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Background: This phase II study evaluated the efficacy and safety/tolerability of sunitinib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC). Methods: Eligible patients received sunitinib 37.5 mg/day and trastuzumab administered either weekly (loading, 4 mg/kg; then weekly 2 mg/kg) or 3-weekly (loading, 8 mg/kg; then 3-weekly 6 mg/kg). Prior trastuzumab and/or lapatinib treatment were permitted. The primary endpoint was objective response rate (ORR). Results: Sixty patients were enrolled and evaluable for safety; 57 were evaluable for efficacy. The majority of patients (58%) had received no prior chemotherapy in the metastatic setting. The ORR was 37%; the clinical benefit rate (CBR; percent objective response plus stable disease ≥ 24 weeks) was 56%. Among patients who were treatment-naïve or had received only adjuvant therapy, the ORR was 44% and the CBR was 59%. Overall, median overall survival had not been reached and the 1-year survival rate was 91%. The majority of adverse events (AEs) were mild to moderate in severity. Forty percent of patients experienced AEs related to measured left ventricular ejection fraction (LVEF) declines, which occurred more frequently in patients who had received prior anthracycline treatment. Ten percent of patients exhibited symptoms related to LVEF declines. One patient died on study from cardiogenic shock. Antitumor response and several safety parameters appeared to correlate with sunitinib exposure. Conclusions: Sunitinib plus trastuzumab demonstrated antitumor activity in patients with HER2-positive ABC, particularly those who were treatment-naïve or had only received prior adjuvant treatment. Sunitinib plus trastuzumab had acceptable safety and tolerability in patients with HER2-positive ABC who had not received prior anthracycline therapy. [ABSTRACT FROM AUTHOR]

Background: The People’s Republic of China has the largest population affected by osteoporosis in the world. However, no population-based survey of osteoporosis awareness in People’s Republic of China has been reported. This study investigated the level of basic awareness of osteoporosis in a large community in People’s Republic of China. The relationship between level of awareness and quantitative ultrasound (US) measurements at the calcaneus was also assessed. Methods: A questionnaire was completed by 9983 men and women aged 40 years or older in Nanjing, People’s Republic of China, between June and December 2011. During this time, the study participants underwent quantitative US measurement. Data from 9049 of the subjects were included in the final analysis. Results: The proportion of subjects who were aware of osteoporosis was very low. Only 30.7% had heard of osteoporosis, and only 18.5% had heard of osteoporotic fracture. In total, 52.9% of the subjects drank milk, 16.0% took calcium, 7.1% took vitamin D, and 47.2% were performing regular physical activity. Logistic regression showed that more highly educated older women had significantly better awareness of osteoporosis (P < 0.05). Subjects with a history of a previous osteoporotic fracture also had better awareness (P < 0.05) than subjects without such a history, except for those who drank milk. Similar to previous reports, female sex, old age, a low education level, and a personal history of osteoporotic fracture were significantly associated with a low quantitative US measurement (P < 0.001). Further, drinking milk and having not heard of osteoporosis were significantly associated with a higher quantitative US measurement (P < 0.05), while other indicators of osteoporosis awareness were not associated with quantitative US values (P > 0.05). Conclusion: Awareness of osteoporosis in People’s Republic of China is very low. National awareness strategies should be implemented, especially for poorly educated young men. [ABSTRACT FROM AUTHOR]

Intelligent gateways that interconnect home networks, pubic networks, and intelligent household devices play a critical role in smart home systems. However, the existing gateways could hardly be adapted to emerging multiple access methods and the multiple services' requirements for future smart home environments. This paper introduces the work in progress in constructing a stable and efficient Next-generation Broadband Multi-mode Intelligent Gateway (NBMIG) which supports multiple access methods, multiple services, IPv6, security, QoS and remotely web management. It is mainly based on an IXP425 network processor and a Linux kernel. We first present the hardware and software architectures of NBMIG, and then we introduce their in-detailed implementations. In the meantime, a smart home system is proposed based on NBMIG and household appliances equipped with wireless and ZigBee adapters. Finally, the effectiveness and feasibility of NBMIG is verified through testing. [ABSTRACT FROM AUTHOR]

