Perceptions of patients and medical oncologists toward biospecimen donation in the setting of abnormal breast imaging findings

Breast Cancer Research and Treatment - We sought to understand the attitudes of individuals with abnormal breast imaging findings prompting a diagnostic breast biopsy toward donation of blood,...     

Statistical consequences of a successful lung allocation system – recovering information and reducing bias in models for urgency

The lung allocation system has reduced the number of waitlist deaths by ranking transplant candidates on the basis of a lung allocation score that requires estimation of the current 1‐year restricted mean waitlist survival (urgency). Fewer waitlist deaths and the systematic removal of candidates from the waitlist for transplantation present statistical challenges that must be addressed when using recent waitlist data. Multiple overlapping 1‐year follow‐up windows are used in a restricted mean model that estimates patient urgency on the basis of updated risk factors at the start of the window. In simulation studies, our proposed multiple imputation procedure was able to produce unbiased parameter estimates with similar efficiency to those obtained if censoring had never occurred. The analysis of 10,740 lung transplant candidates revealed that for most risk factors incorporating additional follow‐up windows produced more efficient estimates. Copyright © 2017 John Wiley & Sons, Ltd.     

Antituberculosis potential of some ethnobotanically selected Malaysian plants

Aim of the study

Many local plants are used in Malaysian traditional medicine to treat respiratory diseases including symptoms of tuberculosis. The aim of the study was to screen 78 plant extracts from 70 Malaysian plant species used in traditional medicine to treat respiratory diseases including symptoms of tuberculosis for activity against Mycobacterium tuberculosis H37Rv using a colorimetric microplate-based assay.

Materials and methods

Plant extracts were prepared by maceration in methanol (80%) and antituberculosis screening was carried out using Tetrazolium bromide microplate assay (TEMA) method to determine the minimum inhibitory concentration (MIC).

Results

Thirty-eight plant extracts from 36 plant species exhibited antituberculosis activity with MICs in the range of 1600-400 μg/ml. The leaf extract of Angiopteris evecta exhibited the highest activity with MIC of 400 μg/ml. Five other extracts, namely, Costus speciosus (stem and flower), Piper sarmentosum (whole plant), Pluchea indica (leaf), Pluchea indica (flower), and Tabernaemontana coronaria (leaf) exhibited antituberculosis activity, each with MIC of 800 μg/ml. To the best of our knowledge, this is the first report of in vitro high throughput screening of Malaysian medicinal plants for antituberculosis activity.

Conclusions

Antituberculosis activity of extracts of some plants justifies, to a certain extent their ethnomedicinal uses as remedies for symptoms of tuberculosis. These results also support the general view that, selecting the plants based on ethnobotanical criteria would enhance the probability of finding species with antituberculosis activity.     

Prospective Study Testing a Simplified Paclitaxel Premedication Regimen in Patients with Early Breast Cancer

Background

In early trials, hypersensitivity reactions (HSRs) to paclitaxel were common, thus prompting the administration of antihistamines and corticosteroids before every paclitaxel dose. We tested the safety of omitting corticosteroids after cycle 2 during the paclitaxel portion of the dose-dense (DD) doxorubicin-cyclophosphamide (AC)–paclitaxel regimen.

Patients, Materials, and Methods

In this prospective, single-arm study, patients who completed four cycles of DD-AC for stage I–III breast cancer received paclitaxel 175 mg/m² every 2 weeks for four cycles. Patients received a standard premedication protocol containing dexamethasone, diphenhydramine, and a histamine H2 blocker prior to the first two paclitaxel cycles. Dexamethasone was omitted in cycles three and four if there were no HSRs in previous cycles. We estimated the rate of grade 3–4 HSRs.

Results

Among 127 patients enrolled, 125 received more than one dose of protocol therapy and are included in the analysis. Fourteen (11.2%; 90% confidence interval, 6.9%–20.0%) patients had any-grade HSRs, for a total of 22 (4.5%; 3.1%–6.4%) HSRs over 486 paclitaxel cycles. Any-grade HSRs occurred in 1.6% (0.3%–5.0%), 6.5% (3.3%–11.3%), 7.4% (3.9%–12.5%), and 2.6% (0.7%–6.6%) of patients after paclitaxel cycles 1, 2, 3, and 4, respectively. Dexamethasone use was decreased by 92.8% in cycles 3 and 4. Only one patient experienced grade 3 HSR in cycles 3 or 4, for a rate of grade 3/4 HSR 0.4% (0.02%–2.0%) (1/237 paclitaxel infusions). That patient had grade 2 HSR during cycle 2, and the subsequent grade 3 event occurred despite usual dexamethasone premedication. A sensitivity analysis restricted to patients not known to have received dexamethasone in cycles 3 and 4 found that any-grade HSRs occurred in 2.7% (3/111; 0.7%–6.8%) and 0.9% (1/109; 0.05%–4.3%) of patients in cycle 3 and 4, respectively.

Conclusion

Corticosteroid premedication can be safely omitted in cycles 3 and 4 of dose-dense paclitaxel if HSRs are not observed during cycles 1 and 2.

Implications for Practice

Because of the potential for hypersensitivity reactions (HSRs) to paclitaxel, corticosteroids are routinely prescribed prior to each dose, on an indefinite basis. This prospective study, including 125 patients treated with 486 paclitaxel cycles, demonstrates that corticosteroids can be safely omitted in future cycles if HSRs did not occur during cycles 1 and 2 of paclitaxel and that this strategy reduces the use of corticosteroids in cycles 3 and 4 by 92.8% relative to current standard of care.

     

Prevalence and Factors Associated with Smartphone Addiction among Adolescents–A Nationwide Study in Malaysia

Smartphone ownership among adolescents is getting common in this decade especially in Malaysia; Adolescent are strongly devoted to their smartphone and this may lead to smartphone addiction. Studies have reported that smartphone addiction has become an emerging social and health problem especially among the youth in many countries however there is lack of study among adolescents in Malaysia. This study aimed to examine the prevalence and factors associated with smartphone addiction among adolescents in Malaysia. This was a cross-sectional study involving adolescents from 15 primary care clinics throughout the country. Respondents were assessed on their smartphone activities using the Malaysian short version of the Smartphone addiction scale (SAS-M-SV). Multiple logistic regression was used to determine the predictors of smartphone addiction among adolescents. The study was conducted among 921 adolescents with 49.6% male (n = 457). The mean age of adolescents was 16.4 ± 2.4 years. The ethnicity distribution were 74.6% Malay, 7.3% Chinese, 4.7% Indian and 13.4% other ethnicities. The prevalence of smartphone addiction was 37.1% (342/921); 37.4% in male and 36.9% in female. Based on multiple logistic regression analysis, longer duration of smartphone use per week was associated with higher odds of smartphone addiction among adolescent (odd ratio = 1.005%, 95% confidence interval = 1.000–1.009, p-value = 0.039). Smartphone addiction is present in nearly four in ten adolescents in Malaysia. Adolescents who spend longer duration in smartphone usage per week were associated with higher odds of having smartphone addiction. Parents should be more alert and vigilant about this finding. Hence, parents should limit their children from spending too much of time with smartphone in order to prevent their children from getting smartphone addiction.     

Outcomes after treatment of breast cancer during pregnancy including taxanes and/or granulocyte colony-stimulating factor use: findings from a multi-institutional retrospective analysis

Breast Cancer Research and Treatment - Guidelines support comparable treatment for women diagnosed with breast cancer during pregnancy (PrBC) and nonpregnant women with limited case-specific...     

A phase II study of efficacy,toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer

Purpose

There are limited data on trastuzumab–pertuzumab (HP)-based treatments beyond the first-line, HER2+ metastatic breast cancer (MBC) setting. We conducted a phase II study of eribulin mesylate, which extends survival in MBC, with HP in patients with previously treated HER2+ MBC to evaluate efficacy, toxicity, and genomic alterations driving therapeutic response.

Methods

After a run-in phase for eribulin dosing, two cohorts were enrolled (Cohort A-no prior pertuzumab; Cohort B-prior pertuzumab). All patients received eribulin 1.4 mg/m² on days 1, 8 with standard-dose HP on day 1 (21-day cycles). The primary endpoint was objective response rate (ORR). Genomic characterization via whole exome sequencing (WES) was completed on tumor DNA and matched germline DNA from 19 patients.

Results

The six-patient run-in established a dose of eribulin 1.4 mg/m² with HP. Cohorts A and B enrolled 17 and 7 patients, respectively. Accrual stopped early due to an evolving treatment landscape and slow enrollment. The ORR was 26.3% (95% Confidence Interval [CI] 9.2–51.2%) in Cohort A and 0% in Cohort B (95% CI 0–41.0%). WES revealed more frequent alterations in TP53 (p?<?0.05, q?>?0.05) in patients without clinical benefit (disease control for?<?24 weeks) which was not significant after multiple hypothesis correction.

Conclusion

Eribulin–HP had manageable toxicity and modest clinical activity in patients without prior pertuzumab exposure. This study provides a preliminary landscape of somatic alterations in this patient cohort. Our data add to the literature on how genomic alterations may predict for therapy response/resistance, as we work to individualize choices in a quickly evolving HER2+ MBC treatment landscape.

Trial registration

www.clinicaltrials.gov, NCT01912963. Registered 24 July 2013.