tbuckley/cabot-search huggingface dataset:
Associations between age discrimination and health and wellbeing: cross-sectional and prospective analysis of the English Longitudinal Study of Ageing
Authors: Sarah E Jackson, Ruth A Hackett, Andrew Steptoe
Journal: The Lancet Public Health (2019)

BackgroundAge discrimination (or ageism) is pervasive in society. Other forms of discrimination (such as racism) have been linked with adverse health outcomes, but age discrimination has not been well studied in public health. We aimed to examine associations between perceived age discrimination and health and wellbeing in England.MethodsWe did a longitudinal observational population study with data from the English Longitudinal Study of Ageing, a nationally representative sample of older men and women. Participants were aged 50 years or older and reported experiences of age discrimination via a face-to-face computer-assisted personal interview and a self-completed questionnaire between July, 2010, and June, 2011. Self-rated health, chronic health conditions, and depressive symptoms were assessed between July, 2010, and June, 2011, and between May, 2016, and June, 2017. We used logistic regression to test cross-sectional associations between perceived age discrimination and baseline health status and prospective associations between perceived age discrimination and incident ill health over 6 years. Analyses were adjusted for age, sex, and wealth.FindingsOur sample for cross-sectional analyses of 2010–11 data comprised 7731 people who took part in the face-to-face interview, returned the self-completion questionnaire, and had available data for age discrimination. Perceived age discrimination was reported by 1943 (25·1%) participants. Patients who perceived age discrimination were more likely to self-report fair or poor health (odds ratio [OR] 1·32 [95% CI 1·17–1·48]) and to have coronary heart disease (1·33 [1·14–1·54]), chronic lung disease (1·37 [1·11–1·69]), arthritis (1·27 [1·14–1·41]), limiting long-standing illness (1·35 [1·21–1·51]), and depressive symptoms (1·81 [1·57–2·08]) than those who did not perceive age discrimination. Follow-up data collected 6 years after the baseline assessment were available for 5595 participants. Longitudinally, perceived age discrimination was associated with the deterioration of self-rated health (OR 1·32 [95% CI 1·10–1·58]) and incident coronary heart disease (1·66 [1·18–2·35]), stroke (1·48 [1·08–2·10]), diabetes (1·33 [1·01–1·75]), chronic lung disease (1·50 [1·10–2·04]), limiting long-standing illness (1·32 [1·10–1·57]), and depressive symptoms (1·47 [1·16–1·86]) over 6 years.InterpretationAmong older adults living in England, perceived age discrimination was associated with increased odds of poor self-rated health and risk of incident serious health problems over a 6-year period. These findings underscore the need for effective interventions at the population level to combat age stigma and discrimination.FundingUK Economic and Social Research Council.
Abstract 20064: DOCA-salt Hypertension Activates PlGF in the Spleen to Couple Sympathetic Drive and Immune System Activation
Authors: Marialuisa Perrotta, Giuseppe Cifelli, Stefania Fardella, Lorenzo Carnevale, Francesco Mastroiacovo, Fabio Pallante, Giuseppe Lembo, Daniela Carnevale
Journal: Circulation (2017)

Introduction: A significant proportion of hypertensive patients is characterized by low-renin hypertension and salt-sensitivity. Deoxycorticosterone acetate (DOCA)-salt challenge resembles this con...
Chiari malformations: principles of diagnosis and management
Authors: Rory J Piper, Michael Pike, Richard Harrington, Shailendra A Magdum
Journal: BMJ (2019)

### What you need to know

Chiari malformations are a heterogeneous group of hindbrain anomalies. Six different malformations are described. Most common are Chiari 1 malformation (CM1) and Chiari 2 malformation (CM2, also termed “Arnold-Chiari malformation”) and are the focus of this review.

These are rare conditions, but symptoms may impair quality of life in both adults and children,1 causing disruption to work or education and social exclusion. The diagnosis is often delayed or missed as symptoms may be mistaken for other neurological conditions or attributed as psychogenic.2 Not enough information or explanation from healthcare professionals3 can aggravate patients’ fears on being diagnosed. Although some patients improve after surgery, others experience lifelong symptoms, progression of deficits, need for re-operation, and complications.

