tbuckley/cabot-search huggingface dataset:
Shedding Some Light in the Dark—A Comparison of Personal Measurements with Satellite-Based Estimates of Exposure to Light at Night among Children in the Netherlands
Authors: Anke Huss, Luuk van Wel, Lily Bogaards, Tanja Vrijkotte, Luzian Wolf, Gerard Hoek, Roel Vermeulen
Journal: Environmental Health Perspectives (2019)

Exposure to light at night (LAN) can perturb the biological clock and affect sleep and health. Previous epidemiological studies have evaluated LAN levels measured by satellites, but the validity of this measure as a proxy for personal LAN exposure is unclear. In addition, outdoor satellite-measured LAN levels are higher in urban environments, which means that this measure could potentially represent a proxy for other, likely urban, environmental exposures.We evaluated correlations of satellite-assessed LAN with measured bedroom light levels and explored correlations with other environmental exposures, in particular, air pollution, green space, and area-level socioeconomic position (SEP).We compared satellite measurements with evening and nighttime bedroom measurements of illuminance (in units of lux) for 256 children, and we evaluated correlations between satellite-based measures and other urban exposures such as air pollution, area-level SEP, and surrounding green space for 3,021 children.Satellite-measured LAN levels (nanowatts per centimeter squared per steradian) were not correlated with measured evening or nighttime lux levels [Spearman correlation coefficients ([Formula: see text]) [Formula: see text] to 0.04]. There was a weak correlation with measurements during the darkest time period if parents and their children reported that outdoor light sometimes or usually influenced indoor light levels ([Formula: see text], [Formula: see text]). In contrast, satellite-measured LAN levels were correlated with air pollution ([Formula: see text] with [Formula: see text], [Formula: see text] with [Formula: see text]), and surrounding green space ([Formula: see text] for green space within [Formula: see text] of the home). A weak correlation with area-level SEP was also observed ([Formula: see text]).Outdoor satellite-assessed outdoor LAN exposure levels were correlated with urban environmental exposures, but they were not a good proxy for indoor evening or nighttime personal exposure as measured in our study population of 12-y-old children. Studies planning to evaluate potential risks from LAN should consider such modifying factors as curtains and indoor lighting and the use of electronic devices and should include performing indoor or personal measurements to validate any exposure proxies. The moderate-to-strong correlation of outdoor LAN with other environmental exposures should be accounted for in epidemiological investigations. https://doi.org/10.1289/EHP3431.
Characterisation of morbidity in a COPD hospital cohort
Authors: A. Duarte-de-Araújo, P. Teixeira, V. Hespanhol, J. Correia-de-Sousa
Journal: Pulmonology (2019)

To characterise the morbidity of COPD out-patients based on symptoms, acute exacerbations, FEV1 and comorbidities, and to explore the association between different patients' characteristics such as social, demographic, clinical history or exposure.Stable COPD outpatients over 40 years old diagnosed according to GOLD criteria were included consecutively; the exclusion criteria were only refusal to participate and inability to understand clinical questionnaires. A survey of demographic and clinical data was conducted. Symptoms were evaluated using the CAT and mMRC questionnaires. The number of COPD acute exacerbations reported in the previous year was assessed, and spirometry performed on all participants according to ATS/ERS recommendations. Different variables were collected and then related to each other.We studied 303 COPD outpatients, all Caucasians, 79.5% males and mostly elderly. 65.7% of participants reported having low monthly income and 87.8% a low education level. Tobacco smoking was the most common exposure identified but a substantial proportion of COPD patients were non-smokers (26%). Frequent acute exacerbations were reported by 38.0% of patients. The mean post-bronchodilator FEV1 was 53.2%. The distribution of patients according to GOLD 2017 stage and classification was respectively 9.9%, 41.9%, 35.0% and 13.2% from 1 to 4 and 23.1%, 39.6%, 2.3% and 35.0% from GOLD A to D. Only 29 patients (9.5%) presented no comorbid conditions, and the most common were hypertension, heart diseases and dyslipidaemia.Our data confirms COPD as a complex and heterogeneous disorder, with a significant morbidity due to the nature of symptoms, frequent comorbidities and exacerbations. A substantial proportion of COPD patients were never-smokers, mainly women, calling attention to the need for COPD recognition in these cases. COPD in women, in never-smokers and in patients with a previous diagnosis of asthma presented some specific characteristics. Some patient characteristics are associated with frequent acute exacerbations. FEV1 was strongly related both to symptoms and exacerbations.
Cost-effectiveness of once weekly carfilzomib 70 mg/m<sup>2</sup> plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States.
Authors: Shaji Kumar, Istvan Majer, Sumeet Panjabi, Jean Malacan, Rohan Medhekar, Marco Campioni, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2019)

