Dissecting Dynamic and Hydration Contributions to Sequence-Dependent DNA Minor Groove Recognition.

Sequence selectivity is a critical attribute of DNA-binding ligands and underlines the need for detailed molecular descriptions of binding in representative sequence contexts. We investigated the binding and volumetric properties of DB1976, a model bis(benzimidazole)-selenophene diamidine compound with emerging therapeutic potential in acute myeloid leukemia, debilitating fibroses, and obesity-related liver dysfunction. To sample the scope of cognate DB1976 target sites, we evaluated three dodecameric duplexes spanning >103-fold in binding affinity. The attendant changes in partial molar volumes varied substantially, but not in step with binding affinity, suggesting distinct modes of interactions in these complexes. Specifically, whereas optimal binding was associated with loss of hydration water, low-affinity binding released more hydration water. Explicit-atom molecular dynamics simulations showed that minor groove binding perturbed the conformational dynamics and hydration at the termini and interior of the DNA in a sequence-dependent manner. The impact of these distinct local dynamics on hydration was experimentally validated by domain-specific interrogation of hydration with salt, which probed the charged axial surfaces of oligomeric DNA preferentially over the uncharged termini. Minor groove recognition by DB1976, therefore, generates dynamically distinct domains that can make favorable contributions to hydration release in both high- and low-affinity binding. Because ligand binding at internal sites of DNA oligomers modulates dynamics at the termini, the results suggest both short- and long-range dynamic effects along the DNA target that can influence their effectiveness as low-MW competitors of protein binding.

Mechanism of cognate sequence discrimination by the ETS-family transcription factor ETS-1.

Functional evidence increasingly implicates low-affinity DNA recognition by transcription factors as a general mechanism for the spatiotemporal control of developmental genes. Although the DNA sequence requirements for affinity are well-defined, the dynamic mechanisms that execute cognate recognition are much less resolved. To address this gap, here we examined ETS1, a paradigm developmental transcription factor, as a model for which cognate discrimination remains enigmatic. Using molecular dynamics simulations, we interrogated the DNA-binding domain of murine ETS1 alone and when bound to high-and low-affinity cognate sites or to nonspecific DNA. The results of our analyses revealed collective backbone and side-chain motions that distinguished cognate versus nonspecific as well as high- versus low-affinity cognate DNA binding. Combined with binding experiments with site-directed ETS1 mutants, the molecular dynamics data disclosed a triad of residues that respond specifically to low-affinity cognate DNA. We found that a DNA-contacting residue (Gln-336) specifically recognizes low-affinity DNA and triggers the loss of a distal salt bridge (Glu-343/Arg-378) via a large side-chain motion that compromises the hydrophobic packing of two core helices. As an intact Glu-343/Arg-378 bridge is the default state in unbound ETS1 and maintained in high-affinity and nonspecific complexes, the low-affinity complex represents a unique conformational adaptation to the suboptimization of developmental enhancers.

A method for calculating BMI z-scores and percentiles above the 95th percentile of the CDC growth charts.

BACKGROUND: The 2000 CDC growth charts are based on national data collected between 1963 and 1994 and include a set of selected percentiles between the 3rd and 97th and LMS parameters that can be used to obtain other percentiles and associated z-scores. Obesity is defined as a sex- and age-specific body mass index (BMI) at or above the 95th percentile. Extrapolating beyond the 97th percentile is not recommended and leads to compressed z-score values. AIM: This study attempts to overcome this limitation by constructing a new method for calculating BMI distributions above the 95th percentile using an extended reference population. SUBJECTS AND METHODS: Data from youth at or above the 95th percentile of BMI-for-age in national surveys between 1963 and 2016 were modelled as half-normal distributions. Scale parameters for these distributions were estimated at each sex-specific 6-month age-interval, from 24 to 239 months, and then smoothed as a function of age using regression procedures. RESULTS: The modelled distributions above the 95th percentile can be used to calculate percentiles and non-compressed z-scores for extreme BMI values among youth. CONCLUSION: This method can be used, in conjunction with the current CDC BMI-for-age growth charts, to track extreme values of BMI among youth.

