHP) at the University of Arkansas for Medical Sciences from July 2013 to June 2016. We excluded respondents <18 years of age or who did not consent to having their information used for research purposes. Demographic information, past and current medical histories, and medication history were obtained from written and electronic medical records. Chronic pain complaints and medication history are presented as counts and percentages. In an ongoing prospective, longitudinal study of pregnant women with chronic pain, women are enrolled before 20 weeks gestation and followed throughout pregnancy and the first 3 months postpartum. Study visits occur at 4-week intervals; and pain characteristics, analgesic exposures, other medications, and depressive measures are collected. Obstetrical and neonatal outcomes are obtained following delivery. Subjects will be compared based on pain types (ie, neuropathic pain, non-neuropathic pain, and controls) and treatment exposures (eg, +/− opioids). Primary outcome measures include visual analog scale (VAS). Secondary outcome measures include other pain and depression assessments. Data will be analyzed using SAS 9.4. A p-value of<0.05 was considered statistically significant. RESULTS/ANTICIPATED RESULTS: (1) Chronic pain conditions were reported by 28.2% (44/156) of the initial referrals to the WMHP. (2) 95.5% of respondents with chronic pain were taking at least 1 medication, and 59.5% were taking 2 or more medications. Mean number of medications used were 2.6±2.1.3. The most common medications reported were acetaminophen (43.2%), opioids (43.2%), and sedative/hypnotics (36.4%). Non-pharmacological therapy (eg, physical therapy and transcutaneous electrical nerve stimulation) was reported by 20.5% of respondents. (4) We anticipate that measures of pain severity will increase in pregnancy, peak in the third trimester, and decline in the postpartum period. (5) We foresee that the prospective results will confirm the chart review as indicated by a higher rate of medication exposures during pregnancy, including non-analgesic medications in the women with chronic pain syndromes. (6) We expect women with chronic pain syndromes to have a higher rate of obstetrical complications, specifically pre-term delivery and operative delivery. (7) Finally, we anticipate that chronic pain syndromes and management will result in a higher rate of neonatal complications, specifically neonatal intensive care unit admission, neonatal respiratory problems, and small for gestational age infants. DISCUSSION/SIGNIFICANCE OF IMPACT: Chronic pain syndromes are prevalent in more than one-quarter of pregnant women in our study with the majority of women using pharmacological agents to manage their condition. This prevalence is greater or equal to than other common obstetrical conditions, such as gestational diabetes or preterm delivery. The novel prospective data will be germane to the clinical care of pregnant women with chronic pain disorders. Clinical practice will be better informed by our data regarding the potential impact of chronic pain and its management on pregnancy course and perinatal outcomes. These data will provide the initial foundation for the development of treatment guidelines for the management of chronic pain syndromes during the perinatal period.

OBJECTIVES/SPECIFIC AIMS: Individuals with autism spectrum disorder (ASD) and developmental coordination disorder (DCD) share overlap in their motor symptom profile and underlying neurology (Sumner, Leonard, & Hill, 2016, JADD). DSM-5 guidelines allow these 2 disorders to be independent or co-occurring (APA, 2013), but common clinical practice does not include systematic assessment to determine the presence or absence of co-occurring DCD in children with ASD, or vice versa. Furthermore, in many cases DCD is managed in a nonspecific manner, with schools making accommodations for a child’s motor challenges without formally assigning a diagnosis of DCD. Thus, somewhat subjective, qualitative judgments are made by clinicians to classify children as DCD, ASD, or ASD+DCD in the absence of a reliable, valid, quantitative measure to distinguish between these profiles. As a first step toward developing such a measure, researchers must tease apart the nuanced differences in the motor symptoms of these 2 developmental disorders using methods that are scalable to clinical and educational settings. These methods must also be developed with consideration for logistical variables such as cost, clinical utility of data output, and ease-of-use if they are to be transferrable to physicians, school nurses, and other community health workers outside of academic laboratory settings. To that end, we conducted 2 complementary studies: 1 in the lab and 1 in the community. METHODS/STUDY POPULATION: In the community-based study, we used an affordable, user-friendly, portable balance testing system to assess postural stability during quiet standing (feet shoulder-width apart) with eyes open for 30 seconds. Data were generated from a single force plate in the balance platform. Potential participants were screened for other medical and neurological conditions that might impact their postural stability, and those with significant comorbidities were excluded. We tested 15 children with a reported diagnosis of ASD, 8 children with suspected or diagnosed DCD who were enrolled in a motor intervention program, and 30 typically-developing (TD) children with no significant developmental history reported. The ASD group ranged in age from 7 to 20, the DCD group ranged from 7 to 10, and the TD group ranged from 7 to 19. In the lab-based study, we again obtained force plate data during quiet standing (feet shoulder-width apart) with eyes open for 30 seconds, in our system that also included full-body motion capture, virtual reality, and mobile eye tracking. (Data from these additional sources are not discussed in this disseminaton, as our current focus is on identifying a simple, scalable metric that can be used to distinguish ASD from DCD.) We tested 10 children with a diagnosis of ASD that was confirmed by the research team, 10 children with a diagnosis of DCD that was confirmed by the research team, and 5 TD children with no significant developmental history reported. The ASD group ranged in age from 7 to 18, the DCD group ranged from 8 to 12, and the TD group ranged from 9 to 18. RESULTS/ANTICIPATED RESULTS: Primary outcome measures in both studies were related to Center of Pressure (CoP), including CoP sway, CoP velocity, and amount of sway relative to the base of support. Data analysis from both studies is ongoing, but preliminary trends suggest that CoP metrics may effectively differentiate between ASD, DCD, and TD. During quiet standing, individuals with DCD exhibited the greatest postural sway. Individuals with ASD followed, having greater instability than the TD group. Differences were also evident in the velocity profiles of postural sway. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary findings suggest that CoP offers a means of differentiating between typical and atypical development specifically with respect to motor symptoms. This simple, quantifiable measure may prove a sensitive and specific means of systematically assessing co-occurrence of ASD and DCD in clinical and educational settings, leading to more accurate diagnostic classification and tailored intervention. Future directions include conducting analyses that account for participant age and developmental stage with respect to motor skills, determining whether trends hold in a larger sample, and using advanced statistical methods to determine whether CoP variables have predictive validity in discriminating between classifications of ASD, DCD, ASD+DCD, and TD. Eye-movement data were also obtained during these tasks, and may further aid in understanding the factors contributing to atypical postural control. These 2 studies also yielded methodological findings, namely that the portable force platform carries the benefit of high ease-of-use, low cost, and portability, but also has important drawbacks. Specifically, it is not capable of registering accurate CoP data for participants who weigh <40 lbs, and the error variance for the load cells is greater than that of most nonportable, higher-end plates like those embedded in our laboratory’s platform. As technological advances continue to facilitate development of more portable, higher-resolution systems, these drawbacks may be significantly reduced. Future directions include further assessment of portable, affordable solutions for this type of testing to identify whether higher-resolution options are available, whether this added resolution increases classification accuracy, and how ease-of-use is perceived by clinical and community health workers.

