Real-world anti-seizure treatment and adverse events among individuals living with drug-resistant focal epilepsy in the United States.

OBJECTIVE: This study aimed to understand how people living with drug-resistant focal epilepsy (DRE) navigate through lines of antiseizure medications (ASM) and experience adverse events (AEs) in the real-world setting in the United States. METHODS: A retrospective study was conducted with medical chart data from clinical practices in the United States. Eligible adults had a confirmed diagnosis of DRE and initiated a third-line ASM therapy between January 2013 and January 2020 (i.e., the index date). Subjects must have medical history data available for ≥1 year prior to (the baseline) and ≥2 years after the index date (the follow-up). Treatment patterns were captured from first to fourth lines. After the emergence of drug resistance, time to ASM discontinuation, reasons for discontinuation, AE experience and AE management were reported separately during third and fourth lines of treatment and beyond. RESULTS: The study included a total of 345 individuals, with an average (standard deviation) age of 23.9 (11.9) years at first diagnosis. All individuals had at least three lines of ASMs with first and second lines during baseline, and third line during follow-up. The first line for most individuals was monotherapy. As individuals progressed through additional lines of ASM therapy, they were more likely to receive polytherapy. The regimens were more individualized after meeting drug resistance criteria. The top reasons for discontinuing were uncontrolled seizure and/or intolerance/AEs for both third and subsequent lines. More than a third of individuals experienced at least one AE. Among those with at least one AE, many individuals had to manage these AEs with dose adjustment (39.4%), discontinuation of offending ASM (37.9%), de novo pharmacotherapy (25.8%), emergency room visit (13.6%), and hospitalization (12.1%). SIGNIFICANCE: This study demonstrated that individuals living with DRE experience significant AEs, and many of these AEs lead to treatment disruption and significant healthcare resource utilization. PLAIN LANGUAGE SUMMARY: This study examined how individuals with focal epilepsy are treated across various clinics in United States and reported the adverse events these individuals experienced during treatment, along with the consequence associated with these adverse events. We found that as individuals progressed through additional treatments, they were more and more likely to receive more than one antiseizure medication, and a significant portion of individuals experienced at least one adverse event, often manifested as headache, somnolence, dizziness, and fatigue.

Improving the Performance of Polydimethylsiloxane-Based Triboelectric Nanogenerators by Introducing CdS Particles into the Polydimethylsiloxane Layer.

Energy harvesting and power generation technologies hold significant potential for meeting future energy demands and improving environmental sustainability. A triboelectric nanogenerator (TENG), which harnesses energy from the surrounding environment, has garnered significant attention as a promising and sustainable power source applicable in various fields. In this study, we present a technique to improve the triboelectric performance of a PDMS-based TENG by incorporating nanostructured cadmium sulfide (N-CdS). This study investigates the utilization of CdS nanomaterials in TENG production, where mechanical energy is converted into electrical energy. We conducted a comparative analysis of TENGs utilizing N-CdS/PDMS, commercial CdS/PDMS (C-CdS/PDMS), and pure PDMS substrates. The N-CdS/PDMS substrates demonstrated superior triboelectric performance compared to TENG devices based on pure PDMS and C-CdS/PDMS. The triboelectric open-circuit voltage (Voc) and short-circuit current (Isc) of the N-CdS/PDMS-based TENG device were approximately 236 V and 17.4 µA, respectively, when operated at a 2 Hz frequency. These values were approximately 3 times and 2.5 times higher, respectively, compared to the pure PDMS-based TENGs. They were further studied in detail to understand the effect of different parameters such as contact-separation frequency and contact force on the TENGs' operation. The stability of the TENG devices was studied, and their potential to be integrated into self-powered smart textiles as power sources was demonstrated.

Real-world antiseizure medication treatment outcomes in drug-resistant focal epilepsy patients.