Maternal buprenorphine treatment and fetal neurobehavioral development.

BACKGROUND: Gestational opioid use/misuse is escalating in the United States; however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders. OBJECTIVE: The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development. STUDY DESIGN: Forty-nine buprenorphine-maintained women who attended a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (ie, heart rate, motor activity, and their integration [fetal movement-fetal heart rate coupling]) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchic linear modeling. RESULTS: Fetal heart rate, heart rate variability, and heart rate accelerations were significantly reduced at peak vs trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks gestation and tended to intensify with advancing gestation. Fetal motor activity and fetal movement-fetal heart rate coupling were depressed from peak to trough at 36 weeks gestation. Polysubstance exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks gestation. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough. CONCLUSION: Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (≥13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine-exposed infants, and recognition of the benefits of medication-assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes.

Criminal Charges Prior to and After Enrollment in Opioid Agonist Treatment: A Comparison of Methadone Maintenance and Office-based Buprenorphine.

BACKGROUND: Entry into methadone maintenance is associated with a reduction in criminal activity; less is known about the effects of office-based buprenorphine. OBJECTIVE: To compare criminal charges before and after enrollment in methadone maintenance or office-based buprenorphine. METHODS: Subjects were opioid-dependent adults who initiated either methadone maintenance (n = 252) or office-based buprenorphine (n = 252) between 2003 and 2007. Medical records were reviewed to gather demographic data and a state-maintained web-based database to collect data on criminal charges. Overall charges and drug charges in the 2 years prior to and after treatment enrollment were compared. Multivariable analysis was used to examine risk factors for charges after treatment enrollment. RESULTS: In the 2 years after enrolling in treatment, subjects receiving methadone had a significant decline in the proportion of subjects with any charges (49.6% vs. 32.5%, p < .001) or drug charges (25.0% vs. 17.5%, p = .015), as well as the mean number of cases (0.97 vs. 0.63, p = .002) and drug cases (0.38 vs. 0.23, p = .008), while those who initiated buprenorphine did not have significant changes in any of these measures. On multivariable analysis, the strongest predictor of criminal charges in the 2 years after treatment enrollment was prior charges (adjusted odds ratio 3.35, 95% confidence interval, 2.24-5.01). CONCLUSIONS: Enrollment in office-based buprenorphine treatment did not appear to have the same beneficial effect on subsequent criminal charges as methadone maintenance. If this observation is replicated in other settings, it may have implications for matching individuals to these treatment options.

Sequence diversity and differential expression of major phenylpropanoid-flavonoid biosynthetic genes among three mango varieties.

BACKGROUND: Mango fruits contain a broad spectrum of phenolic compounds which impart potential health benefits; their biosynthesis is catalysed by enzymes in the phenylpropanoid-flavonoid (PF) pathway. The aim of this study was to reveal the variability in genes involved in the PF pathway in three different mango varieties Mangifera indica L., a member of the family Anacardiaceae: Kensington Pride (KP), Irwin (IW) and Nam Doc Mai (NDM) and to determine associations with gene expression and mango flavonoid profiles. RESULTS: A close evolutionary relationship between mango genes and those from the woody species poplar of the Salicaceae family (Populus trichocarpa) and grape of the Vitaceae family (Vitis vinifera), was revealed through phylogenetic analysis of PF pathway genes. We discovered 145 SNPs in total within coding sequences with an average frequency of one SNP every 316 bp. Variety IW had the highest SNP frequency (one SNP every 258 bp) while KP and NDM had similar frequencies (one SNP every 369 bp and 360 bp, respectively). The position in the PF pathway appeared to influence the extent of genetic diversity of the encoded enzymes. The entry point enzymes phenylalanine lyase (PAL), cinnamate 4-mono-oxygenase (C4H) and chalcone synthase (CHS) had low levels of SNP diversity in their coding sequences, whereas anthocyanidin reductase (ANR) showed the highest SNP frequency followed by flavonoid 3'-hydroxylase (F3'H). Quantitative PCR revealed characteristic patterns of gene expression that differed between mango peel and flesh, and between varieties. CONCLUSIONS: The combination of mango expressed sequence tags and availability of well-established reference PF biosynthetic genes from other plant species allowed the identification of coding sequences of genes that may lead to the formation of important flavonoid compounds in mango fruits and facilitated characterisation of single nucleotide polymorphisms between varieties. We discovered an association between the extent of sequence variation and position in the pathway for up-stream genes. The high expression of PAL, C4H and CHS genes in mango peel compared to flesh is associated with high amounts of total phenolic contents in peels, which suggest that these genes have an influence on total flavonoid levels in mango fruit peel and flesh. In addition, the particularly high expression levels of ANR in KP and NDM peels compared to IW peel and the significant accumulation of its product epicatechin gallate (ECG) in those extracts reflects the rate-limiting role of ANR on ECG biosynthesis in mango.

