tbuckley/cabot-search huggingface dataset:
Migration, ethnicity and psychoses: evidence, models and future directions
Authors: Craig Morgan, Gemma Knowles, Gerard Hutchinson
Journal: World Psychiatry (2019)

There is a large body of research reporting high rates of psychotic disorders among many migrant and minority ethnic groups, particularly in Northern Europe. In the context of increasing migration and consequent cultural diversity in many places worldwide, these findings are a major social and public health concern. In this paper, we take stock of the current state of the art, reviewing evidence on variations in rates of psychoses and putative explanations, including relevant theories and models. We discuss in particular: a) the wide variation in reported rates of psychotic disorders by ethnic group, and b) the evidence implicating social risks to explain this variation, at ecological and individual levels. We go on to set out our proposed socio-developmental model, that posits greater exposure to systemic social risks over the life course, particularly those involving threat, hostility and violence, to explain high rates of psychoses in some migrant and minority ethnic groups. Based on this analysis, the challenge of addressing this social and public health issue needs to be met at multiple levels, including social policy, community initiatives, and mental health service reform.
Development and validation of multivariable prediction models of remission, recovery, and quality of life outcomes in people with first episode psychosis: a machine learning approach
Authors: Samuel P Leighton, Rachel Upthegrove, Rajeev Krishnadas, Michael E Benros, Matthew R Broome, Georgios V Gkoutos, Peter F Liddle, Swaran P Singh, Linda Everard, Peter B Jones, David Fowler, Vimal Sharma, Nicholas Freemantle, Rune H B Christensen, Nikolai Albert, Merete Nordentoft, Matthias Schwannauer, Jonathan Cavanagh, Andrew I Gumley, Max Birchwood, Pavan K Mallikarjun
Journal: The Lancet Digital Health (2019)

BackgroundOutcomes for people with first-episode psychosis are highly heterogeneous. Few reliable validated methods are available to predict the outcome for individual patients in the first clinical contact. In this study, we aimed to build multivariable prediction models of 1-year remission and recovery outcomes using baseline clinical variables in people with first-episode psychosis.MethodsIn this machine learning approach, we applied supervised machine learning, using regularised regression and nested leave-one-site-out cross-validation, to baseline clinical data from the English Evaluating the Development and Impact of Early Intervention Services (EDEN) study (n=1027), to develop and internally validate prediction models at 1-year follow-up. We assessed four binary outcomes that were recorded at 1 year: symptom remission, social recovery, vocational recovery, and quality of life (QoL). We externally validated the prediction models by selecting from the top predictor variables identified in the internal validation models the variables shared with the external validation datasets comprised of two Scottish longitudinal cohort studies (n=162) and the OPUS trial, a randomised controlled trial of specialised assertive intervention versus standard treatment (n=578).FindingsThe performance of prediction models was robust for the four 1-year outcomes of symptom remission (area under the receiver operating characteristic curve [AUC] 0·703, 95% CI 0·664–0·742), social recovery (0·731, 0·697–0·765), vocational recovery (0·736, 0·702–0·771), and QoL (0·704, 0·667–0·742; p<0·0001 for all outcomes), on internal validation. We externally validated the outcomes of symptom remission (AUC 0·680, 95% CI 0·587–0·773), vocational recovery (0·867, 0·805–0·930), and QoL (0·679, 0·522–0·836) in the Scottish datasets, and symptom remission (0·616, 0·553–0·679), social recovery (0·573, 0·504–0·643), vocational recovery (0·660, 0·610–0·710), and QoL (0·556, 0·481–0·631) in the OPUS dataset.InterpretationIn our machine learning analysis, we showed that prediction models can reliably and prospectively identify poor remission and recovery outcomes at 1 year for patients with first-episode psychosis using baseline clinical variables at first clinical contact.FundingLundbeck Foundation.
Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial
Authors: Rajiv Agarwal, Patrick Rossignol, Alain Romero, Dahlia Garza, Martha R Mayo, Suzette Warren, Jia Ma, William B White, Bryan Williams
Journal: The Lancet (2019)
Abstract 10990: Plasma Heart-type Fatty Acid Binding Protein Level is Associated With Outcomes in Out-of-hospital Cardiac Arrest Patients
Authors: Chien-Hua Huang, Min-Shan Tsai, Kuo-Liong Chien, Chiunag-Yuan Hsu, Wei-Tien Chang, Tzung-Dau Wang, Matthew Huei-Ming Ma, Shyr-Chyr Chen, Wen-Jone Chen
Journal: Circulation (2012)

Introduction: Biomarkers would be helpful for early prognosis in out-of-hospital cardiac arrest (OHCA) patients. Heart-type fatty acid binding protein (H-FABP) is a tissue-specific protein which is...
Colonic Dieulafoy lesion successfully treated by endoclips: a rare cause of lower gastrointestinal bleeding
Authors: Takaaki Kishino, Saiyu Tanaka
Journal: Endoscopy (2019)