OBJECTIVE: To gather real-world evidence on antiseizure medications (ASMs) treatment patterns and related outcomes in patients with drug-resistant focal epilepsy. METHODS: Medical insurance claims from the start of 2014 till the end of 2019 were used. Patient selection criteria included International Classification of Diseases (ICD) codes followed by documented ASM use. Baseline patient demographics along with ASM and rescue medication use patterns and related patient outcome were documented for first (index) ASM regimen. Patients who failed the first regimen and then failed the second regimen were considered drug resistant. Multivariate analyses were performed to identify risks and other characteristics for positive or negative treatment outcomes. RESULTS: Study cohort consisted of 46 474 patients with a mean age of 47.23 (SD: 16.94). Levetiracetam was the most first-encountered ASM (37.94%). At baseline, 87.14% were treated with ASMs prior to having study-confirmed diagnoses. Mental comorbidities were present in 37.86% of patients. After first-year ASM treatment, 34.61% of patients persisted on their index regimen and 5.91% were seizure-free. Patients failing first ASM regimen numbered 12 868 (27.69%). Drug-resistant patients who failed first and then second ASM regimens numbered 6335 (49.23%). Percentages of patients who had successful second treatment and seizure-free were 21.32 and 3.65, respectively. Initiating patients on lamotrigine or carbamazepine (relative to levetiracetam), baseline use of index ASM, rescue medications, and older age or male gender all lowered the risk for treatment failure. Having higher comorbidity, comorbid mental illness, headache, or neoplasty increased such a risk. Baseline use of index ASM, depressive episode, or anxiety disorder all entailed higher risk of failing second ASM treatment. SIGNIFICANCE: Overall, reported findings indicated that patient history at baseline and the early selection of an ASM all influenced treatment outcomes. Findings pointed to the complex nature of ASM treatment in drug-resistant focal epilepsy patients calling for additional research to identify the optimal treatment to achieve beneficial patient outcomes.

Real-world treatment patterns, healthcare resource utilization, and cost among adults with pulmonary arterial hypertension in the United States.

Treatment for pulmonary arterial hypertension (PAH) has evolved over the past decade, including approval of new medications and growing evidence to support earlier use of combination therapy. Despite these changes, few studies have assessed real-world treatment patterns, healthcare resource utilization (HCRU), and costs among people with PAH using recent data. We conducted a retrospective cohort study using administrative claims from the HealthCore Integrated Research Database®. Adult members with claims for a PAH diagnosis, right heart catheterization, and who initiated PAH treatment (index date) between October 1, 2015 and November 30, 2020 were identified. Members had to be continuously enrolled in the health plan for 6 months before the index date (baseline) and ≥30 days after. Treatment patterns, HCRU, and costs were described. A total of 843 members with PAH (mean age 62.3 years, 64.2% female) were included. Only 21.0% of members received combination therapy as their first-line treatment, while most members (54.6%) received combination therapy as second-line treatment. All-cause HCRU remained high after treatment initiation with 58.0% of members having ≥1 hospitalization and 41.3% with ≥1 emergency room visit. Total all-cause costs declined from $15,117 per patient per month at baseline to $14,201 after treatment initiation, with decreased medical costs ($14,208 vs. $6,349) more than offsetting increased pharmacy costs ($909 vs. $7,852). In summary, despite growing evidence supporting combination therapy, most members with PAH initiated treatment with monotherapy. Total costs decreased following treatment, driven by a reduction in medical costs even with increases in pharmacy costs.

Comorbidity and comedication burden among people living with HIV in the United States.

