Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in gynecologic oncology group trials of cisplatin-based chemoradiation

OBJECTIVE: Conflicting results have been reported for adeno- and adenosquamous carcinomas of the cervix with respect to their response to therapy and prognosis. The current study sought to evaluate impact of adeno- and adenosquamous histology in the randomized trials of primary cisplatin-based chemoradiation for locally advanced cervical cancer. METHODS: Patients with adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation. RESULTS: Among 1671 enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.9%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB2 (27.5% versus 20.0%) and fewer had stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous. Adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). When treated with radiation therapy alone, the 70 patients with adeno- and adenosquamous carcinoma of the cervix showed a statistically poorer overall survival (p=0.0499) compared to the 647 patients with squamous cell carcinoma of the cervix. However, when treated with radiation therapy with concurrent cisplatin-based chemotherapy, the 112 patients with adeno- and adenosquamous carcinomas had a similar overall survival (p=0.459) compared the 842 patients with squamous cell carcinoma. Adverse effects to treatment were similar across histologies. CONCLUSION: Adeno- and adenosquamous carcinomas of the cervix are associated with worse overall survival when treated with radiation alone but with similar progression-free and overall survival compared to squamous cell carcinomas of the cervix when treated with cisplatin based chemoradiation

Development and preliminary results of an Electronic Medical Record (EMR)-integrated smartphone telemedicine program to deliver asthma care remotely

Background: Technology-based interventions that can function within real-world practice and improve outcomes without increasing provider burden are needed, yet few successfully cross the research-to-practice divide. This paper describes the process of developing a clinically-integrated smartphone-telemedicine program for adults with asthma and results from proof-of-concept testing. Methods: To ensure integration with practice, we used a contextually-grounded intervention development approach and May\u27s implementation theory to design the intervention, with emphasis on systems capabilities and stakeholder needs. The intervention incorporated symptom monitoring by smart phone, smartphone telemedicine visits and self-management training with a nurse, and clinical decision support software, which provided automated calculations of asthma severity, control, and step-wise therapy. Seven adults (aged 18-40) engaged in a 3-month beta-test. Asthma outcomes (control, quality of life, FEV1) and healthcare utilization patterns were measured at baseline and end-of-study. Results: Each participant received an average of 4 telemedicine visits with 94% patient satisfaction. All participants had uncontrolled asthma at baseline; by end-of-study 5/7 classified as well controlled. Mean asthma control improved 1.55 points (CI=0.59-2.51); quality of life improved 1.91 points CI=0.50-3.31), and FEV1 percent predicted increased 14.86% (CI=-3.09-32.80) with effect sizes of d=1.16, 1.09, and 0.96, respectively. Preventive healthcare utilization increased significantly (1.86 visits/year vs. 0.28/year prior, CI 0.67-2.47) as did prescriptions for controller medications (9.29 refills/year vs. 1.57 refills/year, CI 4.85-10.58) Conclusion: Smartphone telemedicine may be an effective means to improve outcomes and deliver asthma care remotely. However, careful attention to systems capabilities and stakeholder acceptability is needed to ensure successful integration with practice

Disease Extent at Secondary Cytoreductive Surgery is Predictive of Progression-free and Overall Survival in Advanced Stage Ovarian Cancer: an NRG Oncology/Gynecologic Oncology Group study

Purpose GOG 152 was a randomized trial of secondary cytoreductive surgery (SCS) in patients with suboptimal residual disease (residual tumor nodule >1 cm in greatest diameter) following primary cytoreductive surgery for advanced stage ovarian cancer. The current analysis was undertaken to evaluate the impact of disease findings at SCS on progression-free survival (PFS) and overall survival (OS). Methods Among the 550 patients enrolled on GOG-152, two-hundred-sixteen patients were randomly assigned following 3 cycles of cisplatin and paclitaxel to receive SCS. In 15 patients (7%) surgery was declined or contraindicated. In the remaining 201 patients the operative and pathology reports were utilized to classify their disease status at the beginning of SCS as; no gross disease/microscopically negative N= 40 (19.9%), no gross disease/microscopically positive N= 8 (4.0%), and gross disease N=153 (76.1%). Results The median PFS for patients with no gross disease/microscopically negative was 16.1 months, no gross disease/microscopically positive was 13.5 months and for gross disease was 11.7 months, p=0.002. The median OS for patients with no gross disease/microscopically negative was 51.5 months, no gross disease/microscopically positive was 42.6 months and for gross disease was 34.9 months, p=0.018. Conclusion Although as previously reported SCS did not change PFS or OS, for those who underwent the procedure, their operative and pathologic findings were predictive of PFS and OS. Surgical/pathological residual disease is a biomarker of response to chemotherapy and predictive of PFS and OS

A mixed‐methods analysis of younger adults\u27 perceptions of asthma, self‐management, and preventive care: This isn\u27t helping me none

Background: Young adults (ages 18‐44) have increased emergency department use for asthma and poor adherence to medications. The objective of this mixed‐methods study was to understand experiences with and approaches to managing asthma, of which little is known in this age group. Methods: Surveys (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire) and 1:1 semi‐structured interviews were used to explore experiences with asthma, symptoms, self‐management behaviors, and relationship to asthma control and quality of life. Qualitative data were analyzed using content analysis techniques. Descriptive statistics and bivariate correlations were used to examine distributive characteristics and associations between variables. Results: Forty urban adults participated (mean age 32.7 ± 6.2, 1σ). Coughing was reported nearly 46% more often than wheezing, with 42.5% (17/40) coughing until the point of vomiting most days. Most participants delayed using medication for symptoms due to misperceptions about inhalers. Higher symptom frequency and worse asthma control were associated with greater use of non‐pharmacologic symptom management strategies (r=0.645, p\u3c0.001; r=0.360, p=0.022, respectively). Five themes were identified regarding young adults experiences with asthma: (1) having asthma means being limited and missing out on life; (2) healthcare for asthma is burdensome and other things are more important; (3) there is not enough personal benefit in medical interactions to make preventive care worthwhile; (4) there is insufficient support and education about asthma for adults; and (5) people normalize chronic symptoms over time and find ways of coping that fit with their lifestyle. Conclusions & Clinical Relevance: Young adults may tolerate symptoms without using quick‐relief medication or seeking preventive care. Increasing engagement with preventive services will require decreasing perceived burdens and increasing the personal benefits of care. Evaluating for non‐pharmacologic approaches to managing symptoms and asthma‐related coughing may identify uncontrolled asthma. Enhanced training for clinicians in patient‐centric asthma care may be needed

Going Mobile with Primary Care: Smartphone-Telemedicine for Asthma Management in Young Urban Adults (TEAMS)

Background: The majority of adults with persistent asthma have chronically uncontrolled disease and interventions to improve outcomes are needed. We evaluated the efficacy, feasi- bility, and acceptability of a multi-component smartphone-telemedicine program (TEAMS) to deliver asthma care remotely, support provider adherence to asthma management guide- lines, and improve patient outcomes. Methods: TEAMS utilized: (1) remote symptom monitoring, (2) nurse-led smartphone-tele- medicine with self-management training for patients, and (3) Electronic medical record- based clinical decision support software. Adults aged 18-44 (N=33) and primary care providers (N=4) were recruited from a safety-net practice in Upstate New York. Asthma con- trol, quality of life, and FEV1 were measured at 0, 3 and 6 months. Acceptability was assessed via survey and end-of-study interviews. Paired t-test and mixed effects modeling were used to evaluate the effect of the intervention on asthma outcomes. Results: At baseline, 80% of participants had uncontrolled asthma. By 6-months, 80% classi- fied as well-controlled. Improvements in control and quality of life were large (d=1.955, d=1.579). FEV%pred increased 4.2% (d=1.687) with the greatest gain in males, smokers, and lower educational status. Provider adherence to national guidelines increased from 43.3% to 86.7% (CI = 22.11-64.55) and patient adherence to medication increased from 45.58% to 85.29% (CI = 14.79-64.62). Acceptability was 95.7%; In follow up interviews, 29/30 patients and all providers indicated TEAMS worked better than usual care, supported effective self- management, and reduced symptoms over time, which led to greater self-efficacy and motivation to manage asthma. Discussion: Based on these findings, we conclude that smartphone telemedicine could substantially improve clinical asthma management, adherence to guidelines, and patient outcomes

Is age a prognostic biomarker for survival among women with locally advanced cervical cancer treated with chemoradiation? An NRG Oncology/Gynecologic Oncology Group ancillary data analysis

Objective To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I–III trials. Methods An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths. Results One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60–70 years and an additional 5% were >70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p = 0.006). Histology and tumor stage did not significantly differ., Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p = 0.022 and p 50 for all-cause mortality (HR 1.02; 95% CI, 1.01–1.04) was found, but no association between age and disease specific mortality was found. Conclusion This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were >60 years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities

Predictive modeling for determination of microscopic residual disease at primary cytoreduction: An NRG Oncology/Gynecologic Oncology Group 182 Study

Microscopic residual disease following complete cytoreduction (R0) is associated with a significant survival benefit for patients with advanced epithelial ovarian cancer (EOC). Our objective was to develop a prediction model for R0 to support surgeons in their clinical care decisions.Demographic, pathologic, surgical, and CA125 data were collected from GOG 182 records. Patients enrolled prior to September 1, 2003 were used for the training model while those enrolled after constituted the validation data set. Univariate analysis was performed to identify significant predictors of R0 and these variables were subsequently analyzed using multivariable regression. The regression model was reduced using backward selection and predictive accuracy was quantified using area under the receiver operating characteristic area under the curve (AUC) in both the training and the validation data sets.Of the 3882 patients enrolled in GOG 182, 1480 had complete clinical data available for the analysis. The training data set consisted of 1007 patients (234 with R0) while the validation set was comprised of 473 patients (122 with R0). The reduced multivariable regression model demonstrated several variables predictive of R0 at cytoreduction: Disease Score (DS) ( < 0.001), stage ( = 0.009), CA125 ( < 0.001), ascites ( < 0.001), and stage-age interaction ( = 0.01). Applying the prediction model to the validation data resulted in an AUC of 0.73 (0.67 to 0.78, 95% CI). Inclusion of DS enhanced the model performance to an AUC of 0.83 (0.79 to 0.88, 95% CI).We developed and validated a prediction model for R0 that offers improved performance over previously reported models for prediction of residual disease. The performance of the prediction model suggests additional factors (i.e. imaging, molecular profiling, etc.) should be explored in the future for a more clinically actionable tool

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong