tbuckley/cabot-search huggingface dataset:
SAT0249 Gastrointestinal health care resource use and costs associated with nonsteroidal antiinflammatory drugs: analysis of a population cohort in israel
Authors: Y Cohen, NL Freeman, SX Kong, D Arbel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Gastrointestinal (GI) toxicity is one of the major adverse effects of nonsteroidal antiinflammatory drugs (NSAIDs). Studies in several countries have demonstrated that NSAID-related gastropathy is associated with a considerable economic burden, which includes increased hospitalizations, physician visits, diagnostic tests and use of gastroprotective agents (GPAs) for prophylaxis or treatment. <h3>Objectives</h3> This study estimated the gastropathy-related health care resource consumption and costs associated with prescriptions of NSAIDs, in a large cohort in Israel. <h3>Methods</h3> We analysed the Maccabi clinical database which covers a population of 1.5 million. Patients who received any NSAID prescription between June 1998 and May 1999 were identified and sub-grouped according to patterns of NSAID consumption (incidental: 1–2 vs chronic: 3 or more prescriptions) and age (&lt;65 vs 65 years or older). As a population baseline measure of gastropathy rate, age- and sex-matched controls, defined as patients who did not have any NSAID prescriptions during the study period, were randomly selected. Outcome measures included the use of GPAs, gastroenterologist consultations, gastroendoscopy and upper GI imaging tests. Hospitalizations for GI complications were not included in this study. <h3>Results</h3> During the one-year study period, 194,814 patients were identified with a total of 365,624 NSAID prescriptions filled. About 82% were incidental users and 18% were chronic NSAID users. Overall, 22% of the NSAID users had GPA prescriptions, compared to 8% of matched controls (a 14% increase in GPA use for patients on NSAIDs). The increases in GPA use were higher among chronic NSAID users and those aged 65 years or older than incidental users and patients below 65 years (20–38% vs 9–10%). H2-blockers comprised 75–80% of the GPA prescriptions, whereas PPI comprised 20–25%. Thus, for each 1 NIS spent on NSAIDs, an additional 0.52 NIS were spent on the treatment or prevention of GI NSAID toxicity (ie, iatrogenic cost factor defined as NSAID drug plus GI costs divided by NSAID drug cost is 1.52); 70% of these costs were spent on GPAs. <h3>Conclusion</h3> Our study showed that the healthcare expenditures for management of NSAID-related gastropathy in Israel were substantial and comparable to published data in other countries. This study may have underestimated the total economic impact of NSAID gastropathy in Israel since hospitalizations for GI complications were not included. Efficacy and safety should be the primary parameters for selecting an antiinflammatory agent. When cost is considered, policy and clinical decision-makers need to take into account the total economic impact, which, in addition to the acquisition costs of these agents, should include health care expenditures for diagnosing, treating and preventing GI side effects.
Two Sorts of Microthrombi in a Patient With Coronavirus Disease 2019 and Lung Cancer
Authors: Fiorella Calabrese, Francesco Fortarezza, Chiara Giraudo, Federica Pezzuto, Eleonora Faccioli, Federico Rea, Demetrio Pittarello, Christelle Correale, Paolo Navalesi
Journal: Journal of Thoracic Oncology (2020)
Phase I study of peptide vaccine with chemotherapy in patients with unresectable colorectal cancer
Authors: K. Yoshimatsu, H. Yokomizo, T. Otani, G. Osawa, K. Ogawa
Journal: Journal of Clinical Oncology (2009)

