tbuckley/cabot-search huggingface dataset:
Real-world treatment patterns of metastatic non-small cell lung cancer (mNSCLC) patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).
Authors: Rahul Shenolikar, Sizhu Liu, Jenny Tse, Yao Cao, Aimee Near
Journal: Journal of Clinical Oncology (2021)

289 Background: Among mNSCLC patients positive for EGFR mutation (EGFRm), first-line (1L) treatment with an EGFR TKI is recommended for best outcomes. This study describes real-world treatment patterns of mNSCLC patients using EGFR TKIs in the 1L setting, including osimertinib, the most recently approved EGFR TKI for 1L use. Methods: Patients with ≥1 claim for an EGFR TKI (1st generation [1G]: gefitinib, erlotinib; 2nd generation [2G]: afatinib, dacomitinib; 3rd generation: osimertinib) from January 1, 2015 – April 30, 2020 were identified in IQVIA’s prescription (LRx) and medical claims (Dx) databases; first date of EGFR TKI was the index date. Patients had 12-month baseline period before index, variable follow-up after index, ≥1 lung cancer diagnosis on index or in baseline, and earliest metastatic cancer diagnosis on or 90 days before index. Kaplan-Meier analysis was used to estimate 1L treatment duration, where treatment discontinuation was defined as &gt;60-day gap in medication supply of the index EGFR TKI. Patient characteristics and treatment patterns were stratified by 1L EGFR TKI. Results: Overall, 2,505 mNSCLC patients received 1L EGFR TKI (982 osimertinib, 1,060 1G, 463 2G). Median ages were 66-69 years, 64.6-67.1% were female, and 32.4-38.9% had central nervous system metastases on or before index. Most patients were commercially insured (50.8-62.9%), 35.3-45.9% had Medicare, and 0.6-3.3% had other payer types. Nearly all patients had 1L EGFR TKI monotherapy (97.6-99.7%). 1L treatment duration was longer for osimertinib compared to 1G or 2G EGFR TKI (median months, 17.8, 8.7, 10.5 respectively). 2L treatment was observed in 32.5% of 1G and 36.3% of 2G EGFR TKI cohorts. Osimertinib monotherapy, chemotherapy, and immunotherapy (monotherapy or combined with chemotherapy) accounted for 58.3%, 7.0%, and 4.3% of 2L treatments after 1L 1G EGFR TKI, respectively, and 60.7%, 4.2%, and 4.8% of 2L treatments after 1L 2G EGFR TKI. Conclusions: In real-world practice, 1L treatment duration is longer with osimertinib compared with other EGFR TKIs. Future studies with longer follow-up are recommended to understand treatment patterns after progression on EGFR TKIs, mainly osimertinib, given its recent approval.
Lesion-level heterogeneity of radiologic progression in patients treated with pembrolizumab
Authors: B.G. Topp, K. Thiagarajan, D.P. De Alwis, A. Snyder, M.D. Hellmann
Journal: Annals of Oncology (2021)

Disease progression is often considered a binary state reflecting presence or absence of response. Meaningful heterogeneity between metastatic sites of a given patient may exist, however, and may impact therapeutic outcomes. To characterize the heterogeneity of progression with immunotherapy, we evaluated lesion-level dynamics of pembrolizumab-treated patients across three tumor types.Individual metastatic lesion dynamics were analyzed retrospectively in patients with advanced melanoma, non-small-cell lung cancer (NSCLC), and gastric or gastroesophageal junction (G/GEJ) cancer who received pembrolizumab in KEYNOTE-001 or KEYNOTE-059. Primary progression was defined as radiologic progression as per RECIST v1.1 occurring at the first on-treatment study scan (∼9-12 weeks, +2-week window) and secondary progression as progression occurring beyond the first scan (∼14 weeks and beyond). The change in sum of target lesions and of individual lesions was examined, as were patterns and timing of progression.9239 individual lesions from 1194 patients were analyzed. Among patients with primary progression [39% (200/511) of patients with melanoma, 41% (179/432) with NSCLC, 61% (154/251) with G/GEJ cancer], most patients (51%-63%) had a mixture of growing, stable, and shrinking lesions. Despite overall primary progression, a minority of patients (19%-25%) had tumor growth at every metastatic site and 17%-32% had ≥1 shrinking lesion. Among patients with secondary progression [22% (113/511) of patients with melanoma, 27% (117/432) with NSCLC, 18% (44/251) with G/GEJ cancer], few patients had rebound growth (>20% increase in diameter from nadir) in all lesions whereas the majority (74%-84%) had sustained regression in ≥1 lesion.Lesion-level heterogeneity at the time of disease progression was common in pembrolizumab-treated patients, with many patients demonstrating ongoing disease control in a subset of tumor sites. These results may inform clinical decision-making, trial design, and tumor sampling in the future.
Monitoring Drinking Water Quality in Nationally Representative Household Surveys in Low- and Middle-Income Countries: Cross-Sectional Analysis of 27 Multiple Indicator Cluster Surveys 2014–2020
Authors: Robert Bain, Richard Johnston, Shane Khan, Attila Hancioglu, Tom Slaymaker
Journal: Environmental Health Perspectives (2021)

