tbuckley/cabot-search huggingface dataset:
Incorporating dose effects in network meta-analysis
Authors: Jennifer A Watt, Cinzia Del Giovane, Dan Jackson, Rebecca M Turner, Andrea C Tricco, Dimitris Mavridis, Sharon E Straus, Areti-Angeliki Veroniki
Journal: BMJ (2022)

Systematic reviews with network meta-analysis that ignore potential dose effects could limit the applicability and validity of review findings. This article aims to help content experts (eg, clinicians), methodologists, and statisticians better understand how to incorporate dose effects in network meta-analysis. Three models are described that make different clinical and statistical assumptions about how to model dose effects. This article also illustrates the importance of dose effects in understanding the potential risk of harm in people with dementia from cerebrovascular events associated with atypical antipsychotic drug use (quetiapine, olanzapine, and risperidone) and the potential risk of harm in people with nausea and headache associated with cholinesterase inhibitor use (donepezil, galantamine, and rivastigmine). Finally, important considerations when choosing between different network meta-analysis models incorporating dose effects are discussed.
Agent Orange Exposure and Dementia Diagnosis in US Veterans of the Vietnam Era—Reply
Authors: Deborah E. Barnes, Steven Martinez, Kristine Yaffe
Journal: JAMA Neurology (2021)

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Correction: Update in Infectious Diseases
Journal: Annals of Internal Medicine (2002)

Corrections4 June 2002Correction: Update in Infectious DiseasesFREESearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-136-11-200206040-00021 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the 2001 Update in Infectious Diseases (1), the fourth sentence under the heading “Unusual Infections and Modes of Transmission” should read “The patients died 5 to 17 days after symptoms developed” rather than “… after having been bitten.”Reference1. Mandell GL. Update in infectious diseases. Ann Intern Med. 2001;135:897-905. [PMID: 1712880] LinkGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoUpdate in Infectious Diseases Gerald L. Mandell Metrics 4 June 2002Volume 136, Issue 11Page: 855KeywordsInfectious diseases ePublished: 4 June 2002 Issue Published: 4 June 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
An educational programme in neonatal intensive care units (SEPREVEN): a stepped-wedge, cluster-randomised controlled trial
Authors: Laurence Caeymaex, Dominique Astruc, Valérie Biran, Leila Marcus, Florence Flamein, Stephane Le Bouedec, Bernard Guillois, Radia Remichi, Faiza Harbi, Xavier Durrmeyer, Florence Casagrande, Nolwenn Le Saché, Darina Todorova, Ali Bilal, Damien Olivier, Audrey Reynaud, Cécile Jacquin, Jean-Christophe Rozé, Richard Layese, Claude Danan, Camille Jung, Fabrice Decobert, Etienne Audureau
Journal: The Lancet (2022)
Alcohol-related harm during the COVID-19 pandemic
Authors: None The Lancet Gastroenterology & Hepatology
Journal: The Lancet. Gastroenterology & hepatology (2021)

In 2020, deaths from alcohol-specific causes in England and Wales increased by almost 20% compared with 2019, according to the UK's Office for National Statistics; 80% of the alcohol-specific deaths were due to alcohol-related liver disease.
Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth — Eight Integrated Health Care Organizations, United States, December 15, 2020–July 22, 2021
Authors: Heather S. Lipkind, Gabriela Vazquez-Benitez, Malini DeSilva, Kimberly K. Vesco, Christina Ackerman-Banks, Jingyi Zhu, Thomas G. Boyce, Matthew F. Daley, Candace C. Fuller, Darios Getahun, Stephanie A. Irving, Lisa A. Jackson, Joshua T.B. Williams, Ousseny Zerbo, Michael M. McNeil, Christine K. Olson, Eric Weintraub, Elyse O. Kharbanda
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).
The association between tumour sidedness, clinicopathological characteristics and outcomes in patients undergoing curative resection for colon cancer.
Authors: Allan Matthew Golder, Kathryn AF Pennel, David Mansouri, Paul G. Horgan, Campbell SD Roxburgh, Andrew V Biankin, Joanne Edwards, Donald C. McMillan
Journal: Journal of Clinical Oncology (2022)