Design and estimation for the national health interview survey, 2006-2015.

OBJECTIVES: This report presents an overview, a detailed description of the sample design features, and estimation structures for the 2006-2015 National Health Interview Survey NHIS). It fulfills the same role for the current 2006-2015 NHIS design as NCHS Series 2, No. 130, "Design and Estimation for the National Health Interview Survey, 1995-2004" provided for the previous design, which was extended through 2005. METHODS: The 2006-2015 NHIS sample design uses cost-effective complex sampling techniques including stratification, clustering, and differential sampling rates to achieve several objectives, among them improved reliability of racial, ethnic, and geographical domains. This report describes these methods. RESULTS: This report presents operating characteristics of NHIS 2006-2015. The general sampling structure is presented, along with a discussion of weighting and variance estimation techniques. This report is intended for general users of NHIS data systems.

Co-infection of Haemonchus contortus and Trichostrongylus spp. among livestock in Malaysia as revealed by amplification and sequencing of the internal transcribed spacer II DNA region.

BACKGROUND: Haemonchus contortus and Trichostrongylus spp. are reported to be the most prevalent and highly pathogenic parasites in livestock, particularly in small ruminants. However, the routine conventional tool used in Malaysia could not differentiate the species accurately and therefore limiting the understanding of the co-infections between these two genera among livestock in Malaysia. This study is the first attempt to identify the strongylids of veterinary importance in Malaysia (i.e., H. contortus and Trichostrongylus spp.) by amplification and sequencing of the Internal Transcribed Spacer II DNA region. RESULTS: Overall, 118 (cattle: 11 of 98 or 11.2%; deer: 4 of 70 or 5.7%; goats: 99 of 157 or 63.1%; swine: 4 of 91 or 4.4%) out of the 416 collected fecal samples were microscopy positive with strongylid infection. The PCR and sequencing results demonstrated that 93 samples (1 or 25.0% of deer; 92 or 92.9% of goats) contained H. contortus. In addition, Trichostrongylus colubriformis was observed in 75 (75.8% of 99) of strongylid infected goats and Trichostrongylus axei in 4 (4.0%) of 99 goats and 2 (50.0%) of 4 deer. Based on the molecular results, co-infection of H. contortus and Trichostrongylus spp. (H. contortus + T. colubriformis denoted as HTC; H. contortus + T. axei denoted as HTA) were only found in goats. Specifically, HTC co-infections have higher rate (71 or 45.2% of 157) compared to HTA co-infections (3 or 1.9% of 157). CONCLUSIONS: The present study is the first molecular identification of strongylid species among livestock in Malaysia which is essential towards a better knowledge of the epidemiology of gastro-intestinal parasitic infection among livestock in the country. Furthermore, a more comprehensive or nationwide molecular-based study on gastro-intestinal parasites in livestock should be carried out in the future, given that molecular tools could assist in improving diagnosis of veterinary parasitology in Malaysia due to its high sensitivity and accuracy.

A comparison of characteristics and outcomes of opioid-dependent patients initiating office-based buprenorphine or methadone maintenance treatment.