e18356 Background: Carfilzomib plus dexamethasone (Kd) dosed once weekly at 70 mg/m 2 (QW Kd70) was recently approved in the US for treating patients with relapsed and refractory multiple myeloma (RRMM). To assess the cost-effectiveness (CE) of QW Kd70 vs twice weekly Kd dosed at 27 mg/m 2 (BIW Kd27), data from the phase 3 ARROW trial, which directly compared these regimens in patients with 2-3 prior lines of therapy were used. Methods: A partitioned survival model was developed for the CE analysis. Time to treatment discontinuation, progression-free survival, and overall survival (OS) were estimated from the ARROW trial. Long-term OS was extrapolated using Surveillance Epidemiology and End Results registry data after matching characteristics of patients in the registry and ARROW trial. Direct costs were estimated from a US health care payer perspective. Utilities collected in the ARROW trial using the five-level version of the EuroQol questionnaire (EQ-5D-5L) were applied to estimate the quality-adjusted life years (QALYs). Uncertainty was explored using sensitivity analyses. Two subgroups of patients refractory to lenalidomide or bortezomib were assessed. Main outcomes were mean life-years (LYs), QALYs, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Results: For QW Kd70 and BIW Kd27, the model predicted mean LYs of 4.17 and 3.07 years, QALYs of 2.98 and 2.03 years, and mean total lifetime costs of $444,563 and $373,364, respectively. The incremental LYs gain, QALY gain, and incremental costs of QW Kd70 vs BIW Kd27 were estimated to be 1.10 years, 0.95 year, and $71,199, respectively, resulting in an ICER of $64,595 per LY gained and $75,204 per QALY gained. For patients refractory to lenalidomide and bortezomib, similar results were found with ICERs of $79,988 and $76,793, respectively. Conclusions: In line with ARROW trial results, this CE analysis showed that QW Kd70 is expected to provide considerable additional benefit in terms of LYs and QALYs gained compared with BIW Kd27. In the RRMM setting, QW Kd70 is cost-effective with ICERs below accepted willingness to pay thresholds in US and represents an efficient utilization of the health care budget.
Respiratory virus infection triggers acute psoriasis flares across different clinical subtypes and genetic backgrounds
Authors: E. Sbidian, M. Madrange, M. Viguier, M. Salmona, S. Duchatelet, A. Hovnanian, A. Smahi, J. Le Goff, H. Bachelez
Journal: British Journal of Dermatology (2019)

diseases according to the Global Burden of Disease (GBD) and the current portfolio of CS reviews. 5 Diseases were grouped as to whether or not they were in the 'top 15', and whether or not previous work had identified a low representation within the CS portfolio.The final list of grouped titles was then reviewed by the CS clinical editors with respect to current titles and potential number of reviews that could be supported.The rankings were combined to generate an overall priority list.New titles were advertised for competitive application from suitably qualified and resourced author teams; priority titles currently in progress were supported with extra editorial resources.If an author team did not make adequate progress, extra support was offered from CS, or titles were readvertised for review by a new qualified and resourced team.For these priority titles, CS aims to produce high-quality systematic reviews within 18 months of title registration.Going forward, CS will continue to support our existing portfolio of reviews and protocols and consider author suggestions for new review titles on an annual basis in relation to editorial capacity at CS and ranking of related titles in the most recent prioritization exercise.Potential disadvantages include limited GBD data in some global regions that may skew title priority.CS will have an increasing focus on supporting high-priority, potentially high-impact systematic review titles generated by a formal prioritization process.This is consistent with the Cochrane Collaboration Strategy 2020, which aims to produce timely, high-priority reviews of evidence to guide health decision-making. 6CS will repeat the 2017 prioritization process every 2-3 years to ensure our portfolio continues to include important and timely systematic review titles.This methodological shift in the production of CS systematic reviews is necessary to ensure that Cochrane authors and editorial resources continue to be utilized in areas where evidence synthesis is needed.Routine updates of existing reviews, redundant reviews, and incongruent methodologies can dilute the quality and relevance of systematic reviews.The implementation of a prioritization system allows Cochrane to commit their resources to high-impact reviews that are produced in a timely manner.Embracing newer methodologies such as network meta-analysis allows Cochrane to ensure that our in-house methodological expertise is used to its fullest extent.CS will no longer aim to maintain an up-to-date portfolio covering all skin diseases but will focus on the rapid delivery of a smaller number of high-priority, potentially practice-changing reviews.Using cutting-edge review methodologies, CS will ensure that information gaps are addressed and will facilitate the timely support of relevant clinical guidelines.
Multi-parametric MRI as supplement to mRANO criteria for response assessment to MDNA55 in adults with recurrent or progressive glioblastoma.
Authors: Diana Roettger, Faiq Shaikh, Sotirios Bisdas, Martin Bexon, Melissa Coello, Fahar Merchant, Nina Merchant
Journal: Journal of Clinical Oncology (2019)

e13559 Background: Modified response assessment in neuro-oncology (mRANO) criteria are widely used in GBM but seem insufficient to capture Pseudoprogression (PsP), which occurs due to extensive inflammatory infiltration, increased vascular permeability, tumor necrosis and edema. mRANO criteria recommend volumetric response evaluation using contrast-enhanced T1 subtraction maps for identifying PsP. Our approach incorporates multi-parametric MRI biomarkers to unravel the true PsP from recurrence or distinguish Pseudo Response (PsR) - following anti-VEGF agents - from delayed (immuno)response. Methods: Multiple time-points MRI (18-24h after convection-enhance delivery of the anti-IL4-R agent MDNA55, then at 30-day intervals) was utilized to determine response. Multi-parametric MRI biomarkers analyzed included (1) 3D-FLAIR-T2-based tumor volume assessment reflecting edema, necrosis and tumor infiltration; (2) 3D-gadolinium-enhanced-based tumor volume estimation reflecting active tumor infiltration, neo-angiogenesis and disrupted blood brain barrier; (3) Dynamic susceptibility contrast-based relative cerebral blood volume (rCBV) measurements for estimation of the vascular tumour properties; and (4) Diffusion weighted imaging – Apparent diffusion coefficient measurements that assess interstitial edema, tumor cellularity and ischemic injury. Results: We demonstrate similar imaging phenotypes on conventional FLAIR-T2- and enhanced T1- MR images among different disease states (PsP vs true progression, PsR vs and immuno-response) and describe the perfusion and diffusion MRI biomarkers that improve response staging including PsP masking true progression, PsP masking clinical response, early progression with delayed response, and differentiation between true and PsR. The results are compared with the mRANO-based assessments for concurrence. Conclusions: Incorporating multi-parametric MRI measurements to determine the complex underlying tissue processes enables a better assessment of PsP, PsR and delayed tumour response, and can supplement mRANO-based response assessments in GBM patients undergoing novel immunotherapies.
The effect of neoadjuvant chemotherapy with gemcitabine and S-1 for resectable pancreatic cancer (randomized phase II/III trial; Prep-02/JSAP-05).
Authors: Sohei Satoi, Michiaki Unno, Fuyuhiko Motoi, Yutaka Matsuyama, Ippei Matsumoto, Suefumi Aosasa, Hirofumi Shirakawa, Keita Wada, Tsutomu Fujii, Hideyuki Yoshitomi, Shinichiro Takahashi, Masayuki Sho, Hideki Ueno, Tomohisa Yamamoto, Tomoo Kosuge
Journal: Journal of Clinical Oncology (2019)

