The Diabetes Tune-Up Group: A Multidisciplinary Approach to Improve Diabetes Distress and A1C Among Adults With Type 1 and Type 2 Diabetes.

PURPOSE: The purpose of this study was to assess the feasibility of delivering the Diabetes Tune-Up Group (DTU), a cognitive-behavioral-therapy-based (CBT) multidisciplinary intervention for adults with diabetes distress and elevated A1C using a group in-person delivery format. METHODS: The DTU intervention consisted of 6 weekly group sessions (90 minutes in duration per session). The groups were cofacilitated by a diabetes care and education specialist (DCES) and a master's-level clinical psychology trainee. The intervention integrated CBT with patient-centered diabetes education. Using a pre/post study design, participants completed assessments at baseline, post-intervention, and 3 months following the intervention. RESULTS: The sample consisted of 29 adults with type 1 diabetes (N = 8) or type 2 diabetes (N = 21) who were predominantly female (79%), White (59%), and educated (56% with a college degree or greater). Participants attended 131 total sessions out of 174 possible sessions, for an overall attendance rate of 75.3%. At 3-month follow-up, significant improvements were observed in A1C values (mean decrease = 0.39%). Diabetes distress improved significantly from baseline (mean = 3.44, SD = 0.68) to post-intervention (mean = 2.94, SD = 0.68), and 3-month follow-up (mean = 2.55, SD = 0.75). Significant improvements were also observed in diabetes self-efficacy from baseline to post-intervention and at 3-month follow-up. CONCLUSIONS: This group-based, multidisciplinary intervention resulted in improvements in A1C, diabetes distress, and patient self-efficacy in caring for diabetes. Future studies to validate this intervention approach across settings and delivery platforms are needed.

Challenges to Pap Smear Follow-up among Women in the Criminal Justice System.

Women involved in the United States criminal justice system face a variety of challenges in maintaining their health. Histories of sexual abuse, early initiation of sex, and substance abuse are reflected in more negative reproductive health outcomes, including cervical cancer, than those found among non-incarcerated women. Little is known about how to close this health gap. The present study assessed what incarcerated women perceived to be facilitators and inhibitors of obtaining recommended follow-up for abnormal Pap tests. In-depth individual interviews were conducted with 44 women in an urban county jail about experiences with Pap tests and how they followed-up on abnormal results. We analyzed data using the process of thematic content analysis. Four themes were found, Pap test abnormality as an all-inclusive phrase for women's health problems, unstable lives, the structural challenges of money, and competing demands. Women with criminal justice histories have numerous and complex challenges in following-up abnormal Pap test results, as well as other health problems. Understanding the context around the follow-up for abnormal Pap tests in this population may increase providers' ability to help women effectively obtain cancer prevention care that can be life-saving, as well as to more effectively provide care for other health problems.

Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone.

AIM: The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). METHODS: In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. RESULTS: Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P < 0.001) and there was interindividual variability in the magnitude of this interaction (range, 1.8- to 12.1-fold). When pioglitazone was administered alone, the mean AUC(0,∞) was 29.7% lower (P = 0.01) in CYP2C8*3 carriers compared with CYP2C8*1 homozygotes. The relative change in pioglitazone plasma exposure following gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P = 0.02). CONCLUSION: CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil-pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug-drug interactions.

Influence of SLCO1B1 polymorphisms on the drug-drug interaction between darunavir/ritonavir and pravastatin.

The authors investigated whether SLCO1B1 polymorphisms contribute to variability in pravastatin pharmacokinetics when pravastatin is administered alone versus with darunavir/ritonavir. HIV-negative healthy participants were prospectively enrolled on the basis of SLCO1B1 diplotype: group 1 (*1A/*1A, n = 9); group 2 (*1A/*1B, n = 10; or *1B/*1B, n = 2); and group 3 (*1A/*15, n = 1; *1B/*15, n = 5; or *1B/*17, n = 1). Participants received pravastatin (40 mg) daily on days 1 through 4, washout on days 5 through 11, darunavir/ritonavir (600/100 mg) twice daily on days 12 through 18, with pravastatin 40 mg added back on days 15 through 18. Pharmacokinetic studies were conducted on day 4 (pravastatin alone) and day 18 (pravastatin + darunavir/ritonavir). Pravastatin area under the plasma concentration-time curve (AUC(tau)) was 21% higher during administration with darunavir/ritonavir compared with pravastatin alone; however, this difference was not statistically significant (P = .11). Group 3 variants had 96% higher pravastatin AUC(tau) on day 4 and 113% higher pravastatin AUC(tau) on day 18 compared with group 1. The relative change in pravastatin pharmacokinetics was largest in group 3 but did not differ significantly between diplotype groups. In sum, the influence of SLCO1B1*15 and *17 haplotypes on pravastatin pharmacokinetics was maintained in the presence of darunavir/ritonavir. Because OATP1B1 inhibition would be expected to be greater in carriers of normal or high-functioning SLCO1B1 haplotypes, these findings suggest that darunavir/ritonavir is not a potent inhibitor of OATP1B1-mediated pravastatin transport in vivo.

Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.

Cytochrome P450 (CYP) 2C8 is responsible for the oxidative metabolism of many clinically available drugs from a diverse number of drug classes (e.g., thiazolidinediones, meglitinides, NSAIDs, antimalarials and chemotherapeutic taxanes). The CYP2C8 enzyme is encoded by the CYP2C8 gene, and several common nonsynonymous polymorphisms (e.g., CYP2C8*2 and CYP2C8*3) exist in this gene. The CYP2C8*2 and *3 alleles have been associated in vitro with decreased metabolism of paclitaxel and arachidonic acid. Recently, the influence of CYP2C8 polymorphisms on substrate disposition in humans has been investigated in a number of clinical pharmacogenetic studies. Contrary to in vitro data, clinical data suggest that the CYP2C8*3 allele is associated with increased metabolism of the CYP2C8 substrates, rosiglitazone, pioglitazone and repaglinide. However, the CYP2C8*3 allele has not been associated with paclitaxel pharmacokinetics in most clinical studies. Furthermore, clinical data regarding the impact of the CYP2C8*3 allele on the disposition of NSAIDs are conflicting and no definitive conclusions can be made at this time. The purpose of this review is to highlight these clinical studies that have investigated the association between CYP2C8 polymorphisms and CYP2C8 substrate pharmacokinetics and/or pharmacodynamics in humans. In this review, CYP2C8 clinical pharmacogenetic data are provided by drug class, followed by a discussion of the future of CYP2C8 clinical pharmacogenetic research.