148 Background: Right-sided colon cancer is associated with worse outcomes than left-sided disease, likely due to an association between tumour/host factors and tumour sidedness. The present study analyses the association between tumour sidedness, clinicopathological features and common mutations to better understand this discrepancy in outcomes. Methods: The association between tumour sidedness, clinicopathological characteristics and survival was examined within a cohort of patients undergoing curative surgery for TNM I-III colon cancer. Results: 3,419 patients were identified. 54% of cases were right-sided and associated with worse 3-year OS/CSS. On multivariate analysis for clinical factors: sex (OR 0.63), Systemic Inflammatory Grade (SIG), anaemia and differentiation (OR 0.80/0.31/0.57) were associated with T3 cancer sidedness and: sex, anaemia and differentiation (OR 0.61/0.46/0.57) were associated with T4 cancer sidedness. On further MVA including mutational factors anaemia/BRAF status remained significant in T3/T4 cancer respectively (OR 0.08/0.09). BRAF mutant status was associated with SIG in all patients/T3 disease (p=0.046/0.016). Conclusions: Worse outcomes seen in right-sided colon cancer are likely explained predominantly by factors including tumour stage, SIG, anaemia and BRAF mutational status. BRAF mutations are associated with the Systemic Inflammatory Response and further research is required to better understand this relationship taking into the tumour microenvironment, microsatellite instability.[Table: see text]
Another KRAS Inhibitor Holds Its Own
Journal: Cancer Discovery (2020)

Abstract According to the KRYSTAL-1 study, the KRASG12c inhibitor adagrasib, also known as MRTX849, is largely well tolerated and shows considerable efficacy in patients with non–small cell lung cancer harboring this mutation. The drug is also active, albeit more modestly, in colorectal cancer and several other solid tumor types.
EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced, Relapsing, and Castration-Resistant Prostate Cancer
Authors: Axel Heidenreich, Patrick J. Bastian, Joaquim Bellmunt, Michel Bolla, Steven Joniau, Theodor van der Kwast, Malcolm Mason, Vsevolod Matveev, Thomas Wiegel, Filiberto Zattoni, Nicolas Mottet
Journal: European Urology (2013)
Impact of Heparin Preadministration for Detection of Prosthetic Valve Endocarditis With FDG PET/CT
Authors: Basak Soydas Turan, M. Fani Bozkurt
Journal: Clinical Nuclear Medicine (2022)

A 57-year-old woman with history of aortic and mitral valves replacement was referred to FDG PET/CT before valvular prosthesis renewal surgery. First FDG PET/CT was suboptimal for interpretation due to prominent physiological myocardial FDG uptake, despite patient preparation including 12 hours of fasting and low-carbohydrate, fat-rich diet. Therefore, scan was repeated with IV heparin preadministration at another day and revealed focal FDG uptake on the region of prosthetic heart valves, suggesting endocarditis. FDG PET/CT has been proven to be a useful technique to detect endocarditis, but appropriate patient preparation for adequate suppression of physiological myocardial uptake is important. Heparin preadministration seems to be an important component of patient preparation.
Trends in Breast Cancer Incidence, by Race, Ethnicity, and Age Among Women Aged ≥20 Years — United States, 1999–2018
Authors: Taylor D. Ellington, Jacqueline W. Miller, S. Jane Henley, Reda J. Wilson, Manxia Wu, Lisa C. Richardson
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Breast cancer is commonly diagnosed among women, accounting for approximately 30% of all cancer cases reported among women.* A slight annual increase in breast cancer incidence occurred in the United States during 2013-2017 (1). To examine trends in breast cancer incidence among women aged ≥20 years by race/ethnicity and age, CDC analyzed data from U.S. Cancer Statistics (USCS) during 1999-2018. Overall, breast cancer incidence rates among women decreased an average of 0.3% per year, decreasing 2.1% per year during 1999-2004 and increasing 0.3% per year during 2004-2018. Incidence increased among non-Hispanic Asian or Pacific Islander women and women aged 20-39 years and decreased among non-Hispanic White women and women aged 50-64 and ≥75 years. The U.S. Preventive Services Task Force currently recommends biennial screening mammography for women aged 50-74 years (2). These findings suggest that women aged 20-49 years might benefit from discussing potential breast cancer risk and ways to reduce risk with their health care providers. Further examination of breast cancer trends by demographic characteristics might help tailor breast cancer prevention and control programs to address state- or county-level incidence rates† and help prevent health disparities.
Phase 1/1b trial of fruquintinib in patients with advanced solid tumors: Preliminary results of the dose expansion cohorts in refractory metastatic colorectal cancer.
Authors: Arvind Dasari, Joleen M. Hubbard, Cathy Eng, Heather Yeckes-Rodin, Stacey M Ukrainskyj, Zhao Yang, William R. Schelman, Marek K. Kania, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2022)

93 Background: Fruquintinib (F) is a highly selective, novel, oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3. The phase (Ph) 3 FRESCO study (NCT02314819) that investigated F (5mg daily, 3 weeks (wks) on 1 wk off) showed improved median overall survival in patients (pts) with metastatic colorectal cancer (mCRC) in third line and beyond when compared to placebo (9.3 vs. 6.6 months); hazard ratio 0.65 (P &lt; 0.001) and led to its approval in China. Methods: This is an ongoing Ph 1/1b open-label, dose escalation/expansion study conducted in the US. Here we present the preliminary safety and antitumor efficacy data from pts with refractory mCRC in Cohort (Coh) B (progressed on all standard therapies including TAS-102 [TAS] and/or regorafenib [R]) and in Coh C (did not receive TAS or R). Results: As of data cutoff on 27 July 2021, 81 mCRC pts had been treated (41 in Coh B and 40 in Coh C); median age of 57 years (range: 34─77), Caucasian (81.5%), female (44.4%), and ECOG PS 1 (59.3%). In Coh B, the median number of prior therapies was 5 (range: 3-9), 8 pts (19.5%) received R, 19 (46.3%) received TAS and 14 (34.1%) received both R and TAS. In Coh C, the median number of prior therapies was 4 (range: 1-10). Five pts remain on treatment; reasons for treatment discontinuation included: 56 pts (69.1%) due to progressive disease or death, 8 pts (9.9%) due to adverse events (AE), and 12 pts (14.8%) due to withdrawal of consent or physician decision. The median duration of F treatment was 4.4 months (range: 0.7– 20.0) in Coh B and 3.7 months (range: 0.02-14.3) in Coh C. The most frequently reported AEs of any grade in Coh B were fatigue (53.7%), proteinuria (51.2%), and hypertension (HTN; 48.8%). In Coh C the most frequently reported AEs of any grade were HTN (75.0%), proteinuria (40.0%), and myalgia (32.5%). Hand-foot syndrome (HFS) was reported in 29.3% of Coh B pts and 22.5% of Coh C pts. The disease control rate [DCR] was 68.3% in Coh B (1 partial response [PR] and 27 stable disease [SD]) and 59.5% for the 37 patients with at least one post-baseline tumor assessment in Coh C (2 PRs and 20 SDs). Conclusions: F is generally well-tolerated in heavily-pretreated pts with refractory mCRC. Evidence of antitumor activity was observed in cohorts B and C. The multi-cohort dose expansion is ongoing. F is being further investigated in refractory mCRC in a global Ph 3 study (NCT04322539). Clinical trial information: NCT03251378.
Abstract 8: Effectiveness of Combination Allogeneic Stem Cells in a Novel Large Animal Model of Chronic Kidney Disease-induced Heart Failure With Preserved Ejection Fraction (HFpEF)
Authors: Angela Castellanos Rieger, Bryon A Tompkins, Makoto Natsumeda, Victoria Florea, Kevin Collon, Jose Rodriguez, Marcus Rosado, Wayne Balkan, Joshua M Hare, Ivonne H Schulman
Journal: Circulation Research (2017)

