Common elements in opioid use disorder guidelines for buprenorphine prescribing.

OBJECTIVES: This study sought to formulate a consolidation of guidelines representing best practices related to office-based opioid treatment (OBOT) of opioid use disorder (OUD) using buprenorphine. It also demonstrates how a set of evidence-based guidelines may be linked with claims data to leverage analytic techniques that drive cost-effective, positive health outcomes. STUDY DESIGN: Literature review of US and international guidelines for OBOT using buprenorphine for OUD. METHODS: The study conducted a review of currently available US and several international guidelines from 2009 to 2018 published on OUD and the use of buprenorphine in OBOT. Guidelines were consolidated based on common elements. The process of correlating common elements with available commercial and state Medicaid claims data is described, including which elements are amenable to analysis along with relative complexity. RESULTS: Seven guidelines met inclusion criteria and are presented as 3 tables, organized by clinical themes and phase of care related to OBOT use of buprenorphine for OUD. Themes included establishing care, monitoring treatment stability and engagement, and nonpharmacologic treatment to improve outcomes. Areas of agreement and divergence between guidelines are highlighted. Specific components are identified as they relate to metrics of interest to public and private payers. CONCLUSIONS: Among US and international guidelines for treatment of OUD, common themes are readily identified and may indicate agreement in regard to interventions. Linking pharmacy and medical billing claims data to evidence-supported best practices provides public and private payers the ability to track individual patients, facilitate high-quality care, and monitor outcomes.

Urine drug testing results and paired oral fluid comparison from patients enrolled in long-term medication-assisted treatment in Tennessee.

Urine drug testing is recommended for individuals receiving medication-assisted treatment. It provides objective information for practitioners to consider and may serve as a protective factor against drug-related mortality. The primary objective of our study was to describe urine drug testing results for patients undergoing long-term medication-assisted treatment (≥6months). The secondary objective was to provide further evidence to establish oral fluid as a reliable alternative to urine. All subjects (n=639) included in the study were enrolled in one of five treatment centers in the state of Tennessee, and all urine specimens were positive for either methadone or buprenorphine. Nicotine (87%), caffeine (70%), marijuana (15%), alcohol (14%) and gabapentin (10%) were the most prevalent substances identified through urine drug testing. The presence of non-maintenance opioids (prescription and/or heroin) may represent relapse; these drugs were present in 10% of specimens tested. Evidence of illicit drug use (cocaine, heroin, marijuana and/or methamphetamine) was detected in 19% specimens. For 126 of the 639 subjects included in the study, paired oral fluid and urine test results were compared for agreement. Of the total paired urine and oral fluid tests, approximately 7% were positive for a drug in both specimen types and 91% were negative in both, resulting in an overall agreement of 98%. The study demonstrates continued use of illicit and commercially available medications in a medication-assisted treatment population undergoing long-term treatment. The results affirm the reliability of oral fluid as an alternative specimen type for compliance testing in this population.

Rectal cancer and exposure to metalworking fluids in the automobile manufacturing industry.

BACKGROUND: Rectal cancer has been previously associated with exposure to metalworking fluids in a cohort mortality study of autoworkers. OBJECTIVE: To better specify the exposure-response relationship with straight metalworking fluids (mineral oils) by applying non-parametric regression methods that avoid linearity constraints and arbitrary exposure cut points and by lagging exposure to account for cancer latency, in a nested case-control analysis. METHODS: In addition to the classical Poisson regression with categorical exposure, survival models with penalised splines were used to estimate the exposure-response relationship between cumulative exposure to straight metalworking fluid and mortality from rectal cancer. Exposures to water-based metalworking fluids were treated as potential confounders, and all exposures were lagged by 5, 10, 15 and 20 years to account for cancer latency. The influence of the highest exposures was dealt with by a log transformation and outlier removal. The sensitivity of the penalised splines to alternative criteria for model selection and to the placement of knots was also examined. RESULTS: The hazard ratio for mortality from rectal cancer increased essentially linearly with cumulative exposure to straight metalworking fluid (with narrow confidence bands) up to a maximum of 2.2 at the 99th centile of exposure and then decreased (with wide confidence bands). Lagging exposure up to 15 years increased the initial steepness of the curve and raised the maximum hazard ratio to 3.2. CONCLUSIONS: Non-parametric smoothing of lagged exposures has shown stronger evidence for a causal association between straight metalworking fluid and rectal cancer than was previously described using standard analytical methods. This analysis suggests an exposure-response trend that is close to linear and statistically significant over most of the exposure range and that increases further with lagged exposures. Smoothing should be regularly applied to environmental studies with quantitative exposure estimates to refine characterisation of the dose-response relationship.

