Erlotinib as salvage treatment after failure to first-line Gefitinib in non-small cell lung cancer

Purpose Chemotherapy is the mainstay treatment for advanced non-small cell lung cancer (NSCLC). Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recently shown to be effective as a first-line treatment in Asian patients with advanced NSCLC, especially for those with favourable clinical features such as female, non-smoker and adenocarcinoma. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment. The purpose of this study is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib. Method Retrospective review of NSCLC patients with favourable clinical features who received gefitinib as firstline treatment and subsequent salvage treatment with erlotinib. Results A total of 21 patients with NSCLC were included in the study. Among them, 18 (85.7%) patients had disease control with gefitinib and 12 (57.1%) patients with salvage erlotinib. There was an association between the disease control with gefitinib and erlotinib (p = 0.031). The disease control rate of erlotinib was independent of the chemotherapy use between the two EGFR-TKIs. Conclusion For NSCLC patients with favourable clinical features, erlotinib was effective in those who had prior disease control with first-line gefitinib. © Springer-Verlag 2009.published_or_final_versionSpringer Open Choice, 01 Dec 201

Tests of scaling assumptions and construct validity of the Chinese (HK) version of the SF-36 Health Survey

Few health-related quality of life (HRQOL) survey instruments are available to the Chinese, although many have been developed for Western populations. This article describes the testing of the acceptability, conceptual equivalence, scaling assumptions and construct validity of a Chinese (HK [Hong Kong]) version of the MOS SF-36 Health Survey. A Chinese (HK) SF-36 survey form was developed by an iterative translation process. It was administered to 236 Chinese subjects who also rated the understanding, difficulty, relevance, and acceptability of each question. The scores were tested against the original scaling assumptions. The SF-36 profile of our subjects was compared to U.S. results for conceptual equivalence. Most subjects did not have any problem in understanding and answering the SF-36. Item means were generally clustered as hypothesized. All but a few items satisfied all scaling assumptions. The shape of the eight-scale SF-36 profile was similar to that of American patients, suggesting conceptual equivalence. We conclude that the Chinese (HK) version of the SF-36 Health Survey has achieved conceptual equivalence and satisfied the psychometric scaling assumptions well enough to warrant further use and testing, using the standard scoring algorithms.postprin

Efficacy and side effects of an oral appliance in the treatment of mild and moderate obstructive sleep apnoea in Chinese subjects

Conference Theme: Challenges to specialists in the 21st centurypublished_or_final_versio

A study on the effect of testosterone replacement on the development of obstructive sleep apnoea (OSA)

published_or_final_versio

Not even the past: The joint influence of former leader and new leader during leader successions in the midst of organizational change

Leader succession often occurs during organizational change processes, but the implications of leader succession, in terms of reactions to the change, rarely have been investigated. Employee attitudes and behaviors during organizational change may be influenced jointly by a former leader who recently has transitioned out of the team and the new leader who recently has transitioned into it. We predict an interaction between former and new leaders’ transformational leadership on employees’ behavioral resistance to and support for change. Based on contrast effect theory, a highly transformational former leader constrains the potential effectiveness of the new leader, but a former leader low in transformational leadership enhances this potential effectiveness. We also propose conditional indirect effects transmitted through commitment to the changing organization. Our research was conducted in a large Chinese hospitality organization that was implementing radical organizational change, during which virtually all aspects of processes and products are changed. We collected a 2-wave multisource data from employees who had recently experienced a leader succession and their newly assigned leaders. Based on a final sample of 203 employees from 22 teams, we find empirical support for the proposed interaction effects. The conditional indirect effects were also consistent with our expectations, but the effect on behavioral resistance to change was stronger than the effect on behavioral support for change.postprin

Systematic review recommends the European Organization for Research and Treatment of Cancer colorectal cancer–specific module for measuring quality of life in colorectal cancer patients

Objectives: To critically appraise the measurement properties of standardized health-related quality of life (HRQOL) instruments for colorectal cancer (CRC) patients and to provide recommendations on the choice of HRQOL instruments. Study Design and Setting: Systematic review of English language literature published between January 1985 and May 2014 identified through a database search of PubMed, Web of Science, Embase, and Ovid MEDLINE. HRQOL instruments were rated on methodological quality and overall levels of evidence using a Consensus-based Standards for the selection of health Measurement Instrument checklist. Results: Internal consistency and hypothesis testing were evaluated most frequently in 63 studies identified. The Functional Assessment of Cancer Therapy-Colorectal (FACT-C) was the most extensively evaluated. The highest number of positive ratings in the overall level of evidence was found in the CRC-specific quality of life questionnaire module (QLQ-CR38) in European Organization for Research and Treatment of Cancer (EORTC) module, followed by the Memorial Sloan Kettering Cancer Center Bowel instrument, FACT-C, and Quick-FLIC. The EORTC QLQ-CR38 had the most positive ratings on measurement property and was recommended. Conclusion: The EORTC QLQ-CR38 was recommended to assess HRQOL in patients with CRC, regardless of disease stage and primary tumor site.postprin

