tbuckley/cabot-search huggingface dataset:
SAT0234 Evolution in the use of nsaids between 1991 and 2000. impact of the new marketed drugs
Authors: C Llop, S Paredes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used drugs. In Catalonia (Spain), this group of drugs is the fourth most used group in the number of packages dispensed in recent years. Furthermore, new NSAIDs have recently become available on the Spanish pharmaceutical market. <h3>Objectives</h3> To study the evolution in the use of NSAIDs in the province of Tarragona (Catalonia, Spain), with 450,000 inhabitants, during the period between 1991 and 2000. We also studied the commercial impact of the new marketed drugs in recent years. <h3>Methods</h3> Data of all NSAIDs prescribed and dispensed in the Public Health System during the period of the study were obtained from the Catalonian Pharmacy Database. These data were converted into Defined Daily Doses (DDD) per 1,000 inhabitants per day (DHD), according the definition of the Nordisk Council of Medicine. Population of the province was obtained from the official census of various years. <h3>Results</h3> The total amount of NSAIDs used has increased in these ten years from 24.12 to 42.54 DHD. Throughout the ten years period diclofenac, piroxicam, naproxen, ibuprofen, aceclofenac and indomethacin were the most used NSAIDs. The use of ibuprofen increased greatly and in the last year was the second most used drug in the group. Diclofenac and naproxen were used a lot throughout the period and even increased in the last years. Piroxicam and indomethacin decreased slightly over the period studied. The use of new NSAIDs (dexketoprofen, nimesulide, celecoxib, lornoxicam and particularly meloxicam and rofecoxib) increased considerably. Rofecoxib was the fourth most used drug in the group in its first year on the market. New NSAIDs are more than 20% of the total NSAIDs used in the year 2000. Since the new NSAIDs have become available, other minoritary drugs such as ketoprofen, flurbiprofen or tenoxicam have been used much less. <h3>Conclusion</h3> Despite the considerable number of NSAIDs available in Spain, only ten represent almost 95% of the total NSAIDs used in the year 2000. Concerns about a possible overprescription of these drugs are reflected in the increase of use between 1991 and 2000. Data from the last year show that more than 40 people out of every 1,000 daily use a NSAID. The increase in the use of ibuprofen is noticeable but the new NSAIDs have had a commercial impact that was both considerable and fast. We conclude that aggressive advertising by pharmaceutical companies greatly influences the use and the selection of these drugs. <h3>References</h3> Brooks PM, Day RO. Non-steroidal anti-inflammatory drugs. Differences and similarities. N Engl J Med. 1991;324:1716–25 Llop C, Paredes S, Llor C. Criteria for selecting and using non-steroidal anti-inflammatory drugs in primary health care. Fam Practice 2000;17:63–5
SAT0177 Gender, age and anthropometric correlations of hip axis length
Authors: M Salvador, CA Silva, V Rodrigues, JA Da Silva
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Hip axis length (HAL) has been proposed as an important risk factor for hip fracture, independent of bone mineral density. Significant differences of HAL have been demonstrated in relation to gender, age and ethnic origin. The latter have been proposed to play a role in the different incidence of osteoporotic hip fractures among different countries. <h3>Objectives</h3> Our objective consisted of studying the normal distribution of HAL in the Portuguese population and try to identify clinical parameters capable of predicting HAL, therefore reinforcing indication of bone densitometry. <h3>Methods</h3> A randomly selected sample of 1705 inhabitants from the centre of Portugal, (474 males; 1231 females), aged 19 to 89 were included in the study. HAL was evaluated by DEXA (Hologic) using inbuilt software. Patients were asked and examined for age, present height and weight and at age 25, age at menarche and arm span. Following correlation studies, significant variables were included in stepwise regression analysis (SPSS). <h3>Results</h3> HAL was significantly longer in males than in females (12,44 ± 0,69 vs 10,84 ± 0,69; p &lt; 0.001). In men, significant correlations (p &lt; 0.001) were found between HAL and height at age 25 (r:0.483), weight at age 25 (r:0.176) and arm span (r:0.0272). Using stepwise regression only height at age 25 was retained as significant (Model r: 0.490; Adj. R2: 0,238 – p &lt; 0.001). In women, age (r: 0,06), height at 25 (0,304), present height (0,314), weight at 25 (0,214), present weight (0,058) and arm span (0,267), all showed significant correlations. Stepwise regression showed significant contributions for armspan, height and weight at age 25. The best fitting model explained 16,5% of the variance. In our population no major difference in HAL has been observed between the young (20–30 years old) and the elderly (&gt;70), the difference being less than 1%. <h3>Conclusion</h3> Although HAL is correlated with height at age 25 for both sexes, and also with arm span and weight at age 25 in females, the percent variance explained by the best fitting model using these parameters is too small to allow for reasonable prediction and inherent implications.