Background: The 2030 Sustainable Development Goals (SDGs) set an ambitious new benchmark for safely managed drinking water services (SMDWs), but many countries lack national data on the availability and quality of drinking water. Objectives: We quantified the availability and microbiological quality of drinking water, monitored SMDWs, and examined risk factors for Escherichia coli (E. coli) contamination in 27 low-and middle-income countries (LMICs). Methods: A new water quality module for household surveys was implemented in 27 Multiple Indicator Cluster Surveys. Teams used portable equipment to measure E. coli at the point of collection (PoC, n=61,170) and at the point of use (PoU, n=64,900) and asked respondents about the availability and accessibility of drinking water. Households were classified as having SMDW services if they used an improved water source that was free of E. coli contamination at PoC, accessible on premises, and available when needed. Compliance with individual SMDW criteria was also assessed. Modified Poisson regression was used to explore household and community risk factors for E. coli contamination. Results: E. coli was commonly detected at the PoC (range 16–90%) and was more likely at the PoU (range 19–99%). On average, 84% of households used an improved drinking water source, and 31% met all of the SMDW criteria. E. coli contamination was the primary reason SMDW criteria were not met (15 of 27 countries). The prevalence of E. coli in PoC samples was lower among households using improved water sources [risk ratio (RR)=0.74; 95% confidence interval (CI): 0.64, 0.85] but not for households with water accessible on premises (RR=0.99; 95% CI: 0.94, 1.05) or available when needed (RR=0.95; 95% CI: 0.88, 1.02). E. coli contamination of PoU samples was less common for households in the richest vs. poorest wealth quintile (RR=0.70; 95% CI: 0.55, 0.88) and in communities with high (>75%) improved sanitation coverage (RR=0.94; 95% CI: 0.90, 0.97). Livestock ownership (RR=1.08; 95% CI: 1.04, 1.13), rural vs. urban residence (RR=1.10; 95% CI: 1.04, 1.16), and wet vs. dry season sampling (RR=1.07; 95% CI: 1.01, 1.15) were positively associated with contamination at the PoU. Discussion: Cross-sectional water quality data can be collected in household surveys and can be used to assess inequalities in service levels, to track the SDG indicator of SMDWs, and to examine risk factors for contamination. There is an urgent need for better risk management to reduce widespread exposure to fecal contamination through drinking water services in LMICs. https://doi.org/10.1289/EHP8459
Association of lung cancer incidence and COVID-19 case fatality with income level in Ohio.
Authors: Rohan Desai, Raoul Wadhwa, Jacob Scott
Journal: Journal of Clinical Oncology (2021)