Quantifying bias due to allele misclassification in case-control studies of haplotypes.

OBJECTIVES: Genotyping errors can induce biases in frequency estimates for haplotypes of single nucleotide polymorphisms (SNPs). Here, we considered the impact of SNP allele misclassification on haplotype odds ratio estimates from case-control studies of unrelated individuals. METHODS: We calculated bias analytically, using the haplotype counts expected in cases and controls under genotype misclassification. We evaluated the bias due to allele misclassification across a range of haplotype distributions using empirical haplotype frequencies within blocks of limited haplotype diversity. We also considered simple two- and three-locus haplotype distributions to understand the impact of haplotype frequency and number of SNPs on misclassification bias. RESULTS: We found that for common haplotypes (>5% frequency), realistic genotyping error rates (0.1-1% chance of miscalling an allele), and moderate relative risks (2-4), the bias was always towards the null and increases in magnitude with increasing error rate, increasing odds ratio. For common haplotypes, bias generally increased with increasing haplotype frequency, while for rare haplotypes, bias generally increased with decreasing frequency. When the chance of miscalling an allele is 0.5%, the median bias in haplotype-specific odds ratios for common haplotypes was generally small (<4% on the log odds ratio scale), but the bias for some individual haplotypes was larger (10-20%). Bias towards the null leads to a loss in power; the relative efficiency using a test statistic based upon misclassified haplotype data compared to a test based on the unobserved true haplotypes ranged from roughly 60% to 80%, and worsened with increasing haplotype frequency. CONCLUSIONS: The cumulative effect of small allele-calling errors across multiple loci can induce noticeable bias and reduce power in realistic scenarios. This has implications for the design of candidate gene association studies that utilize multi-marker haplotypes.

XPA, haplotypes, and risk of basal and squamous cell carcinoma.

Nucleotide excision repair (NER) is instrumental in removing DNA lesions caused by ultraviolet (UV) radiation, the dominant risk factor for keratinocyte carcinoma, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We evaluated whether BCC or SCC risk was influenced by the A23G single nucleotide polymorphism (SNP) in Xeroderma pigmentosum group A (XPA), which codes for an essential protein in NER. We also investigated whether haplotypes of XPA, determined by seven haplotype-tagging SNPs, better define susceptibility to keratinocyte carcinoma. Incident cases of BCC and SCC from New Hampshire were identified through dermatologists and pathology laboratories. Population-based controls were frequency-matched to cases by gender and age. Cases of BCC (886) and of SCC (682) were compared with controls (796). Models controlled for age, gender, pigmentation factors and severe sunburns and were restricted to Caucasians. Using GG as the reference, the A allele was less frequent among cases of BCC (OR(AG) = 0.82, 95% CI (0.66, 1.01); OR(AA)= 0.74, 95% CI (0.53, 1.03); trend test P = 0.03) and SCC (OR(AG) = 0.85, 95% CI (0.67, 1.07); OR(AA) = 0.74, 95% CI (0.52, 1.05); trend test P = 0.05) than controls. Risk from > or =3 severe sunburns was elevated for those with the GG genotype only, and this interaction was nearly significant for BCC (P = 0.07). XPA genotype also modified a relationship between SCC and the amount of pigmentation (P = 0.02). Using a haplotype analysis identifying seven common XPA haplotypes indicated that the A23G polymorphism alone captured the differences in susceptibility to keratinocyte carcinoma. The common G allele of the A23G polymorphism was associated with an increased risk of BCC and SCC and this polymorphism appeared to be the determining polymorphism in XPA that alters cancer susceptibility.

The C3435T polymorphism of MDR1 and susceptibility to adult glioma.

INTRODUCTION: The multidrug resistance-1 (MDR1) gene encodes a pump that prevents potentially carcinogenic substances from crossing the blood-brain barrier. We compare adult glioma cases and controls for the C3435T polymorphism that has been associated with reduced MDR1 expression. METHODS: Adult glioma in the San Francisco Bay area and population-based controls were identified between 1991-1994 and 1997-1999. Genotyped cases (n = 458) and controls (n = 528) were compared using logistic regression controlling for age, gender and ethnicity, with later stratification by ethnicity, gender and histology. RESULTS: With CC as the referent, the TT genotype was nonsignificantly less frequent among cases compared to controls (OR, 0.87; 95% CI: 0.6, 1.2). After stratification, only male glioblastoma was associated with TT genotype (OR, 0.51; 95% CI: 0.3, 1.0). CONCLUSIONS: Although the C3435T polymorphism does not appear to be associated with other types of glioma, we cannot rule out that this MDR1 polymorphism may be associated with glioblastoma among men.