4126 Background: Despite recent progress of adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), its survival remains limited. We conducted a randomized controlled trial to compare neoadjuvant chemotherapy (NAC) with upfront surgery (UP-S) for patients with resectable PDAC. Methods: Patients with resectable PDAC, all confirmed cytologically or histologically were enrolled. Patients received 2 cycles of gemcitabine and S-1 regimen (GS) followed by surgery (NAC) or UP-S after randomization (1:1). Patients in both arms received adjuvant chemotherapy using S-1 for 6 months after surgical resection. The primary endpoint was overall survival (OS); secondary endpoints included adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases, and tumor marker kinetics. Results: A total 362 patients were randomly assigned to NAC-GS (n=182) or UP-S (n=180) for 3 years (2013-16). The median OS was 36.7 months in NAC-GS and 26.6 months in UP-S; HR 0.72 (p=0.015, stratified log-rank test) at 2.5 year after final enrollment. Crude resection rate for NAC and UP-S were 77%, 72% respectively. There was no operative mortality in both groups. Although G3/4 adverse events were observed frequently (73%) during NAC, no significant difference for both groups was observed for perioperative outcomes including blood loss, operation time, R0 resection rate and post-operative morbidity. Significant decrease of pathological nodal metastases in NAC was noted compared to those in UP-S by pathological evaluation for resected patients(p&lt;0.01). Although significant decrease of viable tumor cells was observed in primary tumor after NAC compared to UP-S (p&lt;0.01), Evans IIb or more was found in only 14 % of resected patients in NAC. Hepatic recurrence after surgery was significantly reduced in NAC (30.0%) compared to UP-S (47.5%) in observed period. Conclusions: The strategy of NAC showed significant longer survival compared to that of UP-S with acceptable feasibility. The effect of NAC might imply the control of subdiagnostic liver metastases before surgery for resectable PDAC. Clinical trial information: UMIN000009634.
A multicentered randomized phase II comparison of single-agent carboplatin versus the combination of carboplatin and everolimus for the treatment of advanced triple-negative breast cancer.
Authors: Jami Aya Fukui, Charles L. Shapiro, Meng Ru, Paula Klein, Julie Fasano, Aarti Bhardwaj, Hanna Irie, John P. Mandeli, Anupama Goel, Neha Kumarley, Joni Gomes, Nicholas Shuman, Damien Francois, Amy Tiersten
Journal: Journal of Clinical Oncology (2019)

TPS1109 Background: Triple negative breast cancer (TNBC) is an aggressive disease with unmet clinical needs. Women with TNBC tend to be younger and demonstrate early recurrence, higher histological grade, higher rate of visceral metastasis and increased mortality rates when compared to hormone positive breast cancer. Prognosis for metastatic TNBC is especially poor. Due to lack of targeted therapies, there is no standard treatment of choice for triple negative breast cancer and chemotherapy remains the accepted standard. Many chemotherapeutic agents have been reported to have clinical activity either as single agent or in combination. Seventy percent of breast cancers with BRCA-1 germline mutations are triple negative, which suggests a shared carcinogenic pathway between them. In preoperative and metastatic settings, both TNBC and BRCA-1 associated breast cancers are particularly sensitive to DNA cross-linking agents such as platinum compounds due to defective DNA repair by homologous recombination. The recent TNT trial showed in patients with triple negative metastatic or recurrent locally advanced breast cancer with BRCA1/2 mutations, carboplatin resulted in a significantly higher overall response rate versus docetaxel (68% versus 33.3%; p=0.03). Triple negative breast cancers are associated with a high frequency of PTEN loss, which leads to mTOR activation. Moreover, it has been reported that mTOR activation may confer resistance to platinum agents such as cisplatin, a phenomenon that may be reversible by the addition of an mTOR inhibitor such as everolimus. There are reports of synergy between mTOR inhibitors and platinum compounds in pre-clinical and clinical data. Methods: We have opened a multi-centered randomized phase II trial comparing carboplatin AUC 4 q 3 weeks vs carboplatin AUC 4 q 3 weeks combined with daily 5 mg everolimus. 41 of planned 72 patients from the Mount Sinai Health System have been enrolled and are randomized in a 2:1 allocation. The primary objective is to compare progression-free survival in patients treated with carboplatin+everolimus to patients treated with carboplatin alone. Patients may have had up to 3 prior regimens for metastatic disease. Exploratory biomarker assessment is being done to identify markers of response. Clinical trial information: NCT02531932.
Real-world tumor response (rwTR) to ramucirumab plus docetaxel (R+D) post platinum-based (Pt) and immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (aNSCLC) patients (pts).
Authors: Jeffrey Melson Clarke, Raina Mathur, Cliff Molife, Marta Batus, Victoria Jennifer Stefaniak, Katherine B. Winfree, Shrujal Baxi, Zhanglin Lin Cui, David Lenis, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2019)