110 Background: Social determinants of health (SDOH) have an impact of health and quality-of-life. However, most models of clinical disease and risk calculators do not incorporate SDOH. Many diseases have residual, unexplained risk after known risk factors have been incorporated. SDOH is important component of this residual risk and resources should be allocated to study their relation to disease. Here, we investigate the role of SDOH on the incidence and severity of respiratory diseases by evaluating the association of income level with lung cancer incidence and COVID-19 case fatality ratio in the state of Ohio. Methods: Socioeconomic data for the state of Ohio was manually collected. Lung cancer incidence was acquired from the National Cancer Institute’s online portal. COVID-19 case fatality ratios were downloaded from Johns Hopkins University’s GitHub repository. All three datasets contained complete information for each of Ohio’s 88 counties and were merged by county name. The first two datasets are up-to-date as of 2019, while the COVID-19 data was up-to-date as of 22 May 2021. Data manipulation, visualization, and statistical inference was conducted in the R programming language. Results: Median county-level income across Ohio was $52,722 (IQR: 47,273-59,166). Median county-level lung cancer incidence was 68.4 per 100,000 population (IQR: 62.0-80.6) and median COVID-19 case fatality ratio was 1.98% (IQR: 1.65-2.36). Data for counties with highest and lowest median income are shown in table. Lung cancer incidence and COVID-19 case fatality ratio were not significantly correlated ( n = 88, p &gt; 0.05). Median income was significantly correlated with both, lung cancer incidence ( r = -0.49, p &lt; 0.001) and COVID-19 case fatality ratio ( r = -0.41, p &lt; 0.001). This implies that 24% of the variation in lung cancer incidence and 17% of the variation in COVID-19 case fatality ratio in counties across Ohio can be explained by median county income. Conclusions: SDOH is significantly associated with the incidence and severity of infectious and oncologic respiratory diseases. This association is strengthened since the disease variables themselves are uncorrelated, decreasing the likelihood of confounding. COVID-19 incidence was not used because of uncertainty in the mechanism of SDOH affecting transmission. However, theories suggest that oncologic incidence and infectious disease treatment are affected by SDOH. We validate these theories and encourage the incorporation of SDOH into clinical care and public health. Future directions include testing the association between income level and lung cancer severity in clinical datasets from medical institutions in Ohio.[Table: see text]
Validation of self-reported incident cancer diagnoses in the U.S. Health and Retirement Study: A tool for population-based cancer and aging research.
Authors: Megan Mullins, Jasdeep Kler, Marissa Eastman, Mohammed Kabeto, Lauren P. Wallner, Lindsay Kobayashi
Journal: Journal of Clinical Oncology (2021)

312 Background: Population aging and improving cancer survival rates are resulting in a growing population of older cancer survivors in the United States (US). As a result, there is an increasing need for longitudinal, population-representative data for interdisciplinary cancer research among older adults. The US Health Retirement Study (HRS) is an ongoing population-representative cohort of US adults over age 50 that contains rich interview and biomarker data on health during aging. Interviews have collected self-reported cancer diagnoses since 1998, but these self-reports have not been validated. We compared first incident cancer diagnoses self-reported in HRS interviews against diagnostic claims from linked Medicare records. Methods: We examined the validity of first incident cancer diagnoses self-reported in biennial HRS interviews from 2000 through 2016 against ICD-9 and ICD-10 diagnostic claim records among 8,242 HRS participants aged ≥65 with 90% continuous enrollment in fee-for-service Medicare, using the claim records as the gold standard. We calculated the sensitivity, specificity, and k for first incident cancer diagnoses (all cancers combined, excluding non-melanoma skin cancer, and each of bladder, breast, colorectal/anal, uterine, kidney/renal, lung/bronchus, and prostate cancers) cumulatively over the follow-up, and at each biennial study interview. Results: Self-reports of first incident cancer diagnosis (agnostic of site) between 2000 and 2016 had 73.2% sensitivity and 96.2% specificity against Medicare claims (k = 0.73). For site-specific self-reports, sensitivities ranged from 44.7% (kidney) to 75.0% (breast), and specificities ranged from 99.2% (prostate) to 99.9% (bladder, uterine, and kidney). Results were similar in sensitivity analyses restricting to individuals with 100% continuous fee-for-service Medicare enrollment and when restricting to individuals with at least 24 months of Medicare enrollment. Conclusions: Self-reported cancer diagnoses in the HRS have reasonable validity for population-based research on cancer and aging across cancer types. Apart from breast cancer, cancer site specific analyses will greatly benefit from the improved validity of self-report with Medicare claim linkage.
이번 호의 간 영상 : 단일 결절 종괴로 나타난 호산구성 간농양
Authors: 신용문 ( Yong Moon Shin )
Journal: Clinical and Molecular Hepatology (2010)

간을 침범하는 호산구성 농양은 소형, 다발성, 일과성으로 나타는 경향이 많으나, 단발성으로 종괴를 형성하여 종양과의 감별이 어려웠던 증례의 영상 소견을 예시하였다. 영상 소견에 대한 이해도 중요하지만 임상 양상 및 혈액검사 소견과의 연계가 진단을 내리는 데 필수적이다.
P-158 Deciphering the immunological determinants of response to neoadjuvant chemo-radiation in esophageal adenocarcinoma
Authors: G. Arbore, L. Albarello, G. Bucci, M. Punta, V. Bilello, L. Fanti, A. Cossu, G. Tonon, R. Rosati, G. Casorati, P. Dellabona
Journal: Annals of Oncology (2021)
No limits in the future of sports and exercise medicine!
Authors: John Bjørneboe, Arnlaug Wangensteen
Journal: British Journal of Sports Medicine (2021)