Background: Chronic Kidney Disease (CKD) is an independent risk factor for cardiovascular morbidity and mortality. Left ventricular (LV) hypertrophy and heart failure with preserved ejection fraction (HFpEF) are the primary manifestations of the cardiorenal syndrome in 60 to 80% of CKD patients. Therapies that improve morbidity and mortality in HFpEF are lacking. Stem cell therapy reduces fibrosis, increases neovascularization, and promotes cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that stem cell treatment ameliorates HFpEF in a CKD model. Methods: Yorkshires pigs (n=27) underwent 5/6 nephrectomy via renal artery embolization and 4-weeks later received either: allogeneic (allo-) MSC (10х10 6 ), allo-kidney c-kit + cells (c-kit; 10х10 6 ), combination (MSC+c-kit; 1:1 ratio [5х10 6 each]), or placebo (each n=5). Cell therapy was delivered via the patent renal artery. Kidney function, renal and cardiac MRI, and PV loops were measured at baseline, and at 4- and 12-weeks (euthanasia) post-embolization. Results: The CKD model was confirmed by increased creatinine and BUN and decreased GFR. Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks (p=0.7). HFpEF was demonstrated at 4 weeks by increased LV mass (20.3%; p= 0.0001), wall thickening (p&lt;0.008), EDP (p=0.01), EDPVR (p=0.005), and arterial elastance (p=0.03), with no change in EF. Diffuse intramyocardial fibrosis was evident in histological analysis and delayed enhancement MRI imaging. After 12 weeks, there was a significant difference in MAP between groups (p=0.04), with an increase in the placebo group (19.97± 8.65 mmHg, p=0.08). GFR significantly improved in the combination group (p=0.033). EDV increased in the placebo (p=0.009) and c-kit (p=0.004) groups. ESV increased most in the placebo group (7.14±1.62ml; p=0.022). EF, wall thickness, and LV mass did not differ between groups at 12 weeks. Conclusion: A CKD large animal model manifests the characteristics of HFpEF. Intra-renal artery allogeneic cell therapy was safe. A beneficial effect of cell therapy was observed in the combination and MSC groups. These findings have important implications on the use of cell therapy for HFpEF and cardiorenal syndrome.
Who should be doing gastrointestinal endoscopy?
Authors: M. Schapiro
Journal: JAMA (1981)

THE QUESTION of who should be doing gastrointestinal (GI) endoscopy is a problem that confronts hospital committees charged with granting endoscopic privileges.<sup>1</sup>The Joint Commission on Accreditation of Hospitals requires that individual medical staffs set criteria for privileges and have a process for delineation of these privileges. The Federation of Digestive Disease Societies has approved<i>Guidelines for Training in Endoscopy</i><sup>2</sup>and the American Society for Gastrointestinal Endoscopy has prepared<i>Guidelines for Standards of Practice of Gastrointestinal Endoscopy</i>.<sup>3</sup>These two documents may guide hospital committees and require further interpretation in that event. <h3>Training Guidelines</h3> The<i>Guidelines for Training</i>apply to residency-fellowship programs and, when adhered to, provide for physicians who are skillful in the ability both to perform endoscopy and to relate the procedures to the care of the patient. Some gastroenterologists as well as many general and colorectal surgeons have not had their training in programs that
QoL analysis: A randomized phase 3 study of sequential versus combination treatment in first-line chemotherapy for metastatic colorectal cancer—The C-cubed study.
Authors: Shingo Noura, Ryo Inada, Hitoshi Ojima, Takeshi Nagasaka, Hiroaki Tanioka, Yoshinori Munemoto, Yasuhiro Shimada, Keiichiro Ishibashi, Yoshiaki Shindo, Mototsugu Shimokawa, Hideyuki Mishima, Yoshiyuki Yamaguchi, Masazumi Okajima
Journal: Journal of Clinical Oncology (2022)

