A Multipreceptor Approach to Ambulatory Care Topic Discussions

Objective. To assess the impact of a multipreceptor approach to facilitating topic discussions on students'' knowledge and confidence in clinical decision-making during an ambulatory care advanced pharmacy practice experiences (APPEs).Design. Faculty members with relevant expertise and experience facilitated discussions with fourth-year doctor of pharmacy (PharmD) students regarding 7 ambulatory care topics. A student self-assessment survey and knowledge-assessment instrument was administered before and after discussions.Assessment. Students'' examination scores increased significantly from 59.1% ± 13.9% at baseline to 76.5% ± 12.6% at the end of the 5-week experience (p<0.001). The majority of participants were comfortable making therapeutic decisions regarding medication use as it related to all discussion topics except heart failure.Conclusions. Participation in topic discussions led by faculty members with expertise and experience for each ambulatory care topic was associated with a significant improvement in knowledge-assessment scores.     

Addressing Challenges to Providing Peer-Based Recovery Support

As more systems of care deploy peer-based recovery support (P-BRS) programs, challenges to the effective use of P-BRS have emerged. These include external challenges, embedded in the organization and culture of traditionally organized services, and individual challenges, associated with the nonprofessional status of individual peer support staff members. The Living Centers, recovery resource centers providing P-BRS, have developed methods for addressing these challenges. These include organizing the P-BRS as stand-alone programs, having peer support staff and clients organize the P-BRS, emphasizing organizational values and culture as the basis for staff training, and implementing measures designed to encourage accountability among peer support staff. In the future, research into the types of barriers to P-BRS that may exist in traditionally organized behavioral health services and the types and content of training that contribute to the provision of P-BRS will facilitate the use of these services.     

Computer assisted remediation of a homophone comprehension disorder in surface dyslexia

Abstract

An information processing model of reading was used to identify the locus of a reading and spelling disorder. The patient was found to exhibit the symptoms of surface dyslexia with surface dysgraphia, with a reliance on phonological decoding of the printed word to achieve comprehension. As a result, many errors were made in comprehending homophones. A remediation progrmmae presented on a microcomputer was implemented to retrain the recognition and comprehension of a set of written homophones. The patient improved in her ability to both recognise and comprehend homophones, but no generalization of the improvement to spelling of homophones took place.     

Evaluating training methods for transporting contingency management to therapists

The effects of three increasingly intensive training methods on therapist use, knowledge, and implementation adherence of contingency management (CM) with substance abusing adolescents were evaluated. Ten public sector substance abuse or mental health provider organizations were randomized to one of three training conditions: workshop and resources (WS +), WS + and computer assisted training (WS +/CAT), or WS +/CAT and supervisory support (WS +/CAT/SS). Across conditions, 161 therapists participated in the training experiences, and measures were obtained at baseline and 2-month intervals for 12 months following workshop participation. Across training conditions, therapists reported increased CM use, knowledge, and implementation adherence through the 12-month follow-up. The findings show that community-based practitioners are amenable to the adoption of evidence-based treatments when provided access to useful resources. Moreover, high quality workshops in combination with resource access can increase knowledge of the evidence-based treatment and might enhance intervention adherence to a level needed to improve youth outcomes.     

Xeroderma pigmentosum genes and melanoma risk

Xeroderma pigmentosum is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. The presence of a distinct the nucleotide excision repair (NER) mutation signature in melanoma suggests that perturbations in this critical repair process are likely to be involved with disease risk. We hypothesized that persons with polymorphic NER gene(s) are likely to have reduced NER activity and are consequently at an increased risk of melanoma development. We assessed the association between 94 SNPs within seven XP genes (XPA–XPG) and the melanoma risk in the Polish population. We genotyped 714 unselected melanoma patients and 1,841 healthy adults to determine if there were any polymorphisms differentially represented in the disease group. We found that a significantly decreased risk of melanoma was associated with the Xeroderma pigmentosum complementation (XPC) rs2228000_CT genotype (odds ratio [OR] = 0.15; p < 0.001) and the rs2228000_TT genotype (OR = 0.11; p < 0.001) compared to the reference genotype. Haplotype analysis within XPC revealed the rs2228001_A + G1475A_G + G2061A_A + rs2228000_T + rs3731062_C haplotype (OR = 0.26; p < 0.05) was associated with a significantly decreased disease risk. The haplotype analysis within the Xeroderma pigmentosum group D (XPD) showed a modest association between two haplotypes and a decrease in melanoma risk. There were no major differences between the prevalence of the XP polymorphisms among young or older patients with melanoma. Linkage disequilibrium of XPC: rs2228001, G1475A, G2061A, rs2228000 and rs3731062 was found. The data from our study support the notion that only XPC and XPD genes are associated with melanoma susceptibility.     

Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington’s Disease

Using an iterative structure–activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC₅₀, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington’s disease.     

A Concise Panel of Biomarkers Identifies Neurocognitive Functioning Changes in HIV-Infected Individuals

Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV. Despite substantial effort, no biomarkers have been sufficiently validated for diagnosis and prognosis of NCI in the clinic. The goal of this project was to identify diagnostic or prognostic biomarkers for NCI in a comprehensively characterized HIV cohort. Multidisciplinary case review selected 98 HIV-infected individuals and categorized them into four NC groups using normative data: stably normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints separated by a median of 6.2 months. Eight biomarkers were measured in CSF and blood by immunoassay. Results were analyzed using mixed model linear regression and staged recursive partitioning. At the first visit, subjects were mostly middle-aged (median 45) white (58 %) men (84 %) who had AIDS (70 %). Of the 73 % who took antiretroviral therapy (ART), 54 % had HIV RNA levels below 50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in CSF was associated with neurocognitive change group. Recursive partitioning models aimed at diagnosis (i.e., correctly classifying neurocognitive status at the first visit) were complex and required most biomarkers to achieve misclassification limits. In contrast, prognostic models were more efficient. A combination of three biomarkers (sCD14, MCP-1, SDF-1α) correctly classified 82 % of Wo and SN subjects, including 88 % of SN subjects. A combination of two biomarkers (MCP-1, TNF-α) correctly classified 81 % of Im and SI subjects, including 100 % of SI subjects. This analysis of well-characterized individuals identified concise panels of biomarkers associated with NC change. Across all analyses, the two most frequently identified biomarkers were sCD14 and MCP-1, indicators of monocyte/macrophage activation. While the panels differed depending on the outcome and on the degree of misclassification, nearly all stable patients were correctly classified.