BACKGROUND: The purpose of this study was to compare demographic factors and 1-year treatment outcomes of patients treated with buprenorphine or methadone. METHODS: The study included 252 subjects who received a prescription for buprenorphine in an academic internal medicine practice and 252 subjects who enrolled in a methadone maintenance program located on the same campus over the same time frame. Data were collected retrospectively. Patients were classified as "opioid-positive" or "opioid-negative" each month for a year based on urine drug testing and provider assessment. Successful treatment was defined as remaining in treatment after 1 year and achieving 6 or more opioid-negative months. RESULTS: Buprenorphine patients were more likely to be male, have health insurance, be employed, abuse prescription opioids, and be human immunodeficiency virus (HIV) infected; they were less likely to abuse benzodiazepines. At 12 months, 140 (55.6%) of buprenorphine patients and 156 (61.9%) of methadone patients remained in treatment (P =.148). Patients on methadone had a higher mean number of opioid-negative months (6.96 vs. 5.43; P <.001) and mean number of months in treatment (9.38 vs. 8.59; P <.001). On multivariable analysis, methadone maintenance was significantly associated with successful treatment (adjusted odds ratio: 2.10; 95% confidence interval: 1.43-3.07). CONCLUSIONS: Office-based buprenorphine and methadone maintenance programs serve very different populations. Both are effective, but patients on methadone had mildly better treatment outcomes.

Challenges and outcomes of parallel care for patients with co-occurring psychiatric disorder in methadone maintenance treatment.

OBJECTIVE: Most opioid users seeking treatment in community-based substance abuse treatment programs have at least one co-occurring psychiatric disorder, and the presence of psychiatric comorbidity in this population is associated with increased psychological distress, poorer quality of life, and reduced response to substance abuse treatment. This observational study describes clinical outcomes of referring patients receiving methadone maintenance with at least one co-occurring psychiatric disorder to a community psychiatry program located on the same hospital campus. METHODS: Participants (n = 156) were offered priority referrals to a community psychiatry program that included regularly scheduled psychiatrist appointments, individual and group therapy, and enhanced access to psychiatric medications for 1 year. Psychiatric distress was measured with the Symptom Checklist (SCL-90-R), which participants completed monthly. RESULTS: While about 80% of the sample (n = 124) initiated psychiatric care, the average length of treatment was only 128.2 days (SD = 122.8), participants attended only 33% of all scheduled appointments (M = 14.9 sessions, SD = 14.1), and 84% (n = 104) did not complete a full year of care. Of those who did not complete a full year, over half (55%, n = 68) left psychiatric care while still receiving substance abuse treatment. Exploratory negative binomial regression showed that baseline cocaine and alcohol use disorder (p = .002 and .022, respectively) and current employment (p = .034) were associated with worse psychiatric treatment retention. Modest reductions in psychiatric distress over time were observed (SCL-90-R Global Severity Index change score = 2.5; paired t = 3.54, df = 121, p = .001). CONCLUSIONS: Referral of patients with co-occurring psychiatric disorders receiving methadone maintenance to a community psychiatry program is often ineffective, even after reducing common barriers to care. Service delivery models designed to improve attendance and retention, such as integrated care models, should be evaluated. This study is part of a larger clinical trial, registered at www.clinicaltrials.gov under #NCT00787735.

Engagement of a community advisory group to shape and build up participation in TB research.

It is essential that communities at risk from TB are involved in TB research. Community advisory groups (CAGs) are one mechanism for involving communities in research and creating platforms for discussions between researchers and community members. We organised a CAG meeting with community members and people with lived experience in Ho Chi Minh City, Vietnam, to explore the community's knowledge about TB and their perspectives on different diagnostic tests in Vietnam, a low-middle-income country with a high TB burden. Researchers shared basic information and addressed questions about TB. CAG members commented on preference of TB screening tests, and suggested that chest X-rays and blood tests were more acceptable than sputum tests because of the difficulty in sputum expectoration. In addition, clinical studies that required fewer visits to the hospitals would be preferred, even if this meant a greater reliance on blood sampling.

Il est essentiel que les communautés exposées au risque de TB soient impliquées dans la recherche sur la TB. Les groupes consultatifs communautaires (CAG, pour l'anglais « community advisory groups ¼) constituent un mécanisme permettant d'impliquer les communautés dans la recherche et de créer des plateformes de discussion entre les chercheurs et les membres de la communauté. Nous avons organisé une réunion du CAG avec des membres de la communauté et des personnes ayant une expérience vécue à Ho Chi Minh Ville, au Viêt Nam, afin d'explorer les connaissances de la communauté sur la TB et leurs perspectives sur les différents tests de diagnostic au Viêt Nam, un pays à revenu faible et moyen où la charge de la TB est élevée. Les chercheurs ont partagé des informations de base et répondu à des questions sur la TB. Les membres du CAG ont fait part de leur préférence pour les tests de dépistage de la TB et ont suggéré que les radiographies pulmonaires et les analyses de sang étaient plus acceptables que les tests d'expectoration en raison de la difficulté d'expectoration des crachats. En outre, les études cliniques qui nécessitent moins de visites dans les hôpitaux seraient préférées, même si cela implique une plus grande dépendance à l'égard des prélèvements sanguins.

Assessing men with opioid use disorder for testosterone deficiency after the development of symptoms.

OBJECTIVE: Individuals with opioid use disorder (OUD) have reduced life expectancy and inferior outcomes when treated for depression, diabetes, and fractures. Their elevated risk of testosterone deficiency may contribute to all of these relationships, however few individuals prescribed opioids are evaluated with testosterone assays. The purpose of this study is to determine whether patients with opioid use disorder are evaluated for testosterone deficiency after development of a symptom that may merit investigation, such as erectile dysfunction (ED). METHOD: We conducted a retrospective longitudinal cohort study that utilized data from a national database called TriNetX. Patients were eligible for inclusion if they were 20 to 90 years of age, male, and diagnosed with erectile dysfunction. We utilized descriptive statistics and logistic regression to address study aims. RESULTS: Testosterone testing was uncommon for all patients with ED. Among 20,658 patients, it was assessed in 11.2% with OUD and 15.1% without OUD. Among those screened, 40% individuals with OUD and ED had testosterone deficiency. Odds of screening those with OUD were lower than matched controls (RR 0.74). CONCLUSIONS: Individuals with OUD are at increased risk of testosterone deficiency than the general population, but nearly 90% are not evaluated for this condition even after development symptoms. That 40% of individuals assessed were classified as testosterone deficient suggests endocrine disorders may be contributing to increased fracture risk, chronic pain, and severe depression commonly encountered in patients with OUD. Addressing this care gap may reduce morbidity and mortality associated with opioid use disorder.

Enhancing massed prolonged exposure with cannabidiol to improve posttraumatic stress disorder: Design and methodology of a pilot randomized clinical trial.

Background: The impact of posttraumatic stress disorder (PTSD) is substantial and often results in pervasive functional impairments. Although evidence-based treatments for PTSD are established, there remains room for improvement as many individuals continue to meet diagnostic criteria even after successful treatment completion. Cannabidiol (CBD) has attracted considerable attention based on its potential to treat a myriad of health conditions. CBD may decrease anxiety and facilitate extinction learning processes, two critical targets of trauma-focused psychotherapies. We present the design and methods for a pilot randomized clinical trial to examine the combination of CBD and prolonged exposure for PTSD. Methods: Participants (n = 24) will be randomized to CBD or placebo for 18 days delivered in combination with ten daily prolonged exposure sessions over two weeks. The study medication will be Epidiolex® (250 mg BID). The PTSD Checklist for DSM-5 will be the primary outcome to assess PTSD severity at baseline, during treatment, and at 1-month follow-up. Blood, saliva, and heart rate will be collected during treatment to assess intervention effects on biological outcomes related to PTSD and the endocannabinoid system. Results: Consistent with the purpose of a pilot, our goals are to evaluate the feasibility of study procedures, safety of the intervention, and the preliminary effect of CBD to inform a larger trial. Descriptive and inferential statistics will be used to address study aims. Conclusion: Findings will inform decision making on combining CBD with behavioral interventions for PTSD to enhance outcomes and mitigate the morbidity of this debilitating condition.

Activation of basophils by the double-stranded RNA poly(A:U) exacerbates allergic inflammation.

BACKGROUND: It is commonly acknowledged that asthma is exacerbated by viral infections. On the other hand, basophil infiltration of lung tissues has been evidenced postmortem in cases of fatal disease, raising the question of a possible link between these two observations. OBJECTIVES: Herein, we addressed the relationship between asthma exacerbation by viral infection and basophil activation and expansion by investigating how stimulation with the dsRNA polyadenylic/polyuridylic acid [poly(A:U)] affected basophil activities and recruitment in an allergic airway inflammation model. METHODS: The effect of dsRNA on basophils was assessed by measuring the cytokine levels produced upon stimulation. We used an OVA-induced experimental model of allergic asthma. Airway hyperreactivity, recruitment of infiltrating cells, and cytokine production were determined in the lung of mice having received poly(A:U), as compared with untreated controls. The exacerbating effect of basophils was assessed both by adoptive transfer of poly(A:U)-treated basophils and by their in vivo depletion with Ba103 antibody. RESULTS: We found that in vitro treatment with poly(A:U) increased basophil functions by inducing TH 2-type cytokine and histamine production, whereas in vivo treatment increased peripheral basophil recruitment. Furthermore, we provide the first demonstration for increased infiltration of basophils in the lung of mice suffering from airway inflammation. In this model, disease symptoms were clearly exacerbated upon adoptive transfer of basophils exposed to poly(A:U), relative to their unstimulated counterpart. Conversely, in vivo basophil depletion alleviated disease syndromes, thus validating the transfer data. CONCLUSIONS: Our findings provide the first evidence for airway inflammation exacerbation by basophils following dsRNA stimulation.

An observation of lower rates of drug use over time in community syringe exchangers.

BACKGROUND AND OBJECTIVES: The present study evaluated changes in rates of self-reported heroin and cocaine use in opioid-dependent individuals newly registered to a syringe exchange program (SEP), and examined the effects of recovery-oriented longitudinal variables (i.e., substance abuse treatment, self-help group participation, employment) on changes in drug use. METHODS: Study participants (n = 240) were opioid-dependent and drawn from a larger study evaluating strategies to improve treatment-seeking. Mixed model analyses were used to evaluate changes in rates of heroin and cocaine use, and longitudinal correlates of change in these substances, over a one-year period. RESULTS: Results showed reductions in days of heroin and cocaine use over time, and that participation in recovery-oriented activities was strongly associated with greater changes in drug use. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These results suggest SEPs can play a vital role in facilitating reductions in drug use through motivating participation in treatment and other recovery-oriented activities.

Calibration Weighting Methods for the National Center for Health Statistics Research and Development Survey.

Objectives The Research and Development Survey (RANDS) is a series of web-based, commercial panel surveys that have been conducted by the National Center for Health Statistics (NCHS) since 2015. RANDS was designed for methodological research purposes,including supplementing NCHS' evaluation of surveys and questionnaires to detect measurement error, and exploring methods to integrate data from commercial survey panels with high-quality data collections to improve survey estimation. The latter goal of improving survey estimation is in response to limitations of web surveys, including coverage and nonresponse bias. To address the potential bias in estimates from RANDS,NCHS has investigated various calibration weighting methods to adjust the RANDS panel weights using one of NCHS' national household surveys, the National Health Interview Survey. This report describes calibration weighting methods and the approaches used to calibrate weights in web-based panel surveys at NCHS.

A collaborative approach to teaching medical students how to screen, intervene, and treat substance use disorders.

Few medical schools require a stand-alone course to develop knowledge and skills relevant to substance use disorders (SUDs). The authors successfully initiated a new course for second-year medical students that used screening, brief intervention, and referral to treatment (SBIRT) as the course foundation. The 15-hour course (39 faculty teaching hours) arose from collaboration between faculty in Departments of Medicine and Psychiatry and included 5 hours of direct patient interaction during clinical demonstrations and in small-group skills development. Pre- and post-exam results suggest that the course had a significant impact on knowledge about SUDs. The authors' experience demonstrates that collaboration between 2 clinical departments can produce a successful second-year medical student course based in SBIRT principles.

