tbuckley/cabot-search huggingface dataset:
A comparative study on costs of cancer and access to medicines in Europe.
Authors: Nils Erik Wilking, Gunnar Brådvik, Peter Lindgren, Christer Svedman, Bengt Jönsson, Thomas Hofmarcher
Journal: Journal of Clinical Oncology (2020)

e19051 Background: Cancer care is evolving rapidly, and costs and value of new treatments are often causing headlines without being discussed in a larger context. This study estimates the cost of cancer and access to medicines in Europe in 2018 and extends a previous analysis for 1995–2014. Methods: Cancer-specific health expenditure for 31 countries (EU-27 plus Iceland, Norway, Switzerland, and the UK) were derived from national estimates. Data on cancer drug sales were obtained from IQVIA. The productivity loss from premature mortality was estimated from data from Eurostat and the WHO. Estimates of the productivity loss from morbidity and informal care costs were based on previous studies. Results: The total cost of cancer was €199 billion in 2018. Total costs ranged from €160 per capita in Romania to €578 in Switzerland (after adjustment for price differentials). Health expenditure on cancer care was €103 billion, of which €32 billion was spent on cancer drugs. Informal care costs were €26 billion. The total productivity loss was €70 billion, composed of €50 billion from premature mortality and €20 billion from morbidity. Between 1995 and 2018, cancer incidence increased by 50 percent from 2.1 million to 3.1 million cases in Europe. Cancer mortality increased only by 20 percent. Health spending on cancer care doubled from €52 billion to €103 billion (in 2018 prices and exchange rates), whereas the share of cancer care on the total health expenditure remained stable at around 4 to 7 percent. A shift from treatment in inpatient care to ambulatory care has probably saved costs. Expenditure on cancer medicines more than tripled from €10 billion to €32 billion between 2005 and 2018 (excluding confidential rebates). Productivity loss from premature mortality decreased over time, linked to mortality reductions in working-age patients. Conclusions: There are large country differences in spending on cancer care and outcomes in Europe. Access to new cancer medicines is low or very low in certain parts of Europe. Inequalities are mainly related to countries’ economic strength and not to the disease burden of cancer.
Comparison of chemotherapy dose intensity for AYAs on COG AALL1131 versus CALGB 10403.
Authors: Jennifer Lynn McNeer, Lingyun Ji, Xinxin Xu, Michael Burke, Wanda Salzer, Meenakshi Devidas, Kristina M Laumann, Charlotte Wood, Anjali S. Advani, Richard A. Larson, Selina M. Luger, Wendy Stock, Mignon L. Loh, Stephen Hunger, Elizabeth A. Raetz
Journal: Journal of Clinical Oncology (2020)