OBJECTIVES/SPECIFIC AIMS: Sudden death in the young (SDY) occurs in people between 1 and 40 years of age who do not have a known premortem risk factor for early death. Cardiovascular diseases account for the majority of causes of SDY. Sequencing of genes associated with congenital arrhythmia susceptibility and familial cardiomyopathy reveals pathogenic variants in 30% of postmortem cases (often called “molecular autopsy”). However, better data are needed to determine the prevalence of phenotype and genotype abnormalities in surviving relatives. METHODS/STUDY POPULATION: A retrospective cohort study was performed at a tertiary pediatric center including all subjects with a family history of SDY. Cases were identified using ICD-9 codes (798.1 or .9, V17.41, V17.49, V19.8, V61.07), search of cardiology databases, and by recursive identification of all family members of a subject. Phenotype data was independently reviewed by a pediatric cardiologist. Genotype results were available when obtained by the original treating physician. RESULTS/ANTICIPATED RESULTS: Cardiac evaluations were performed in 279 subjects from 175 families, of whom 117 subjects (42%) were first-degree relatives of the proband. Mean age of the subject at time of evaluation was 9 years (SD 5.9). Most probands were over 18 years at the time of SDY: 1–4 years of age (9%); 5–12 (5%); 13–17 (16%); 18–24 (18%); 25–40 (42%). A final diagnosis was determined in 55 families (20%), and a variant in a gene potentially causative of SDY was discovered in 20/55 (36%) of those families. Variants were classified as 50% pathogenic/likely pathogenic, 50% variants of unknown significance. Cardiac testing (ECG, echo, EST, signal averaged ECG, cardiac MRI, or EP study) was abnormal in 124/279 subjects (44%). Among those with abnormal studies, 57/124 (46%) were from a family where a final diagnosis could be determined (LQT 43%, HCM 21%, ARVC 4%, other cardiomyopathy 19%, WPW 5%, CPVT 2%). However, 67/279 of total subjects (24%) had at least 1 abnormal study and a final diagnosis was not determined in the family. DISCUSSION/SIGNIFICANCE OF IMPACT: An abnormal phenotype is common among relatives referred for cardiac evaluation after SDY. While testing identifies a family diagnosis in 20% of families, many patients have abnormal cardiac testing and no clear diagnosis can be made. An improved postmortem protocol for phenotype testing in relatives of a SDY victim and improved postmortem genetic testing may lead to a higher diagnosis rate and improved risk determination in surviving family members.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to understand factors that are associated with identifying which eligible pregnant women in Baltimore City accept a referral for HV services. Taking into account demographic and obstetrical variables, we will examine the extent to which 13 medical and 14 psychosocial risk factors differentiate pregnant women who (1) accepted a HV referral, (2) could not be located, or (3) refused a HV referral. METHODS/STUDY POPULATION: In this observational study, we will use secondary data on 8172 pregnant women collected by Health Care Access Maryland (HCAM) between 2014 and 2016. HCAM is the single point of entry for all pregnant women in Baltimore City into HV. HV eligibility includes being a pregnant woman, residing in Baltimore City, being uninsured or receiving Medicaid, and being identified by a prenatal care provider who completed an assessment profile of the woman’s medical and psychosocial risk (prenatal risk assessment). The outcome variable, HV engagement status (ie, accepted referral, could not be located, refused referral), will be based on HCAM discharge codes. Medical risk factors include BMI, hypertension, anemia, asthma, sickle cell, diabetes, vaginal bleeding, genetic risk, sexually transmitted disease, last dental visit >1 year ago, and taking prescription medications. Psychosocial risk factors include current pregnancy unintended; <1 year since last delivery; late entry to prenatal care (>20 wk gestation); mental, physical, or developmental disability; history of abuse or violence within past 6 months; tobacco use; alcohol use; illegal substance use within the past 6 months; resides in home built before 1978; homelessness; lack of social/emotional support; exposure to long-term stress; lack of transportation; and history of depression or mental illness. All risk factor variables are categorical (yes/no). Control variables will include demographics (eg, age, race, ethnicity, marital status, educational level) and OB history (eg, history of preterm labor, history of fetal or infant death). We will conduct descriptive statistics to characterize the sample and look for interrelatedness among the risk factors. Where there is a high level of inter-relatedness we will consider combining or omitting variables to reduce redundancy. We will use multinomial regression to examine which medical and psychological factors are associated with referral category. RESULTS/ANTICIPATED RESULTS: We hypothesize that (a) women with more medical risk factors will be more likely to accept a referral for HV services, (b) women with more psychosocial risk factors will be more likely to refuse HV or not be located, and (c) certain risk factors, such as depression/mental illness, history of abuse/violence, illegal substance use, homelessness, and exposure to long-term stress will be the strongest predictors of not accepting HV referral and/or not being located. DISCUSSION/SIGNIFICANCE OF IMPACT: The translation of effective randomized control trials (RCTs) to successful implementation in community-based programs can be challenging. Community-based programs serving low-income communities typically lack the same resources available to recruit and retain participants in RCTs. And, exclusion criteria applied in RCTs are often not applied in real world implementation which can open program to participants with more complex social and medical characteristics. Findings from this study will inform the translation of evidence-based HV programs into real world settings through an enhanced understanding of the characteristics of women who are not engaged by HV programs. This will inform development of improved outreach methods that may more effectively engage at-risk women for prenatal HV services.