Dieulafoy lesions account for 1 % – 2 % of cases of acute gastrointestinal bleeding. Approximately 71 % of Dieulafoy lesions are detected in the stomach, whereas only 2 % are in the colon [1] [2]. We encountered a patient with a colonic Dieulafoy lesion that was successfully treated by endoclips.
Aromatase inhibitors (AI) are highly effective in uterine sarcomas (US) expressing estrogen receptors
Authors: J. Fayette, I. Ray-Coquard, E. Bompas, L. Zufferey, S. Tabone-Eglinger, D. Ranchère, P. Thiesse, P. Méeus, M. Sunyach, J. Blay
Journal: Journal of Clinical Oncology (2006)

9576 Background: US frequently recur despite adequate locoregional treatments. Estrogen (ER) and progesterone (PR) receptors are expressed by 43–88% of US, mostly in endometrial stromal sarcomas (ESS) without correlation with survival. Whether hormonal treatment may be useful in estrogenreceptor (ER) expressing connective tumors of the uterus and pelvis is not known. Here, we report on the clinical antitumor effect of aromatase inhibitors (AI) in patients with US. Methods: Since september 2002, 8 menopaused women relapsing uterine leiomyosarcoma, ESS or intravascular leiomyomatosis, (all of grade 1 or 2 in WHO grading) were treated with AI (letrozole, n=5 or anastrozole, n=3). Median age was 62 (41–84), 7/8 expressed ER and 8/8 progesterone (PgR). Progression free, overall survival, and response to AI in evaluable patients were analyzed. Results: After a median follow-up of 16.5 months [1–38], 6 patients are currently non progressive under treatment by AI, without toxicity. All 8 (100%) evaluable patients experienced tumor control with 2 complete response -CR- (1 after lung surgery 25+, 38+), 2 PR (21 and 17+) and 4 stabilizations -SD- (15 months and at 1+, 3+ and 9+ months). Time to response was 3, 5 and 6 months respectively. Two patients progressed after 15 and 21 months; 3 patients are currently treated after 17+, 25+ and 38+ months. At 2 years. Median survival was not reached. 2 years DFS is 60% currently. Conclusions: AI enables prolonged progression free survival in uterine sarcoma expressing hormonal receptors. A prospective study for treatment of relapses and later in adjuvant setting is needed in these rare diseases. No significant financial relationships to disclose.
Health checks: no convincing evidence in favour exists, argue academic GPs
Authors: Elisabeth Mahase
Journal: BMJ (2019)

NHS health checks are unlikely to be cost effective, can expose patients to unnecessary interventions, and risk overdiagnosis, concludes the UK Centre for Evidence-Based Medicine.1

The review, carried out by two academic GPs from the University of Oxford, looked at existing evidence on general health checks, including a recent Cochrane review,2 which it said showed that such checks had no significant effect on mortality or cardiovascular outcomes.

In England the NHS Health Checks scheme …
Improving Adverse Event Reporting for Compounded Drugs
Authors: Julie Dohm, Jenny Kim, Janet Woodcock
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
Efficacy of Copanlisib Monotherapy in Patients with Relapsed or Refractory Marginal Zone Lymphoma: Subset Analysis from the CHRONOS-1 Trial
Authors: Martin Dreyling, Panayiotis Panayiotidis, Miklos Egyed, George Follows, Luigina Mollica, Arnon Nagler, Muhit Ozcan, Armando Santoro, Tatiane Ishida, Cindy Lu, Florian Hiemeyer, Jose Garcia-Vargas, Barrett H. Childs, Pier Luigi Zinzani
Journal: Blood (2017)
Sonic Hedgehog repression underlies gigaxonin mutation–induced motor deficits in giant axonal neuropathy
Authors: Yoan Arribat, Karolina Mysiak, Léa Lescouzères, Alexia Boizot, Maxime Ruiz, Mireille Rossel, Pascale Bomont
Journal: Journal of Clinical Investigation (2019)

Growing evidence shows that alterations occurring at early developmental stages contribute to symptoms manifested in adulthood in the setting of neurodegenerative diseases. Here, we studied the molecular mechanisms causing giant axonal neuropathy (GAN), a severe neurodegenerative disease due to loss-of-function of the gigaxonin-E3 ligase. We showed that gigaxonin governs Sonic Hedgehog (Shh) induction, the developmental pathway patterning the dorso-ventral axis of the neural tube and muscles, by controlling the degradation of the Shh-bound Patched receptor. Similar to Shh inhibition, repression of gigaxonin in zebrafish impaired motor neuron specification and somitogenesis and abolished neuromuscular junction formation and locomotion. Shh signaling was impaired in gigaxonin-null zebrafish and was corrected by both pharmacological activation of the Shh pathway and human gigaxonin, pointing to an evolutionary-conserved mechanism regulating Shh signaling. Gigaxonin-dependent inhibition of Shh activation was also demonstrated in primary fibroblasts from patients with GAN and in a Shh activity reporter line depleted in gigaxonin. Our findings establish gigaxonin as a key E3 ligase that positively controls the initiation of Shh transduction, and reveal the causal role of Shh dysfunction in motor deficits, thus highlighting the developmental origin of GAN.
Reply re: Murali Varma, Brett Delahunt, Theodorus van der Kwast. Grading Noninvasive Bladder Cancer: World Health Organisation 1973 or 2004 May Be the Wrong Question. Eur Urol 2019;76:413–5
Authors: Eva Compérat, Mahul Amin, Victor Reuter
Journal: European Urology (2019)
Protein tyrosine kinase 6 (PTK6, BRK) amplification in HER2+ breast cancer as a mechanism of HER2 resistance.
Authors: Tatyana A. Grushko, Maria J. Gomez-Vega, Aleix Prat, Jeffrey Mueller, Mariann Coyle, Charles M. Perou, Rodrigo Santa Cruz Guindalini, Elias Obeid, Hanna Irie, Olufunmilayo I. Olopade
Journal: Journal of Clinical Oncology (2013)