10520 Background: Outcomes for adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) are superior with pediatric-inspired therapy. CALGB 10403, the first US adult cooperative group prospective trial using a pediatric-inspired augmented BFM (ABFM)-based regimen, demonstrated feasibility and improved survival. We examined differences in drug delivery and targeted toxicities in AYAs who received the same therapy on C10403 vs the Children’s Oncology Group (COG) study AALL1131. Methods: The proportion of AYAs receiving full dose (within 10% of protocol- specified) vincristine (VCR) and pegaspargase (PEG) during induction (IND), consolidation (CON), and delayed intensification (DI); the likelihood of selected grade ≥3 adverse events (AEs); and the impact of patient characteristics were compared in AYAs 16-30 years. Targeted AEs with analogous reporting requirements in both studies included hyperbilirubinemia, pancreatitis, sensory neuropathy, and GI/intracranial hemorrhage. Thrombosis, transaminitis and hyperglycemia were not comparably captured. Fisher’s Exact test and logistic regression models were used for analyses. Results: After excluding AYAs removed from study after induction, 87 AALL1131 AYAs (accrued 2012-2016) and 188 C10403 AYAs (accrued 2007-2012) were analyzed with median ages of 17 (16-26) vs 22 (17-30) years, p &lt; 0.001. There was no difference in the intensity of VCR delivery during IND, but in CON and DI, AALL1131 AYAs were more likely to receive all specified VCR (93.1% vs 81.9%, p = 0.02; 92.7% vs 72.1%, p = 0.01). Women were less likely to receive all specified VCR (OR 0.57, 95% CI 0.34-0.94, p = 0.03), and overweight/obese AYAs were somewhat less likely to receive all VCR compared to those considered normal weight (OR 0.88 and 0.59, p = 0.09). More C10403 AYAs were obese/overweight compared to AALL1131 AYAs (p = 0.04). There were no significant differences in dosing of PEG during IND/CON, but in DI AALL1131 AYAs were more likely to receive both doses (75.6% vs 57.1%, p = 0.03). No patient variables impacted delivery of PEG. There was no significant difference in grade ≥3 toxicities captured similarly on both studies. Conclusions: AYAs enrolled on AALL1131 were more likely to receive all protocol-specified VCR and PEG compared to those on C10403. Selected AE rates were comparable, suggesting that older AYAs do not tolerate doses of VCR and PEG for reasons other than toxicity, with body habitus as one potential variable. Further analyses to compare dose density, toxicities, and outcomes experienced by younger AYAs versus older are ongoing.
Awareness of diagnostic criteria for irritable bowel syndrome in physicians in Shanghai
Authors: Guang-yu Chen, Yu-qi Qiao, Hui-qing Zhou, Ying-wei Chen, Ding-guo Li
Journal: BMJ (2010)

Objective To investigate physicians' awareness of diagnostic criteria for irritable bowel syndrome (IBS). Methods Questionnaire was used to investigate awareness of diagnostic criteria for IBS among 782 physicians in 34 hospitals in Shanghai during August 2008. Results Overall, 82. 7 percent (647/782) of physicians surveyed thought they knew or partly knew diagnostic criteria for IBS. More than 70. 0 percent of physicians knew Rome criteria, but less than 25.0 percent knew other criteria. Awareness of current Rome criteria, whether mental symptoms included in it, and its time frame differed significantly among physicians in varied specialties (P ＜ 0. 01 ). Gastroenterologists had more knowledge about Rome criteria than other specialists, but most physicians, including gastroenterologists, did not fully understand its applicability. Conclusions Although gastroenterologists knew more about diagnostic criteria for IBS, their knowledge still needed to be perfected and updated. Awareness of diagnostic criteria for IBS was poor in nongastroenterological physicians and general practitioners knew it to certain extent.

Key words: 
Irritable bowel syndrome; Physicians; Questionnaires
Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results.
Authors: Nikhil C. Munshi, Larry D. Anderson, Jr, Nina Shah, Sundar Jagannath, Jesus G. Berdeja, Sagar Lonial, Noopur S. Raje, David Samuel DiCapua Siegel, Yi Lin, Albert Oriol, Philippe Moreau, Ibrahim Yakoub-Agha, Michel Delforge, Fabio Petrocca, Jamie Connarn, Payal Patel, Liping Huang, Timothy Brandon Campbell, Kristen Hege, Jesus San Miguel
Journal: Journal of Clinical Oncology (2020)

