Clinical and economic impact of long-acting injectable antipsychotics in patients previously treated with short-acting oral antipsychotics.

BACKGROUND: Available literature supports the use of long-acting injectable (LAI) antipsychotics over short-acting oral (SAO) formulations. The majority of evidence is centered on patients with schizophrenia insured under the Medicaid benefit. OBJECTIVE: To assess real-world clinical and economic outcomes of LAI compared with SAO antipsychotics in patients with psychiatric conditions insured under commercial, health care exchange, or Medicare plans. METHODS: In this exploratory treatmenteffectiveness study, a retrospective, before and after study design was used to evaluate differences in clinical and economic outcomes in patients switching from SAO to LAI antipsychotics. Patients who had at least 1 claim for an LAI antipsychotic and a psychiatric diagnosis were considered eligible for the study if they were continuously enrolled in a commercial, health care exchange, or Medicare plan for 12 months before (preperiod) and 12 months after (postperiod) their first LAI antipsychotic claim. During the preperiod, patients were required to have filled at least a 30-day supply of any SAO antipsychotic medication. Clinical outcomes included health care resource utilization (eg, hospitalizations per member per year [PMPY]), adherence measures, and medication switch trends. Economic outcomes included total per member per month (PMPM) spending across the medical benefit alone, the pharmacy benefit alone, and the combined spending across both benefits. Additionally, we examined patient costs and health plan spending within each of these categories. RESULTS: There was a significant decrease in overall hospitalizations PMPY (1.80 vs 0.88; P < 0.001) and psychiatric hospitalizations PMPY (0.65 vs 0.20; P <0.001) when comparing patients treated with SAO antipsychotics in the preperiod to the same patients treated with LAI antipsychotics in the postperiod, respectively. No differences were observed in the percentage of days covered with SAO and LAI agents (87.4% vs 85.8%; P=0.312). More patients switched between SAO antipsychotics during the preperiod, as compared with the number who switched between LAI antipsychotics during the postperiod (57.4% vs 10.3%; P < 0.001). On average, patients switched medications sooner in the preperiod vs the postperiod (114.50 vs 211.26 days; P < 0.001). No difference was observed between the preperiod and postperiod in total spending PMPM ($3,798.76 vs $3,702.63; P = 0.826) CONCLUSIONS: Patients switching from SAO to LAI antipsychotics experienced fewer hospitalizations, with no change in overall spending. Adherence was similar, though fewer medication switches occurred and there was a longer time before switching medications with LAI compared with SAO antipsychotics DISCLOSURES: Funding for this study was provided by Highmark Inc., but the sponsor had no role in the study outside the final review of the submitted manuscript.

A portable, low-cost device for precise control of specimen temperature under stereomicroscopes.

To facilitate precise and convenient control of biological sample temperature, we developed a low-cost device that can be used independently or with any stereomicroscope. The purpose of the device is to control the thermal environment during experimental intervals in which a specimen must be manipulated outside of an incubator, e.g. for dissection or slide-mounting in preparation for imaging. Sample temperatures can be both cooled to below and heated to above room temperatures, and stably maintained at a precision of +/- 0.1˚C. To demonstrate the utility of this device, we report improved characterization of the penetrance of a short-acting temperature-sensitive allele in C. elegans embryos, and identification of the upper temperature threshold for embryonic viability for six Caenorhabditis species. By controlling the temperature environment even as a specimen is manipulated, this device offers consistency and flexibility, reduces environmental noise, and enables precision timing in experiments requiring temperature shifts.

The sex-limited effects of mutations in the EGFR and TGF-ß signaling pathways on shape and size sexual dimorphism and allometry in the Drosophila wing.