Non-specialists can play an important role in early diagnosis and referral, counselling, and supporting long term care for these patients. In this clinical update, we summarise the definitions, epidemiology, and …
Concept of placebo should be discarded
Authors: P. C Gotzsche
Journal: BMJ (1995)

progestogens desogestrel and gestodene.Rawlins claims that the committee has to take on the responsibilities of peer reviewers with regard to unpublished information.2In this it presumes to act as both judge and jury, a single role that the United States Food and Drug Administration rightly refuses to assume.Presented with similar problems, the administration embarks on detailed public hearings, with the eventual publication of a comprehensive report.3The necessity for such consultation is evident in the dissent from John Guillebaud, with his great experience of oral contraceptive prescribing4; Clifford Kay, who directed the Royal College of General Practitioners' classic investigation into the safety of oral contra-ceptives5; and W 0 Spitzer, whose transnational study was used by the Committee on Safety of Medicines in reaching its decision.6In justifying the committee's decision Rawlins dismisses the methodological problems in the recent studies of venous thromboembolism in women using the pill yet attempts to undermine the importance to be attached to the accumulating data on stroke and myocardial infarction.2He also denigrates the importance of changes in lipoprotein concentrations induced by oral con- traceptives, on the basis of a review that hardly discusses this issue.The risks of stroke and myocardial infarction are a critical consideration.Women of childbearing age are 15 times more likely to die of arterial disease than of venous thromboembolic disease, and the third generation pills were introduced specifically to reduce the risks of arterial disease in women using oral contraceptives.This is acknowledged in the fact that the European Committee for Proprietary Medicinal Products is to defer a decision on the safety of the third generation pills.Unfortunately, the precipitate action of the Committee on Safety of Medicines may have seriously damaged our chances of learning just what effect the new pills have on arterial disease.More importantly still, it may also have irrevocably undermined any further research and development on oral contraceptives by the pharmaceutical industry.What justification can there be for such work if it is to be rendered irrelevant overnight by a single rush to judgment?VICTORWYNN
Video-assisted thoracic lobectomy<i>versus</i>stereotactic body radiotherapy for stage I nonsmall cell lung cancer in elderly patients: a propensity matched comparative analysis
Authors: Deniece D.E.M.A. Detillon, Mieke J. Aarts, Katrien De Jaeger, Casper H.J. Van Eijck, Eelco J. Veen
Journal: European Respiratory Journal (2019)

Comparative studies of the overall survival (OS) in elderly patients with nonsmall cell lung cancer (NSCLC) after surgery or stereotactic body radiotherapy (SBRT) have been limited by mixed extents of resection and different surgical approaches. 792 patients aged ≥65 years with clinical stage I NSCLC underwent video-assisted thoracic surgery (VATS) lobectomy or SBRT between 2010 and 2015. The propensity score-matched primary analysis included data from the full cohort; the secondary analysis included data from a subgroup of patients with data on pulmonary function. Median OS for unmatched patients was 77 months for patients undergoing VATS lobectomy and 38 months for SBRT. The 1-, 3- and 5-year OS rates after VATS lobectomy were 92%, 76% and 65%, and after SBRT were 90%, 52% and 29% (p&lt;0.001). Median OS for matched patients in the primary analysis was 77 months for patients undergoing VATS lobectomy and 33 months for SBRT. The 1-, 3- and 5-year OS rates after VATS lobectomy were 91%, 68% and 58%, and after SBRT were 87%, 46% and 29% (p&lt;0.001). The survival advantage with VATS lobectomy persisted in the secondary analysis after adjusting for non-matched variables (p=0.034). We suggest that elderly patients with stage I NSCLC undergoing VATS lobectomy have a better rate of OS than patients undergoing SBRT, irrespective of matching. This could be clinically important in decision-making for elderly patients who can tolerate surgery.
A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer
Authors: J. Veeraraghavan, C. De Angelis, R. Mao, T. Wang, S. Herrera, A.C. Pavlick, A. Contreras, P. Nuciforo, I.A. Mayer, A. Forero, R. Nanda, M.P. Goetz, J.C. Chang, A.C. Wolff, I.E. Krop, S.A.W. Fuqua, A. Prat, S.G. Hilsenbeck, B. Weigelt, J.S. Reis-Filho, C. Gutierrez, C.K. Osborne, M.F. Rimawi, R. Schiff
Journal: Annals of Oncology (2019)