8503 Background: Outcomes are poor in triple-class exposed RRMM patients (pts) who progress on immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), and CD38 antibodies (mAbs). Ide-cel, a BCMA targeted CAR T cell therapy, showed promising tolerability and efficacy in RRMM pts in the phase I CRB-401 study ( NEJM2019;380:1726). We present primary efficacy and safety data from the pivotal phase II KarMMa trial of ide-cel in RRMM (NCT03361748). Methods: Enrolled pts had ≥3 prior regimens (including IMiD, PI, and CD38 mAb) and were refractory to their last regimen per IMWG criteria. After lymphodepletion (cyclophosphamide 300 mg/m 2 + fludarabine 30 mg/m 2 x 3), pts received 150─450 × 10 6 CAR+ T cells (target dose range). Endpoints included overall response rate (ORR; primary), complete response (CR) rate, duration of response (DoR), and PFS. Results: Of 140 pts enrolled, 128 received ide-cel. Median age was 61 y; median no. of prior regimens was 6; 84% were triple- and 26% were penta-refractory. Most pts (88%) had bridging therapy. At data cutoff (16 Oct 2019), median follow up was 11.3 mo. ORR was 73% and median PFS was 8.6 mo; both increased with higher dose (Table). All subgroups had an ORR ≥50%, including older and high-risk pts. Most common any-grade (Gr) toxicities were cytopenias (97%) and cytokine release syndrome (CRS; 84%). CRS was mainly Gr 1/2; 5 pts (5%) had Gr 3, 1 had Gr 4, and 1 had Gr 5 (at 300 × 10 6 ). Neurotoxicity developed in 23 pts (18%); 4 (3%) Gr 3 and 0 Gr ≥4. Median peak CAR+ T cell expansion occurred at 11 d. Expansion was higher in responders and parameters (AUC 0 −28d , C max ) increased with higher dose, with exposure overlap across doses. Persistence was durable, with CAR+ T cells detected in 29/49 (59%) and 4/11 pts (36%) at 6 and 12 mo. Conclusions: Ide-cel demonstrated deep, durable responses in heavily pretreated RRMM pts. Efficacy and safety reflected prior reports and support a favorable ide-cel clinical benefit-risk profile across the target dose range. Clinical trial information: NCT03361748 . [Table: see text]
Prevalence and clinical characterization of MMR-D/MSI extra-colonic cancers among germline PMS2 mutation carriers.
Authors: Alicia Latham, Erin E. Salo-Mullen, Amanda Catchings, Megha Ranganathan, Elise Fiala, Yelena Kemel, Jason A. Konner, Robert A. Soslow, Amir Momeni-Boroujeni, Jinru Shia, Diana Mandelker, Ozge Birsoy, Jaclyn Frances Hechtman, Michael F. Berger, Maria Isabel Carlo, Michael Francis Walsh, Mark E. Robson, Kenneth Offit, Zsofia Kinga Stadler, Karen Anne Cadoo
Journal: Journal of Clinical Oncology (2020)

1527 Background: PMS2-associated Lynch syndrome (LS) may have a more modest phenotype than that associated with other mismatch repair (MMR) genes ( MLH1, MSH2, MSH6, EPCAM). Recent studies suggest limited extra-colonic cancers, and modified risk-reducing measures can be provided. Understanding the spectrum of risk is of critical importance as some LS-associated cancers do not have effective screening, requiring risk-reducing surgery (endometrial, ovarian). As MMR-deficiency (MMRD)/ microsatellite instability (MSI) is associated with LS pan-cancer, we sought to characterize PMS2-associated malignancies according to MMR/MSI status. Methods: Review of cancer patients (pts) consented to an IRB-approved protocol of tumor/germline next-generation sequencing (NGS) identified 43 germline heterozygous PMS2 mutation carriers. Tumors were evaluated for MSI via MSIsensor and/or corresponding MMR protein expression via immunohistochemical staining (IHC). Clinical variables were correlated with MMR/MSI status, comparing via Chi-square or standard T-test. Results: There were &gt; 10 tumor types; 69.8% (30/43) were extra-colonic cancers (endometrial (n = 4), ovarian (n = 6), small bowel (n = 3), urothelial (n = 2), pancreas (n = 3), prostate (n = 3), breast (n = 3), brain (n = 3), biliary (n = 1), spindle cell sarcoma (n = 1), and hepatoblastoma (n = 1)). 46.5% (20/43) of tumors were MMRD/MSI. 61.5% (8/13) of colorectal cancers (CRC) were MMRD/MSI, compared to 40% (12/30) of extra-colonic tumors. All endometrial and small bowel cancers were MMRD/MSI. Of 6 ovarian cancers, 3 were clear-cell, 1 endometrioid, and 2 high-grade serous (HGS). The only MMRD/MSI ovary tumor was HGS. 73.9% (17/23) of pts with MMRP/MSS tumors had recurrent/metastatic disease vs 30% (6/20) of pts with MMRD/MSI tumors ( p= 0.004). Mean age at diagnosis did not differ significantly between MMRP/MSS and MMRD/MSI groups (49 vs. 57, respectively, p= 0.146). 11.6% (5/43) of pts had a prior cancer, with only one patient having prior CRC. Pts with extra-colonic tumors were less likely to meet clinical pt and family history LS testing criteria than those with CRC (63.3% (19/30) vs. 7.7% (1/13); p&lt; 0.001). Conclusions: While PMS2-related LS may have a more modest clinical phenotype, in this single-institution study, 60% (12/20) of patients with MMRD/MSI tumors presented with extra-colonic cancers. We caution counseling pts with PMS2-associated LS about reduced extra-colonic risk until more complete information about penetrance, spectrum, and age distribution of cancer is available.
Covid-19 in care homes: the many determinants of this perfect storm
Authors: Desmond O’Neill
Journal: BMJ (2020)