3067 Background: RNF43 is a cancer testis antigen expressed in colorectal cancer (CRC) but not in normal organs. RNF43–721 induces HLA A24 restricted cytotoxic T lymphocytes (CTL) against RNF43 expressed target. S-1/CPT-11 chemotherapy (CT) is reported to be obtained the similar result to FOLFOX or FOLFIRI as first-line for advanced CRC. We plan phase I study to evaluate the safety of different doses of RNF43–721 emulsified with Montanide ISA51 in combination with S-1/CPT-11 CT expecting synergistic effect. Methods: Inclusion criteria as follows: HLA A24 positive, pathological CRC, life expectancy &gt; 3 months, WBC&gt;3000/mm3, Hb&gt;10mg/dl, Plt&gt;75000/mm3, creatinine&lt;1.2mg/dl, T. bil.&lt;1.5mg/dl, AST, ALT&lt;3x normal limits, written informed consent. Other malignancy, infection, treatment with steroids and immunosuppressive agents, and HBV, HCV, HIV infection are excluded. The study design is dose escalation of peptide (0.5, 1.0, 3.0 mg) with three patients’ cohort. The study regimen is that oral administration of S-1 at 40 mg b.i.d. for 21 consecutive days followed by a 7-day rest period and intravenous infusion of CPT-11 at a dose of 80 mg on days 1 and 15 are performed with weekly subcutaneous injection of peptide vaccine. Two courses are study periods and there is no restriction of therapy after study. Primary endpoint is safety and secondary are CTL, objective response rate and TTP. Results: Twelve patients (pts) were enrolled and 3 pts canceled treatment due to patient's proposal. In 9 evaluable pts, median age of pts with 7 males and 2 females was 61. Standard chemotherapy for CRC were failed in 8 pts. Systemic toxicities were observed in one pt with grade 2 and others were grade 1. Skin reactions were occurred in 7 pts. No pts were obtained CR and PR, 6 pts were SD and 3 were PD. CTL response was observed in 5 pts. TTP was calculated as 204 days. Conclusions: Treatment with peptide vaccine and S-1/CPT-11 CT was well tolerated. These results encourage further clinical trials of peptide vaccine with standard CT for advanced CRC. No significant financial relationships to disclose.
Evaluation of ALK-1 expression in circulating endothelial cells (CECs) as an exploratory biomarker for PF-03446962 undergoing phase I trial in cancer patients
Authors: P. Mancuso, D. R. Shalinsky, A. Calleri, J. Quarna, P. Antoniotti, I. Jilani, D. Hu-Lowe, X. Jiang, C. Gallo-Stampino, F. Bertolini
Journal: Journal of Clinical Oncology (2009)

3573 Background: ALK-1 is a member of the TβRI family &amp; a novel target for antiangiogenic therapy (Rx). PF- 03446962 (PF) is a fully human mAB (IgG2, κ) generated against ALK-1 with dose-dependent preclinical antiangiogenic activities (Hu-Lowe et al, Proc AACR, 2009). This study's objectives were to determine whether: 1) CECs in cancer patients express ALK-1; and 2) whether therapy with PF against ALK-1 will modulate ALK-1 expression or CEC function in an ongoing Ph I trial. Methods: The human mAb was conjugated with alexa fluor 647. ALK-1 expression was assayed by a standardized multicolor flow cytometry assay (Mancuso et al, CCR 2009). Results: ALK-1 expression was characterized on human vascular (HUVEC) &amp; lymphatic (HDLC) endothelial cells; HUVEC &amp; HDLC cells highly express ALK-1 (&gt;99% of these cells are ALK- 1 + ). ALK-1 expression was assessed in healthy controls (n=17) &amp; cancer patients after normalizing for CEC viability. Patients with advanced malignancies had increased numbers of ALK-1 + CECs: Patients with breast ca (n=12), melanoma (n=8), NSCLC (n=11), &amp; CRC (n=4) had 16±12, 39±23, 50±30, &amp; 62±25 ALK-1 + CECs/mL, respectively, vs 7±6 ALK-1 + CECs/mL in controls. In contrast, ALK-1 expression was minimally or not expressed in pts with hematologic malignancies; ALK-1 was absent in CD117 + or CD34 + bone marrow cells. In the Ph I trial, preliminary evidence suggests that PF may alter CEC function; ALK-1 + CECs were markedly reduced in the 1 st two pts studied at EIO after 22 days on Rx. Conclusions: ALK-1 is expressed in CECs. Flow cytometry enables rapid assay of ALK-1 expression in cancer patient blood. ALK-1 is expressed in an increased number of CECs/mL in cancer pts with solid malignancies vs controls. ALK-1 expression in CECs in pts with NSCLC &amp; CRC may correspond to high ALK-1 expression observed in corresponding nonmatched tumor microarrays in addition to other malignancies such as sarcoma, SCLC &amp; neuroendrocine pancreatic ca (Fiedler, Proc ASCO, 2009). Additional preliminary Ph I results will be reported as part of assessing whether CECs may have any role as biomarkers to potentially detect patients with ALK-1 + solid malignancies or monitor anti-ALK-1 therapy. [Table: see text]
Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis
Authors: Thibault Fiolet, Anthony Guihur, Mathieu Edouard Rebeaud, Matthieu Mulot, Nathan Peiffer-Smadja, Yahya Mahamat-Saleh
Journal: Clinical Microbiology and Infection (2020)
Re: The Key Combined Value of Multiparametric Magnetic Resonance Imaging, and Magnetic Resonance Imaging–targeted and Concomitant Systematic Biopsies for the Prediction of Adverse Pathological Features in Prostate Cancer Patients Undergoing Radical Prostatectomy
Authors: Jan Philipp Radtke, Joanne Nyarangi-Dix, Manuel Wiesenfarth, Boris Hadaschik
Journal: European Urology (2020)
SYNTHETIC DRUGS III
Authors: JULIUS STIEGLITZ
Journal: JAMA (1918)

Since the publication of the last article in this series, information supplementary to that given previously has been received as follows:  Neo-Arsphenamin.  —An importing license has been granted by the Federal Trade Commission to the Diarsenol Company, Inc., 475 Elicott Square, Buffalo, for the Canadian brand of neo-arsphenamin, Neodiarsenol. Licenses for neo-arsphenamin have also been issued to the Takamine Laboratories, New York; Farbwerke-Hoechst Company, New York, and Dermatological Research Laboratories, Philadelphia. The price has not been fixed at yet, but the understanding is that the market price will be about $2.25 per 0.6 gm. ampule.  Holocaine Hydrochloride (see Article II, p. 689).  —This may be obtained from the Farbwerke-Hoechst Company, 111 Hudson Street, New York, which still has supplies of the German-made article at the price of 50 cents and 45 cents per gram in containers of 1 and 5 gm., respectively. As the drug may be easily prepared from
Clinical Characteristics and Viral RNA Detection in Children With Coronavirus Disease 2019 in the Republic of Korea
Authors: Mi Seon Han, Eun Hwa Choi, Sung Hee Chang, Byoung-Lo Jin, Eun Joo Lee, Baek Nam Kim, Min Kyoung Kim, Kihyun Doo, Ju-Hee Seo, Yae-Jean Kim, Yeo Jin Kim, Ji Young Park, Sun Bok Suh, Hyunju Lee, Eun Young Cho, Dong Hyun Kim, Jong Min Kim, Hye Young Kim, Su Eun Park, Joon Kee Lee, Dae Sun Jo, Seung-Man Cho, Jae Hong Choi, Kyo Jin Jo, Young June Choe, Ki Hwan Kim, Jong-Hyun Kim
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> There is limited information describing the full spectrum of coronavirus disease 2019 (COVID-19) and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection in children. <h3>Objective</h3> To analyze the full clinical course and the duration of SARS-CoV-2 RNA detectability in children confirmed with COVID-19 in the Republic of Korea, where rigorous public health interventions have been implemented. <h3>Design, Setting, and Participants</h3> This case series of children with COVID-19 was conducted in 20 hospitals and 2 nonhospital isolation facilities across the country from February 18, 2020, to March 31, 2020. Children younger than 19 years who had COVID-19 were included. <h3>Exposures</h3> Confirmed COVID-19, detected via SARS-CoV-2 RNA in a combined nasopharyngeal and oropharyngeal swab or sputum by real-time reverse transcription–polymerase chain reaction. <h3>Main Outcomes and Measures</h3> Clinical manifestations during the observation period, including the time and duration of symptom occurrence. The duration of SARS-CoV-2 RNA detection was also analyzed. <h3>Results</h3> A total of 91 children with COVID-19 were included (median [range] age, 11 [0-18] years; 53 boys [58%]). Twenty children (22%) were asymptomatic during the entire observation period. Among 71 symptomatic cases, 47 children (66%) had unrecognized symptoms before diagnosis, 18 (25%) developed symptoms after diagnosis, and only 6 (9%) were diagnosed at the time of symptom onset. Twenty-two children (24%) had lower respiratory tract infections. The mean (SD) duration of the presence of SARS-CoV-2 RNA in upper respiratory samples was 17.6 (6.7) days. Virus RNA was detected for a mean (SD) of 14.1 (7.7) days in asymptomatic individuals. There was no difference in the duration of virus RNA detection between children with upper respiratory tract infections and lower respiratory tract infections (mean [SD], 18.7 [5.8] days vs 19.9 [5.6] days;<i>P</i> = .54). Fourteen children (15%) were treated with lopinavir-ritonavir and/or hydroxychloroquine. All recovered, without any fatal cases. <h3>Conclusions and Relevance</h3> In this case series study, inapparent infections in children may have been associated with silent COVID-19 transmission in the community. Heightened surveillance using laboratory screening will allow detection in children with unrecognized SARS-CoV-2 infection.
Challenges for the evaluation of digital health solutions—A call for innovative evidence generation approaches
Authors: Chaohui Guo, Hutan Ashrafian, Saira Ghafur, Gianluca Fontana, Clarissa Gardner, Matthew Prime
Journal: npj Digital Medicine (2020)

Abstract The field of digital health, and its meaning, has evolved rapidly over the last 20 years. For this article we followed the most recent definition provided by FDA in 2020. Emerging solutions offers tremendous potential to positively transform the healthcare sector. Despite the growing number of applications, however, the evolution of methodologies to perform timely, cost-effective and robust evaluations have not kept pace. It remains an industry-wide challenge to provide credible evidence, therefore, hindering wider adoption. Conventional methodologies, such as clinical trials, have seldom been applied and more pragmatic approaches are needed. In response, several academic centers such as researchers from the Institute of Global Health Innovation at Imperial College London have initiated a digital health clinical simulation test bed to explore new approaches for evidence gathering relevant to solution type and maturity. The aim of this article is to: (1) Review current research approaches and discuss their limitations; (2) Discuss challenges faced by different stakeholders in undertaking evaluations; and (3) Call for new approaches to facilitate the safe and responsible growth of the digital health sector.
Efficacy of Remdesivir in COVID-19
Authors: Erin K. McCreary, Derek C. Angus
Journal: JAMA (2020)

Christoph D. Spinner, MD; Robert L. Gottlieb, MD, PhD; Gerard J. Criner, MD; José Ramón Arribas López, MD; Anna Maria Cattelan, MD; Alex Soriano Viladomiu, MD; Onyema Ogbuagu, MD; Prashant Malhotra, MD; Kathleen M. Mullane, DO; Antonella Castagna, MD; Louis Yi Ann Chai, MD; Meta Roestenberg, MD; Owen Tak Yin Tsang, MD; Enos Bernasconi, MD; Paul Le Turnier, MD; Shan-Chwen Chang, MD; Devi SenGupta, MD; Robert H. Hyland, DPhil; Anu O. Osinusi, MD; Huyen Cao, MD; Christiana Blair, MS; Hongyuan Wang, PhD; Anuj Gaggar, MD, PhD; Diana M. Brainard, MD; Mark J. McPhail, MD; Sanjay Bhagani, MD; Mi Young Ahn, MD; Arun J. Sanyal, MD; Gregory Huhn, MD; Francisco M. Marty, MD; for the GS-US-540-5774 Investigators
Epidermal growth factor receptor as a molecular determinant of glioblastoma response to dopamine receptor D2 inhibitors
Authors: Yuyu He, Jie Li, Tomoyuki Koga, Jun Ma, Sanjay Dhawan, Yuta Suzuki, Frank Furnari, Varun V Prabhu, Joshua E Allen, Clark C Chen
Journal: Neuro-Oncology (2020)