e20725 Background: In REVEL, adding ramucirumab to docetaxel improved response rates among Pt-treated aNSCLC pts. This observational study evaluated rwTR in aNSCLC pts treated with R+D after Pt &amp; ICI or other (non-ICI) therapies. Methods: Adult aNSCLC pts receiving 2L/3L R+D between 3/1/15 &amp; 6/30/18, after 1L/2L Pt therapy, with ≥ 1 documented rwTR assessment, &amp; ≥ 3 months of potential follow-up were selected from the Flatiron Health EHR-derived de-identified database (n = 172). Based on prior ICI exposure, pts were assigned to either the R+D post-ICI or the R+D post non-ICI [other] unmatched cohort. Study endpoints during R+D therapy included real-world (rw) objective response rate [rwORR], rw disease control rate [rwDCR], rw time to first response [rwTTFR], rw duration of response [rwDOR] &amp; rw best response [rwBR]. Results: Overall, median age was 66.0 years and most pts were male (54.7%), white (70.3%), treated in the community (99.4%), had nonsquamous histology (79.7%), were stage IV at diagnosis (70.9%), had a low (≤ 1) Charlson comorbidity index (90.7%) &amp; ECOG ≤ 1 (57.6%). Among tested pts, most were negative for EGFR (93.0%), ALK (94.9%) ROS1 (96.6%), or PD-L1 (75.0%). Baseline characteristics were similar between cohorts. Table shows significant differences in rwBR &amp; rwDCR when stratified by cohort. Conclusions: Pts receiving R+D in the post-ICI setting had improved rwDCR compared to the R+D post-Other group, driven by a greater proportion of rwPR &amp; a higher rate of rwSD as rwBR. The proportion of rwPD as rwBR was lower in R+D post-ICI pts. rwTR rates were generally similar to tumor response outcomes reported in REVEL. Understanding impact on OS is warranted given the increasing use of ICIs in earlier lines of therapy. [Table: see text]
Impact of an oncology urgent care clinic on emergency department rates.
Authors: Tannaz Sedghi, Maureen Canavan, Cary Philip Gross, Amy J. Davidoff, Bonnie Elyssa Gould Rothberg, Michael Strait, Naralys Sinanis, Kerin B. Adelson
Journal: Journal of Clinical Oncology (2019)

6615 Background: Oncology-specific urgent care clinics (UCC) may play a key role in reducing unscheduled emergency department (ED) visits among patients with cancer. We sought to determine if establishment of an Oncology UCC was associated with lower ED utilization among patients receiving cancer care at Yale’s Smilow Cancer Hospital (SCH) and two nearby, integrated community practices. Methods: SCH opened its UCC in April 2017 to provide supportive care and symptom management for patients with cancer who need acute medical attention outside of regular clinic visits. We identified patients who had at least one visit with an oncology provider during the Pre-UCC period (9/1/16 – 12/31/16) or Post-UCC period (9/1/17 – 12/31/17) and received chemotherapy within a year preceding their provider visit. For each patient, we captured all ED visits in a four-month window starting from their last provider visit in each study period. The ED visit rate for both periods was defined as the total number of ED visits divided by the total number of unique patients in the period. To determine the impact of the UCC on ED utilization, we evaluated the absolute difference in the ED visit rate between the Pre- and Post-UCC period using a two-sample t test. Results: There were 3,754 patients in the Pre-UCC period and 4,734 patients in the Post-UCC period. In the full study sample, the mean age was 62.9 and most common cancer types were Hematologic, Gastrointestinal, and Breast. Prior to opening the UCC, the ED visit rate was 0.27 per unique patient. After opening the UCC, we found a 13.9% relative decrease in the overall ED visit rate from 0.27 to 0.23 (p = 0.02). The SCH patient ED visit rate declined by 12.5% (p = 0.03) and the community practice rate declined by 37.1%; however, the latter decline was not statistically significant, potentially due to a small sample size (p = 0.19). Conclusions: Our study found a decrease in the ED visit rate after the opening of an Oncology UCC. An urgent care strategy for cancer centers may serve as an efficient way to manage patients while minimizing ED use. [Table: see text]