OBJECTIVES/SPECIFIC AIMS: To assess the association between probable OSA and the sudden unexpected death in epilepsy (SUDEP-7) risk profiling index in monitored adult inpatients with epilepsy. METHODS/STUDY POPULATION: We analyzed 49 consecutive adults (>18 years) with refractory epilepsy admitted to our inpatient epilepsy monitoring unit. The SUDEP-7 inventory was performed for all subjects. Probable OSA was identified using overnight oximetry, the Sleep Apnea Sleep Disorder Questionnaire (SA-SDQ), and STOP-BANG inventory. RESULTS/ANTICIPATED RESULTS: Thirty-nine percent of participants screened positive for probable sleep apnea. Patients with high SUDEP-7 scores were more likely to have a positive screen for OSA. DISCUSSION/SIGNIFICANCE OF IMPACT: OSA is an independent risk factor for sudden cardiac death. OSA may be a hitherto unrecognized contributor to sudden death risk in epilepsy. Further studies determining the relationship between OSA, neural circulatory control and SUDEP are warranted.

OBJECTIVES/SPECIFIC AIMS: The goal of the study is to evaluate the prognostic importance and accuracies of a biomarker, human epidermal receptor 2 (Her2), for breast cancer recurrence in a cohort study, namely Lifetime after Cancer Epidemiology (LACE). We specifically interested in the role that Her2 plays in prognosis of breast tumor recurrence for women after a previously diagnosed and treated breast cancer. METHODS/STUDY POPULATION: The study cohort includes 2267 women enrolled in LACE who had previously diagnosed breast cancer. Patients were enrolled from each of the 2 LACE registries in California and Utah. The main endpoint of the study is the right-censored time to breast cancer recurrence. Patients’ enrollments were, on average, 2 years after diagnosis of the first breast cancer. The patients’ characteristics at baseline were obtained through self-administered questionnaires. Cox proportional hazard model with time-varying covariates was used to relate the Her2 status (Her2+ and Her2−) to the primary end point (time to breast cancer recurrence). Hazard ratios (HRs) and their 95% confidence interval comparing Her2+ and Her2− arms were estimated. Time-dependent sensitivity and specificity were used to investigate the performance of using Her2 for classifying patients into high and low risk (Her2 + is classified as hi risk and Her− as low risk) of future breast cancer recurrence at time points after baseline. The time-dependent sensitivity was calculated as the proportion of patients being classified as high risk of recurrence who had breast cancer recurrence before a series of pre-specified time points after baseline, and the time-dependent specificity was calculated as the proportion of subjects being classified as low risk of recurrence who did not have breast cancer recurrence at the same time points. RESULTS/ANTICIPATED RESULTS: The average patient follow-up time was 9.8 years, and 18% of the women got positive Her2 test results at baseline. Among 2267 patients in the study cohort, 2031 had records on their Her2 status, among whom 326 (16.1%) patients were Her2+ and 1705 (83.9%) were Her2−. The mean tumor size among the 2031 patient was 2.10±1.22 cm. A majority of the patients (78.9%) were White. Over one-half of these patients were neither current nor past smokers. Only 3% of the patient had a baseline stage IIIA or higher. About 49% of the patients underwent a mastectomy. Radiation therapy was used by 63.5% of the patients, and Tamoxifen users accounted for 78% of the study cohort. We found a statistically significant association between Her2 and breast cancer recurrence (HR=1.33, log-ran p-value=0.006). However, the HRs of breast cancer recurrence comparing Her2+ and Her2− patients decreased over time. We also investigate the effect of combined Her2, estrogen (ER), and progesterone (PR) on breast cancer recurrence and found that patients with Her2+/ER+/PR− had the highest risk of breast cancer recurrence. The hazard of recurrence for this group of patients was 85% higher than patients with Her2−/ER+/PR+. We also investigate the prognostic accuracies of Her2 in terms of time-dependent sensitivity and specificity. Using Her2 as the prognostic biomarker resulted in a specificity consistently over 80% from baseline up until 15 years post-baseline. The time-dependent sensitivity of Her2 was above 90% between baseline and 1.5 years. Then, the sensitivity dropped gradually to 40% from 1.5 years to 3 years post-baseline. For prognosis of breast cancer over 3 years from baseline, the sensitivity was between 30% and 40%. DISCUSSION/SIGNIFICANCE OF IMPACT: As a single biomarker and risk factor, Her2 was statistically significantly associated with the recurrence of breast cancer among patients in the LACE cohort. A composite biomarker by combining Her2, ER, and PR status was also significantly associated with the breast cancer recurrence. However, the HRs of breast cancer recurrence comparing Her2+ and Her2− patients decreased over time, implying that the Her2 status had a high impact on early recurrent breast tumors. Single biomarkers, usually, have very limited ability for prognosis of future events. However, we found that using HER2 as a single biomarker can give a relatively larger specificity consistently over 15 years of the study period. The sensitivity of Her2 is high for detecting early breast cancer recurrence. However, after 2.5 years from baseline, using Her2 for breast cancer recurrence detection is not reliable. Due to the relatively high accuracies of using Her2 status for prognosis of breast cancer recurrence, we conclude that Her2 should be considered in clinical studies related to prognosis of breast cancer recurrence. Future studies will investigate if prognostic accuracies can be improved by combining Her2 with baseline clinical risk factors such as age, tumor size and lymph nodes. In conclusion, our study has the clinical impact on prognosis (or early detection) of breast cancer recurrence among women with previously diagnosed and treated breast cancers.