There are ongoing clinical trials exploring the efficacy of dopamine receptor D2 (DRD2) inhibition against glioblastomas, the most common primary brain tumor. Here we examine potential molecular determinants of this efficacy.The Cancer Genome Atlas glioblastoma database and other published mRNA profiles were used to analyze the DRD2 and epidermal growth factor receptor (EGFR) expression pattern. In vitro and in vivo responses to DRD2 inhibitors were determined using patient-derived xenograft (PDX) glioblastoma models. Immunohistochemical studies were performed on clinically annotated glioblastoma samples derived from patients treated with ONC201.Analysis of clinical glioblastoma specimens derived from independent patient cohorts revealed an inverse correlation between EGFR and DRD2 mRNA expression, with implication that signaling mediated by these proteins shares overlapping functions. In independent panels of PDX glioblastoma lines, high EGFR expression was associated with poor in vitro and in vivo response to DRD2 inhibitors, including haloperidol and ONC201. Moreover, ectopic expression of a constitutively active EGFR, variant (v)III, suppressed glioblastoma sensitivity to ONC201. DRD2 expression positively correlated with expression of rate-limiting enzymes for dopamine synthesis as well as dopamine secretion, suggesting contribution of autocrine DRD2 signaling. Analysis of specimens from patients treated with ONC201 (n = 15) showed an inverse correlation between the intensity of EGFR staining and clinical response. The median overall survival for patients with high and low EGFR staining was 162 and 373 days, respectively (0.037).High EGFR expression is a determinant of poor glioblastoma response to DRD2. This finding should inform future clinical trial designs.
A phase II trial of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with relapsed and/or refractory stage IIIb or stage IV non-small cell lung cancer (NSCLC) stratified by EGFR mutation status
Authors: L. V. Sequist, S. Gettinger, R. Natale, R. Martins, R. Lilenbaum, P. Jänne, J. Gray, T. A. Samuel, D. Grayzel, T. J. Lynch
Journal: Journal of Clinical Oncology (2009)

8073 Background: IPI-504 (retaspimycin hydrochloride) is a potent, water-soluble heat shock protein 90 (Hsp90) inhibitor. IPI-504 causes the degradation of mutated epidermal growth factor receptor (mtEGFR) kinase and cMET in NSCLC cell lines. IPI-504 also significantly reduces tumor growth in murine xenograft models, including tumors resistant to tyrosine kinase inhibitors (TKIs). Methods: This phase II trial is investigating the safety and antitumor activity of intravenous (IV) 400 mg/m 2 IPI-504 given twice weekly for 2 out of 3 weeks. Eligible patients (pts) had stage IIIb (w/ malignant effusion) or stage IV NSCLC that progressed after TKI treatment. EGFR mutation analysis was performed on all pts. Two cohorts (n=10 each) were initially enrolled and stratified by EGFR status (mtEGFR or wtEGFR). Planned cohort expansion to 29 pts occurred if ≥ 1 pt from that cohort had a best response of stable disease (SD) ≥12 wks or partial response (PR). Pts were evaluated for safety and RECIST response every 6 weeks. Central, independent radiology review was performed for all imaging studies. Results: 43 pts have been enrolled: 10 mtEGFR, 17 wtEGFR, 12 pending analysis, and 4 EGFR-failed samples. 19 pts are currently on study. Median age is 62 yrs (range 31–77). Median no. of prior therapies is 3. Common related adverse events are fatigue, nausea, and diarrhea. Anti-tumor activity has been observed, see table. Both cohorts have been expanded. Conclusions: IPI-504 monotherapy has been well tolerated, with evidence of anti-tumor activity, particularly and unexpectedly in the wtEGFR cohort. These data suggest that IPI-504 may have antitumor activity in heavily pretreated pts with advanced NSCLC. Further evaluation continues in the expansion phase of the trial. [Table: see text] [Table: see text]
Stereotactic robotic radiosurgery for localized prostate cancer: Initial evaluation of acute toxicities
Authors: L. E. Ponsky, C. Lillibridge, J. Brindle, Y. Zhang, B. Wessels, D. B. Einstein
Journal: Journal of Clinical Oncology (2009)