Abstract #3265: RGB-286638, a multi-targeted protein kinase inhibitor, induces apoptosis involving the inhibition of RNA polymerase II carboxyl-terminal domain phosphorylation and the loss of the anti-apoptotic BCL2 family member Mcl-1.
Authors: Maureen Caligiuri, Gabriele Zybarth, Igor Ivanov, Peter Amon, Hannes Loferer, Nikolai Kley
Journal: Cancer Research (2009)

The indeno-pyrazole compound RGB-286638 is a multi-targeted inhibitor with targets comprising the family of cyclin-dependent kinases (CDKs) and a range of other cancer-relevant Tyrosine- and Serine/Threonine kinases. The compound was also shown to have anti-proliferative activity against several tumor cell lines. In this study we further explored the broad cellular activity of RGB-286638 and investigated the kinetics and mechanism of its cell killing activity in more detail. We performed a comparative analysis of the anti-proliferative activity of RGB-286638 with a number of anticancer agents using a panel of 50 cancer cell lines representing 14 different solid tumor types. Our analysis confirmed the broad cellular activity of RGB-286638 (mean GI50=25nM, mean GI90=49 nM, mean TGI=73 nM). Furthermore, the comparison of cellular activity profiles revealed that the highest level of similarity was found to be with RGB-344064, a pre-clinical stage selective inhibitor of the CDKs (R=0.76). Next in similarity were etoposide (R=0.60) and SN-38 (R=0.49), an active metabolite of irinotecan. The lowest levels of similarity were found with gemcitabine (R=0.19) and staurosporine (R=0.17). Among the most sensitive tumor cell lines were A2780, CAKI1, MDA-MB231, ACHN and HCT116 (GI50  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3265.
Does non-TME surgery of rectal cancer compromise the chance of cure? Preliminary surgical salvage data from OPERA phase III randomized trial.
Authors: Arthur Sun Myint, Brice Thamphya, Jean-Pierre Gerard
Journal: Journal of Clinical Oncology (2021)

12 Background: Non-operative modality (NOM) treatment of rectal cancer is gaining popularity as it avoids extirpative TME surgery and a stoma. OPERA trial was set up to evaluate the role of dose escalation using Contact X-ray brachytherapy [CXB] in improving the chance of organ preservation compared to the standard of care (EBCRT and TME surgery). We report on the preliminary surgical salvage data for treatment failures in the OPERA trial (NCT02505750). Methods: OPERA is a European phase 3 randomised trial between (Arm A- standard arm) EBCRT 45Gy/25/5weeks with oral capecitabine 825mg/m 2 and EBRT boost of 9Gy/5/5 days randomised against (Arm B- experimental arm) EBCRT followed by CXB boost (90 Gy/3/4 weeks). Patients were assessed at 14, 20 and 24 weeks. Watch &amp; wait policy was adopted for patients with cCR at 24 weeks after randomisation and surgery (TME or local excision) was offered for residual disease and also for local regrowth (recurrence) at a later date. Results: From July 2015 –June 2020, 148 patients were randomised of which 144 were evaluable (table). There were 71 patients in Arm A (standard) and 73 patients in Arm B (experimental). Median follow-up was 19 months (range 2-36 m). Overall clinical complete response (cCR) was observed in 103 out of 127 evaluable patients (81%) at 24 week in both arms (blinded). Surgery was carried out in 36/ 127 (28%) patients with suspected residual tumour. Further 13 patients had salvage surgery at a later date for local regrowth. At 19 months, 49/144 (34%) patients in total cohort had surgery. Local excision was carried out in 24 /49(49%) of which 3 