<h3>Abstract</h3> Gene-expressing compartments assembled from simple, modular parts, are a versatile platform for creating minimal synthetic cells. In a manner synonymous with natural cells, these life-like assemblies utilise information encoded in DNA within the compartment’s interior to dictate which proteins are expressed and consequently the overall function of the synthetic cell. Hence, by incorporating gene regulatory motifs into the DNA templates, <i>in situ</i> gene expression can be controlled according to specific stimuli. In this work, cell-free protein synthesis within synthetic cells was controlled using light by encoding genes of interest on light-activated DNA templates. Light-activated DNA contained a photocleavable blockade within the T7 promoter region that tightly repressed transcription until the blocking groups were removed with UV light. In this way, synthetic cells were activated remotely, in a spatiotemporally controlled manner. By applying this strategy to the expression of an acyl homo-serine lactone synthetase, BjaI, quorum-sensing based communication between synthetic cells and bacteria was controlled with light. This work provides a framework for the remote-controlled production and delivery of small molecules from non-living matter to living matter, with applications in biology and medicine.
Development of a Patient Centered Outcome Set for Patients With Multiple Myeloma to be Used in Clinical Practice
Authors: Simone Oerlemans, M. Christine Bennink, Mark David Levin, Annemiek Broijl, Marjolein Van der Klift, Judith Van Deursen, Daphne Vogels, Lonneke V. Van de Poll‐Franse, Pieter Sonneveld, Jan A. Hazelzet, Lidwine W. Tick
Journal: HemaSphere (2020)

Supplemental Digital Content is available in the text
755例麻疹流行病学和临床特征分析
Authors: 崔建军, 蒋小玲, 周伯平, 刘水腾, 刘艳, 汤佩, 陈心春
Journal: BMJ (2007)

对2006年1月至10月深圳市流行麻疹期间东湖医院收治的755例麻疹患者临床资料进行分析,比较4个年龄段中外来人口和本地人口患者的比例,＞8月龄患者的麻疹疫苗接种史等.男女性别比为1.5:1;非深圳户籍人口454例,占60.1%;发病年龄高峰集中在8月龄～5岁(372例,占49.3%)和14～49岁(259例,占34.3%);＞8月龄患者未接种疫苗者占78.3%(526例);发病集中在5～7月份;血清麻疹IgM抗体阳性率为36.3%,热峰39℃以上者546例(72.3%),并发急性气管支气管炎380例(50.3%).说明预防接种不健全及接种后抗体滴度下降可能是本次麻疹流行的主要原因。
Autologous stem cell transplantation versus no transplant in patients above 70 with multiple myeloma.
Authors: Christopher Lemieux, Lori S. Muffly, David Joseph Iberri, Andrew Rezvani, Robert Lowsky, Matthew Joshua Frank, Juliana K. Craig, Michaela Liedtke, Robert Negrin, Wen-Kai Weng, Everett Meyer, Laura J. Johnston, Judith Shizuru, Parveen Shiraz, Sally Arai, David Bernard Miklos, Surbhi Sidana
Journal: Journal of Clinical Oncology (2020)