It is been almost 18 months since the COVID-19 outbreak closed the borders and forced us to change the way of communicating and interacting across our communities. But despite that we have been limited in terms of physical assemblies, it appears to be no limits in how to keep ourselves connected through virtual communication. And some changes over the last year are probably here to stay, such as digital patient communication and broadcasting of conferences to increase the reach of the conference. In Norway, our yearly SEM conference was digitalised last fall, increasing the number of participants from 500 to 1000. In addition, the sessions were available online after the conference. This year, we are happy to announce that the conference will be held on site in Oslo 29–31 October (figure 1). However, due to last year’s success, the conference will also be available for virtual participation, mirroring that there are no limits in the future of SEM. This year’s theme is physical activity and sports medicine in children, adolescents and …
Prognostic value of sonorrheometry in coagulopathy in covid-19 patients
Authors: F. J. L. Jaime, A. Doblas-Marquez, S. Martin-Tellez, I. Marquez-Gomez, M. Perez-Raya, A. M. M. Santano, D. F. Munoz-Lopez, A. Perez-Gomez, J. M. Reguera-Iglesias, M. I. Munoz-Perez, A. Montano
Journal: HemaSphere (2021)
Why and for whom are we decolonising global health?
Authors: Ong’era F Mogaka, Jenell Stewart, Elizabeth Bukusi
Journal: The Lancet Global Health (2021)

The growing calls to decolonise global health are welcome but also worrisome. Suggestions for decolonisation vary greatly, with a common view to shift power to local ownership but without clear plans on how to make this suggestion a reality. Many researchers are calling for global health research to be led by local leaders in low-income and middle-income countries (LMICs), with expatriate academics providing peripheral support rather than the other way around.1 Others call for radical transformation as the only reasonable response to addressing the complexity of reforming global health research when many leaders in global health have built their careers in institutions that advance and sustain white supremacy.
“The waiting is the worst”: Development of a next day access (NDA) program for patients with cancer.
Authors: Sarah Schellhorn Mougalian, Lisa Shomsky, Maureen Major Campos, Anne C. Chiang
Journal: Journal of Clinical Oncology (2021)

205 Background: Delays in access to treatment can cause anxiety and distress in patients with cancer. Time to treatment is increasing nationally, with retrospective analyses showing worse outcomes in patients with longer times to treatment initiation. It is critical to implement interventions that enhance navigation, improve access to cancer care, and eliminate operational and cultural barriers to prompt establishment of care and subsequent treatment initiation. We piloted a program for oncologic consultation within 1 business day in two subspecialty clinics and two network sites within our NCI designated comprehensive cancer center. Methods: Each pilot team created an implementation plan, with algorithms defining patients “eligible” for NDA. Generally, patients with a diagnosis or findings suggestive of cancer were eligible; full records were not required prior to the NDA visit. Interventions included adjusting physician templates and use of specific scripting to set expectations for patients prior to NDA visit. An institutional dashboard was created to display metrics--including new patient volume, % NDA visits, and reasons for non-utilization. Plan-Do-Study-Act cycles were completed every 2 weeks to assess data input/validity and address challenges. Patients seen via NDA completed a brief anonymous survey regarding their experience. Results: In 7 months, a total of 3107 new patients were seen across the 4 pilot sites, 900 (29.8%) of whom met “next day appropriate” criteria, and 370 (12%) of whom were seen via NDA. Uptake of NDA appointments was higher in patients with breast cancer. NDA patient satisfaction was extremely high, with 96% indicating that expectations were met or exceeded. Over half (56%) responded that a timely appointment was important when choosing a cancer center. The most common reasons patients were not seen via NDA included: specific provider requested (41%), specific date requested (23%), unavailable next day appointment (6%). Cultural barriers, particularly from treating physicians, included feeling that NDA appointments were inefficient with incomplete data, less time for clinical review, and increased burden due to last minute new patients; operational challenges included insufficient staffing and ensuring complete/accurate data collection. During 12/2019 – 2/2020, median time to first visit ranged from 17 to 36 days; median time to first visit decreased in 3 of the 4 pilot sites to 6-20 days 1 year later. Conclusions: Overall, 12% of patients were seen via NDA Success of this pilot required extensive effort to address change management and perceived barriers. Deployment in other disease teams and community sites is underway.[Table: see text]
Glioblastoma Clinical Trials: Current Landscape and Opportunities for Improvement
Authors: Stephen J. Bagley, Shawn Kothari, Rifaquat Rahman, Eudocia Q. Lee, Gavin P. Dunn, Evanthia Galanis, Susan M. Chang, Louis Burt Nabors, Manmeet S. Ahluwalia, Roger Stupp, Minesh P. Mehta, David A. Reardon, Stuart A. Grossman, Erik P. Sulman, John H. Sampson, Simon Khagi, Michael Weller, Timothy F. Cloughesy, Patrick Y. Wen, Mustafa Khasraw
Journal: Clinical Cancer Research (2021)