102 Background: The C-cubed (C3) study demonstrated a sequential approach start from ﬂuoropyrimidines (FP) plus bevacizumab (Bmab) followed by oxaliplatin (OX) adding significantly improved a median Treatment failure of strategy (TFS) for a combination approach start from FP+OX+Bmab [15.2 months vs. 7.6 months, HR, 0.475; 95% CI, 0.362 to 0.623; p &lt; 0.0001] in first-line metastatic colorectal cancer (mCRC). In this congress, we focus on the quality of life (QOL) assessments as a pre-planned analysis. (Study information: UMIN000015405). Methods: The C3 study was a randomized phase III study which evaluated the time to discontinuation of OX-containing therapy (sequential approach [Capecitabine/5-FU (FP)+Bmab followed by OX-FP+Bmab] vs. combination approach [OX-FP+Bmab]. The primary endpoint was TFS and secondary endpoints were ORR, OS, PFS, Safety and QoL. QOL assessments included European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire for cancer (QLQ-C30) (EORTC QLQ C-30), EuroQol 5D 5L (EQ5D) and the Patient Neurotoxicity Questionnaire (PNQ) in both arm as a pre-planned analysis. Each questionnaire was collected at the time of enrolment, 6, 12, 18 months and end of treatment. QOL scores were compared using a mixed-effects models for repeated measures (MMRM). Results: A total 292 patients participated in QoL part (arm A: n =148; arm B: n =144). The returned questionnaire sheets were 292 (reply rate: 97%), 206 (68%), 199 (65%), 61 (20%) at baseline, 6, 12, 18 months, respectively. Sequential approach was statistically improved than combination approach as follows: Physical functioning (p&lt;0.001), Cognitive functioning (p=0.012), Social functioning (p=0.0004), and Fatigue (p=0.013) in EORTC QLQ C-30. In addition, at 6 months (after which attrition in the combination arm was more than 50%) after randomization, the mean change rate from baseline of EQ5D score in the sequential approach versus combination approach were: –1.91 (SD 27.57) versus –9.62 (29.60). In contract, PNQ sensory score showed that sequential approach was not statistically improved for combination approach (0.22 [SD: 0.89] vs. 0.61 [SD: 0.95], p=0.115). Conclusions: The further clarification of patients’ characteristics are needed, but this sequential approach can be advocated as a valuable treatment option in first-line mCRC for current guideline based on these QoLs and main efficacy data.
Mammographic Parenchymal Patterns-Reply
Authors: Peter B. Dean
Journal: JAMA (1982)

<h3>In Reply.—</h3> We are not surprised that Dr Frankl's results are not in concordance with ours. Like those of Dr Wolfe, her data suffer from the bias of referral.<sup>1</sup>Our own, much smaller referral patient series (Table 3 in our article) shows a parenchymal pattern distribution similar to hers. The larger proportion of women with N1 and P1 patterns in our screening population reflects the effectiveness of the Kopparberg program in bringing 92.5% of our population younger than 70 years to mammographic evaluation, even in the absence of breast symptoms in most of these women. It seems to us that the relative lack of cancers in the N1 and P1 groups in Dr Frankl's "prevalent" and "incident" series reflects the fact that surgeons often do not refer such patients to preoperative mammography when palpatory findings are unequivocal. The fact that relatively few women with N1 and P1 patterns having
The zebrafish model system for dyslipidemia and atherosclerosis research: Focus on environmental/exposome factors and genetic mechanisms
Authors: Marina Vasyutina, Asiiat Alieva, Olga Reutova, Victoria Bakaleiko, Lada Murashova, Vyacheslav Dyachuk, Alberico L. Catapano, Andrea Baragetti, Paolo Magni
Journal: Metabolism (2022)