e20509 Background: We evaluated outcomes of patients with multiple myeloma (MM) ≥ 70 years who were seen for Autologous Stem Cell Transplant (ASCT) consult, based on whether they underwent transplant vs. non-transplant treatment. Methods: 138 patients with MM ≥ 70 years (median 71, range 70-78) were evaluated in the BMT clinic from 1/2010 to 11/2019 for a transplant consult. Results: Of the 138 patients, 53 proceeded to ASCT. ASCT was not pursued in 85 patients despite most (79%) being eligible for transplant. Reasons for deferring ASCT in eligible patients included patient preference (48%, n = 32) and physician preference (52%, n = 35). 68 patients were seen during first-line therapy, of which 29 underwent upfront transplant. The remainder were seen at second-line or beyond. There was no difference in baseline characteristics among the 113 patients with available follow-up (ASCT = 53, non-ASCT = 60), including median age (71 vs. 72 years, p = 0.4), high-risk cytogenetics (41% vs. 31%, p = 0.4), high-risk HCT-CI (32% vs. 20% p = 0.2), and ISS stage III (34% vs. 27%, p = 0.6). In the 53 patients who underwent transplant, conditioning melphalan dose was 200 mg/m 2 (75%, n = 40) and 140 mg/m 2 (25%, n = 13). Day 100 transplant related mortality was 0% (n = 0). Progression-free survival (PFS) and overall survival (OS) were compared in patients who were seen for consultation within 1 year of diagnosis (n = 80). With a median follow-up of 27 months, median PFS amongst patients ≥ 70 years undergoing ASCT (n = 39) was 47 months compared to 34 months in the non-ASCT (n = 41) group, p = 0.006. Median OS was not reached in either group. Estimated 5-years OS was 76% in the ASCT group and 82% in the non-ASCT group (p = 0.6). There was no difference in PFS of patients ≥ 70 undergoing ASCT compared to a cotemporaneous cohort of patients &lt; 70 (n = 639) from our institution (47 vs. 57 months, p = 0.3). Conclusions: Selected patients ≥ 70 years with MM undergoing ASCT have better PFS compared to patients with similar characteristics who do not undergo ASCT. ASCT is safe in this older population and outcomes were similar compared to younger patients. [Table: see text]
Teaching base of general internal medicine in Peking Union Medical College Hospital
Authors: Xiao-ming Huang
Journal: BMJ (2009)

Department of General Internal Medicine (DGIM) in the Peking Union Medical College (PUMC) Hospital is the first academic general internal medicine division in teaching hospitals in China. We attempted to construct DGIM teaching base in 2005, and the teaching reform was conducted in a part of the students. Primary assessment was based on examinations and questionnaires. The results show that the students could not only master the basic medical knowledge, but also improve overall capability. We conclude that DGIM in teaching hospital would become an important teaching base in China.

Key words: 
Hospitals teaching; Internal medicine
科学的产后护理
Authors: 周仲华
Journal: BMJ (2006)

大家都知道中国人有让产妇坐月子的传统,从北到南,从东到西,几乎所有的产妇都在或多或少地遵循着千百年来流传下来的这个习惯.月子中,产妇一般要1个月不出门,家中门窗紧闭,穿很多衣服,不刷牙,不梳头,不洗澡,只吃月子饭,不吃蔬菜和水果,甚至不吃盐,有些地方的限制可能更甚.我们也常常听人说某某病症是因为月子没有坐好引起的.但是我们应仔细思考一下:坐月子真的有什么道理吗?为什么外国人不坐月子也不落病呢?
Evolution of clinical outcomes of metastatic pancreatic adenocarcinoma: A 10-year single-institution retrospective study.
Authors: Moataz Ellithi, Mohamed A. Abdallah, Mahum Shahid, Isaak Ailts, Kate Waligoske, John Fanta, Matthew Bell, McKenna Fischer, Morgan Nelson, Jonathan Bleeker
Journal: Journal of Clinical Oncology (2020)