Therapeutic advances for glioblastoma have been minimal over the past 2 decades. In light of the multitude of recent phase III trials that have failed to meet their primary endpoints following promising preclinical and early-phase programs, a Society for Neuro-Oncology Think Tank was held in November 2020 to prioritize areas for improvement in the conduct of glioblastoma clinical trials. Here, we review the literature, identify challenges related to clinical trial eligibility criteria and trial design in glioblastoma, and provide recommendations from the Think Tank. In addition, we provide a data-driven context with which to frame this discussion by analyzing key study design features of adult glioblastoma clinical trials listed on ClinicalTrials.gov as "recruiting" or "not yet recruiting" as of February 2021.
The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload
Authors: Raquel F Videira, Anne Marie C Koop, Lara Ottaviani, Ella M Poels, Jordy M M Kocken, Cristobal Dos Remedios, Pedro Mendes-Ferreira, Kees W Van De Kolk, Gideon J Du Marchie Sarvaas, André Lourenço, Aida Llucià-Valldeperas, Dian aS Nascimento, Leon J De Windt, Frances S De Man, Inês Falcão-Pires, Rolf M F Berger, Paula A da Costa Martins
Journal: Cardiovascular Research (2021)

Abstract Aims Research on the pathophysiology of right ventricular (RV) failure has, in spite of the associated high mortality and morbidity, lagged behind compared to the left ventricle (LV). Previous work from our lab revealed that the embryonic basic helix-loop-helix transcription factor heart and neural crest derivatives expressed-2 (Hand2) is re-expressed in the adult heart and activates a ‘foetal gene programme’ contributing to pathological cardiac remodelling under conditions of LV pressure overload. As such, ablation of cardiac expression of Hand2 conferred protection to cardiac stress and abrogated the maladaptive effects that were observed upon increased expression levels. In this study, we aimed to understand the contribution of Hand2 to RV remodelling in response to pressure overload induced by pulmonary artery banding (PAB). Methods and results In this study, Hand2F/F and MCM- Hand2F/F mice were treated with tamoxifen (control and knockout, respectively) and subjected to six weeks of RV pressure overload induced by PAB. Echocardiographic- and MRI-derived haemodynamic parameters as well as molecular remodelling were assessed for all experimental groups and compared to sham-operated controls. Six weeks after PAB, levels of Hand2 expression increased in the control-banded animals but, as expected, remained absent in the knockout hearts. Despite the dramatic differences in Hand2 expression, pressure overload resulted in impaired cardiac function independently of the genotype. In fact, Hand2 depletion seems to sensitize the RV to pressure overload as these mice develop more hypertrophy and more severe cardiac dysfunction. Higher expression levels of HAND2 were also observed in RV samples of human hearts from patients with pulmonary hypertension. In turn, the LV of RV pressure-overloaded hearts was also dramatically affected as reflected by changes in shape, decreased LV mass, and impaired cardiac function. RNA-sequencing revealed a distinct set of genes that are dysregulated in the pressure-overloaded RV, compared to the previously described pressure-overloaded LV. Conclusion Cardiac-specific depletion of Hand2 is associated with severe cardiac dysfunction in conditions of RV pressure overload. While inhibiting Hand2 expression can prevent cardiac dysfunction in conditions of LV pressure overload, the same does not hold true for conditions of RV pressu re overload. This study highlights the need to better understand the molecular mechanisms driving pathological remodelling of the RV in contrast to the LV, in order to better diagnose and treat patients with RV or LV failure.
Chickens &amp; Eggs, Pigs and Their Lipstick: The Trouble with Asking Principlism to Do Too Much
Authors: Jon C. Tilburt
Journal: The American Journal of Bioethics (2021)

"Chickens & Eggs, Pigs and Their Lipstick: The Trouble with Asking Principlism to Do Too Much." The American Journal of Bioethics, 21(10), pp. 13–14
Cortisone and Skin Sensitivity to Tuberculin in Reticuloses
Authors: G. H. Fairley, J. Q. Matthias
Journal: BMJ (1960)

SCHIZOPHRENIA B 433MmDICu JOWVUL with a maximum deviation from normal with respect to the androgyny score.We thank Dr. H. C. Beccle, medical superintendent of Springfield Hospital, for allowing us to examine