Mixed-Methods Exploration of Group Therapy for Substance Use Disorders: Prospects for Evidence-Based Practice.

Evidence-based treatments (EBTs) for substance use disorders (SUDs) often are not utilized in clinical practice or lag years behind in their uptake. One underappreciated dimension of this research-practice gap is a mismatch in treatment modality: Whereas research efforts have focused on individual therapy, the majority of SUD treatment is in group format. In this mixed-methods three-study dissertation, I aim to narrow this gap by exploring how SUD clinicians facilitate group therapy. First, I conducted a national online survey with 566 SUD group therapy clinicians about their most commonly utilized group practices. Survey results confirm that group therapy is the most widely used SUD treatment modality, with especially high prevalence of open groups; clinicians also reported high utilization of EBT components (especially motivational interviewing and cognitive behavioral therapy) but with varying use of 35 specific practices and moderate use of questionable/less-effective practices. For the remaining two studies, I conducted qualitative thematic content analyses of semi-structured interviews with 13 clinicians at three outpatient SUD specialty clinics in the Midwestern U.S. The first qualitative analysis, which also included interviews with clinical directors, focused on organizational factors that facilitate and impede EBT implementation. Results indicate considerable challenges for integrating EBTs within each clinic, in terms of complexities with clinics’ provision of group therapy, exclusive use of open groups, use of treatment structures (e.g., group duration and session length) that are not readily compatible with existing EBTs, and use of a suite of treatments rather than standalone interventions; considerable adaptations are thus necessary to utilize existing EBTs. For the second qualitative analysis, I present complexities and barriers for group therapy facilitation, including use of EBTs, among individual clinicians. Results indicate that clinicians emphasized the importance of providing individualized and engaging treatment, necessitating considerable flexibility for group facilitation; however, clinicians also had serious challenges in this regard, due to complex group dynamics and organizational deficits and barriers (limited group therapy experience, limited quality control efforts, the predominance of psychoeducation, and limited attention to clients’ demographic diversity). For each study, I discuss recommended strategies for researchers and clinicians toward improved innovation and implementation of evidence-based practice.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113429/1/dcwendt_1.pd

Substance use and treatment outcomes among Spanish-speaking Latino/as from four acculturation types.

The purpose of this study was to examine the association of acculturation with substance use treatment outcomes in a sample of treatment-seeking Latino/as (N = 405). The study used data from a multisite randomized controlled trial of a culturally adapted version of Motivational Enhancement Therapy delivered in Spanish. Berry, Kim, Minde, and Mok\u27s (1987) acculturation model was used to divide the sample into 4 types (integrated, assimilated, separated, marginalized), based on Bicultural Involvement Questionnaire scores. One-way analyses of variance, chi-squared tests, and repeated-measures regression were used to examine baseline acculturation, posttreatment outcomes, and follow-up outcomes. All participants were of Latino/a background, and 88.4% of the sample was male. Participants with greater acculturation to American culture (i.e., integrated and assimilated acculturation types) reported more substance use and associated problems at baseline, χ²(3) = 20.5, p \u3c .001, with the integrated type reporting the highest percentage of substance use disorder symptoms and problems (67.6%). No significant differences in substance use were detected among acculturation types posttreatment or at follow-up. Although the integrated and assimilated acculturation types were associated at baseline with more substance use and associated problems, all acculturation types seemed to benefit at posttreatment from an evidence-based culturally adapted treatment. (PsycINFO Database Recor

Advancing Community‐Based Research with Urban American Indian Populations: Multidisciplinary Perspectives

The US has witnessed significant growth among urban American Indian (AI) populations in recent decades, and concerns have been raised that these populations face equal or greater degrees of disadvantage than their reservation counterparts. Surprisingly little urban AI research or community work has been documented in the literature, and even less has been written about the influences of urban settings on community‐based work with these populations. Given the deep commitments of community psychology to empowering disadvantaged groups and understanding the impact of contextual factors on the lives of individuals and groups, community psychologists are well suited to fill these gaps in the literature. Toward informing such efforts, this work offers multidisciplinary insights from distinct idiographic accounts of community‐based behavioral health research with urban AI populations. Accounts are offered by three researchers and one urban AI community organization staff member, and particular attention is given to issues of community heterogeneity, geography, membership, and collaboration. Each first‐person account provides “lessons learned” from the urban context in which the research occurred. Together, these accounts suggest several important areas of consideration in research with urban AIs, some of which also seem relevant to reservation‐based work. Finally, the potential role of research as a tool of empowerment for urban AI populations is emphasized, suggesting future research attend to the intersections of identity, sense of community, and empowerment in urban AI populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/117185/1/ajcp9643.pd

PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1

Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.Peer reviewe

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Background: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers.Aim: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.Methods: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy.Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)].Conclusion: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.Peer reviewe

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection