Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study.

Limited data exist regarding treatment patterns and outcomes in elderly patients with HER2-positive metastatic breast cancer (MBC). registHER is an observational study of patients (N = 1,001) with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up 27 months). Outcomes were analyzed by age at MBC diagnosis: younger (<65 years), older (65-74 years), elderly (≥75 years). For progression-free survival (PFS) and overall survival (OS) analyses of first-line trastuzumab versus nontrastuzumab, older and elderly patients were combined. Cox regression analyses were adjusted for baseline characteristics and treatments. Estrogen receptor/progesterone receptor status was similar across age groups. Underlying cardiovascular disease was most common in elderly patients. In patients receiving trastuzumab-based first-line treatment, elderly patients were less likely to receive chemotherapy. In trastuzumab-treated patients, incidence of left ventricular dysfunction (LVD) and congestive heart failure (CHF) (grades ≥ 3) were highest in elderly patients (LVD: elderly 4.8 %, younger 2.8 %, older 1.5 %; CHF: elderly 3.2 %, younger 1.9 %, older 1.5 %). Unadjusted median PFS (months) was significantly higher in patients treated with first-line trastuzumab than those who were not (<65 years: 11.0 vs. 3.4, respectively; ≥65 years: 11.7 vs. 4.8, respectively). In patients <65 years, unadjusted median OS (months) was significantly higher in trastuzumab-treated patients; in patients ≥65 years, median OS was similar (<65 years: 40.4 vs. 25.9; ≥65 years: 31.2 vs. 28.5). In multivariate analyses, first-line trastuzumab use was associated with significant improvement in PFS across age. For OS, significant improvement was observed for patients <65 years and nonsignificant improvement for patients ≥65 years. Elderly patients with HER2-positive MBC had higher rates of underlying cardiovascular disease than their younger counterparts and received less aggressive treatment, including less first-line trastuzumab. These real-world data suggest improved PFS across all age groups and similar trends for OS

Antennal transcriptomic analysis of carboxylesterases and glutathione S-transferases associated with odorant degradation in the tea gray geometrid, Ectropis grisescens (Lepidoptera, Geometridae)

Introduction: Carboxylesterases (CXEs) and glutathione S-transferases (GSTs) can terminate olfactory signals during chemosensation by rapid degradation of odorants in the vicinity of receptors. The tea grey geometrid, Ectropis grisescens (Lepidoptera, Geometridae), one of the most devastating insect herbivores of tea plants in China, relies heavily on plant volatiles to locate the host plants as well as the oviposition sites. However, CXEs and GSTs involved in signal termination and odorant clearance in E. grisescens remains unknown.Methods: In this study, identification and spatial expression profiles of CXEs and GSTs in this major tea pest were investigated by transcriptomics and qRT-PCR, respectively.Results: As a result, we identified 28 CXEs and 16 GSTs from female and male antennal transcriptomes. Phylogenetic analyses clustered these candidates into several clades, among which antennal CXEs, mitochondrial and cytosolic CXEs, and delta group GSTs contained genes commonly associated with odorants degradation. Spatial expression profiles showed that most CXEs (26) were expressed in antennae. In comparison, putative GSTs exhibited a diverse expression pattern across different tissues, with one GST expressed specifically in the male antennae.Disscussion: These combined results suggest that 12 CXEs (EgriCXE1, 2, 4, 6, 8, 18, 20-22, 24, 26, and 29) and 5 GSTs (EgriGST1 and EgriGST delta group) provide a major source of candidate genes for odorants degradation in E. grisescens

Calcium channels and pumps in cancer: changes and consequences

Increases in intracellular free Ca2+ play a major role in many cellular processes. The deregulation of Ca2+ signaling is a feature of a variety of diseases, and modulators of Ca2+ signaling are used to treat conditions as diverse as hypertension to pain. The Ca2+ signal also plays a role in processes important in cancer, such as proliferation and migration. Many studies in cancer have identified alterations in the expression of proteins involved in the movement of Ca2+ across the plasma membrane and subcellular organelles. In some cases, these Ca2+ channels or pumps are potential therapeutic targets for specific cancer subtypes or correlate with prognosis

