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991.
Monica Tang Sallie-Anne Pearson Andrea L. Schaffer Craig R. Lewis Thomas John Robert J. Simes Chee Khoon Lee 《Journal of Geriatric Oncology》2021,12(6):930-936
ObjectivesOlder adults constitute the majority of patients with lung cancer. However, they are under-represented in clinical trials as eligibility criteria often restrict enrolment based on comorbidities that are common with aging. We aimed to describe comorbidities relating to trial exclusion criteria in older adults with lung cancer, determine the proportion that would typically be excluded from trials, and examine the impact on treatment uptake.Materials and MethodsWe conducted a population-based study of people aged ≥65 years diagnosed with metastatic lung cancer using linked data for clients of the Australian Government Department of Veterans' Affairs (2005–2015). We defined trial-typical patients based on the absence of comorbidities related to the following: inadequate organ (cardiac, renal, hepatic, marrow) function; cognitive dysfunction; poor performance status (PS); prior malignancy within 5 years. We report systemic therapy uptake within 3 months of diagnosis.ResultsOur study included 677 patients (median age 84). Over half (53.4%) were not trial-typical, with the most common reasons being poor PS (37.5%), cardiac disease (19.2%), and prior cancer (12.9%). Eighty-two (12.1%) received systemic therapy. Patients with poor PS, cardiac disease, and dementia had lower treatment uptake rates. However, there was no significant difference in treatment uptake between trial-typical and non-trial-typical patients (13.4 vs 11.0%).ConclusionMore than half of older adults with advanced lung cancer would be typically excluded from trial participation. Future clinical trials of older adults need to consider broader eligibility criteria to better reflect this population to gain the best evidence for their care. 相似文献
992.
993.
Man-Lai Tang Shi-Fang Qiu Nian-Sheng Tang 《Journal of biopharmaceutical statistics》2013,23(2):368-386
Investigating the prevalence of a disease is an important topic in medical studies. Such investigations are usually based on the classification results of a group of subjects according to whether they have the disease. To classify subjects, screening tests that are inexpensive and nonintrusive to the test subjects are frequently used to produce results in a timely manner. However, such screening tests may suffer from high levels of misclassification. Although it is often possible to design a gold-standard test or device that is not subject to misclassification, such devices are usually costly and time-consuming, and in some cases intrusive to the test subjects. As a compromise between these two approaches, it is possible to use data that are obtained by the method of double-sampling. In this article, we derive and investigate four test statistics for testing a hypothesis on disease prevalence with double-sampling data. The test statistics are implemented through both the asymptotic method suitable for large samples and approximate unconditional method suitable for small samples. Our simulation results show that the approximate unconditional method usually produces a more satisfactory empirical type I error rate and power than its asymptotic counterpart, especially for small to moderate sample sizes. The results also suggest that the score test and the Wald test based on an estimate of variance with parameters estimated under the null hypothesis outperform the others. An real example is used to illustrate the proposed methods. 相似文献
994.
Sarah DeLozier Peter Speltz Jason Brito Leigh Anne Tang Janey Wang Joshua C Smith Dario Giuse Elizabeth Phillips Kristina Williams Teresa Strickland Giovanni Davogustto Dan Roden Joshua C Denny 《J Am Med Inform Assoc》2021,28(1):126
Identifying acute events as they occur is challenging in large hospital systems. Here, we describe an automated method to detect 2 rare adverse drug events (ADEs), drug-induced torsades de pointes and Stevens-Johnson syndrome and toxic epidermal necrolysis, in near real time for participant recruitment into prospective clinical studies. A text processing system searched clinical notes from the electronic health record (EHR) for relevant keywords and alerted study personnel via email of potential patients for chart review or in-person evaluation. Between 2016 and 2018, the automated recruitment system resulted in capture of 138 true cases of drug-induced rare events, improving recall from 43% to 93%. Our focused electronic alert system maintained 2-year enrollment, including across an EHR migration from a bespoke system to Epic. Real-time monitoring of EHR notes may accelerate research for certain conditions less amenable to conventional study recruitment paradigms. 相似文献
995.
996.
Junjie Zhao Xuhong Fu Hao Chen Lingqiang Min Jie Sun Jingyi Yin Jianping Guo Haojie Li Zhaoqing Tang Yuanyuan Ruan Xuefei Wang Yihong Sun Liyu Huang 《British journal of cancer》2021,124(2):425
BACKGROUND A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.METHODS Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.RESULTS G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1highYWHAZhigh gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.CONCLUSIONS The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.Subject terms: Gastric cancer, Cell death 相似文献
997.
Context: Pterocephalus hookeri (C. B. Clarke) Hock., a traditional Tibetan herbal medicine rich in glycosides, has been used to treat several diseases including rheumatoid arthritis.Objective: To evaluate the anti-arthritic activity of total glycosides from P. hookeri, and its possible mechanisms of action.Materials and methods: Anti-arthritic activity of total glycosides from P. hookeri (oral administration for 30 days at 14–56?mg/kg) was evaluated using paw swelling, arthritis scores and histopathological measurement in adjuvant-induced arthritis (AA) Sprague-Dawley rats. The NF-κB p65 expression in synovial tissues, and serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels was measured in AA rats, respectively. Further assessment of anti-inflammatory and analgesic activities of these glycosides were carried out using inflammation and hyperalgesia models induced by xylene, carrageenan, agar and acetic acid, respectively.Results: Total glycosides (56?mg/kg) decreased the paw swelling (38.0%, p?0.01), arthritis scores (25.3%, p?0.01) and synovial inflammation in AA rats. The glycosides significantly (p?0.05–0.01) attenuated the inflammation induced by xylene, carrageenan, acetic acid and agar, increased the pain threshold in acetic acid-induced writhing in mice and mechanical stimuli-induced hyperalgia in AA rats. The glycosides (14, 28, 56?mg/kg) also suppressed the NF-κB p65 expression (33.1–78.2%, p?0.05–0.01), reduced MDA (21.3–35.9%, p?0.01) and NO (20.3–32.4%, p?0.05–0.01) levels, respectively, enhanced the SOD activity (7.8%, p?0.05) at 56?mg/kg in AA rats.Discussion and conclusion: Our findings confirmed the anti-arthritic property of the total glycosides from P. hookeri, which may be attributed to its inhibition on NF-κB signalling and oxidative stress. 相似文献
998.
999.
Angel Chu Kee Lee Professor Siu Wa Tang Gabriel Ka Kui Yu Raymond Tak Fai Cheung 《International journal of psychiatry in clinical practice》2013,17(3):200-206
Objective. Depression after stroke (DAS) poses a treble burden to patients, families and health care system. The purpose of this paper is to estimate the incidence of depression among first-ever ischemic stroke patients and identify the predictors of DAS. Methods. A longitudinal study design was undertaken. Of 836 patients admitted to the stroke unit of two regional hospitals in Hong Kong during the period 1 June 2004 to 31 May 2005, 295 patients fulfilled the inclusion and exclusion criteria. A total of 260 patients had given their consents and were interviewed at 1 month after stroke onset. Results. Nearly one-quarter of the first ischemic stroke patients, who were known to be free of personal and family history of psychiatric illnesses, were found to satisfy the criteria of depression using Diagnostic and Statistical Manual IV (24%, 48 out of 200 participants; 95% CI: 18.6%, 30.4%). This result was close to that assessed by the Geriatric Depression Scale (GDS) – 15 items. The psycho-emotional factor and level of dependency were found to be most significant predictors for DAS onset. Conclusion. The high incidence of DAS and low rate of accessibility to treatment indicate timely action to be undertaken. 相似文献
1000.