Cost-Effectiveness of Aripiprazole Tablets with Sensor versus Oral Atypical Antipsychotics for the Treatment of Schizophrenia Using a Patient-Level Microsimulation Modeling Approach.

Objective: Strategies designed to track drug ingestion may improve medication adherence and clinical outcomes in adults with schizophrenia. This study aimed to estimate the cost-effectiveness of aripiprazole tablets with sensor (AS; Abilify MyCite®) versus generic oral atypical antipsychotics (AAPs) in schizophrenia from the United States payer and societal perspectives over 12 months. Methods: An individual-level microsimulation was developed to generate individual trajectories using data from a phase 3b multicenter, open-label, mirror-image trial in adults with schizophrenia treated prospectively for 6 months with AS. The patient's clinical characteristics and outcomes were computed as a function of the Positive and Negative Syndrome Scale (PANSS) scores. Direct and indirect medical cost estimates were sourced from the literature; EuroQol 5-Dimensions (EQ-5D) utilities were derived using risk equations based on patient and clinical characteristics. Scenario analyses were also conducted to assess outcomes under the assumption of treatment durability over 12 months. Results: Over 12 months, AS showed a 12.2% improvement in PANSS score. AS had an incremental cost of $2168 and incremental cost savings of $22,343 from the payer and societal perspectives, respectively, with an incremental quality-adjusted life-year (QALY) gain of 0.0298 versus oral AAPs. Further, AS resulted in a 28.2% reduction in hospitalizations over 12 months. At a willingness-to-pay of $100,000 per QALY, the net monetary benefit over 12 months was $25,323 from the payer perspective. Under the assumption of the durability of the treatment effect of AS, the findings were similar to those of the base case analyses, though with greater cost savings and QALYs gained with AS. The results from the sensitivity analyses were consistent with those of the base case analysis. Conclusion: AS may be a cost-effective strategy, with lower costs and improved quality of life among patients with schizophrenia over 12 months, from the payer and societal perspectives.

The current use and evolving landscape of nutraceuticals.

The nutraceutical market is currently a high-impact multi-billion-dollar industry, and it is anticipated to grow rapidly over the next decade. Nutraceuticals comprise diverse food-derived product categories that have become widespread due to increased consumer awareness of potential health benefits and the need for improved wellness. This targeted review is designed to identify the current global trends, market opportunities, and regulations that drive the nutraceutical industry. Safety and efficacy concerns are also explored with a view to highlighting areas that necessitate further research and oversight. Key drivers of the nutraceutical market include aging populations, consumer awareness, consumer lifestyle, increasing cost of healthcare, and marketing channels. Although some nutraceuticals hold promising preventive and therapeutic opportunities, there is a lack of a universal definition and regulatory framework among countries. Moreover, there is a lack of adequate evidence for their efficacy, safety, and effectiveness, which was even further highlighted during the ongoing coronavirus pandemic. Future prospective epidemiological studies can delineate the health impact of nutraceuticals and help set the scientific basis and rationale foundation for clinical trials, reducing the time and cost of trials themselves. Together, an understanding of the key drivers of the nutraceutical market alongside a consistent and well-defined regulatory framework will provide further opportunities for growth, expansion, and segmentation of nutraceuticals applications.

Estimating the global prevalence of transthyretin familial amyloid polyneuropathy.

INTRODUCTION: This study sought to estimate the global prevalence of transthyretin familial amyloid polyneuropathy (ATTR-FAP). METHODS: Prevalence estimates and information supporting prevalence calculations was extracted from records yielded by reference-database searches (2005-2016), conference proceedings, and nonpeer reviewed sources. Prevalence was calculated as prevalence rate multiplied by general population size, then extrapolated to countries without prevalence estimates but with reported cases. RESULTS: Searches returned 3,006 records; 1,001 were fully assessed and 10 retained, yielding prevalence for 10 "core" countries, then extrapolated to 32 additional countries. ATTR-FAP prevalence in core countries, extrapolated countries, and globally was 3,762 (range 3639-3884), 6424 (range, 1,887-34,584), and 10,186 (range, 5,526-38,468) persons, respectively. DISCUSSION: The mid global prevalence estimate (10,186) approximates the maximum commonly accepted estimate (5,000-10,000). The upper limit (38,468) implies potentially higher prevalence. These estimates should be interpreted carefully because contributing evidence was heterogeneous and carried an overall moderate risk of bias. This highlights the requirement for increasing rare-disease epidemiological assessment and clinician awareness. Muscle Nerve 57: 829-837, 2018.

Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands.

Immune and inflammatory death ligands expressed within neoplastic tissue could potentially target apoptosis to transformed cells. To develop approaches that accentuate the anti-cancer potential of the inflammatory response, the Chembridge DIVERSet (TM) library was screened for compounds that accentuated apoptosis in a strictly TNF-dependent manner. We identified a number of novel compounds with this activity, the most active of these, AK3 and AK10, sensitized colon cancer cells to TNF at 0.5 µM and 2 µM, respectively, without inducing apoptosis on their own. The activity of these compounds was structure-dependent and general, as they accentuated cell death by TNF or Fas ligation in multiple colon cancer cell lines. Both AK3 and AK10 arrested cells in mitosis, with live cell imaging indicating that mitotically arrested cells were the source of apoptotic bodies. AK3 accentuated caspase-8 and caspase-9 activation with little effect on NFκB target gene activation. Enhanced caspase activation corresponded to an increased expression of TNFR1 on the cell surface. To determine the general interplay between mitotic arrest and TNF sensitivity, Aurora kinase (MLN8054 and MLN8237) and PLK1 (BI2536) inhibitors were tested for their ability to sensitize cells to TNF. PLK1 inhibition was particularly effective and influenced TNFR1 surface presentation and caspase cleavage like AK3, even though it arrested mitosis at an earlier stage. We propose that AK3 and AK10 represent a new class of mitotic inhibitor and that selected mitotic inhibitors may be useful for treating colon cancers or earlier lesions that have a high level of inflammatory cell infiltrate.