Recurrent pneumothorax in pregnancy: What should we do after placing an intercostal drain

Recurrent pneumothorax is rare during pregnancy. We describe a Chinese woman, with a history of spontaneous pneumothorax managed with an intercostal drain, who developed a recurrent pneumothorax during her 32nd week of pregnancy. There is no consensus on management in this situation. We review the literature and discuss different management approaches. Thirty-six cases of antepartum pneumothorax have been reported in 31 case reports. An intercostal drain only (n=11) or surgeries (thoracotomy, n=9; or video-assisted thoracoscopy, n=2) were common treatment options with no surgical complications reported. Twenty-two (61%) patients progressed to a normal vaginal delivery, while the rest required forceps delivery (22%) or Caesarean section (14%). No single treatment option outweighed the others. There were no maternal or foetal complications reported in those who underwent antepartum surgical intervention. Surgical management of recurrent pneumothorax during pregnancy is well tolerated.published_or_final_versio

Optimized CRISPR-mediated gene knockin reveals FOXP3-independent maintenance of human Treg identity

Regulatory T cell (Treg) therapy is a promising curative approach for a variety of immune-mediated conditions. CRISPR-based genome editing allows precise insertion of transgenes through homology-directed repair, but its use in human Tregs has been limited. We report an optimized protocol for CRISPR-mediated gene knockin in human Tregs with high-yield expansion. To establish a benchmark of human Treg dysfunction, we target the master transcription factor FOXP3 in naive and memory Tregs. Although FOXP3-ablated Tregs upregulate cytokine expression, effects on suppressive capacity in vitro manifest slowly and primarily in memory Tregs. Moreover, FOXP3-ablated Tregs retain their characteristic protein, transcriptional, and DNA methylation profile. Instead, FOXP3 maintains DNA methylation at regions enriched for AP-1 binding sites. Thus, although FOXP3 is important for human Treg development, it has a limited role in maintaining mature Treg identity. Optimized gene knockin with human Tregs will enable mechanistic studies and the development of tailored, next-generation Treg cell therapies

EQ-5D-5L and SF-6D Utility Measures in Symptomatic benign Thyroid Nodules: Acceptability and Psychometric Evaluation

Purpose: The aim of this study was to examine the acceptability, validity, and reliability of the EuroQoL Five-Dimension Five-Level (EQ-5D-5L) and Short-Form Six-Dimension (SF-6D) health utility measures in patients with symptomatic benign thyroid nodules. Methods: Data from a randomized controlled trial (ClinicalTrials.gov identifier: NCT02398721) of 294 patients with symptomatic benign thyroid nodules were utilized for this psychometric evaluation of health-related quality of life (HR-QOL) measurement. Three HR-QOL questionnaires—the generic 12-item Short Form Health Survey (SF-12v2), EQ-5D-5L, and SF-6D—were interviewer-administered at baseline and 2 weeks afterwards. Responses to SF-6D were transformed to SF-6D utility scores using a Hong Kong population scoring algorithm derived by standard gamble, whereas responses to EQ-5D-5L were mapped onto EQ-5D-3L response via interim mapping algorithms and then converted to EQ-5D-5L utility scores using a Chinese-specific value set. Construct validity was determined by evaluating Spearman correlation between SF-12v2 scores and utility scores. Two-week test–retest reliability was assessed using intra-class correlation coefficient. Results: No significant (>15%) floor and ceiling effects were observed for SF-6D utility scores. The SF-6D utility scores had a moderate Spearman rank correlation with the SF-12v2 domain score providing evidence for adequate construct validity. The SF-6D utility scores showed good test–retest reliability (0.794; range 0.696–0.860). Better reliability was observed in SF-6D utility scores than in EQ-5D-5L utility scores. Conclusions: While the EQ-5D-5L instrument was less reproducible, the SF-6D instrument appeared to be an applicable, valid, and reliable measure in assessing the HR-QOL of Chinese patients with symptomatic benign thyroid nodules. The impact of utility score selection on the effectiveness and cost effectiveness of clinical interventions targeted to these patients needs further exploration. Clinical trial number and registry: NCT02398721, ClinicalTrials.gov.postprin