e16006 Background: We evaluated the initial acute toxicities experienced by patients treated with cyberknife fractionated radiosurgery for low and low-intermediate risk prostate cancer. Methods: Twenty-two patients with low or low-intermediate risk prostate cancer (T2a, GG 3+3=6 or 3+4=7, PSA &lt;10) were enrolled prospectively on an IRB approved protocol and treated the planning target volume (PTV)(prostate+5mm margin) with cyberknife fractionated radiosurgery to a dose of 36.25 Gy in 5 fractions (7.25Gy/fraction). The target volume included the prostate and seminal vesicles. PSA values, AUA symptom scores (AUA SS), and NCI CTC acute toxicities were analyzed prior to radiosurgery and at 1 month (N=16), 3 months (N=12) and 6 months (N=5)post-treatment. Results: Patients treated on study included 12 with GG 3+3=6 cancer and 10 with GG 3+4=7 cancer. Mean patient age was 66 years old (range 49–79). Mean pre-treatment PSA was 5.29 (range 0.64–9.36) declining to 3.44 (range 0.00–10.43) at 1 month post treatment, 1.99 (range 0.31–3.99) at 3 months post-treatment and 2.08 (1.05–3.13) at 6 months post-treatment. Mean pre-treatment AUA SS was 7 (range 0.–18) increasing to 12 (range 2–29) at 1 month post treatment, decreasing to 8 (range 2–17) at 3 months post-treatment and 11 (3–17). There were 5 grade 1 acute toxicities including (diarrhea, fatigue, mild urinary frequency, hemorrhoid and a rash) and 7 grade 2 toxicities including (bladder spasms, painful urinary, bowel irregularity, rectal pain, urethritis and numbness in the upper thigh), all grade 1 and 2 toxicities resolved within three months of treatment. The one patient with grade 2 thigh numbness was not thought to be study related toxicity. Two patients developed grade 3 toxicity. One developed bacteremia after the transrectal ultrasound guided placement of the fiducials, the infection completely resolved after treatment with antibiotics. One patient on Coumadin developed hematuria which resolved with conservative management. Conclusions: Cyberknife fractionated radiosurgery for patients with early stage prostate cancer appears to be safe on our early initial assessment.Continued evaluation and longer follow-up ongoing. [Table: see text]
Early Detection of CKD: Implications for Low-Income, Middle-Income, and High-Income Countries
Authors: Marcello Tonelli, James A. Dickinson
Journal: Journal of the American Society of Nephrology (2020)

CKD is common, costly, and associated with adverse health outcomes. Because inexpensive treatments can slow the rate of kidney function loss, and because CKD is asymptomatic until its later stages, the idea of early detection of CKD to improve outcomes ignites enthusiasm, especially in low- and middle-income countries where renal replacement is often unavailable or unaffordable. Available data and prior experience suggest that the benefits of population-based screening for CKD are uncertain; that there is potential for harms; that screening is not a wise use of resources, even in high-income countries; and that screening has substantial opportunity costs in low- and middle-income countries that offset its hypothesized benefits. In contrast, some of the factors that diminish the value of population-based screening (such as markedly higher prevalence of CKD in people with diabetes, hypertension, and cardiovascular disease, as well as high preexisting use of kidney testing in such patients) substantially increase the appeal of searching for CKD in people with known kidney risk factors (case finding) in high-income countries as well as in low- and middle-income countries. For both screening and case finding, detection of new cases is the easiest component; the real challenge is ensuring appropriate management for a chronic disease, usually for years or even decades. This review compares and contrasts the benefits, harms, and opportunity costs associated with these two approaches to early detection of CKD. We also suggest criteria (discussed separately for high-income countries and for low- and middle-income countries) to use in assessing when countries should consider case finding versus when they should consider foregoing systematic attempts at early detection and focus on management of known cases.