Huntington's Disease Drug Development: A Phase 3 Pipeline Analysis.

Huntington's Disease (HD) is a severely debilitating neurodegenerative disorder in which sufferers exhibit different combinations of movement disorders, dementia, and behavioral or psychiatric abnormalities. The disorder is a result of a trinucleotide repeat expansion mutation that is inherited in an autosomal dominant manner. While there is currently no treatment to alter the course of HD, there are medications that lessen abnormal movement and psychiatric symptoms. ClinicalTrials.gov was searched to identify drugs that are currently in or have completed phase III drug trials for the treatment of HD. The described phase III trials were further limited to interventional studies that were recruiting, active not recruiting, or completed. In addition, all studies must have posted an update within the past year. PubMed was used to gather further information on these interventional studies. Of the nine clinical trials that met these criteria, eight involved the following drugs: metformin, dextromethorphan/quinidine, deutetrabenazine, valbenazine, Cellavita HD, pridopidine, SAGE-718, and RO7234292 (RG6042). Of these drug treatments, four are already FDA approved. This systematic review provides a resource that summarizes the present therapies for treating this devastating condition that are currently in phase III clinical trials in the United States.

Community pharmacies and the empowerment of self-care in the United States.

Background: As part of self-care, patients prevent diseases or conditions, maintain, or enhance their current health status, and address current health challenges. As a key member of the healthcare team, the role of the pharmacist in relation to self-care is important, given the ease of access to pharmacists in a variety of care settings. Objectives: To describe the structure and function of self-care within community pharmacies throughout the United States (U.S.). Methods: The literature within the U.S. was reviewed related to self-care definitions and practice, the role and training of the pharmacist, and challenges and opportunities for pharmacists. Results: Within the U.S., self-care is broader than simply products found in the "over-the-counter" (OTC) section of pharmacies; it includes pharmacists involvement in disease prevention, evaluation and maintenance of current health status, and assistance in managing health challenges. There is growing recognition of the significance of pharmacists in aiding patients in self-care, due to publication of outcomes related to pharmacist-provided self-care support. Accreditation standards require student pharmacists to develop knowledge and competency related to the broadest definition of self-care; resources exist related to curricular content and student evaluation and assessment support. The evolving role of the pharmacist in relation to self-care has presented challenges in terms of recognition and renumeration for services and workload issues. Efforts are currently underway to address these challenges. Conclusions: Spiraling health care costs, poor health outcomes, and continued health disparities indicate a need to better support U.S. patients on their health care journey, which often begins with self-care. There is a plethora of opportunities for pharmacists to advocate for expanding roles related to self-care, including participation in national efforts to recognize the outcomes of pharmacists in self-care.

Safety and efficacy of vitamin B in cancer treatments: A systematic review.

BACKGROUND: With rising rates of complementary and alternative medicine use, the exploration of complementary and alternative medicine integration into oncology treatments is becoming increasingly prevalent. Vitamin B compounds including B1, B2, B3, B5, B6, B9, and B12, have all been proposed as potentially beneficial in cancer prevention and treatment as well as side effect management; however, many studies contain contradicting evidence regarding the utility of B vitamins within oncology. Thus, the aim of this study was to evaluate the safety and efficacy of Vitamin B supplementation in the oncology setting. DESIGN: A systematic review was conducted following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Reviews guidelines, using pre-specified search terms in PubMed to include randomized control trials, clinical trials, and case studies. Two reviewers independently reviewed titles, abstracts, and full-text articles for inclusion, with a third reviewer resolving conflicts, before the included articles underwent data extraction and quality appraisal. Data extraction was conducted through COVIDENCE, which was used to manage and track the data during the search process. RESULTS: Out of 694 articles initially identified, 25 articles met the inclusion criteria and were included in the review. Designs of the studies varied, including randomized control trials, clinical trials, and case/cohort studies. The impact of vitamin supplementation on cancer risk varied. Several studies found that certain B vitamin supplementation lowered cancer risk: B9 and B6 in nasopharyngeal carcinoma (n = 1200 patients) and in pancreatic cancer (n = 258 patients); B3 in hepatocellular carcinoma (n = 494,860 patients); B6 in breast cancer (n = 27,853 patients); and B9 in BRCA1-positive breast cancer (n = 400 patients). However, some studies found that certain B vitamin supplementation increased the risk or negative outcomes of cancer: B6 during nasopharyngeal carcinoma treatment (n = 592 patients); B6 in risk of hepatocellular carcinoma (n = 494,860 patients); and B9 plasma levels in breast cancer (n = 164 patients). Due to the many adverse effects that occur in cancer treatment, the effectiveness of Vitamin B supplementation in alleviating adverse effects was evaluated. In two separate studies, Vitamin B6 and Vitamin B12 supplementation with acupuncture was found to be effective as adjunct therapies aimed to reduce chemotherapy-induced peripheral neuropathy (n = 23 patients and n = 104 patients, respectively). No significant findings were established regarding B vitamin supplementation in chemotherapy-induced hand-foot syndrome. CONCLUSIONS: In this systematic review we concluded that B vitamin supplements have varying data regarding safety and efficacy in cancer. Taking into account the etiology of the cancer, the specific B-vitamin, and the presence of any side effects could help guide utilization of the data found in this review. Large, randomized controlled trials are needed to confirm these findings among various cancer diagnoses and stages. Given the widespread utilization of supplements, healthcare providers should understand the safety and efficacy of vitamin B supplementation to address questions that arise in caring for those with cancer.

Synthesis of diphenyl-(2-thienyl)phosphine, its chalcogenide derivatives and a series of novel complexes of lanthanide nitrates and triflates.

A novel synthesis of diphenyl(2-thienyl)phosphine, along with its' oxide, sulfide and selenide derivatives, is reported here. These phosphines have been characterized by NMR, IR, MS and X-Ray crystallography. The phosphine oxide derivative was reacted with a selection of lanthanide(III) nitrates and triflates, LnX3, to give the resultant metal-ligand complexes. These complexes have also been characterized by NMR, IR, MS and X-Ray crystallography. Single crystal X-Ray diffraction data shows a difference in metal-ligand complex stoichiometry and stereochemistry depending on the counteranion (nitrate vs. triflate). The [Ln(Ar3PO)3(NO3)3] ligand-nitrate complexes are nine-coordinate to the metal in the solid state (bidentate nitrate), featuring a 1 : 3 lanthanide-ligand ratio and bear an overall octahedral arrangement of the six, coordinated ligands. Our [Ln(Ar3PO)3(NO3)3] ligand-nitrate complexes gave three examples of fac-stereochemistry, where mer-stereochemistry is almost universally observed in the literature of highly related [Ln(Ar3PO)3(NO3)3] complexes. For the Tb complexes, two different arrangements of the ligands around the metal were observed in the solid state for [Tb(Ar3PO)3(NO3)3] and [Tb(Ar3PO)4(OTf)2] [OTf]. [Tb(Ar3PO)3(NO3)3] is strictly nine-coordinate, ligand mer-stereochemistry in the solid state, and [Tb(Ar3PO)4(OTf)2] [OTf] is strictly octahedral, six-coordinate, with a square-planar stereochemical arrangement of the phosphine oxide ligands around the metal.