Sample Design and Estimation Structures for the National Health Interview Survey, 2016-2025.

This report presents operating characteristics of the NHIS 2016-2025 sample design. The general sampling structure is presented, along with a discussion of weighting and variance estimation techniques primarily for 2016-2018. This report is organized into four major sections. The first section presents a general overview of NHIS and its sample design. The second section describes the redesign process, updates for 2016-2025, and includes general frame and sample design considerations. The third section provides a more detailed description of the sample design and how the sample was selected. The last two sections present a description of the estimators used in NHIS for analyzing and summarizing survey results. Documentation for subsequent changes to the sampling and weighting procedures is available on the NCHS website as separate reports and through each year's survey description document. This report is intended for general users of NHIS data.

Adapting and scaling a single site DEA X-waiver training program to a statewide initiative: Implementing GetWaiveredTX.

OBJECTIVES: To address the critical need for opioid use disorder (OUD) treatment by rapidly planning and implementing a statewide DEA X-waiver training initiative expanding office-based OUD treatment in Texas by: (1) facilitating access to buprenorphine waiver trainings to targeted regions and health care providers across the state; and (2) supporting completion of DEA X-waiver requirements. METHODS: We used a transdisciplinary and theory-driven approach to adapt and rapidly scale up an existing, previously successful DEA X-waiver initiative. Pre-implementation activities included a literature review to identify OUD treatment barriers and demographic analyses to identify high-need areas of the state. We used geospatial mapping methods to identify regions with highest point prevalence of opioid-overdose mortality and low access to a buprenorphine provider. The study team used the Replicating Effective Programs (REP) framework developed by the Centers for Disease Control and Prevention to support implementation of evidence-based practices. RESULTS: In six months, we trained 451 waiver eligible providers, 133 (29%) of whom received waivers by 6 months post-training. Of the 163 (36.1%) providers who completed the post-waiver evaluation, 97% reported that they were satisfied or very satisfied with the training. Our initiative delivered high quality education to providers and increased the number of waiver trainers in Texas from eight to thirteen. CONCLUSIONS: Despite recent changes to the DEA X-waiver process, barriers to treating OUD with buprenorphine remain. Lack of education and experience treating substance use disorders remains a significant factor in limiting clinician comfort in prescribing buprenorphine. The research team successfully adapted a Texas-wide initiative to increase the number of office-based providers eligible to prescribe buprenorphine for OUD from an existing single-site initiative. Attentiveness to barriers pre-implementation and to adaptations during implementation enabled moderate impact across a large network in a short time and facilitated program sustainment.

Estimating standard errors for life expectancies based on complex survey data with mortality follow-up: A case study using the National Health Interview Survey Linked Mortality Files.

Life expectancy is an important measure for health research and policymaking. Linking individual survey records to mortality data can overcome limitations in vital statistics data used to examine differential mortality by permitting the construction of death rates based on information collected from respondents at the time of interview and facilitating estimation of life expectancies for subgroups of interest. However, use of complex survey data linked to mortality data can complicate the estimation of standard errors. This paper presents a case study of approaches to variance estimation for life expectancies based on life tables, using the National Health Interview Survey Linked Mortality Files. The approaches considered include application of Chiang's traditional method, which is straightforward but does not account for the complex design features of the data; balanced repeated replication (BRR), which is more complicated but accounts more fully for the design features; and compromise, 'hybrid' approaches, which can be less difficult to implement than BRR but still account partially for the design features. Two tentative conclusions are drawn. First, it is important to account for the effects of the complex sample design, at least within life-table age intervals. Second, accounting for the effects within age intervals but not across age intervals, as is done by the hybrid methods, can yield reasonably accurate estimates of standard errors, especially for subgroups of interest with more homogeneous characteristics among their members.