OBJECTIVE: To describe the burden of comorbid conditions and comedications among people living with HIV (PLWH) vs. people living without HIV (PLWoH). METHODS: This was a case-control study conducted among insured patients using administrative claims data. Adult PLWH were identified by antiretroviral therapy (ART) claims or HIV/AIDS diagnosis codes from 1 January 2018 to 31 December 2018 (index date was set by the earliest claim). Continuous enrollment was required for ≥12 months pre-index (baseline) and ≥30 days post-index (follow-up). Patients were required to have ≥1 HIV diagnosis during baseline or follow-up. Those with only HIV prophylaxis were excluded. PLWoH were matched 2:1 to PLWH on demographic characteristics. Study outcomes were compared using z-tests with robust standard errors in an ordinary least squares regression or Rao-Scott tests. RESULTS: The study included 20,256 PLWH and 40,512 matched PLWoH, mean age 52 years. PLWH vs. PLWoH had higher mean (SD) Charlson comorbidity index scores (0.93 [1.59] vs. 0.61 [1.28]; p < .001) and a greater proportion had ≥1 comorbidity (69.1% vs. 54.5%, p < .001). The most prevalent comorbidities included hypertension (33.9% vs. 32.2%; p < .001), hyperlipidemia (29.4% vs. 24.6%; p < .001), chronic kidney disease (13.6% vs. 9.4%, p < .001), depression (13.1% vs. 7.3%, p < .001) and substance abuse (12.8% vs. 7.1%, p < .001). Mean (SD) non-ART prescription fills were higher among PLWH vs. PLWoH (11.9 [10.1] vs. 9.2 [9.4]; p < .001). CONCLUSIONS: Multimorbidity and polypharmacy were more prevalent among PLWH vs. matched PLWoH. Findings support the need to consider comorbidities and comedications when choosing ART and to minimize drug-drug interactions and adverse events to improve patient outcomes.

Burden of illness and costs associated with eosinophilic granulomatosis with polyangiitis: evidence from a managed care database in the United States.

BACKGROUND: Data on the clinical and economic burden of eosinophilic granulomatosis with polyangiitis (EGPA) are limited. OBJECTIVE: To assess the real-world clinical and economic outcomes of patients diagnosed with EGPA vs patients with asthma (present in > 90% of EGPA cases) receiving treatment in the United States. METHODS: This retrospective cohort study (HO-17-17742) used administrative claims data (July 1, 2007-May 31, 2017) from the Optum Research Database. Eligible patients were aged at least 18 years at index (first date that patients met the EGPA or asthma cohort definition), with a minimum of 6 months of continuous health plan coverage before the index (baseline) period and 12 months following and including the index date (follow-up period). Patients with EGPA were identified either via published algorithms using claim code combinations for conditions and medications (before October 1, 2015) or via a claim with the EGPA ICD-10-CM code (M30.1, after October 1, 2015). Patients with asthma were identified based on ICD-9-CM and ICD-10-CM diagnosis codes and at least 3 pharmacy asthmarelated medication claims within a year of diagnosis. Outcomes included all-cause health care costs (primary), all-cause health care resource utilization (HCRU), systemic corticosteroid (SCS) use, and EGPA relapses requiring hospitalization and EGPA-related (based on EGPA-related HCRU) relapses during the follow-up period (all secondary). EGPA and asthma cohorts were matched (1:3) via propensity score matching based on demographic, insurance, and index timing covariates. RESULTS: 8,904 patients were included in the matched EGPA (n = 2,226) and asthma (n = 6,678) cohorts (mean [SD] age: 59.7 [14.2] vs 59.6 [14.7] years; Quan-Charlson Comorbidity Index scores: 1.8 [1.7] vs 0.8 [1.4]). During follow-up, mean (SD) all-cause costs ($49,593 [$88,161] vs $21,122 [$40,110]; P < 0.001), all-cause HCRU (P < 0.001), and the proportion of patients with 1 or more SCS claims (72.3% vs 66.9%; P < 0.001) were significantly greater in the EGPA vs asthma cohorts, respectively. Mean daily SCS dose (43.6-45.5 mg/day) was similar between cohorts; patients with EGPA had significantly (P < 0.001) longer periods taking SCS doses at least 4 mg/day (mean [SD]: 64.9 [95.6] vs 14.6 [39.3] days) and at least 7 mg/day (52.8 [82.0] vs 12.1 [30.6] days). 35.2% (n = 784/2,226) and 44.1% (n = 981/2,226) of patients with EGPA experienced a minimum of 1 EGPA relapse requiring hospitalization, and at least 1 EGPA-related relapse, respectively. Mean (SD) total all-cause costs were greater than 3-fold higher in patients with vs without a relapse requiring hospitalization ($92,825 [$128,562] vs $26,087 [$38,082]; P < 0.001) and for patients with vs without an EGPA-related relapse ($78,081 [$120,775] vs $27,145 [$35,584]; P < 0.001). CONCLUSIONS: Patients with EGPA have more comorbidities, greater health care costs and HCRU, and use SCS more frequently than patients with asthma. Additionally, more than one third of patients with EGPA experienced disease relapses over 12 months. These results highlight the high disease burden in patients with EGPA and the need for improved treatment options. DISCLOSURES This study was funded by GlaxoSmithKline (GSK ID: HO-17-17742). Bell is an employee of GSK and holds stock/share options in GSK. Blauer-Peterson is an employee of Optum, which was funded by GSK to conduct the study. Mao was an employee of Optum at the time the study was conducted. The authors report no other potential conflicts of interest. These data have previously been presented as a poster at the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting, Chicago, IL, October 19-24, 2018.