proceeded to TME surgery due to R (1) or ypT2 adverse histology. TME surgery was carried out in 28/49 of which 8/28 (28.6%) had APER and 20/28(71.4%) had AR. In total, organ preservation (blinded) was achieved in 116/144 (80.5%) for the whole cohort. Kaplan Meier estimate of TME free survival is 76% at 19 months. Conclusions: Non-TME surgical treatment for cT2-cT3a-b rectal cancer is feasible in those who are fit and wish to avoid surgery (Watch &amp; Wait). Those who needed surgery can be offered salvage surgery immediately for local residual disease or for local regrowth at a later date. Organ preservation of 80.5% (blinded) can be achieved without compromising their chance of cure. Clinical trial information: NCT02505750. [Table: see text]
‘If not TB, what could it be?’ Chest X-ray findings from the 2016 Kenya Tuberculosis Prevalence Survey
Authors: Brenda Nyambura Mungai, Elizabeth Joekes, Enos Masini, Angela Obasi, Veronica Manduku, Beatrice Mugi, Jane Ong’angò, Dickson Kirathe, Richard Kiplimo, Joseph Sitienei, Rose Oronje, Ben Morton, Stephen Bertel Squire, Peter MacPherson
Journal: Thorax (2021)

Background The prevalence of diseases other than TB detected during chest X-ray (CXR) screening is unknown in sub-Saharan Africa. This represents a missed opportunity for identification and treatment of potentially significant disease. Our aim was to describe and quantify non-TB abnormalities identified by TB-focused CXR screening during the 2016 Kenya National TB Prevalence Survey. Methods We reviewed a random sample of 1140 adult (≥15 years) CXRs classified as ‘abnormal, suggestive of TB’ or ‘abnormal other’ during field interpretation from the TB prevalence survey. Each image was read (blinded to field classification and study radiologist read) by two expert radiologists, with images classified into one of four major anatomical categories and primary radiological findings. A third reader resolved discrepancies. Prevalence and 95% CIs of abnormalities diagnosis were estimated. Findings Cardiomegaly was the most common non-TB abnormality at 259 out of 1123 (23.1%, 95% CI 20.6% to 25.6%), while cardiomegaly with features of cardiac failure occurred in 17 out of 1123 (1.5%, 95% CI 0.9% to 2.4%). We also identified chronic pulmonary pathology including suspected COPD in 3.2% (95% CI 2.3% to 4.4%) and non-specific patterns in 4.6% (95% CI 3.5% to 6.0%). Prevalence of active-TB and severe post-TB lung changes was 3.6% (95% CI 2.6% to 4.8%) and 1.4% (95% CI 0.8% to 2.3%), respectively. Interpretation Based on radiological findings, we identified a wide variety of non-TB abnormalities during population-based TB screening. TB prevalence surveys and active case finding activities using mass CXR offer an opportunity to integrate disease screening efforts. Funding National Institute for Health Research (IMPALA-grant reference 16/136/35).
Racial disparity in KRAS mutation frequency and outcomes in colorectal cancer (CRC): A U.S. population based study.
Authors: Jeffrey Bien, Mayada Aljehani, Jerry S.H. Lee, Albert Y. Lin
Journal: Journal of Clinical Oncology (2021)

