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.

Tree-ring history of Swiss needle cast impact on Douglas-fir growth in Western Oregon: correlations with climatic variables.

The fungal pathogen, Nothophaeocryptopus gaeumannii, occurs wherever Douglas-fir is found but disease damage is believed to be limited to the Coast Range and is of no concern outside the coastal fog zone (Shaw, et al., 2011). However, knowledge remains limited on the history and spatial distribution of Swiss Needle Cast (SNC) impacts in the Pacific Northwest (PNW). We reconstructed the history of SNC impacts on mature Douglas-fir trees based on tree ringwidth chronologies from the west slope of the Coast Range to the high Cascades of Oregon. Our findings show that SNC impacts on growth occur wherever Douglas-fir is found in western Oregon and is not limited to the coastal fog zone. The spatiotemporal patterns of growth impact from SNC disease were synchronous across the region, displayed periodicities of 25-30 years, strongly correlated with winter and summer temperatures and summer precipitation, and matched the patterns of enriched cellulosic stable carbon isotope indicative of physiological stress. While winter and summer temperature and summer precipitation influenced pathogen dynamics at all sites, the primary climatic factor of these three limiting factors varied spatially by location, topography, and elevation. In the 20th century, SNC impacts at low- to mid-elevations were least severe during the warm phase of the Pacific Decadal Oscillation (PDO, 1924-1945) and most severe in 1984-1986, following the cool phase of the PDO (1945-1977). At high elevations on the west slope of the Cascade Mountains, SNC impacts were the greatest in the 1990s and 2000s, a period of warmer winter temperatures associated with climate change. Warmer winters will likely continue to increase SNC severity at higher elevations, north along the coast from northern Oregon to British Columbia, and inland where low winter temperatures currently limit growth of the pathogen. Surprisingly, tree-ring records of ancient Douglas-fir logs dated ~53K radioactive years B.P. from Eddyville, OR displayed 7.5- and 20-year periodicities of low growth, similar to those found in modern day coastal Douglas-fir tree-ring records which we interpret as being due to cyclic fluctuations in SNC severity. Our findings indicate that SNC has persisted for as long as its host, and as a result of changing climate, may become a significant forest health problem in areas of the PNW beyond the coastal fog zone.

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.

Initiating a Standard Venous Thromboembolism Prophylaxis Order Set Designed to Improve Patient Outcomes at Los Angeles County+University of Southern California.

Improving patient safety is vital for all hospitals due to increasing public reporting and pay-for-performance reimbursement. Venous thromboembolism (VTE) remains a leading cause of preventable mortality accounting for 5 per cent of inpatient deaths. The purpose of this study was to outline the process of implementing standard VTE prophylactic order sets in a 600-bed academic safety net hospital and assess the resulting change in patient outcomes. Outcomes were assessed by comparing the rate that eligible inpatients receive VTE prophylaxis and the rate of preventable VTE's compared with total VTE's. From 2011 to 2015, random samples of 60 Los Angeles County+University of Southern California inpatients were generated monthly to examine compliance rates by comparing ICD-9 diagnostic codes to ordered VTE prophylaxis. All inpatient VTE's are retrospectively analyzed. Baseline-ordered VTE prophylaxis was 37 per cent in 2010. The target of 85 per cent was exceeded by the second quarter of 2012 to 2013 when compliance reached 88 per cent, a 51 per cent increase from baseline (P < 0.01). These results suggest VTE protocols are effective though standardization across service lines is often difficult. Despite these challenges, after implementing standard order sets, we saw compliance increase significantly. Ongoing analysis to determine whether VTE rates have significantly decreased is presently underway.

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.

Improving door-to-balloon time by decreasing door-to-ECG time for walk-in STEMI patients.