Healthcare resource utilization and costs in patients with HIV-1 who switched first-line antiretroviral therapy.

Objectives: This study compared healthcare utilization and costs associated with switching the first-line protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) based antiretroviral (ARV) regimen due to reasons other than virologic failure among patients with HIV-1. Methods: This was a retrospective analysis of commercial and Medicare Advantage with Part D enrollees in two US administrative claims databases. The study population comprised adults with HIV-1 infection initiating antiretroviral therapy (ART) on PI- or NNRTI-containing regimens from 1 January 2006 to 31 December 2015. Patients with a subsequent change in anchor agent were assigned to the switch cohort; the non-switch cohort was constructed using propensity score matching of three non-switching patients for each patient in the switch cohort. Patient characteristics and per patient per month healthcare resource utilization and costs were compared between the cohorts during the pre-switch, switch (15 days before and after switching) and post-switch periods. Costs during the switch period were also estimated with a multivariable-adjusted model. Results: The matched study population consisted of 1204 patients who switched their first-line PI- or NNRTI-based regimen and 3612 patients who did not. Compared with the non-switch cohort, patients who switched had higher healthcare resource utilization during the pre-switch, switch and post-switch periods. Mean unadjusted non-ART costs in the switch cohort were nearly double ($2944 versus $1530, p < .001), more than double ($2562 versus $1215, p < .001) and 1.5 times higher ($1473 versus $968, p < .001) than costs in the non-switch cohort in the pre-switch, switch and post-switch periods, respectively. Conclusions: Patients with HIV-1 who initiated PI- or NNRTI-based regimens and switched ARTs for reasons other than virologic failure used more healthcare resources and incurred greater costs relative to patients in the non-switch cohort. This study highlights the importance of initiating patients on appropriate first-line ART to avoid the need to switch due to reasons other than virologic failure.

2D Single Crystal WSe2 and MoSe2 Nanomeshes with Quantifiable High Exposure of Layer Edges from 3D Mesoporous Silica Template.

The design and fabrication of layered transition metal chalcogenides with high exposure of crystal layer edges is one of the key paths to achieve distinctive performances in their catalysis and electrochemistry applications. Two-dimensional WSe2 and MoSe2 nanomeshes with orderly arranged nanoholes were synthesized by using a mesoporous silica material KIT-6 with three-dimensional mesoporous structure as a hard template via a nanocasting strategy. Each piece of the nanomesh is a single crystal, and its c axis is always perpendicular to the nanomesh plane. The highly porous structure brings these nanomeshes extremely high exposure of layer edges, and the well-defined nanostructure provides an opportunity to quantitatively estimate the specific length of the crystal layer edges for the WSe2 and MoSe2 nanomeshes synthesized in this work, which are estimated to be 3.8 × 1010 and 6.0 × 1010 m g-1, respectively. The formation of a 2D sheet-like nanomesh structure inside a 3D confined pore space should be attributed to the synergistic effect from the crystal self-limitation growth that is caused by their layered crystal structures and the space-limitation effect coming from the unique pore structure of the KIT-6 template. The catalytic activities of the nanomeshes in an electrocatalytic hydrogen evolution reaction were also investigated.

Compliance with clinical guidelines and adherence to antiretroviral therapy among patients living with HIV.

Objective: Evaluation of provider compliance with antiretroviral (ARV) treatment guidelines and patient adherence to ARVs is important for HIV care quality assessment; however, there are few current real-world data for guideline compliance and ARV adherence in the US. This study evaluated provider compliance with US Department of Health and Human Services (DHHS) guidelines and patient adherence to ARVs in a US population of patients with HIV.Methods: This was a retrospective claims study of adults with HIV-1 receiving ARV treatment between January 2010-December 2014. Follow-up began at first ARV treatment and ended at health plan disenrollment or study end. ARV regimens for treatment-naïve patients were categorized as "preferred/recommended", "alternative", or "non-preferred/recommended/alternative" according to DHHS guidelines. ARV adherence was evaluated using proportion of days covered (PDC) and medication possession ratio (MPR).Results: The analysis included 25,320 patients (84.4% male, mean age 45.3 years) and 39,071 regimens. Preferred/recommended regimens were most common during each study year, but the proportion of non-preferred/recommended/alternative regimens was substantial (15.9-20.6%). Only 53.6% of patients had optimal adherence by PDC ≥0.95, and 57.9% by MPR ≥0.95. Guideline non-compliance and sub-optimal adherence were more prevalent among female vs male patients (22.6% vs 14.8% [in 2014] and 65.9% vs 53.7%, respectively).Conclusions: Provider non-compliance with DHHS guidelines and sub-optimal ARV adherence among patients with HIV remain common in real-world practice, particularly for female patients. Healthcare providers should follow the latest clinical guidelines to ensure that patients receive recommended therapy, and address non-adherence when selecting ARV regimens.

Cost of subcutaneous immunotherapy in a large insured population in the United States.

OBJECTIVE: Allergic rhinitis (AR) affects up to 40% of the United States population, with approximately $11 billion annual medical costs. Allergy immunotherapy is the best option for long-term symptomatic relief, but treatment compliance can be low. The objective was to describe subcutaneous immunotherapy (SCIT)-related costs for patients overall and those with inconsistent treatment. METHODS: This study observed commercial and Medicare Advantage with Part D health plan enrollees. Included subjects had claims with AR diagnostic codes during 1 January 2011-31 December 2015 and ≥1 SCIT claim during 1 January 2013-31 December 2015 (index date = first SCIT claim date). A control sample was chosen randomly at a 1:3 ratio of SCIT to controls. Inconsistent use was defined as a ≥90 day gap after ≥1 SCIT. Patient characteristics were compared between SCIT patients and controls. Costs were calculated for all SCIT patients and the inconsistent subgroup. RESULTS: Compared with controls (n = 394,479), SCIT (n = 131,493) patients were younger (39.3 vs. 41.4 years), more likely female (56.4% vs. 50.7%) and more likely in a commercial plan (91.6% vs. 83.6%); all p < .001. Among SCIT patients, 15.1% had inconsistent use. Among all SCIT patients, the 3 year total plan-paid SCIT-related costs were $205,741,125 (18% was for inconsistent subgroup) and patient-paid costs were $47,560,450 (15% for inconsistent). Per-member-per-month costs were $0.48 plan-paid and $0.11 patient-paid, with $0.09 plan-paid and $0.02 patient-paid for inconsistent use. CONCLUSIONS: This study showed 15% of patients may have costly inconsistent SCIT treatment. Greater understanding is needed regarding the reasons for inconsistent use of subcutaneous allergy immunotherapy.

Herpes zoster incidence and cost in patients receiving autologous hematopoietic stem-cell transplant.

OBJECTIVE: Among patients receiving autologous hematopoietic stem cell transplant (Auto-HSCT), this study estimated the incidence of herpes zoster (HZ), compared healthcare costs among patients with and without HZ, and evaluated antiviral prophylaxis (AP) use. RESEARCH DESIGN AND METHODS: A retrospective study was conducted using data from a large health plan to identify patients ≥18 years with ≥1 claim for an Auto-HSCT procedure during 2006-2011 (n = 2,530). Patients were followed from date of Auto-HSCT until risk-end date, defined as development of HZ, end of enrollment, death, or December 31, 2011. HZ incidence was calculated as cases observed after Auto-HSCT, divided by accrued time-at-risk in person-years (PY). AP use and duration were defined by prescription fills. One-year medical and pharmacy costs were calculated as combined health plan and patient paid amounts. MAIN OUTCOME MEASURES: HZ incidence and healthcare costs were calculated using administrative claims data. RESULTS: Overall HZ incidence was 62.2/1,000 PY (95% CI = 54.3-70.9). Most (72.3%) patients were prescribed AP. During the first 90-days post-Auto-HSCT, patients without AP had increased incidence (151.6/1,000 PY, 95% CI = 88.3-242.6) compared to those prescribed AP pre- (30.9/1,000 PY, 95% CI = 11.3-67.2) or post-Auto-HSCT (33.0/1,000 PY, 95% CI = 13.3-67.9). Total adjusted mean 1-year all-cause healthcare costs were $74,875 for patients who developed HZ and $70,279 for patients who did not (difference = $4,596 (cost ratio = 1.07, 95% CI = 0.86-1.32, p = .566)). CONCLUSIONS: HZ incidence was high, despite AP use. Mean annual healthcare costs were higher for patients with HZ, but the difference was not statistically significant. An effective vaccine against HZ could be useful in decreasing both incidence of and cost for HZ in this population.

Healthcare costs for allergic rhinitis patients on allergy immunotherapy: a retrospective observational study.

OBJECTIVE: Subcutaneous immunotherapy (SCIT) for allergic rhinitis (AR) has been shown to control symptoms for up to several years following treatment discontinuation, but the effect of SCIT on healthcare costs for commercially insured patients is unknown. The objective of this study was to compare healthcare costs and resource utilization for patients with AR who received SCIT compared with those who discontinued SCIT shortly after initiation. METHODS: This retrospective cohort study evaluated medical and pharmacy claims from the Optum Research Database from January 2009 through February 2014 for adults and pediatric patients with >7 (continuers) vs. ≤7 (discontinuers) injection visits for SCIT within 60 days of initiation. RESULTS: After 1:1 propensity score matching, each cohort included 6710 patients. Continuers were less likely than discontinuers to use oral corticosteroids (27.7% vs. 29.6%, p = .018), or to have ≥1 respiratory-related emergency room visit (5.4% vs. 6.5%, p = .008) and ≥1 inpatient stay (1.1% vs. 1.7%; p = .002). Continuers were more likely than discontinuers to have ≥1 AR-related office (98.8% vs. 94.6%, p < .001) or outpatient visit (2.4% vs. 1.7%, p = .002). Continuers had greater mean total AR-related costs than discontinuers ($1918 vs. $646, p < .001). Unadjusted mean total respiratory-related costs were lower for continuers than discontinuers, although the difference was not statistically significant ($1589 vs. $1785, p = .077); when adjusted with a generalized linear model, these costs were significantly lower among continuers (p < .001). CONCLUSIONS: Continued SCIT use is associated with decreased emergency room visits and inpatient stays, decreased oral corticosteroid use, and lower respiratory-related costs, compared with early discontinuation.

Healthcare utilization and costs among patients with herpes zoster and solid tumor malignancy on chemotherapy: A retrospective cohort study.

Immunosuppressed patients with solid tumor malignancies (STMs) are particularly vulnerable to herpes zoster (HZ). This study estimated the incidence of HZ and evaluated healthcare resource utilization and costs for persons with STM receiving chemotherapy with and without incident HZ.We conducted a retrospective claims study of adults with STM receiving chemotherapy between January 1, 2010 and June 30, 2014. Patients were followed from their first chemotherapy date through development of HZ, health plan disenrollment, the study end date, or 24 months. HZ incidence was calculated and stratified by patient characteristics. Adjusted HZ incidence was estimated using Poisson regression. Healthcare resource utilization and costs were compared between patients with HZ (cases) and propensity score-matched controls without HZ during a variable follow-up period. Adjusted healthcare costs were estimated using Lin regression to control for informative censoring.Of 155,480 patients with STM receiving chemotherapy, 3100 (2.0%) developed HZ, yielding an adjusted HZ incidence rate of 13.8/1000 person-years (PY). HZ cases (n = 3004) had significantly higher healthcare resource utilization than matched controls (n = 15,020). Adjusted annual costs were $48,077 for cases vs $41,645 for matched controls, corresponding to a differential cost of $6432 annually.After adjustment for potential confounders, patients with STM receiving chemotherapy had an HZ incidence of 13.8/1000 PY; those who developed HZ used more healthcare resources and incurred higher costs than those who did not. These findings suggest that HZ prevention by vaccination could improve outcomes and reduce costs in this population.