e16760 Background: Pancreatic adenocarcinoma represents the fourth leading cause of cancer-related death in the United States. A majority of patients have locally advanced or metastatic disease at the time of diagnosis. For many years, gemcitabine monotherapy was the standard of care for advanced disease, until recent studies demonstrated survival benefits for FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) and Gem/nab-P (gemcitabine/nab-paclitaxel). In this study, we evaluated the clinical outcomes in patients with metastatic pancreatic adenocarcinoma in a single health system before and after the incorporation of these newer treatments into practice. Methods: A retrospective study of metastatic pancreatic adenocarcinoma patients diagnosed between January 2009 to December 2018 with follow up until December 2019. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier survival analysis. Univariate and multivariable Cox regression analyses were used to explore predictors of survival. Results: 394 patients were diagnosed with metastatic pancreatic adenocarcinoma at Sanford Health hospitals during the study period. There was no statistically significant difference in OS between the cohort diagnosed between 2009-2013 compared to 2014-2018, with median OS of 4.7 and 3.6 months respectively; in those receiving at least one line of chemotherapy, the median OS was 6.7 and 7.3 months. While subgroup analysis of all study population based on the type of first-line chemotherapy showed improved survival with FOLFIRINOX and Gem/nabP as compared to gemcitabine monotherapy [10.7, 6.9, 4 months respectively] (Wilcoxon Test of Homogeneity of Survival Curves p = 0.0002). Univariate and multivariate Cox regression analysis of all study data revealed that at the time of the diagnosis, age (HR: 1.021, p = 0.0013), ECOG performance status &gt; 1 (HR: 3.47, p = 0.0001), serum albumin (HR: 0.708, p = 0.0002), Neutrophil-to-Lymphocytes ratio (HR: 1.076, p≤0.0001) and platelets-to-lymphocyte ratio (HR: 0.998, p = 0.0031) were predictors of survival. Conclusions: Although newer treatments appear to offer improved survival for eligible patients, overall outcomes for metastatic pancreatic adenocarcinoma in this cohort were similar before and after the incorporation of newer treatment regimens. Further advances in the treatment and early detection of pancreatic cancer are needed to improve clinical outcomes.
Prognostic relevance and inter-observer reliability of chest-imaging in pediatric ARDS: a pediatric acute respiratory distress incidence and epidemiology (PARDIE) study
Authors: Yolanda M. López-Fernández, Lincoln S. Smith, Joseph G. Kohne, Jason P. Weinman, Vicent Modesto-Alapont, Susana B. Reyes-Dominguez, Alberto Medina, Byron E. Piñeres-Olave, Natalie Mahieu, Margaret J. Klein, Heidi R. Flori, Philippe Jouvet, Robinder G. Khemani
Journal: Intensive Care Medicine (2020)
Concurrent versus sequential adjuvant radio-chemotherapy after mastectomy for breast cancer: a Meta-analysis
Authors: Qing Ma, Yao-yao Ren, Li Ma
Journal: BMJ (2010)

With computer and manual search of literatures on the comparison of concurrent with sequential adjuvant radio-chemotherapy after mastectomy for breast cancer, 4 eligible randomized controlled trials were found; the RevMan 5.0 software was used for Meta-analysis. The results showed that concurrent radio-chemotherapy reduced local recurrence more prominently than sequential radio-chemotherapy in patients with positive axillary lymph nodes( P = 0. 003 ). However, differences in 5-year overall survival,5-year disease-free survival and metastasis-free survival between two groups were not significant (P =0. 670,P =0. 200, P =0. 350).

Key words: 
Breast neoplasms;  Meta-analysis