tbuckley/cabot-search huggingface dataset:
Significantly Lower Rates of Kidney Transplantation among Candidates Listed with the Veterans Administration: A National and Local Comparison
Authors: Joshua J. Augustine, Susana Arrigain, Krishna Balabhadrapatruni, Niraj Desai, Jesse D. Schold
Journal: Journal of the American Society of Nephrology (2018)

Background The process for evaluating kidney transplant candidates and applicable centers is distinct for patients with Veterans Administration (VA) coverage. We compared transplant rates between candidates on the kidney waiting list with VA coverage and those with other primary insurance. Methods Using the Scientific Registry of Transplant Recipients database, we obtained data for all adult patients in the United States listed for a primary solitary kidney transplant between January 2004 and August 2016. Of 302,457 patients analyzed, 3663 had VA primary insurance coverage. Results VA patients had a much greater median distance to their transplant center than those with other insurance had (282 versus 22 miles). In an adjusted Cox model, compared with private pay and Medicare patients, VA patients had a hazard ratio (95% confidence interval) for time to transplant of 0.72 (0.68 to 0.76) and 0.85 (0.81 to 0.90), respectively, and lower rates for living and deceased donor transplants. In a model comparing VA transplant rates with rates from four local non-VA competing centers in the same donor service areas, lower transplant rates for VA patients than for privately insured patients persisted (hazard ratio, 0.72; 95% confidence interval, 0.65 to 0.79) despite similar adjusted mortality rates. Transplant rates for VA patients were similar to those of Medicare patients locally, although Medicare patients were more likely to die or be delisted after waitlist placement. Conclusions After successful listing, VA kidney transplant candidates appear to have persistent barriers to transplant. Further contemporary analyses are needed to account for variables that contribute to such differential transplant rates.
Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials
Authors: Cesare Gridelli, Alessandro Morabito, Luigi Cavanna, Andrea Luciani, Paolo Maione, Laura Bonanno, Virginio Filipazzi, Silvana Leo, Saverio Cinieri, Fortunato Ciardiello, Marco Angelo Burgio, Domenico Bilancia, Diego Cortinovis, Francesco Rosetti, Roberto Bianco, Vittorio Gebbia, Fabrizio Artioli, Roberto Bordonaro, Vittorio Fregoni, Manlio Mencoboni, Fabrizio Nelli, Ferdinando Riccardi, Giuditta di Isernia, Raffaele Costanzo, Gaetano Rocco, Gennaro Daniele, Simona Signoriello, Maria Carmela Piccirillo, Ciro Gallo, Francesco Perrone
Journal: Journal of Clinical Oncology (2018)

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.
Identification of CABIN1-beta as a novel target of epigenetic inactivation in gastric cancer
Authors: Minoru Toyota, Hiromu Suzuki, Suguru Ishii, Kimishige Akino, Masanobu Kusano, Hiroaki Mita, Yasushi Sasaki, Fumio Itoh, Yuji Hinoda, Takashi Tokino, Kohzoh Imai
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

916 

Aberrant methylation plays a role in gene silencing in human neoplasia. Using a DNA fragments aberrantly methylated in cancer as molecular markers, genes inactivated in cancer can be obtained. Here, we have identified CABIN1-beta, an alternative transcript of CABIN1, as a target of epigenetic inactivation in human cancer using a DNA fragment obtained by a methylation scanning technique, methylated CpG island amplification (MCA). Absence of expression accompanied by aberrant methylation of CABIN1-beta was detected in 10 of 15 gastric cancer cell lines. Silencing of CABIN1-beta was closely associated with cytosine methylation and histone deacetylation of the region around transcription start site of the genes. In primary gastric cancer, CABIN1-beta CpG island is methylated in 52 of 77 (68%) cases, and gastric cancer xenografts that showed methylation lost of expression of the gene. CABIN1-beta localized to cytoplasm, due to lack of nuclear localization signal, which exists in CABIN1. Introduction of CABIN1 -beta suppressed colony formation in gastric cancer cell lines that lost gene expression due to DNA methylation. These results indicate that CABIN1 -beta is a putative tumor suppressor gene that is frequently inactivated by epigenetic mechanism in gastric cancer.
Differing Structural and Functional Patterns of Optic Nerve Damage in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder
Authors: Ting Shen, Yuyi You, Sukanya Arunachalam, Ariadna Fontes, Sidong Liu, Vivek Gupta, John Parratt, Chenyu Wang, Michael Barnett, Joshua Barton, Nitin Chitranshi, Ling Zhu, Clare L. Fraser, Stuart L. Graham, Alexander Klistorner, Con Yiannikas
Journal: Ophthalmology (2018)
Does obesity change the effect of aromatase inhibitors (AIs) on estradiol, leptin, insulin, and IGF-1 serum levels in breast cancer patients?
Authors: Mehmet Artac, Dudu Askin, Aysel Kiyici, Onder Orhan Eren, Mufide Oncel, Melih Cem Boruban, Hakan Sat Bozcuk
Journal: Journal of Clinical Oncology (2012)

e11008 Background: The complexity of the relationship between obesity and breast cancer reflects important contributions of obesity-related factors in the adjuvant therapy. The efficacy of adjuvant AIs compared to tamoxifen is lower in obese postmenopausal women. Therefore, we aimed to identify whether the effect of AIs on estradiol, leptin, insulin, and IGF-1 serum levels with respect to the status of the obesity in breast cancer patients. Methods: A total of 34 postmenopausal breast cancer patients treated with adjuvant AIs were enrolled in the study. Pretreatment and 3 months after treatment body weight, height, waist-to-hip (WHR) ratio and body mass index (BMI) were recorded. Blood samples for serum estradiol, leptin, insulin and IGF-1 were drawn after 12 hour starvation and stored in – 70 o before and 3 months after the onset of AI treatment. Results: Median age and BMI were 61 years (range 49-84) and 31 (range 22-43), respectively. 18 (%52.9) patients were treated with letrozole and 16 (%47.1) patients were treated with anastrazole. There was no change in the 3 months period in weight, BMI and WHR. Estradiol levels were decreased significantly between the baseline and the 3rd month (p&lt;0.01). There was a slight increase in the leptin levels between the basal and 3rd month (p&gt;0.05). No significant change was detected in insulin and IGF-1 levels in the follow-up period. In the multivariate regression model, there was no difference between the effect of letrozole and anastrazole on estradiol levels. Pretreatment BMI did not alter the effect of AIs on estradiol levels. The only factor related with the effect of the AIs is the pretreatment estradiol levels. Conclusions: This study shows that the suppression of estrogen in obese breast cancer patients with AIs at the standard doses may not be different from non-obese patients. Further researches may show us other mechanisms for the obesity-related factors to improve outcome with aromatase inhibition in obese breast cancer patients.
Efficacy and safety of <scp>SQ</scp> house dust mite sublingual immunotherapy‐tablet in Japanese children
Authors: Keisuke Masuyama, Yoshitaka Okamoto, Kazuhiro Okamiya, Ryuji Azuma, Toshiaki Fujinami, Bente Riis, Katsuyo Ohashi‐Doi, Kensuke Natsui, Toru Imai, Kimihiro Okubo
Journal: Allergy (2018)

Abstract Background The SQ house dust mite ( HDM ) sublingual immunotherapy ( SLIT )‐tablet ( TO ‐203, Torii, Japan/ ALK , Denmark) treatment has been effective against respiratory allergic diseases in patients aged ≥12 years during European, Japanese, and North American trials. This trial was conducted to investigate the efficacy and safety of this treatment in Japanese children (5‐17 years) with moderate‐to‐severe HDM allergic rhinitis ( AR ). Methods In this randomized, double‐blind, placebo‐controlled trial, 458 Japanese children were randomly assigned to a daily SQ HDM SLIT ‐tablet [10 000 Japanese Allergy Unit ( JAU ), equivalent to 6 SQ ‐ HDM in Europe and the US ] or placebo (1:1) treatment for 1 year. Inclusion required an AR symptom score of ≥7 on at least 7 days during a 14‐day run‐in period while symptomatic treatment was withdrawn. The primary endpoint was the total combined rhinitis score ( TCRS ) comprising AR symptom and medication scores during the last 8 weeks of the treatment period. Results The analysis of primary endpoint demonstrated statistically significant absolute reduction in TCRS of 1.22 with a relative difference of 23% (95% confidence interval, 14% to 31%) in the 10 000 JAU compared with placebo. Predefined stratified analyses revealed the same degree of efficacy of 1.11 ( P = 0.002), 21% (8% to 32%) and 1.36 ( P = 0.001), 26% (11% to 38%), respectively, in pediatric (5‐11 years) and adolescent subjects (12‐17 years). The treatment was well tolerated by both pediatric and adolescent subjects. Conclusion This trial, for the first time, demonstrated the efficacy and safety of the HDM SLIT ‐tablet in pediatric patients with moderate‐to‐severe HDM AR (Japic CTI ‐152953).
Abstract 12714: Prevalence and Risk Factors of Peripheral Vascular Disease in Rural India: A cross Sectional Study
Authors: Ramyashree Tummala, Kinjal Banerjee, Kapil Mahajan, Anjan Gupta
Journal: Circulation (2016)

Background: Peripheral vascular disease (PVD) is a major cause of morbidity and mortality especially affecting the elderly. PVD is largely undetected due to its silent progression. Ankle brachial index (ABI) is a symptom independent reliable screening tool for PVD in primary care, but remains underused. Our aim was to estimate the burden of PVD in this region and correlate it to various risk factors both quantitatively and qualitatively. Materials and Methods: From an outpatient medical camp in rural India, 100 patients were recruited randomly. They were assessed for symptoms, medical history and risk factor screening that included 11 well known risk factors using a pre formatted questionnaire. ABI was measured by handheld doppler. ABI &lt;0.9 was considered abnormal. The difference in mean distribution of ABI for risk factors was calculated by Student’s t-test and was considered statistically significant for P &lt; 0.05. Odds ratios for various risk factors were calculated. Results: Based on ABI &lt;0.9, PVD was diagnosed in 57 patients. There was a high prevalence of risk factors like age &gt;55 years (67%), hypertension (66%), smoking (42%) and diabetes mellitus (35%). Mean ABI for hypertensive population is 0.85 (95% CI: 0.83-0.88, P=0.02). Mean ABI for smokers is 0.82 (95% CI:0.79-0.85, P=0.03). Mean ABI for diabetics is 0.80 (95% CI: 0.77-0.87, P=0.04). Multivariate risk analysis for PVD showed significant association with hypertension, smoking and diabetes but less significant for age, gender and family history. Conclusion: There is a very high prevalence of PVD in the Indian Population which can be attributed to modifiable risk factors as mentioned above. Defining the population at risk and using ABI as an early screening tool would help in prompt treatment and prevent further complications. A simple, inexpensive screening test like ABI is useful for diagnosing PVD in clinical practice. It helps prevent complications and consequent death by timely diagnosis and treatment.
Clonal diversity predicts adverse outcome in chronic lymphocytic leukemia
Authors: Alexander C. Leeksma, Justin Taylor, Bian Wu, Jeffrey R. Gardner, Jie He, Michelle Nahas, Mithat Gonen, Wendimagegn G. Alemayehu, Doreen te Raa, Tatjana Walther, Jennifer Hüllein, Sascha Dietrich, Rainer Claus, Fransien de Boer, Koen de Heer, Julie Dubois, Maria Dampmann, Jan Dürig, Marinus H. J. van Oers, Christian H. Geisler, Eric Eldering, Ross L. Levine, Vincent Miller, Tariq Mughal, Nicole Lamanna, Mark G. Frattini, Mark L. Heaney, Andrew Zelenetz, Thorsten Zenz, Omar Abdel-Wahab, Arnon P. Kater
Journal: Leukemia (2018)
Natural History of Venous Thromboembolism
Authors: CliveKearon
Journal: Circulation (2003)

Most deep vein thromboses (DVTs) start in the calf, and most probably resolve spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms or symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins and subsequently cause PE increases with the severity of the initiating prothrombotic stimulus. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Proximal DVTs resolve slowly during treatment with anticoagulants, and thrombi remain detectable in half of the patients after a year. Resolution of DVT is less likely in patients with a large initial thrombus or cancer. About 10% of patients with symptomatic DVTs develop severe post-thrombotic syndrome within 5 years, and recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly fatal, and an additional 5% cause death later, despite diagnosis and treatment. A...
Atorvastatin Versus Placebo for Prostate Cancer Before Radical Prostatectomy—A Randomized, Double-blind, Placebo-controlled Clinical Trial
Authors: Teemu J. Murtola, Heimo Syvälä, Teemu Tolonen, Mika Helminen, Jarno Riikonen, Juha Koskimäki, Tomi Pakarainen, Antti Kaipia, Taina Isotalo, Paula Kujala, Teuvo L.J. Tammela
Journal: European Urology (2018)
Margaret McCartney: Health technology and the modern inverse care law
Authors: Margaret McCartney
Journal: BMJ (2018)

As Jeremy Hunt left his position as England’s health secretary he welcomed his successor with a tweet: “Couldn’t ask for a better successor than @matthancock to take forward long term NHS plan with his brilliant understanding of the power of technology. The new NHS app will be in safe hands!”1

The only thing I knew about Matt Hancock was that he already had an app of his own. This app was accused of basic privacy flaws (such as allowing access to photographs on a smartphone even when the user had denied this option: it has now been updated).2 We all make mistakes, we’re all human, etc.

Hancock told an audience this year …
MicroRNA-218-5p Promotes Endovascular Trophoblast Differentiation and Spiral Artery Remodeling
Authors: Jelena Brkić, Caroline Dunk, Jacob O’Brien, Guodong Fu, Lubna Nadeem, Yan-ling Wang, David Rosman, Mohamed Salem, Oksana Shynlova, Issaka Yougbaré, Heyu Ni, Stephen J. Lye, Chun Peng
Journal: Molecular Therapy (2018)
The NHS plan
Authors: K. Boomla
Journal: BMJ (2000)

Plan represents considerable privatisationEditor-Dixon and Dewar's editorial welcomes the considerable injection of money promised in the NHS plan and claims that the plan is true to the NHS's founding principles. 1 Yet Aneurin Bevan's greatest achievement, and not one demanded of him by the Beveridge report, was the nationalisation of hospitals.He recognised that ownership was important, because with ownership comes control.The NHS plan promises 100 new hospitals by 2010 (69 of which are already in the pipeline).This will involve £7bn of new investment under the private finance initiative.Together with the new plans for some NHS operating to be carried out in the private sector, the NHS plan represents a larger privatisation than even the Tories planned.Curiously, the plan also recognises the failure of past privatisations.I remember unsuccessfully voting against the privatisation of cleaning at the London Hospital when I was a board member of the old Tower Hamlets Health Authority.Squalid wards followed, and they remain with us now.The plan recognises that this policy was a disaster.Altogether £30m of cash is to be injected into hospital trusts before the next election to pay for the consequences of this mistaken minor privatisation.How much money will we have to spend in five, 10, or 20 years' time to correct the disastrous policy of major privatisation that we are now heading for?Mr Milburn, think again, before it is too late.
Medical cannabis will be available on prescription in UK from autumn
Authors: Ingrid Torjesen
Journal: BMJ (2018)

Medicines derived from cannabis will be able to be prescribed on the NHS for patients with an exceptional clinical need by specialist clinicians from the autumn, the government announced today.

A clear definition of what constitutes a cannabis derived medicinal product will be developed by the Department for Health and Social Care for England and the UK Medicines and Health Products Regulatory Agency, and only products meeting this definition will be rescheduled under the UK’s misuse of drugs legislation as schedule 2 …
Three Distinct Patterns of Ventricular Activation in Infarcted Human Hearts
Authors: RobertHatala, PierreSavard, GaétanTremblay, PierrePagé, RenéCardinal, FranckMolin, TeresaKus, RéginaldNadeau
Journal: Circulation (1995)

Background Comprehensive data based on single-beat analysis of the ventricular activation sequence during sinus rhythm in infarcted hearts are currently not available. It was the aim of our study (1) to measure and analyze these activation sequences on the epicardial surface of the right and left ventricles and on the left ventricular endocardial surface, and (2) to correlate specific activation patterns with the surface ECG. Methods and Results Isochronal maps were computed from 127 endocardial and epicardial unipolar electrograms recorded simultaneously during sinus rhythm in 45 post–myocardial infarction patients operated on for recurrent ventricular tachycardia (age, 57±10 years [mean±SD], left ventricular ejection fraction, 29±9%). Patients with bundle-branch block, but not with intraventricular conduction defects, were excluded. Data such as the timing of initial and terminal activation, the number of breakthroughs, the total activation time, and the number of ventricular segments without activation...
Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review
Authors: Giovanni A. Fava, Giada Benasi, Marcella Lucente, Emanuela Offidani, Fiammetta Cosci, Jenny Guidi
Journal: Psychotherapy and Psychosomatics (2018)

Background: Serotonin-noradrenaline reuptake inhibitors (SNRI) are widely used in medical practice. Their discontinuation has been associated with a wide range of symptoms. The aim of this paper is to identify the occurrence, frequency, and features of withdrawal symptoms after SNRI discontinuation. Methods: PRISMA guidelines were followed to conduct a systematic review. Electronic databases included PubMed, the Cochrane Library, Web of Science, and MEDLINE from the inception of each database to June 2017. Titles, abstracts, and topics were searched using a combination of the following terms: “duloxetine” OR “venlafaxine” OR “desvenlafaxine” OR “milnacipran” OR “levomilnacipran” OR “SNRI” OR “second generation antidepressant” OR “serotonin norepinephrine reuptake inhibitor” AND “discontinuation” OR “withdrawal” OR “rebound.” Only published trials in the English language were included. Results: Sixty-one reports met the criteria for inclusion. There were 22 double-blind randomized controlled trials, 6 studies where patients were treated in an open fashion and then randomized to a double-blind controlled phase, 8 open trials, 1 prospective naturalistic study, 1 retrospective study, and 23 case reports. Withdrawal symptoms occurred after discontinuation of any type of SNRI. The prevalence of withdrawal symptoms varied across reports and appeared to be higher with venlafaxine. Symptoms typically ensued within a few days from discontinuation and lasted a few weeks, also with gradual tapering. Late onset and/or a longer persistence of disturbances occurred as well. Conclusions: Clinicians need to add SNRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with other types of psychotropic drugs. The results of this study challenge the use of SNRI as first-line treatment for mood and anxiety disorders.
Timing of Onset of Adverse Cutaneous Reactions Associated With Programmed Cell Death Protein 1 Inhibitor Therapy
Authors: Leo L. Wang, Gopal Patel, Zelma C. Chiesa-Fuxench, Suzanne McGettigan, Lynn Schuchter, Tara C. Mitchell, Michael E. Ming, Emily Y. Chu
Journal: JAMA Dermatology (2018)

An increasing number of cutaneous adverse reactions resulting from use of programmed cell death protein 1 (PD-1) inhibitors have been described, but with relatively little focus to date on the timing of these reactions.To determine the timing of cutaneous drug reactions after initiation of PD-1 inhibitor therapy.This retrospective observational study included patients referred to an academic dermatology clinic by an oncologist from January 1, 2014, through February 28, 2018, with at least 1 skin biopsy specimen of a skin reaction associated with PD-1 inhibitor use. Participants were included if they had a biopsy-proven cutaneous reaction in response to a PD-1 inhibitor used alone or in combination with ipilimumab.All patients included in this study received pembrolizumab, nivolumab, or nivolumab with ipilimumab as immunotherapy for cancer.The main outcome measure was time to onset of biopsy-proven cutaneous reactions that occurred during or after use of pembrolizumab or nivolumab.A total of 17 patients (12 men, 5 women; mean [SD] age, 68.6 [11.1] years) were identified who presented with cutaneous adverse reactions associated with PD-1 inhibitor therapy; these reactions included lichenoid dermatitis, bullous pemphigoid, erythema multiforme, eczema, lupus, and sarcoidosis. Twelve patients presented with reactions at least 3 months after beginning pembrolizumab or nivolumab therapy. The skin reactions presented a median (range) of 4.2 months (0.5-38.0 months) after drug initiation. In 5 cases, the cutaneous adverse reactions attributed to the PD-1 inhibitor therapy developed after the drug therapy was terminated.Diverse cutaneous adverse reactions secondary to PD-1 inhibitor use may present with delayed onsets and even after discontinuation of therapy. Dermatologists should be aware of the potential for delayed presentations of cutaneous adverse reactions.