The myeloperoxidase -463G/A polymorphism and coronary artery disease risk: A meta-analysis of 1938 cases and 1990 controls.

OBJECTIVES: Genetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD. DESIGN AND METHODS: Two investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0. RESULTS: 5 case-control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR=0.595, 95%CI=0.298-1.188, P=0.141; G/G vs G/A+A/A: OR=0.886, 95%CI=0.779-1.008, P=0.066; G/G+G/A vs A/A: OR=0.611, 95%CI=0.334-1.119, P=0.111; OR=0.886, 95%CI=0.779-1.008, P=0.066; G vs A: OR=0.843, 95%CI=0.675-1.053, P=0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic models (P=0.008, P=0.021, P=0.019, respectively); further analyses revealed that age and sex possibly account for the heterogeneity. CONCLUSIONS: Our meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD; larger and well-designed multicenter studies are needed to confirm our results.

Patterns of adjuvant chemotherapy use in a population-based cohort of patients with resected stage II or III colon cancer.

PURPOSE: Previous studies have examined predictors for initiation of adjuvant chemotherapy in stages II and III colon cancer. However, little is known regarding the use of specific chemotherapy regimens or treatment duration. PATIENTS AND METHODS: We studied treatment records for 2,560 patients with stage II or III colon cancer who received adjuvant chemotherapy between January 2004 and April 2010 at US cancer care facilities participating in a nationwide, commercially available chemotherapy order entry system that captures patient demographics, stage, and details of chemotherapy treatment. Multivariate analyses of prospectively recorded patient and provider characteristics identified predictors of specific therapeutic approaches. RESULTS: The addition of oxaliplatin to fluoropyrimidine-based adjuvant therapy increased during the study period (P trend < .001), and this combination represented 78% and 90% of adjuvant chemotherapy in stage II or III disease, respectively, by 2007. Older patients, those with diminished performance status, and those treated in a private practice setting were significantly less likely to receive oxaliplatin. Thirty percent of patients discontinued adjuvant therapy after less than 3 months. Older age, treatment without oxaliplatin, and receipt of treatment from a physician with a low volume of patients were each independently associated with premature discontinuation [corrected]. Six percent of patients received bevacizumab as part of their adjuvant regimen. CONCLUSION: After 2004, oxaliplatin and fluoropyrimidine-based therapy rapidly became the predominant adjuvant treatment for both stage II and stage III colon cancer in this large US cohort. Both increasing patient age and lower volume of an oncologist's practice were associated with early termination of adjuvant therapy.

Advance cueing produces enhanced action-boundary patterns of spike activity in the sensorimotor striatum.

One of the most characteristic features of habitual behaviors is that they can be evoked by a single cue. In the experiments reported here, we tested for the effects of such advance cueing on the firing patterns of striatal neurons in the sensorimotor striatum. Rats ran in a T-maze with instruction cues about the location of reward given at the start of the runs. This advance cueing about reward produced a highly augmented task-bracketing pattern of activity at the beginning and end of procedural task performance relative to the patterns found previously with midtask cueing. Remarkably, the largest increase in activity early during the T-maze runs was not associated with the instruction cues themselves, the earliest predictors of reward; instead, the highest peak of early activity was associated with the beginning of the motor period of the task. We suggest that the advance cueing, reducing midrun demands for decision making but adding a working-memory load, facilitated chunking of the maze runs as executable scripts anchored to sensorimotor aspects of the task and unencumbered by midtask decision-making demands. Our findings suggest that the acquisition of stronger task-bracketing patterns of striatal activity in the sensorimotor striatum could reflect this enhancement of behavioral chunking. Deficits in such representations of learned sequential behaviors could contribute to motor and cognitive problems in a range of neurological disorders affecting the basal ganglia, including Parkinson's disease.