OBJECTIVES/SPECIFIC AIMS: Depression is one of the leading causes of diseases and disability among women of all ages in the United States. Lack of resources to meet one’s daily needs, access to health care, job opportunities, and drug use significantly contribute to depression among women. This paper aimed to explore the determinants of depression among women from a large community-based sample. METHODS/STUDY POPULATION: HealthStreet is a community engagement research initiative at the University of Florida that utilizes the community health worker (CHW) model to assess health concerns and conditions of community members and link them to available social and medical services and health research. From October 2011 through December 2016, CHWs assessed 8469 community members from various locations in the community such as grocery stores, bus stops, health fairs, laundromats, and others. Among these 8469 participants contacted and assessed by the CHWs, 4952 (58.5%) were women. RESULTS/ANTICIPATED RESULTS: Of the total 8469 participants, 4952 were women and 1839 (37.1%) reported ever having depression. Mean age of women who reported depression was 44.1 years (SD±14.4). Women who were current users of 3 or more drugs were 10 times more likely (95% CI: 5.73, 18.40; OR 10.27) to report depression compared with those who did not currently use any drugs. Those who were food insecure in the past 12 months (95% CI: 1.970, 2.576; OR 2.253) were twice more likely to report depression, while never married (95% CI: 0.576, 0.771; OR 0.666), and currently unemployed (95% CI: 0.535, 0.715; OR 0.619) women were less likely to report depression. Chronic health conditions such as hypertension (41.6% vs. 33.7%), diabetes (14% vs. 10.5%), and cancer (12.1% vs. 8.3%), and comorbid psychiatric symptoms such as anxiety (54.2% vs. 10.8%) and bipolar disorder (23.8% vs. 2.8%) were significantly higher (p<0.001) among women with depression compared with their counterparts. Significantly more women without a history of depression had medical insurance (68.8% vs. 64.3%) as compared with women with depression. DISCUSSION/SIGNIFICANCE OF IMPACT: Depression was associated with food insecurity and drug use. The impact of drug use continues to be a major mental health concern among community-based women. Further, these findings emphasize the importance of community engagement programs such as HealthStreet, which utilizes the CHWs’ model to link community members to social and medical services within the community, in improving the mental health of women.

OBJECTIVES/SPECIFIC AIMS: To assess the effect of cannabis on impaired judgment and health outcomes among heart failure patients in the emergency room. METHODS/STUDY POPULATION: Patients with heart failure presenting to the emergency room. Cannabis with confounders such as income level, insurance type, tobacco use, and age. Discharged against medical advice to assess impaired judgment. Hospitalization rates, length of stay, and death rate to assess health outcomes. Multivariate logistic regression to access the odds of each of these outcomes from cannabis RESULTS/ANTICIPATED RESULTS: Cannabis is associated with impaired outcome (increase in discharge against medical advice). Cannabis have poorer health outcome in terms of more hospitalizations from the emergency department. Cannabis also have better health outcome in terms of shorter length of stay and death rate among cannabis users Versus nonusers. DISCUSSION/SIGNIFICANCE OF IMPACT: This is crucial to inform health care providers to ensure better counseling of cannabis users. This result should also be considered to interpret other publications that shows better outcomes in patients taking cannabis. Cannabis users might only seem to have a better outcome because they tend to discharge against medical advice and thereby die outside the hospital, etc.

OBJECTIVES/SPECIFIC AIMS: To compare the accuracy and precision for estimating the diagnostic accuracies (sensitivities and specificities) between differential verification (DV) and partial verification (PV) methods. Comparisons were made under scenarios with different values of design parameters including disease prevalence, proportion of verification for positive results, proportion of verification for negative result, sensitivity and specificity of the brass standard (BS) test in DV method. Through comparing 2 different verification methods under different scenarios, we give suggestions that which verification method is optimal under different design settings. METHODS/STUDY POPULATION: For both PV and DV methods, simulation studies were performed using statistical package R, version 3.1.3. We were primarily interested in studying how the unbiasedness and precision for estimation of diagnostic accuracies (sensitivity and specificity) of an index test change with the following design parameters: disease prevalence, proportion of verification for positive test results, the proportion of verification for negative test results, and the sensitivity and specificity of a BS test. We chose different values for each of the above parameters. For each estimation, we allowed values in only 1 parameter to change by fixing the other 2 parameters, so that the effect of each design parameter on the unbiasedness and precision of both sensitivity and specificity can be determined. For the DV method, we also developed an analytical method to estimate the sensitivity and specificity of an index test using a quadratic equation with a unique solution of the specificity and sensitivity. RESULTS/ANTICIPATED RESULTS: For rare disease with prevalence less than 1%, the PV method resulted in a less biased and more precise estimate of sensitivities and specificities of the index test. If the disease prevalence was between 1% and 10%, the DV method using a BS test with moderate or high sensitivity and specificity (sensitivity and specificity >90%) resulted in a less biased and more precise estimate of diagnostic accuracies of the index test. When the disease prevalence was greater than 10%, the PV method was superior when the BS test had sensitivity and specificity <80%, and the DV method was superior when the BS test had both sensitivity and specificity >90%. When the proportion of verification of positive test results was <30% or >70%, the DV method yielded smaller bias for the estimated specificity than the PV method. However, the PV method generated a much smaller mean square error (MSE) for specificity than the DV method when the proportion of verification for positive test results was >50%. Although the disease prevalence was >10% and the proportion of verification of positive test results was <30%, the DV method resulted in a smaller MSE for specificity. DISCUSSION/SIGNIFICANCE OF IMPACT: Disease prevalence and proportions of verification for patients with positive and negative test results influence the accuracy of a new diagnostic test. If a new index test for a very rare disease is evaluated, the PV method should be used for assessing the performance of the index test. When a disease prevalence is >1%, the DV method will result in a less biased and more precise estimate of diagnostic accuracy of an index test, if the BS test itself used in the DV method has large specificity and specificity. One concern of using BS test for the DV method is the clinical cost. Depending on the disease type, the BS tests usually are imperfect, but may be less aggressive and/or less expensive than the gold standard test. Moreover, as all clinical examinations require professional personnel to perform, verification of the index test for relative large proportion of a large cohort of patients could become a burden on human resources. Thus, the future research of the optimal design method for a diagnostic accuracy study should be based on the comprehensive cost-effectiveness analysis.