18 Background: Racial disparity in CRC survival outcome is well documented. Although the reasons for disparity are unclear, a combination of differences in access to care, quality of care, differential treatment response, and underlying cancer biology are implicated. Further, recent studies have observed differences in KRAS mutation frequency between race/ethnic groups. KRAS mutation in metastatic CRC portends a worse response to EGFR-directed therapy, and predicts a poorer prognosis. In this study, we examined whether racial/ethnic differences in KRAS mutation frequency might impact CRC outcomes on a population-based level. Methods: We examined data from 202,237 CRC patients in the Surveillance, Epidemiology, and End Results (SEER) registry between 2010 and 2015. The differences in tumor mutation status by stage and race/ethnicity were examined by χ 2 testing. Cause-specific survival (CSS) and overall survival by mutation status were plotted by Kaplan-Meir curves. A multivariable Cox-proportional hazards model was used to construct hazard ratios and 95% confidence intervals (CI) using patient demographics, tumor characteristics, and KRAS mutation status. Results: Overall, about 9% of patients (n = 18,248) in the SEER registry had KRAS status available. In this cohort, tumors from Non-Hispanic Black (NHB) (48%) or Hispanic patients (44%) carried a greater KRAS mutation (mKRAS) rate when compared against Non-Hispanic White (NHW) (39%) or Asian or Pacific Islander (API) patients (37%) (p &lt; 0.01). The assessment of the impact of mKRAS within each race/ethnic group, comparing patients with mKRAS versus wild-type KRAS (wKRAS) on CSS risk show a 7% risk increase for NHW, (HR = 1.07; 95%CI:1.02-1.12), a 15% risk increase for NHB, (HR = 1.15; 95%CI:1.04-1.26) and no significant increase among API, (HR = 1.02; 95%CI:0.92-1.4). Among patients with wKRAS, with NHW for reference, the risk of CSS is 11% higher among NHB (HR = 1.11; 95%CI:1.00-1.23), 14% higher for Hispanic, (HR = 1.14; 95%CI:1.02-1.26) and no significant difference observed among API, (HR = 1.03; 95%CI:0.91-1.16). Evaluation of the interaction between race/ethnicity and KRAS status on the CSS risk shows an increase of: 11% for mKRAS NHW, (HR = 1.11; 95%CI:1.00-1.23), 13% risk for NHB (HR = 1.13; 95%CI:1.01-1.25), 11% for Hispanic wKRAS, (HR = 1.11; 95%CI:1.04-1.18), 31% for Hispanic mKRAS (HR = 1.31; 95%CI:1.18-1.145), 16% for wKRAS API (HR = 1.16; 95%CI:1.03-1.29). In contrast, no significant difference in risk is seen for NHB nor API patients, HR = 1.02 (95%CI:0.90-1.14) and 1.04 (95%CI:0.91-1.20) respectively. Conclusions: mKRAS, compared to wKRAS, connotes worse CSS among NHW and NHB patients. Among wKRAS, NHB and Hispanic patients still experience higher mortality risk. This data suggests the negative prognosis heretofore associated with mKRAS may be linked to race/ethnicity and worthy of further study.
A Population-Based Study of Genes Previously Implicated in Breast Cancer
Authors: Chunling Hu, Steven N. Hart, Rohan Gnanaolivu, Hongyan Huang, Kun Y. Lee, Jie Na, Chi Gao, Jenna Lilyquist, Siddhartha Yadav, Nicholas J. Boddicker, Raed Samara, Josh Klebba, Christine B. Ambrosone, Hoda Anton-Culver, Paul Auer, Elisa V. Bandera, Leslie Bernstein, Kimberly A. Bertrand, Elizabeth S. Burnside, Brian D. Carter, Heather Eliassen, Susan M. Gapstur, Mia Gaudet, Christopher Haiman, James M. Hodge, David J. Hunter, Eric J. Jacobs, Esther M. John, Charles Kooperberg, Allison W. Kurian, Loic Le Marchand, Sara Lindstroem, Tricia Lindstrom, Huiyan Ma, Susan Neuhausen, Polly A. Newcomb, Katie M. O’Brien, Janet E. Olson, Irene M. Ong, Tuya Pal, Julie R. Palmer, Alpa V. Patel, Sonya Reid, Lynn Rosenberg, Dale P. Sandler, Christopher Scott, Rulla Tamimi, Jack A. Taylor, Amy Trentham-Dietz, Celine M. Vachon, Clarice Weinberg, Song Yao, Argyrios Ziogas, Jeffrey N. Weitzel, David E. Goldgar, Susan M. Domchek, Katherine L. Nathanson, Peter Kraft, Eric C. Polley, Fergus J. Couch
Journal: New England Journal of Medicine (2021)

Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.
