Zidovudine plus lamivudine in Human T-Lymphotropic Virus type-I-associated myelopathy: a randomised trial

BACKGROUND: No therapies have been proven to persistently improve the outcome of HTLV-I-associated myelopathy. Clinical benefit has been reported with zidovudine and with lamivudine in observational studies. We therefore conducted a randomised, double blind, placebo controlled study of six months combination therapy with these nucleoside analogues in sixteen patients. RESULTS: Primary outcomes were change in HTLV-I proviral load in PBMCs and clinical measures. Secondary endpoints were changes in T-cell subsets and markers of activation and proliferation. Six patients discontinued zidovudine. No significant changes in pain, bladder function, disability score, gait, proviral load or markers of T-cell activation or proliferation were seen between the two arms. Active therapy was associated with an unexplained decrease in CD8 and non-T lymphocyte counts. CONCLUSION: Failure to detect clinical improvement may have been due irreversible nerve damage in these patients with a long clinical history and future studies should target patients presenting earlier. The lack of virological effect but may reflect a lack of activity of these nucleoside analogues against HTLV-I RT in vivo, inadequate intracellular concentrations of the active moiety or the contribution of new cell infection to maintaining proviral load at this stage of infection may be relatively small masking the effects of RT inhibition

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour

Investigating the Prevalence and Types of Clinical Services Offered by Pharmacists in Federally Qualified Health Centers in South Carolina: A Qualitative, Cross-Sectional Survey

Purpose: To investigate the prevalence and type of clinical pharmacy services offered within South Carolina Federally Qualified Health Centers (SC FQHCs) and identify existing implementation barriers. Methods: This study was a cross-sectional survey of pharmacists or Chief Medical Officers practicing in SC FQHCs. Organizations were identified utilizing the Health Resources and Services Administration (HRSA) database and were contacted to participate in a telephone survey. An electronic form was created in REDCap ® software. Descriptive statistics were used to analyze and evaluate data. Results: Twenty-two SC FQHCs were eligible for the survey, with 16 (72.7%) participating. Of the respondents, 9 (56%) offered at least 1 service. The most common services offered were chronic disease state management, diabetes self-management education and support (DSMES), and tobacco cessation (43.8%, n = 7). The least common services offered were chronic care, Hepatitis C, and HIV management (18.9%, n = 3). The most common barriers to implementation were lack of personnel and provider interest (62.5%, n = 10). The least common barrier was a lack of pharmacist interest or time (25%, n = 4). Conclusion: Pharmacists offered at least 1 clinical service within most SC FQHCs. Barriers were identified that prevented expansion of services and further research is needed to overcome these