OBJECTIVES/SPECIFIC AIMS: The morbidity and mortality in adults with single ventricular hearts who have undergone Fontan palliation is poorly defined. These patients have a high burden of arrhythmia, heart failure, and re-operation. We hypothesized that age and type of Fontan predict occurrence of arrhythmia. METHODS/STUDY POPULATION: In total, 205 patients aged 18 years who had undergone a Fontan procedure were identified. Those with incomplete data were excluded. Demographic, anatomic, pharmacologic, imaging, hemodynamic, and electrophysiologic data were collected. The χ2 and Mann-Whitney U tests were used to test significance defined as p<0.05. RESULTS/ANTICIPATED RESULTS: Of the 205 patients identified, 59 had been lost to follow-up. Of the 146 patients (77, 53% female) actively followed 18 (12%) had died at a median (IQR) age of 27 (21–34.3); in patients alive as of 10/2016 the median age was 26 years (22–34). Fontan types were lateral tunnel (LT) (n=79, 54.1%), extracardiac (EC) (n=32, 22%), right atrial to pulmonary artery (RV-PA) (n=28, 19%), and Fontan with Bjork modification (n=4, 2.7%). Systemic left ventricle (n=96, 66%) was more common than systemic right ventricle (n=43, 30%). Of the 146 patients, 101 (69%) had significant morbidity or mortality: 86 (59%) were diagnosed with arrhythmia, 18 (12%) died, and 11 (8%) underwent heart transplants. Frequent procedures included: Fontan revisions/cryoablation in 28 (19%), electrophysiology studies with ablation in 73 (50%), and pacemakers in 53 (36%). Of the arrhythmia diagnoses, 57 (64%) were atrial tachyarrhythmias. RV-PA Fontan procedures were associated with significantly more atrial arrhythmia than all other Fontan types (70% vs. 30%; p<0.01). There was no statistical difference in occurrence of atrial arrhythmia in adults with LT Versus EC Fontans (p=0.3). While patients who had undergone RV-PA and Bjork Fontans were older with median age 34 years, there was no significant difference in age between LT and EC (median 24.0 and 24.5). DISCUSSION/SIGNIFICANCE OF IMPACT: Adult survivors of the Fontan procedure suffer from significant morbidity and mortality. The single most prevalent morbidity is atrial arrhythmia. We conclude that RV-PA Fontans, now obsolete, have the highest prevalence of arrhythmia and that there is no difference in arrhythmia burden between LT and EC Fontans. Given the high prevalence of morbidity and mortality in this population, it is imperative that they be followed by cardiologists with expertise in congenital heart disease.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to characterize children with nonalcoholic fatty liver disease (NAFLD) living in the Southeastern United States. METHODS/STUDY POPULATION: This retrospective electronic medical record chart review was conducted on a random sample of 206 children identified with NAFLD. Patients were included if they met the following criteria: confirmed NAFLD through either an ultrasound or liver biopsy or clinical suspicion of fatty liver disease alongside elevated alanine aminotransferase (ALT) in the absence of other etiologies causing elevated transaminases. Patients were excluded if they had hepatitis or other documented liver disease. Data collected at initial presentation included age, gender, ethnicity, height, weight, body mass index (BMI), BMI percentile, blood pressure, HbA1c, aspartate aminotransferase (AST), ALT, γ-glutamyl transferase (GGT), total cholesterol, total triglycerides, low-density lipoprotein, and high-density lipoprotein. Statistical analysis: for descriptive statistics, frequency counts and percentages alongside means, standard deviation, range, min/max values for the continuous variables were calculated. RESULTS/ANTICIPATED RESULTS: This study included 206 children diagnosed with NAFLD. Subjects were primarily male (n=136, 66%) and Caucasian (n=133, 66%), followed by Hispanic (n=42, 21%), Black (n=25, 12%), and Asian (n=2, 1%). Mean age at diagnosis was 12.3±3.5 years. Mean weight (lbs), height (in), and BMI (kg/m2) of subjects at diagnosis were 192±77 lbs, 61.7±6.6 in, 34.6±9.7 kg/m2, respectively. Patients had an average systolic blood pressure of 124±15.4 mmHg and diastolic blood pressure of 69.6±10.6 mmHg. Mean ALT was 91.8±67.2 U/L, AST was 61±38.8 U/L, and GGT was 55.1±64.6 U/L. Mean HbA1c was 5.8±1.4%, cholesterol was 176±36.3 mg/dL, triglycerides were 200±134 mg/dL, low-density lipoprotein was 107.6±32.1 mg/dL, and high-density lipoprotein was 39.9±8.4 mg/dL. DISCUSSION/SIGNIFICANCE OF IMPACT: In addition to having significantly elevated liver enzymes, children with NAFLD had several derangements in their metabolic profile, most notably high triglyceride levels and HbA1c values in the prediabetic range. Although lifestyle modification is the gold standard treatment for NAFLD, pharmacotherapy may need to be included to address metabolic syndrome.

OBJECTIVES/SPECIFIC AIMS: About 75% of the estimated 2.5 million traumatic brain injuries (TBIs) diagnosed annually classify as mild TBI (mTBI); yet cognitive impairments associated with poor patient outcomes can persist for weeks to years. mTBI symptoms are difficult to measure objectively and often remain undiagnosed in the context of an unknown cognitive baseline. Formal neuropsychological exams hold limited utility due to their extensive resource burden. We aimed to define the clinical importance of a 4-question assessment of subjective cognitive complaints (SCC) in predicting return to work at 6 months following mTBI. METHODS/STUDY POPULATION: mTBI participants from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study were included. A self-report affirmation to at least 1 of 4 subjective cognitive symptoms yielded positive SCC. Regression analysis was used to determine factors associated with return to work by 6-months. RESULTS/ANTICIPATED RESULTS: Of 479 enrolled participants with mTBI, 271 (57%) had complete follow-up data. Of which, 156 (58%) had at least sheltered employment at enrollment. Thirty-four (22%) of workers had no return to work at 6-months. Demographics, prior education, presenting injury severity, work status, and post-traumatic stress disorder were associated with return to work. SCC was associated with lower odds of return to work by 6-months (OR=0.11, p=0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: We suggest a concise 4-question assessment of SCC may be clinically relevant in estimating the likelihood of return to work by 6 months post-mTBI.

OBJECTIVES/SPECIFIC AIMS: Childhood obesity has become an issue of some concern worldwide. Some reviews and a recent study in adults have indicated that obesity-related inflammatory responses produce brain damage. However, studies exploring associations between inflammation and executive functions in children are overlooked. Therefore, the objective of this cross-sectional study is to determine whether difficulties in executive functions and emotional processing are associated with obesity and inflammation. METHODS/STUDY POPULATION: We have recruited 12 of a total of 60 children aged 6–8 years old. They have completed the NIH Toolbox Cognition Battery and the NEPSY II Affect Recognition tests. Samples of plasma and saliva were collected to quantify inflammatory biomarkers cytokines (IL-6 and TNF-α) assay by Luminex procedure. We performed descriptive analysis and Mann-Whitney U test to compare obese Versus nonobese groups. RESULTS/ANTICIPATED RESULTS: Obese children have lower scores in measures of affect recognition than healthy weight children. They also showed higher median scores in both salivary and plasma IL-6 and TNF-α. DISCUSSION/SIGNIFICANCE OF IMPACT: Although no statistical differences were found among groups in either measurement, these preliminary data based on the initial recruitment suggest that children with higher body mass index may have difficulties in emotional processing. More data will be available after completing recruitment to determine if the association between obesity and affect recognition is significant and if it is mediated by inflammation.