HER2-positive (+) breast cancers, defined by HER2 overexpression and/or amplification, are often addicted to HER2 to maintain their malignant phenotype. Yet, some HER2+ tumors do not benefit from anti-HER2 therapy. We hypothesize that HER2 amplification levels and PI3K pathway activation are key determinants of response to HER2-targeted treatments without chemotherapy.Baseline HER2+ tumors from patients treated with neoadjuvant lapatinib plus trastuzumab [with endocrine therapy for estrogen receptor (ER)+ tumors] in TBCRC006 (NCT00548184) were evaluated in a central laboratory for HER2 amplification by fluorescence in situ hybridization (FISH) (n = 56). HER2 copy number (CN) and FISH ratios, and PI3K pathway status, defined by PIK3CA mutations or PTEN levels by immunohistochemistry were available for 41 tumors. Results were correlated with pathologic complete response (pCR; no residual invasive tumor in breast).Thirteen of the 56 patients (23%) achieved pCR. None of the 11 patients with HER2 ratio <4 and/or CN <10 achieved pCR, whereas 13/45 patients (29%) with HER2 ratio ≥4 and/or CN ≥10 attained pCR (P = 0.0513). Of the 18 patients with tumors expressing high PTEN or wild-type (WT) PIK3CA (intact PI3K pathway), 7 (39%) achieved pCR, compared with 1/23 (4%) with PI3K pathway alterations (P = 0.0133). Seven of the 16 patients (44%) with HER2 ratio ≥4 and intact PI3K pathway achieved pCR, whereas only 1/25 (4%) patients not meeting these criteria achieved pCR (P = 0.0031).Our findings suggest that there is a clinical subtype in breast cancer with high HER2 amplification and intact PI3K pathway that is especially sensitive to HER2-targeted therapies without chemotherapy. A combination of HER2 FISH ratio and PI3K pathway status warrants validation to identify patients who may be treated with HER2-targeted therapy without chemotherapy.
Association of NSAID Use and Renal Complications
Authors: Samuel A. Silver, Danielle M. Nash, Ron Wald
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
DECIPHER pooled shRNA library screen identifies PP2A and FGFR signaling as potential therapeutic targets for diffuse intrinsic pontine gliomas
Authors: Kathrin Schramm, Murat Iskar, Britta Statz, Natalie Jäger, Daniel Haag, Mikołaj Słabicki, Stefan M Pfister, Marc Zapatka, Jan Gronych, David T W Jones, Peter Lichter
Journal: Neuro-Oncology (2019)

Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive pediatric brain tumors that are characterized by a recurrent mutation (K27M) within the histone H3 encoding genes H3F3A and HIST1H3A/B/C. These mutations have been shown to induce a global reduction in the repressive histone modification H3K27me3, which together with widespread changes in DNA methylation patterns results in an extensive transcriptional reprogramming hampering the identification of single therapeutic targets based on a molecular rationale.We applied a large-scale gene knockdown approach using a pooled short hairpin (sh)RNA library in combination with next-generation sequencing in order to identify DIPG-specific vulnerabilities. The therapeutic potential of specific inhibitors of candidate targets was validated in a secondary drug screen.We identified fibroblast growth factor receptor (FGFR) signaling and the serine/threonine protein phosphatase 2A (PP2A) as top depleted hits in patient-derived DIPG cell cultures and validated their lethal potential by FGF ligand depletion and genetic knockdown of the PP2A structural subunit PPP2R1A. Further, pharmacological inhibition of FGFR and PP2A signaling through ponatinib and LB-100 treatment, respectively, exhibited strong tumor-specific anti-proliferative and apoptotic activity in cultured DIPG cells.Our findings suggest FGFR and PP2A signaling as potential new therapeutic targets for the treatment of DIPGs.
A Phase 3, Randomized, Double-Masked Study of OTX-101 Ophthalmic Solution 0.09% in the Treatment of Dry Eye Disease
Authors: Damien F. Goldberg, Ranjan P. Malhotra, Barry A. Schechter, Angela Justice, Sidney L. Weiss, John D. Sheppard
Journal: Ophthalmology (2019)