CD4+CD25+ regulatory T cells (Tregs) exert a suppressive activity on atherosclerosis but the underlying mechanism remains unclear. Here, we investigated whether and how Tregs affect oxLDL-induced proinflammatory response in macrophages. Tregs were isolated by magnetic cell sorting-column and analyzed by flow cytometry. Macrophages were cultured with or without Tregs in the presence of oxLDL for 48 hours to induce proinflammatory response. Our data showed that with oxLDL challenge, the Treg-modulated macrophages have decreased NO production and iNOS expression, decreased HLA-DR and CD86 expression, and down-regulated proinflammatory cytokine/chemokine production. Tregs can inhibit the pro-inflammatory properties of macrophages and steer macrophage differentiation toward an anti-inflammatory cytokine producing phenotype. Mechanistic studies reveal that Treg-mediated suppression of the monocyte response to oxLDL was reflected by a reduction in the up-regulation of NF-κB activity accompanied by a decreased expression of TLR2 but not TLR4 at the transcriptional level. These results suggest that CD4+CD25+Foxp3+ regulatory T cells may exert its suppressive functions on pro-inflammatory properties of OxLDL induced-macrophages partly through TLR2-NF-κB signaling pathway. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cost utility analysis (CUA) using SF-36/SF-12 data has been facilitated by the development of several preference-based algorithms. The purpose of this study was to illustrate how decision-making could be affected by the choice of preference-based algorithms for the SF-36 and SF-12, and provide some guidance on selecting an appropriate algorithm. Methods: Two sets of data were used: (1) a clinical trial of adult asthma patients; and (2) a longitudinal study of post-stroke patients. Incremental costs were assumed to be $2000 per year over standard treatment, and QALY gains realized over a 1-year period. Ten published algorithms were identified, denoted by first author: Brazier (SF-36), Brazier (SF-12), Shmueli, Fryback, Lundberg, Nichol, Franks (3 algorithms), and Lawrence. Incremental cost-utility ratios (ICURs) for each algorithm, stated in dollars per quality-adjusted life year ($/QALY), were ranked and compared between datasets. Results: In the asthma patients, estimated ICURs ranged from Lawrence's SF-12 algorithm at $30,769/QALY (95% CI: 26,316 to 36,697) to Brazier's SF-36 algorithm at $63,492/QALY (95% CI: 48,780 to 83,333). ICURs for the stroke cohort varied slightly more dramatically. The MEPS-based algorithm by Franks et al. provided the lowest ICUR at $27,972/QALY (95% CI: 20,942 to 41,667). The Fryback and Shmueli algorithms provided ICURs that were greater than $50,000/QALY and did not have confidence intervals that overlapped with most of the other algorithms. The ICURbased ranking of algorithms was strongly correlated between the asthma and stroke datasets (r = 0.60). Conclusion: SF-36/SF-12 preference-based algorithms produced a wide range of ICURs that could potentially lead to different reimbursement decisions. Brazier's SF-36 and SF-12 algorithms have a strong methodological and theoretical basis and tended to generate relatively higher ICUR estimates, considerations that support a preference for these algorithms over the alternatives. The "second-generation" algorithms developed from scores mapped from other indirect preferencebased measures tended to generate lower ICURs that would promote greater adoption of new technology. There remains a need for an SF-36/SF-12 preference-based algorithm based on the US general population that has strong theoretical and methodological foundations. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the budget impact (BI) of adopting perampanel for adjunctive treatment of partial-onset seizures (POS), with or without secondarily generalized seizures, and the adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS) in patients 12 years or older in the United States. Methods: A BI model was developed to estimate the potential BI of adopting adjunctive perampanel from a US payer (direct costs only) and societal (direct and indirect costs) perspective over a 5-year period. Efficacy data for perampanel and antiepileptic drug (AED) maintenance therapy were obtained from perampanel phase III clinical trials. Drug, direct medical (healthcare provider, emergency room, and hospitalizations), and indirect (productivity loss) costs were obtained from appropriate sources (e.g., AnalySource® Online [wholesale acquisition costs], 2013 Optum Insight Clinformatics Database [market share percentages, direct medical costs per unit], and 2011-2013 National Health and Wellness Survey [NHWS; healthcare resource utilization, overall work impairment, and baseline distribution of patients across the 4 health states]). Mapping of seizure frequency to medical resource utilization and work impairment was obtained from Kantar Health's NHWS. Results: In a hypothetical health plan of 1 million members, 660 (0.066%) members ≥12 years old had uncontrolled POS (395 [59.8%]) or PGTCS (265 [40.2%]). During the first 5 years of adoption of perampanel, absolute BI (including drug, direct medical, and indirect costs) was $852, $2124, $3855, $5318, and $6397, respectively, for a cumulative absolute BI of $18,545. Drug cost was estimated to increase by $13,888, $34,646, $62,863, $86,728, and $104,326, respectively; however, this cost would be mostly offset by decreases in direct medical ($5041, $12,576, $22,818, $31,481, and $37,869, respectively) and indirect ($7995, $19,946, $36,190, $49,929, and $60,060, respectively) costs. Total per-member-per-month cost (drug and direct medical costs) was estimated to increase by $0.0007, $0.0018, $0.0033, $0.0046, and $0.0055 from years 1 to 5. Conclusions: Based on results of this BI model, increased cost of adopting perampanel in a health plan of 1 million members would be minimal for payers, and societal costs would be close to neutral. [ABSTRACT FROM AUTHOR]