OBJECTIVES/SPECIFIC AIMS: Peripheral neuropathy is the dose limiting toxicity of paclitaxel treatment. Paclitaxel pharmacokinetics (PK), specifically the Cmax and amount of time the concentration remains above 0.05 µM (Tc>0.05), have been associated with occurrence of severe, clinician-documented neuropathy. The objective of this study was to confirm that paclitaxel PK predicts progression of patient-reported neuropathy. METHODS/STUDY POPULATION: This observational trial enrolled breast cancer patients receiving weekly 1-hour paclitaxel infusions (80 mg/m2×12 cycles) at the University of Michigan Comprehensive Cancer Center. Paclitaxel concentration was measured via LC/MS in plasma samples collected at the end of (Cmax) and 16–24 hours after (Tc>0.05) first infusion. Patient-reported neuropathy was collected (EORTC CIPN20) at baseline and each cycle. The rate of neuropathy severity increase per treatment cycle is being modeled for each patient. Cmax and Tc>0.05 values will be introduced into the model to confirm that PK independently contributes to neuropathy progression. RESULTS/ANTICIPATED RESULTS: PK and neuropathy data have been collected from 60 patients for ongoing analysis. Our initial model will characterize the expected severity of neuropathy after each cycle of paclitaxel treatment. The PK-neuropathy model will include either PK parameter to validate their contribution to the progression of neuropathy severity during treatment. We anticipate, based on our preliminary analysis of the first 16 patients, that both PK parameters will significantly contribute to the model but Tc>0.05 will be more strongly associated with neuropathy progression. DISCUSSION/SIGNIFICANCE OF IMPACT: This project will generate a model that can be used to predict a patient’s neuropathy severity throughout treatment using a single, conveniently collected and easily measured PK sample during their first cycle. The next steps of this project include identifying genetic and metabolomic biomarkers that predict which patients experienced more severe neuropathy than would be anticipated based on their paclitaxel PK, and a planned interventional trial of personalized paclitaxel dosing to enhance efficacy and/or prevent neuropathy.

OBJECTIVES/SPECIFIC AIMS: Recent data suggest that fecal microbiota and intraluminal organic acids may play an important role in irritable bowel syndrome (IBS) pathogenesis through effects on intestinal secretion and motility. Understanding their contribution will be critical in developing diagnostic and treatment strategies. Objectives and goals of this study will be to: (1) compare fecal microbiota and fecal organic acids in IBS patients and controls and (2) investigate the association between colonic transit and fecal microbiota in IBS patients and controls. METHODS/STUDY POPULATION: We propose a prospective investigation of fecal organic acids, colonic transit and fecal microbiota in 36 IBS patients and 18 healthy controls. The target population will be adults ages 18–65 years meeting Rome IV criteria for IBS (both diarrhea predominant and constipation-predominant, IBS-D, and IBS-C) and asymptomatic controls. Exclusion criteria are: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, liver disease, or elevated AST/ALT>2.0x the upper limit of normal, (b) prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy>6 months before study initiation, (c) ingestion of prescription, over the counter, or herbal medications affecting gastrointestinal transit or study interpretation within 6 months of study initiation for controls or within 2 days before study initiation for IBS patients, (d) pregnant females, (e) antibiotic usage within 3 months prior to study participation, (f) prebiotic or probiotic usage within the 2 weeks prior to study initiation, (g) tobacco users. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid (SCFA) excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100-g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis and frozen. Frozen aliquots will be shipped to the Metabolite Profiling Facility at Purdue University and the Mayo Clinic Department of Laboratory Medicine and Pathology for SCFA and bile acid measurements, respectively. Analysis of fecal microbiota will be performed in the research laboratory of Dr. David Nelson in collaboration with bioinformatics expertise affiliated with the Nelson lab. Colonic transit time will be measured with the previously validated method using radio-opaque markers. Generalized linear models will be used as the analysis framework for comparing study endpoints among groups. RESULTS/ANTICIPATED RESULTS: This study seeks to examine the innovative concept that specific microbial signatures are associated with increased fecal excretion of organic acids to provide unique insights on a potential mechanistic link between altered intraluminal organic acids and fecal microbiota. DISCUSSION/SIGNIFICANCE OF IMPACT: Results may lead to development of targets for novel therapies and diagnostic biomarkers for IBS, emphasizing the role of the fecal metabolome.