NOD1 sensing of house dust mite–derived microbiota promotes allergic experimental asthma
Authors: Saliha Ait Yahia, Camille Audousset, Daniel Alvarez-Simon, Han Vorng, Dieudonnée Togbe, Philippe Marquillies, Myriam Delacre, Stéphanie Rose, Hélène Bouscayrol, Aline Rifflet, Valérie Quesniaux, Ivo Gomperts Boneca, Mathias Chamaillard, Anne Tsicopoulos
Journal: Journal of Allergy and Clinical Immunology (2021)
Defining a research agenda for youth sport specialisation in the USA: the AMSSM Youth Early Sport Specialization Summit
Authors: Stephanie A Kliethermes, Stephen W Marshall, Cynthia R LaBella, Andrew M Watson, Joel S Brenner, Kyle B Nagle, Neeru Jayanthi, M Alison Brooks, Adam S Tenforde, Daniel C Herman, John P DiFiori, Anthony I Beutler
Journal: British Journal of Sports Medicine (2021)

Sport specialisation is becoming increasingly common among youth and adolescent athletes in the USA and many have raised concern about this trend. Although research on sport specialisation has grown significantly, numerous pressing questions remain pertaining to short-term and long-term effects of specialisation on the health and well-being of youth, including the increased risk of overuse injury and burnout. Many current elite athletes did not specialise at an early age. Methodological and study design limitations impact the quality of current literature, and researchers need to prioritise pressing research questions to promote safe and healthy youth sport participation. The American Medical Society for Sports Medicine hosted a Youth Early Sport Specialization Summit in April 2019 with the goal of synthesising and reviewing current scientific knowledge and developing a research agenda to guide future research in the field based on the identified gaps in knowledge. This statement provides a broad summary of the existing literature, gaps and limitations in current evidence and identifies key research priorities to help guide researchers conducting research on youth sport specialisation. Our goals are to help improve the quality and relevance of research on youth sport specialisation and to ultimately assure that opportunities for healthy and safe sport participation continue for all youth.
Confirmed three-year RFS and OS of the randomized trial of adjuvant S-1 versus S-1 plus docetaxel after curative resection of pStage III gastric cancer (JACCRO GC-07).
Authors: Kazuhiro Yoshida, Yasuhiro Kodera, Mitsugu Kochi, Takeshi Sano, Yoshihiro Kakeji, Wataru Ichikawa, Shintaro Kurahashi, Hironori Yamaguchi, Takahiro Toyokawa, Masato Nakamura, Kazumasa Fujitani, Yoshinari Mochizuki, Mitsuhiko Ota, Jun Hihara, Yoichi Makari, Atsushi Takeno, Masahiro Takeuchi, Masashi Fujii
Journal: Journal of Clinical Oncology (2021)

159 Background: JACCRO GC-07 is a randomized controlled trial to explore postoperative S-1/docetaxel compared to S-1 alone after D2 gastrectomy for pStage III gastric cancer (GC) patients. The second interim analysis demonstrated that the significant improvement of RFS was obtained by S-1/docetaxel compared to S-1 alone. The study was terminated by the recommendation of independent data and safety monitoring committee and the results were reported at ASCO 2018 and published in the Journal of Clinical Oncology (Yoshida K et al. 2019; 37:1296-1304). As 3 years have passed after completion of the enrollment, preplanned analysis was performed with the updated information of the patients. Methods: Patients with pStage III GC were randomly assigned to receive either S-1/docetaxel (S-1 80-120mg/body on days 1-14 with a 7-day rest followed by docetaxel 40mg/m 2 on day 1 and S-1 80-120mg/body on days 1-14 every 21 days for 6 cycles followed by S-1 80-120mg/body on days 1-28 every 42 days for 4 cycles) or S-1 (80-120mg/body on days 1-28 every 42 days for 8 cycles) after D2 gastrectomy. Block randomization was performed by a central interactive computerized system stratified by the stage (IIIA, IIIB, IIIC) and histological type (differentiated or undifferentiated). The sample size of 1,100 was necessary to detect a 7% increase in the 3-year RFS. The primary endpoint was 3y RFS and the secondary endpoints were OS, TTF and safety. Results: In the present analysis, 400 recurrences and 324 deaths were confirmed among 912 patients during the median follow-up period of 42.5 months (0.3-85.16). The 3y RFS of 67.7% in the S-1/docetaxel group was significantly superior to 57.4% in the S-1 group (HR 0.715, 95% CI: 0.587-0.871, p = 0.0008) and the 3y OS was 77.7% in the S-1/docetaxel group and that of S-1 group was 71.2%, respectively (HR 0.742, 95% CI: 0.596-0.925, p = 0.0076), confirming the significant improving effect on the survival of the patient. Conclusions: Adjuvant S-1 plus docetaxel is recommended for patients with pStage III gastric cancer who underwent D2 gastrectomy without neoadjuvant chemotherapy. Clinical trial information: UMIN 000010337.