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study

Limited data exist regarding treatment patterns and outcomes in elderly patients with HER2-positive metastatic breast cancer (MBC). registHER is an observational study of patients (N = 1,001) with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up 27 months). Outcomes were analyzed by age at MBC diagnosis: younger (<65 years), older (65–74 years), elderly (≥75 years). For progression-free survival (PFS) and overall survival (OS) analyses of first-line trastuzumab versus nontrastuzumab, older and elderly patients were combined. Cox regression analyses were adjusted for baseline characteristics and treatments. Estrogen receptor/progesterone receptor status was similar across age groups. Underlying cardiovascular disease was most common in elderly patients. In patients receiving trastuzumab-based first-line treatment, elderly patients were less likely to receive chemotherapy. In trastuzumab-treated patients, incidence of left ventricular dysfunction (LVD) and congestive heart failure (CHF) (grades ≥ 3) were highest in elderly patients (LVD: elderly 4.8 %, younger 2.8 %, older 1.5 %; CHF: elderly 3.2 %, younger 1.9 %, older 1.5 %). Unadjusted median PFS (months) was significantly higher in patients treated with first-line trastuzumab than those who were not (<65 years: 11.0 vs. 3.4, respectively; ≥65 years: 11.7 vs. 4.8, respectively). In patients <65 years, unadjusted median OS (months) was significantly higher in trastuzumab-treated patients; in patients ≥65 years, median OS was similar (<65 years: 40.4 vs. 25.9; ≥65 years: 31.2 vs. 28.5). In multivariate analyses, first-line trastuzumab use was associated with significant improvement in PFS across age. For OS, significant improvement was observed for patients <65 years and nonsignificant improvement for patients ≥65 years. Elderly patients with HER2-positive MBC had higher rates of underlying cardiovascular disease than their younger counterparts and received less aggressive treatment, including less first-line trastuzumab. These real-world data suggest improved PFS across all age groups and similar trends for OS

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

ICAR: endoscopic skull‐base surgery

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Analysis of frailty survival models using Poisson variance structures.

A key assumption of the popular Cox model is that the observations in the study are statistically independent of each other. However, it is not uncommon in practice to find that observations are correlated. A frailty model approach, where the correlation is induced by latent random variables, can be applied to correlated survival data. In relative risk models, the frailties are usually assumed to follow a parametric distribution and act multiplicatively on the conditional hazard rate. In this dissertation, new methods using Poisson variance structures are introduced to fit multivariate frailty models. The likelihood functions of both parametric (e.g., with piecewise constant baseline hazard) and semi-parametric multivariate frailty models are shown to be proportional to the likelihood functions of a class of mixed Poisson regression models. For multivariate lognormal frailty models, the penalized quasi-likelihood (PQL) or adaptive Gaussian quadrature numerical procedure can be applied for the maximum likelihood based inference of the mixed Poisson regression models. Thus, a rich variety of random effect structures can be modeled for survival analysis. Simulation studies show that mixed Poisson regression models using PQL or adaptive Gaussian quadrature methods perform well in estimating both the fixed and random effect parameters of multivariate lognormal frailty models. The studies also suggest that using penalized full likelihood instead of partial likelihood in computation yields less biased estimates for lognormal frailty parameters and their standard errors (SE) than those from the penalized partial likelihood (PPL) approach. The procedure is applied to the analysis of the national kidney transplantation dataset, the national patient days of waiting to deceased kidney transplant dataset, and a diabetic retinopathy study dataset. Further extensions to marginal relative risk models are also discussed.Ph.D.Pure SciencesStatisticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/123839/2/3106061.pd