OBJECTIVES/SPECIFIC AIMS: To describe the use of primary debulking surgery and neoadjuvant chemotherapy in advanced-stage ovarian cancer patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) over the period of 1 year. Specifically, identify a subset of patients that are medically eligible to be considered for surgery. Examine the ultimate treatment designation for those patients, assessing the application of the MSKCC resectability algorithm and its utility in guiding treatment choice. METHODS/STUDY POPULATION: Using the prospectively maintained Ovarian Cancer Database at MSKCC, we queried patients who presented for initial management of ovarian cancer from July 1, 2015 to June 30, 2016. All patients with stage IIIB-IV disease who received their primary treatment at MSKCC were included in our study. Patients needed to have pathology-confirmed ovarian cancer and all histological subtypes were included. Data were collected and analyzed in Excel. RESULTS/ANTICIPATED RESULTS: There were a total of 173 patients treated for stage IIIB-IVB ovarian cancer at MSKCC during the study period. Of those 98 patients received PDS, whereas 75 were directed to NACT, making MSKCC’s overall NACT rate 43.4% for the year we studied. Of the patients who received NACT, 19 met full Aletti Criteria at diagnosis, precluding them from being considered for surgery. In addition, 21 patients had medical contraindications to surgery, meaning that a total of 40 patients who were given NACT were not able to be considered for PDS. If we then take into account only the patients who were medically eligible for PDS, the rate of NACT at MSKCC drops to 23.1%, almost half of the original value. These medically eligible patients are the population that should be receiving an MSKCC resectability score. Of the 98 patients who underwent PDS, 73.5% had a preoperative resectability score calculated. Based on the algorithm, 81.3% of those patients were deemed to be “low risk” and 15.2% were deemed to be “high risk” of a suboptimal debulking. The algorithm dictates that all “high risk” patients who go on to PDS should undergo a laparoscopy first to assess for resectability and potentially avoid an unnecessary open procedure. Hundered percent of the “high risk” cases that were taken to the OR had an initial laparoscopy before proceeding with PDS. Overall, 93.1% of patients that underwent PDS had an optimal cytoreduction, or ≤1 cm residual disease at the conclusion of surgery. Of the 6 patients throughout the year that had a suboptimal outcome, or >1 cm residual disease, 3 were initially scored as “low risk,” 1 was scored as “high risk,” and 2 did not receive an MSKCC resectability score prior to their procedure. Of note, 3 of the suboptimal cases had unresectable disease in an anatomical location not accounted for in the resectability algorithm. DISCUSSION/SIGNIFICANCE OF IMPACT: The rates of PDS Versus NACT vary widely between institutions, and it is not always clear how calculations are made. High-volume centers likely see a higher percentage of sicker patients with more advanced disease, which could increase their rates of NACT as many of these patients are not eligible for surgery. It is important to standardize the way our field quotes NACT rates, and to understand how treatment decisions are being made at a given institution. PDS has a demonstrated survival benefit, and while we would ideally use this modality for all of our patients, there will always be a baseline percentage of patients who cannot be considered for the surgery. Since we will never be able to offer those patients PDS, our objective should be to identify patients who can be considered for the procedure and to work toward optimizing their outcomes. In this study we identified the population of patients who are truly the PDS Versus NACT cohort as they were eligible for both modalities. We then examined the application and utility of the MSKCC resectability algorithm in an attempt to further optimize treatment allocation. This scoring system was implemented at our hospital over the past year with the goal that 100% patients going on to PDS would receive a preoperative score. Unfortunately, 26.5% of PDS patients were not scored prior to their procedure. This makes it more difficult to evaluate the efficacy of the scoring system, especially considering 1/3 of the suboptimal cases were not scored. Had these patients received a score, they might have been deemed “high risk” and could have avoided a lengthy operation with a significant chance of a suboptimal outcome. In addition, it is important to note that 3 of the suboptimal PDS outcomes were initially scored as “low risk,” and 3 of the suboptimal outcomes were due to disease locations not accounted for in the original resectability algorithm. We will continue logging disease locations of suboptimal cases, it is possible that a certain disease location not in the scoring system is responsible for a significant portion of suboptimal outcomes. The resectability score model had an overall predictive accuracy of 0.756 when it was initially published, and we must continue tracking scores and outcomes to determine its validity when applied prospectively in our population. In order to accurately do so however, an emphasis should be made to ensure 100% of patients being considered for PDS receive a score going forward.

OBJECTIVES/SPECIFIC AIMS: Falls are a major source of morbidity and disability in the aging population. Twenty to thirty percent of older adults who fall suffer moderate to severe injuries such as lacerations, hip fractures, and head traumas. A serious component of falling often overlooked is the fear of falling. The fear of falling is part of a debilitating spiral that leads to decreased activity and muscle weakness. The goal of this investigation was to determine if a novel 2-phase rehabilitation program designed to reduce the fear of falling and increase muscle strength could improve postural control during falls in older adults with balance impairments. METHODS/STUDY POPULATION: Four older adults participated in 8 cognitive restructuring workshops entitled A Matter of Balance (AMOB): 2 hours/week, total of 16 hours, designed to restructure thought patterns relative to falls and reduce the fear of falling. Within 1–2 weeks of completion, participants enrolled in Phase II: a standardized 10-week lower-extremity strengthening program. Participants performed high-intensity concentric resistance exercise on a modified seated ergometer (Eccentron, BTE Technologies) twice per week for up to 20 minutes per session. Fear of falling was assessed using the Activities-Specific Balance Confidence (ABC) scale. Postural control was assessed during reproducible falls at 3 phases: baseline (T0), after Phase I AMOB (T1), and after Phase II strengthening (T2). Falls were induced by treadmill perturbations (VGait system, MotekForce Link) occurring at slow and fast belt accelerations. A 3×3 ANOVA was conducted on postural control outcomes with phase and stepping cycle as independent factors. Pairwise comparisons were analyzed with the Bonferroni correction. RESULTS/ANTICIPATED RESULTS: Statistically significant main effects were found for phase and stepping cycle (p=0.003, p=0.00). No statistically significant interaction effects were found. However, a trend toward increasing Center of Pressure-Center of Mass (COP-COM) distance occurred after each intervention phase (T1 and T2) during fast treadmill perturbations. The greatest increase in COP-COM distance was found at 100% of the stepping cycle during fast perturbations following 10 weeks of resistance training compared with baseline (p=0.006). No significant differences were found in fear of falling between phases (p=0.682). DISCUSSION/SIGNIFICANCE OF IMPACT: A large COP-COM distance suggests the individual is able to allow straying of the COM outside of the functional base while recovering balance. Meanwhile, a small COP-COM distance represents a conservative approach to postural tasks, in that the performer does not feel stable enough to allow separation of the COP and COM. These pilot data suggest that a 2-phase rehabilitation program can improve specific components of postural control during recovery from falls. Rehabilitation interventions aimed at reducing falls in older adults should consider adding a component of cognitive restructuring in conjunction with standard of care resistance training.

