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The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) afatinib improves survival in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation. We analysed the outcome between EGFR mutation subtypes in a large afatinib‐treated cohort in which 516 EGFR‐mutated NSCLC patients receiving afatinib as front‐line treatment. EGFR uncommon mutations include exon 20 insertion, de novo T790M of high or low allele frequency (dT790MHAF/dT790MLAF), non‐T790M compound mutation and others, where EGFR exon 20 insertion and dT790MHAF were defined as type‐I and the rest as type‐II uncommon mutation. Four hundred and sixty‐one (89.3%) and 55 (10.7%) patients were common and uncommon mutation, respectively. Exon 20 insertion and dT790MHAF patients demonstrated a significantly shortened progression‐free survival (PFS) (2.6 and 4.1 months) compared to EGFR common mutation, dT790MLAF and other uncommon mutation patients (15.1, 27.0 and 18.4 months; P = 3 × 10−8). Type‐I uncommon mutation was an independent predictor of PFS (HR 4.46 [95% CI, 2.60‐7.64]; P <.001) and OS (HR 2.56 [95% CI, 1.37‐4.75]; P =.003). EGFR L858R patients demonstrated a significantly higher CNS progression (cause‐specific HR, 3.16; 95% CI 1.24‐8.08; P =.016), and type‐I uncommon mutation patients exhibited a significantly higher systemic progression (cause‐specific HR, 4.95; 95% CI 2.30‐10.60; P = 4.3 × 10−5). Tendencies of higher CNS and lower systemic progression were observed in type‐II uncommon mutation patients. A PFS ≥ 12 months (OR 2.38 [95% CI, 1.18‐4.89]; P =.016) and uncommon EGFR mutation (OR 0.08 [95% CI, 0.01‐0.48]; P =.021) were independent predictors of secondary T790M. Afatinib‐treated NSCLC patients presented an EGFR genotype‐specific pattern of disease progression and outcome. What's new? For patients with nonsmall cell lung cancer (NSCLC), epidermal growth factor tyrosine kinase inhibitors (EGFR‐TKIs) can significantly improve survival. EGFG‐TKI effectiveness, however, is compromised by acquired EGFR mutations, especially de novo T790M mutations. Here, the impact of EGFR genotypes on the efficacy of afatinib, a second‐generation EGFR‐TKI, was investigated in a cohort of EGFR‐mutated NSCLC patients. Afatinib efficacy was associated with T790M allele quantity in patients with de novo T790M mutation. In particular, front‐line afatinib therapy was associated with favourable survival in EGFR‐mutated patients, whereas resistance was marked by a genotype‐specific pattern of disease progression, with secondary T790M development. [ABSTRACT FROM AUTHOR]

Benzodiazepines that have a long half-life may increase the risk of traffic accidents in elderly people who take them. These drugs are commonly used to treat anxiety and insomnia in the elderly. Researchers analyzed benzodiazepine use among 5,579 elderly drivers who had been involved in a car crash that resulted in injuries. Those who used benzodiazepines with a long half-life were involved in about 50% more crashes than a comparison group of 13,256 drivers. However, the crash rate was no higher in those who took benzodiazepines with a short half-life., Context. -- Benzodiazepines, used by a sizable number of the elderly population, may affect the ability to drive and thus increase the risk of a motor vehicle crash. Epidemiologic studies of this question have produced inconsistent results that may be due to the different effects of long- and short-half-life benzodiazepines and variations in their duration of use. Objective. -- To determine whether the use of benzodiazepines of either long- or short-elimination half-life is associated with the risk of injurious motor vehicle crash in the elderly. Design and Setting. -- Nested case-control design within a cohort of 224734 drivers from the Canadian province of Quebec, aged 67 to 84 years, followed up from 1990 to 1993. Computerized data for the study were obtained from provincial driver&apos;s license files, police reports of injurious crashes, and health insurance records. Patients. -- We identified all 5579 drivers involved in an injurious crash (cases) and a random sample of 10 controls per case selected from a subcohort of 13 256 subjects. Main Outcome. -- Involvement of a cohort member as a driver in a motor vehicle crash in which at least 1 person (not necessarily the driver) sustained bodily injury. Results. -- The adjusted rate ratio of crash involvement within the first week of long-half-life benzodiazepine use was 1.45 (95% confidence interval [CI], 1.04-2.03). The rate ratio for continuous use of longer duration up to 1 year was slightly lower but remained significant (rate ratio, 1.26; 95% CI, 1.09-1.45). In contrast, there was no increased risk after the initiation of treatment with short-half-life benzodiazepines (rate ratio, 1.04; 95% CI, 0.81-1.34) or with their continued use (rate ratio, 0.91; 95% CI, 0.82-1.01). Conclusions. -- Brief or extended periods of exposure to long-half-life benzodiazepines are associated with an increased risk of motor vehicle crash involvement in the elderly population. There is no such elevated risk for short-half-life benzodiazepines.

Since prior studies of individuals' perceptions of career-choice factors have not considered the effect of cognitive styles of subjects, this study, using 68 accounting students, investigated the mediating effects of the field dependent-independent cognitive dimension on perceptions of the importance of career-choice factors. The results, in general, show that cognitive style affected individuals' perceptions of career-choice factors, suggesting that future studies of individuals' perceptions should take into account individual cognitive differences.

Abstract Background Adverse drug events are responsible for up to 7% of all admissions to acute care hospitals. At least 58% of these are preventable, resulting from incomplete drug information, prescribing or dispensing errors, and overuse or underuse of medications. Effective implementation of medication reconciliation is considered essential to reduce preventable adverse drug events occurring at transitions between community and hospital care. An electronically enabled discharge reconciliation process represents an innovative approach to this problem. Methods/Design Participants will be recruited in Quebec and are eligible for inclusion if they are using prescription medication at admission, covered by the Quebec drug insurance plan, admitted from the community, 18 years or older, admitted to a general or intensive care medical or surgical unit, and discharged alive. A sample size of 3,714 will be required to detect a 5% reduction in adverse drug events. The intervention will comprise electronic retrieval of the community drug list, combined with an electronic discharge reconciliation module and an electronic discharge communication module. The primary outcomes will be adverse drug events occurring 30 days post-discharge, identified by a combination of patient self-report and chart abstraction. All emergency room visits and hospital readmission during this period will be measured as secondary outcomes. A cluster randomization approach will be used to allocate 16 medical and 10 surgical units to electronic discharge reconciliation and communication versus usual care. An intention-to-treat approach will be used to analyse data. Logistic regression will be undertaken within a generalized estimating equation framework to account for clustering within units. Discussion The goal of this prospective trial is to determine if electronically enabled discharge reconciliation will reduce the risk of adverse drug events, emergency room visits and readmissions 30 days post-discharge compared with usual care. We expect that this intervention will improve adherence to medication reconciliation at discharge, the accuracy of the community-based drug history and effective communication of hospital-based treatment changes to community care providers. The results may support policy-directed investments in computerizing and training of hospital staff, generate key requirements for future hospital accreditation standards, and highlight functional requirements for software vendors. Trial registration NCT01179867