Much of the morphological diversity in nature-including among sexes within a species-is a direct consequence of variation in size and shape. However, disentangling variation in sexual dimorphism for both shape (SShD), size (SSD), and their relationship with one another remains complex. Understanding how genetic variation influences both size and shape together, and how this in turn influences SSD and SShD, is challenging. In this study, we utilize Drosophila wing size and shape as a model system to investigate how mutations influence size and shape as modulated by sex. Previous work has demonstrated that mutations in epidermal growth factor receptor (EGFR) and transforming growth factor-ß (TGF-ß) signaling components can influence both wing size and shape. In this study, we re-analyze this data to specifically address how they impact the relationship between size and shape in a sex-specific manner, in turn altering the pattern of sexual dimorphism. While most mutations influence shape overall, only a subset have a genotypic specific effect that influences SShD. Furthermore, while we observe sex-specific patterns of allometric shape variation, the effects of most mutations on allometry tend to be small. We discuss this within the context of using mutational analysis to understand sexual size and shape dimorphism.

Context matters: sexual signaling loss in digital organisms.

Sexual signals are important in attracting and choosing mates; however, these signals and their associated preferences are often costly and frequently lost. Despite the prevalence of signaling system loss in many taxa, the factors leading to signal loss remain poorly understood. Here, we test the hypothesis that complexity in signal loss scenarios is due to the context-dependent nature of the many factors affecting signal loss itself. Using the Avida digital life platform, we evolved 50 replicates of ∼250 lineages, each with a unique combination of parameters, including whether signaling is obligate or facultative; genetic linkage between signaling and receiving genes; population size; and strength of preference for signals. Each of these factors ostensibly plays a crucial role in signal loss, but was found to do so only under specific conditions. Under obligate signaling, genetic linkage, but not population size, influenced signal loss; under facultative signaling, genetic linkage does not have significant influence. Somewhat surprisingly, only a total loss of preference in the obligate signaling populations led to total signal loss, indicating that even a modest amount of preference is enough to maintain signaling systems. Strength of preference proved to be the strongest single force preventing signal loss, as it consistently overcame the potential effects of drift within our study. Our findings suggest that signaling loss is often dependent on not just preference for signals, population size, and genetic linkage, but also whether signals are required to initiate mating. These data provide an understanding of the factors (and their interactions) that may facilitate the maintenance of sexual signals.

Sex-specific weight loss mediates sexual size dimorphism in Drosophila melanogaster.

The selective pressures leading to the evolution of Sexual Size Dimorphism (SSD) have been well studied in many organisms, yet, the underlying developmental mechanisms are poorly understood. By generating a complete growth profile by sex in Drosophila melanogaster, we describe the sex-specific pattern of growth responsible for SSD. Growth rate and critical size for pupariation significantly contributed to adult SSD, whereas duration of growth did not. Surprisingly, SSD at peak larval mass was twice that of the uneclosed adult SSD with weight loss between peak larval mass and pupariation playing an important role in generating the final SSD. Our finding that weight loss is an important regulator of SSD adds additional complexity to our understanding of how body size is regulated in different sexes. Collectively, these data allow for the elucidation of the molecular-genetic mechanisms that generate SSD, an important component of understanding how SSD evolves.

Temperature-size rule is mediated by thermal plasticity of critical size in Drosophila melanogaster.

Most ectotherms show an inverse relationship between developmental temperature and body size, a phenomenon known as the temperature-size rule (TSR). Several competing hypotheses have been proposed to explain its occurrence. According to one set of views, the TSR results from inevitable biophysical effects of temperature on the rates of growth and differentiation, whereas other views suggest the TSR is an adaptation that can be achieved by a diversity of mechanisms in different taxa. Our data reveal that the fruitfly, Drosophila melanogaster, obeys the TSR using a novel mechanism: reduction in critical size at higher temperatures. In holometabolous insects, attainment of critical size initiates the hormonal cascade that terminates growth, and hence, Drosophila larvae appear to instigate the signal to stop growth at a smaller size at higher temperatures. This is in contrast to findings from another holometabolous insect, Manduca sexta, in which the TSR results from the effect of temperature on the rate and duration of growth. This contrast suggests that there is no single mechanism that accounts for the TSR. Instead, the TSR appears to be an adaptation that is achieved at a proximate level through different mechanisms in different taxa.