INTRODUCTION: The American Heart Association/American College of Cardiology guidelines recommend rapid door-to-electrocardiography (ECG) times for patients with ST-segment elevation myocardial infarction (STEMI). Previous quality improvement research at our institution revealed that we were not meeting this benchmark for walk-in STEMI patients. The objective is to investigate whether simple, directed changes in the emergency department (ED) triage process for potential cardiac patients could decrease door-to-ECG times and secondarily door-to-balloon times. METHODS: We conducted an interventional study at a large, urban, public teaching hospital from April 2010 to June 2012. All patients who walked into the ED with a confirmed STEMI were enrolled in the study. The primary intervention involved creating a chief complaint-based "cardiac triage" designation that streamlined the evaluation of potential cardiac patients. A secondary intervention involved moving our ECG technician and ECG station to our initial triage area. The primary outcome measure was door-to-ECG time and the secondary outcome measure was door-to-balloon time. RESULTS: We enrolled 91 walk-in STEMI patients prior to the intervention period and 141 patients after the invention. We observed statistically significant reductions in door-to-ECG time (43±93 to 30±72 minutes, median 23 to 14 minutes p<0.01), ECG-to-activation time (87±134 to 52±82 minutes, median 43 to 31 minutes p<0.01), and door-to-balloon time (134±146 to 84±40 minutes, median 85 -75 minutes p=0.03). CONCLUSION: By creating a chief complaint-based cardiac triage protocol and by streamlining ECG completion, walk-in STEMI patients are systematically processed through the ED. This is not only associated with a decrease in door-to-balloon time, but also a decrease in the variability of the time sensitive intervals of door-to-ECG and ECG-to-balloon time.

Importance of hospital entry: walk-in STEMI and primary percutaneous coronary intervention.

INTRODUCTION: Patients with ST elevation myocardial infarction (STEMI) require rapid identification and triage to initiate reperfusion therapy. Walk-in STEMI patients have longer treatment times compared to emergency medical service (EMS) transported patients. While effective triage of large numbers of critically ill patients in the emergency department is often cited as the reason for treatment delays, additional factors have not been explored. The purpose of this study was to evaluate baseline demographic and clinical differences between walk-in and EMS-transported STEMI patients and identify factors associated with prolonged door to balloon (D2B) time in walk-in STEMI patients. METHODS: We performed a retrospective review of 136 STEMI patients presenting to an urban academic teaching center from January 2009 through December 2010. Baseline demographics, mode of hospital entry (walk-in versus EMS transport), treatment times, angiographic findings, procedures performed and in-hospital clinical events were collected. We compared walk-in and EMS-transported STEMI patients and identified independent factors of prolonged D2B time for walk-in patients using stepwise logistic regression analysis. RESULTS: Walk-in patients (n=51) were more likely to be Latino and presented with a higher heart rate, higher systolic blood pressure, prior history of diabetes mellitus and were more likely to have an elevated initial troponin value, compared to EMS-transported patients. EMS-transported patients (n=64) were more likely to be white and had a higher prevalence of left main coronary artery disease, compared to walk-in patients. Door to electrocardiogram (ECG), ECG to catheterization laboratory (CL) activation and D2B times were significantly longer for walk-in patients. Walk-in patients were more likely to have D2B time >90 minutes, compared to EMS- transported patients; odds ratio 3.53 (95% CI 1.03, 12.07), p=0.04. Stepwise logistic regression identified hospital entry mode as the only independent predictor for prolonged D2B time. CONCLUSION: Baseline differences exist between walk-in and EMS-transported STEMI patients undergoing primary percutaneous coronary intervention (PCI). Hospital entry mode was the most important predictor for prolonged treatment times for primary PCI, independent of age, Latino ethnicity, heart rate, systolic blood pressure and initial troponin value. Prolonged door to ECG and ECG to CL activation times are modifiable factors associated with prolonged treatment times in walk-in STEMI patients. In addition to promoting the use of EMS transport, efforts are needed to rapidly identify and expedite the triage of walk-in STEMI patients.

A medical staff peer review system in a public teaching hospital--an internal quality improvement tool.