OBJECTIVES/SPECIFIC AIMS: (1) Evaluate safety of a novel influenza vaccination strategy in patients with plasma cell disorders. (2) Measure laboratory-confirmed influenza infection rates following a novel influenza vaccination strategy in patients with plasma cell disorders. (3) Evaluate clinical correlates of response following a novel influenza vaccination strategy in patients with plasma cell disorders. METHODS/STUDY POPULATION: We conducted a double-blind, randomized study over the 2015–16 flu season, comparing 2 doses of Fluzone® High-Dose influenza vaccination (separated by 30 d) to the current standard of care influenza vaccination. Patients were allocated to the experimental arm in 2:1 ratio compared with standard of care arm. Standard of care influenza vaccination was considered single age-based vaccination (standard dose for those <65 y and high dosefor those ≥65 y) and patients in this arm received a saline placebo injection at 30 days to assist in blinding. Eligibility criteria allowed any patient with a PCD and no contraindication to trivalent inactivated influenza vaccine. The primary endpoint was laboratory-confirmed flu infection rate. Protocol-driven surveillance screened patients for flu-like illnesses and performed laboratory testing for influenza until the end of the flu season in May 2016. Secondary endpoints include HAI titer serologic response rates, clinical correlates of protection from influenza infection, and exploratory studies of cell-mediated immunity through characterization of T cell subpopulations, cytokine profiles, and flu-specific T-cell responsiveness. RESULTS/ANTICIPATED RESULTS: In total, 122 plasma cell disorder patients were enrolled (97 with disease requiring therapy and 25 with asymptomatic gammopathy). Of those 48 patients received a single standard of care influenza vaccination and 74 patients received 2 doses of Fluzone® high-dose vaccine. Median age was 67 years (range 42–90). This 2-dose vaccination strategy was safely tolerated in all patients with no grade 2 adverse events attributed to vaccine. With close clinical follow-up, only 4% of patients receiving 2 vaccine doses developed laboratory confirmed influenza Versus 8.3% of those receiving single vaccine. When compared to the expected CDC influenza infection rate of 10%–15%, 1 sample, 2-tailed binomial testing revealed patients receiving 2 vaccines experienced a significantly lower rate of infection than the expected rate (p<0.05) whereas those receiving single vaccine showed no significant difference (p=0.38). DISCUSSION/SIGNIFICANCE OF IMPACT: This randomized study demonstrates that the 2 dose strategy of Fluzone® high-dose influenza vaccine is safely tolerated in patients with plasma cell disorders and associated with significantly less than expected laboratory-confirmed influenza infections. The results suggest that this novel vaccination strategy may have a clinical benefit in reducing influenza infections in plasma cell disorder patients and thus may have practice changing implications. Final analyses of serologic responses, clinical correlates of response, and cell-mediated immune correlates may provide valuable insights into in vivo “immune-competence” in patients with plasma cell disorders.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is the pharmacology of sublingual Buprenorphine in Hispanics/Latino men and women. Specifically we plan to: (1) Administer sublingual buprenorphine to Hispanic/Latino men and women volunteers, and measure the circulating amounts of the drug in the bloodstream as a function of time; that is, pharmacokinetics of buprenorphine. The goal of the proposed study is to evidence that there are gender and ethnic differences in the pharmacokinetics of sublingual buprenorphine between not only Hispanics/Latinos and non-Hispanics/Latinos (Caucasian), but also within Hispanic/Latino men and women. METHODS/STUDY POPULATION: We are proposing a phase 1 of buprenorphine using 12 healthy volunteers. To test for differences in pharmacokinetics between Hispanic/Latino men and women, 6 Hispanic/Latino men, and 6 Hispanic/Latino women 21 years of age and older will be recruited. The volunteers should be living in Puerto Rico, and must have both parents born in Puerto Rico. Sublingual buprenorphine will be administered using a low dose of 16 mg one time only. Blood samples will be collected from each volunteer at t=0, 1, 2, 4, 6, 8, 12, and 24 hours after administration. The amount of circulating drug in the bloodstream of the volunteers will be measured using liquid chromatography combined with mass spectrometry. Pharmacokinetic obtained parameters will be maximal plasma concentration, minimal plasma concentration, predose concentration, 24 hour post predose concentration, the time for maximum concentration. The area under the curve will be determined by the trapezoidal rule. Male Versus female data will be compared using 2-tailed t-test. RESULTS/ANTICIPATED RESULTS: We anticipate that: (1) Hispanic/Latino women will have longer circulating times of the drug in the bloodstream and higher maximum concentrations, compared with men. (2) Hispanic/Latino men and women will have higher amounts of the circulating drug, compared with already reported pharmacokinetic data of non-Hispanic Caucasian men. DISCUSSION/SIGNIFICANCE OF IMPACT: Gender differences have been elucidated in the prevalence rates of substance abuse, health service utilization, treatment outcomes, and physiological consequences of drug consumption in the United States. It is known that in general, women progress from drug use to dependence must faster than men; women also suffer more severe physical and emotional consequences than men, yet women seek treatment for drug addiction in lower rates compared with men. Women also show lower pharmacological treatment effectiveness as they are less likely to feel satisfied upon entering a substance abuse treatment and they show higher cravings. Sublingual buprenorphine is a very popular and relatively new medication used primarily for opiate addiction since 2002. Gender differences have been elucidated in the pharmacology of buprenorphine sublingual tablets used for the treatment of opioid addiction. One study showed that women had higher concentrations of circulating parent drug and it is metabolites compared with men. One metabolite in particular norbuprenorphine was found in almost double the plasma concentration in women. Interestingly, gender differences were not pursued at all by the Pharmaceutical Company sponsoring the approval of the sublingual Buprenorphine by the FDA. The cytochrome enzyme CYP 3A4 responsible for the metabolism of Buprenorphine has higher activity in Caucasian/African American women compared with men. However these studies failed to design and recruit significant amount of patients with Hispanic ethnicity to adequately elucidate the gender differences within this ethnic group. Higher plasma concentrations and longer circulation times of a drug may result not only in lower efficacy outcomes but also higher toxicity and undesired effects. Unfortunately, the lack of pharmacological effectiveness and lack of satisfaction in women undergoing drug treatment programs has not been adequately studied to understand the gender difference in pharmacological treatment outcomes between Hispanic/Latino men and women. Due to the under-representation of Hispanic/Latino men but most importantly women in s studying the pharmacology of sublingual Buprenorphine, and considering the well-established gender difference of the principal enzyme (CYP 3A4) responsible for the pharmacology of Buprenorphine, we are proposing a pilot study of the pharmacology of sublingual Buprenorphine in Hispanic/Latino volunteers living in Puerto Rico with equal number of male and female patients. We expect our research to clinically and scientifically elucidate the gender differences of sublingual buprenorphine for opioid addiction in Hispanics/Latinos. The outcome of such research will be the foundation of subsequent clinical studies that aim in updating the current standard of care for Hispanic/Latino men and women that require therapy for opioid addiction.