PurposeTo evaluate the safety and efficacy of OTX-101, a novel aqueous nanomicellar formulation of cyclosporine (0.09%), in the treatment of patients with dry eye disease (DED).DesignA randomized, multicenter, vehicle-controlled, double-masked, phase 3 clinical trial.ParticipantsAdults (18–90 years of age) with a history and clinical diagnosis of DED, a global symptom score of 40 or more (range, 0–100), and a lissamine green conjunctival staining score of 3 or more and 9 or less (range, 0–12) in at least 1 eye.MethodsEligible patients entered a run-in period of 14 to 20 days in which all patients administered vehicle twice daily. Patients who remained eligible at the baseline (day 0) visit were randomized in a 1:1 ratio to twice-daily treatment with OTX-101 0.09% or vehicle for 84 days.Main Outcome MeasuresEfficacy assessments included signs (unanesthetized Schirmer tear test, corneal and conjunctival staining) and symptoms (global symptom score) of DED. The primary end point was the proportion of eyes with a clinically meaningful improvement (increase of ≥10 mm) in Schirmer test score at day 84. Safety evaluations included adverse events (AEs), visual acuity, and intraocular pressure monitoring, slit-lamp, dilated ophthalmoscopy, and fundus examinations.ResultsA total of 744 patients were randomized and received study medication (371 to OTX-101 0.09% and 373 to vehicle). The primary end point was achieved; a significantly greater percentage of eyes in the OTX-101 0.09% treatment group achieved an increase of 10 mm or more in the Schirmer test score at day 84 (OTX-101 0.09%, 16.6%; vehicle, 9.2%; P < 0.001). Significant improvements relative to vehicle also were observed for corneal (days 28, 56, and 84) and conjunctival (days 56 and 84) staining. The global symptom score was reduced from baseline in both treatment groups by approximately 30%; however, no significant separation between groups was observed. The OTX-101 0.09% formulation was well tolerated. Treatment-emergent AEs were primarily mild in intensity.ConclusionsClinically and statistically significant improvements in tear production and ocular surface integrity were observed in patients treated with OTX-101 0.09% for DED.
Outbreak of hepatitis A virus infection in Taiwan, June 2015 to September 2017
Authors: Wan-Chin Chen, Po-Hsun Chiang, Yu-Hsin Liao, Lin-Ching Huang, Ying-Jung Hsieh, Chu-Ming Chiu, Yi-Chun Lo, Chin-Hui Yang, Jyh-Yuan Yang
Journal: Eurosurveillance (2019)

The Taiwan Centers for Disease Control (CDC) were notified of increasing acute hepatitis A (AHA) in June 2015. Serum and/or stool from AHA patients and sewage samples were tested for hepatitis A virus (HAV). We defined outbreak cases as AHA patients with illness onset after June 2015 and with an HAV sequence less than 0.5% different from that of the TA-15 outbreak strain. We analysed characteristics and food exposures between outbreak and non-outbreak cases between January 2014 (start of enhanced surveillance) and February 2016. From June 2015 to September 2017, there were 1,563 AHA patients with a median age of 31 years (interquartile range (IQR): 26–38); the male-to-female ratio was 8.8 and 585 (37%) had human immunodeficiency virus (HIV) infection. TA-15 was detected in 82% (852/1,033) of AHA patients, and 14% (74/540) of sewage samples tested since July 2015. Infection with the TA-15 strain was associated with having HIV, sexually transmitted infections (STI), recent oral-anal sex and men who have sex with men (MSM). The Taiwan CDC implemented an HAV vaccine campaign starting from October 2016 where 62% (15,487/24,879) of people at risk were vaccinated against HAV. We recommend HAV vaccination for at-risk populations and continuous surveillance to monitor control measures.
Aspirin and nonsteroidal anti‐inflammatory drug use and keratinocyte cancers: a large population‐based cohort study of skin cancer in Australia
Authors: N. Pandeya, C.M. Olsen, B.S. Thompson, J.C. Dusingize, R.E. Neale, A.C. Green, D.C. Whiteman
Journal: British Journal of Dermatology (2019)

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been postulated as chemopreventive agents for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but findings from observational studies have been inconsistent, and clinical trial data are scant.To examine the association between aspirin and NSAID (nonaspirin) use and the risk of BCC and SCC in a large cohort specifically designed for skin cancer outcomes.We used data from the QSkin Study, a prospective cohort of 43 764 residents of Queensland, Australia (34 630 were included in this study and 23 581 were used in our primary analyses). We used Cox proportional hazards models to estimate the hazard ratios (HRs) between self-reported aspirin and NSAID use 1 year prior to study baseline and the first histologically confirmed BCC or SCC for high-risk (history of skin cancer excisions or more than five actinic lesions treated) and average-to-low-risk participants (no history of skin cancer excision and at most five actinic lesions treated).After a median of 3 years of follow-up, 3421 participants developed BCC and 1470 SCC (2288 BCC and 932 SCC with complete covariate information). Among the high-risk group (1826 BCC and 796 SCC), compared with never use, frequent (at least weekly) NSAID use was associated with reduced risk of BCC (HR 0·84, 95% confidence interval 0·71-0.99) but not SCC. Aspirin use was associated with reduced risk of SCC (HR 0·77, 95% confidence interval 0·64-0·93) only among infrequent (less than weekly) users and was not associated with BCC. We observed no association between NSAID or aspirin use and the risk of BCC or SCC among average-to-low-risk participants.While some weakly inverse associations were observed between prior use of aspirin or NSAIDs and skin cancer, the inconsistent patterns of associations do not provide convincing evidence that these medications reduce subsequent skin cancer risk. Further data on doses, duration and long-term follow-up may help us to comprehend the cumulative dose effect.
An Integrated Safety Analysis of the Next Generation PI3Kδ Inhibitor Umbralisib (TGR-1202) in Patients with Relapsed/Refractory Lymphoid Malignancies
Authors: Matthew S. Davids, Ian W. Flinn, Anthony R. Mato, Owen A. O'Connor, Danielle M. Brander, Matthew A. Lunning, Julie M. Vose, Loretta Nastoupil, Nathan Fowler, Christopher Flowers, Jennifer R. Brown, Marshall T. Schreeder, Nilanjan Ghosh, Frederick Lansigan, Bruce D. Cheson, Paul M. Barr, John M. Pagel, Alexey Danilov, Javier Pinilla-Ibarz, Changchun Deng, John M. Burke, Tanya Siddiqi, Manish R Patel, Charles M. Farber, Parameswaran Venugopal, John G. Gribben, Pier Luigi Zinzani, Hari P Miskin, Peter Sportelli, Michael S. Weiss, Susan M. O'Brien
Journal: Blood (2017)
Normal saline bolus use in pediatric emergency departments is associated with poorer pain control in children with sickle cell anemia and vaso‐occlusive pain
Authors: Marcus A. Carden, David C. Brousseau, Fahd A. Ahmad, Jonathan Bennett, Seema Bhatt, Amanda Bogie, Kathleen Brown, Theron Charles Casper, Laura L. Chapman, Corrie E. Chumpitazi, Daniel Cohen, Carlton Dampier, Angela M. Ellison, Hartmut Grasemann, Robert W. Hickey, Lewis L. Hsu, Sara Leibovich, Elizabeth Powell, Rachel Richards, Syana Sarnaik, Debra L. Weiner, Claudia R. Morris
Journal: American Journal of Hematology (2019)

Abstract Vaso‐occlusive pain events (VOE) are the leading cause of emergency department (ED) visits in sickle cell anemia (SCA). This study assessed the variability in use of intravenous fluids (IVFs), and the association of normal saline bolus (NSB), on pain and other clinical outcomes in children with SCA, presenting to pediatric emergency departments (PED) with VOE. Four‐hundred charts of children age 3‐21 years with SCA/VOE receiving parenteral opioids at 20 high‐volume PEDs were evaluated in a retrospective study. Data on type and amount of IVFs used were collected. Patients were divided into two groups: those who received NSB and those who did not. The association of NSB use on change in pain scores and admission rates was evaluated. Among 400 children studied, 261 (65%) received a NSB. Mean age was 13.8 ± 4.9 years; 46% were male; 92% had hemoglobin‐SS. The IVFs (bolus and/or maintenance) were used in 84% of patients. Eight different types of IVFs were utilized and IVF volume administered varied widely. Mean triage pain scores were similar between groups, but improvement in pain scores from presentation‐to‐ED‐disposition was smaller in the NSB group (2.2 vs 3.0, P = .03), while admission rates were higher (71% vs 59%, P = .01). Use of NSB remained associated with poorer final pain scores and worse change in pain scores in our multivariable model. In conclusion, wide variations in practice utilizing IVFs are common. NSB is given to &gt;50% of children with SCA/VOE, but is associated with poorer pain control; a controlled prospective trial is needed to determine causality.