Peer review of the quality of care of the medical staff in a healthcare delivery system, properly executed and utilized, can bring about changes that improve the quality and safety of patient care, enhance clinical performance, and augment physician education. Although all healthcare facilities are mandated to conduct peer reviews, the process of how it is conducted, reported, and utilized varies widely. In 2007, our institution, a large public teaching acute care facility, developed and implemented an electronic Medical Staff Peer Review System (MS-PRS) that replaced the existing paper-based system and created a centralized database for all peer review activities. Despite limited resources and mounting known challenges, we have developed and implemented a system that includes 100% mortality reviews, an ongoing random review for reappointment and operative procedures, and morbidity peer reviews. Parallel to the 4-year implementation of the system, we observed a steady, significant downward trend in the medical malpractice claim rate, which can be attributable in part to the implementation of MS-PRS. In this paper, we share our experiences in the development, outcomes, challenges encountered, and lessons learned from MS-PRS and provide our recommendations to similar institutions for the development of such a system.

Time of day variation in door-to-balloon time for STEMI patients in Los Angeles County: does time of day make a difference?

OBJECTIVE: Evaluate treatment times and clinical outcome in a consecutive series of ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) in Los Angeles County. BACKGROUND: Primary PCI for STEMI is beneficial if performed in a timely manner. Conflicting data exist regarding potential treatment delays for primary PCI performed during off hours. METHODS: The Emergency Medical Services STEMI Receiving Center Database was queried from 2007 to 2009 to identify patients with a pre-hospital ECG showing STEMI who underwent PCI. On-hour PCI (On-hour Group, n = 1324) was defined as PCI occurring from 8 am to 5 pm and off-hour PCI (Off-hour Group, n = 922) was defined as occurring from 5 pm to 8 am. Treatment times, length of stay, vascular complications, achievement of TIMI 3 flow and in-hospital mortality were evaluated. RESULTS: Off-hours PCI occurred in 41% of patients. Medical contact to door time was similar in the Off-hour Group compared to the On-hour Group, 20.7 ± 14.6 versus 20.3 ± 12.3 min, respectively, P = 0.47. In patients with available data (n = 1366), the door-to-catheterization laboratory (CL) activation time was significantly shorter in the On-hour Group as compared to the Off-hour Group, -4.9 ± 11.9 versus -0.2 ± 27.5 min, respectively, P < 0.0001. Door-to-balloon time was significantly longer in the Off-hour Group compared to the On-hour Group, 74 ± 35 versus 60 ± 26 min respectively, P < 0.0001. Length of stay, vascular complications, final TIMI 3 flow and in-hospital mortality were similar between both groups. CONCLUSIONS: In STEMI patients receiving primary PCI in Los Angeles County, off-hour PCI was common. Short-term clinical outcomes were similar despite longer door-to-balloon time in patients receiving off-hour PCI. The longer door-to-balloon time in the off-hour PCI patients were partly explained by longer door-to-CL activation time.

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.

In-process modification yields improved teaching outcomes for international emergency medicine.

AIMS: To determine if on-going modification of an international teaching course in emergency medicine will improve audience perception and receptivity. METHODS: Over 4 years, we conducted surveys during emergency medicine symposiums given in Ghana, West Africa. In 2003, 2004 and 2006, symposium interventions of content modification (lecture topics/workshops), audience modification (smaller groups, designing workshops for different levels of providers) and in-process modification (modification of lecture technique in two sequential 2006 symposiums) were done. Survey responses were analyzed to determine what interventions resulted in greater participant satisfaction. When comparing the three groups, a one-way ANOVA test was conducted to determine differences among the 3 years. When comparing two groups, Levene's test for equality of variances was conducted for annual variance, and based on that result, an independent t-test was calculated. RESULTS: The one-way ANOVA test indicated that there was a statistically significant difference among the three groups (2003, 2004, 2006) of symposium participants in four questions related to the participants' perception of the instructors. The independent t-test comparing the aggregate data of 2003 and 2004 with 2006 (audience modification and in-process modification between two sequential symposiums) showed a statistically significant improvement in the participants' receptivity. The data indicated that modifying the content of international symposiums and modifying the audience to which it is addressed are equally valuable tools to ensure a positive participant receptivity. Moreover, the data indicated that "in-process" modification conducted between the two sequential 2006 symposiums produced a statistically significant increase in positive perception, facilitating knowledge transfer. CONCLUSION: Statistical analysis of surveys coupled with modification and intervention can improve participant satisfaction in international teaching programs.