11021 Background: PTK6 gene on chromosome 20q13 encodes the intracellular non-receptor tyrosine kinase. Studies in vivo and in vitro revealed a role for PTK6 in cell proliferation and survival, particularly in HER2+ breast cancer cells suggesting that PTK6 may associate with the HER2 pathway and confer resistance to HER2-targeted therapy. PTK6 protein is frequently overexpressed in breast cancer, however, the mechanism(s) underlying PTK6 overexpression and its role in cancer remains unclear. To address this problem, we analyzed the frequency of PTK6 gene copy number variation (CNV) and expression in association with breast cancer subtypes. Methods: Retrospectiveparaffinsamples of invasive tumor and normal epithelium, and matching DCIS and metastases were mounted on TMA. PTK6 CNV was determined using PTK6:CEP20 FISH assay. Tumor subtypes were defined using the five-marker IHC classifier. The correlation between PTK6 CNV and mRNA expression and association of both with the intrinsic PAM50 tumor subtype were studied using TCGA database (547 cases) and publicly available seven breast cancer data sets (1005 cases). Data were normalized, gene median centered and standardized for the purpose of the study. Results: By FISH, 20% of 41 invasive tumors carried PTK6 CNV: amplification (10%) and gene polysomy (10%). The proportion of PTK6 amplified cases differed by subtype, with the largest proportion in HER2-enriched (17%) and LumB (14%). Strikingly, amplified invasive cases also showed amplification in matching DCIS and metastases. Analysis of the public datasets confirmed the frequent PTK6 amplification in breast cancer. Both low and high levels of amplification were detected with the largest proportion in HER2+ tumors (HER2-enriched and LumB; p=2.05e-26). None of the basal-like tumors showed high levels of PTK6 amplification. A high correlation between PTK6 gene copies and mRNA expression was observed (p=1.13e-08). Conclusions: PTK6 gene is amplified early in breast cancer progression, particularly in HER2+ tumors. Further studies on PTK6 biology may help clinicians to understand its potential role in HER2 resistance. Supported by BREAST CANCER SPORE, NCI K12CA139160 and CTSA-ITM CS UL1 RR024999.
Long-Term Outcomes and Cost-Effectiveness of Breast Cancer Screening With Digital Breast Tomosynthesis in the United States
Authors: Kathryn P Lowry, Amy Trentham-Dietz, Clyde B Schechter, Oguzhan Alagoz, William E Barlow, Elizabeth S Burnside, Emily F Conant, John M Hampton, Hui Huang, Karla Kerlikowske, Sandra J Lee, Diana L Miglioretti, Brian L Sprague, Anna N A Tosteson, Martin J Yaffe, Natasha K Stout
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Digital breast tomosynthesis (DBT) is increasingly being used for routine breast cancer screening. We projected the long-term impact and cost-effectiveness of DBT compared to conventional digital mammography (DM) for breast cancer screening in the United States. Methods Three Cancer Intervention and Surveillance Modeling Network breast cancer models simulated US women ages 40 years and older undergoing breast cancer screening with either DBT or DM starting in 2011 and continuing for the lifetime of the cohort. Screening performance estimates were based on observational data; in an alternative scenario, we assumed 4% higher sensitivity for DBT. Analyses used federal payer perspective; costs and utilities were discounted at 3% annually. Outcomes included breast cancer deaths, quality-adjusted life-years (QALYs), false-positive examinations, costs, and incremental cost-effectiveness ratios (ICERs). Results Compared to DM, DBT screening resulted in a slight reduction in breast cancer deaths (range across models 0–0.21 per 1000 women), small increase in QALYs (1.97–3.27 per 1000 women), and a 24–28% reduction in false-positive exams (237–268 per 1000 women) relative to DM. ICERs ranged from $195 026 to $270 135 per QALY for DBT relative to DM. When assuming 4% higher DBT sensitivity, ICERs decreased to $130 533–$156 624 per QALY. ICERs were sensitive to DBT costs, decreasing to $78 731 to $168 883 and $52 918 to $118 048 when the additional cost of DBT was reduced to $36 and $26 (from baseline of $56), respectively. Conclusion DBT reduces false-positive exams while achieving similar or slightly improved health benefits. At current reimbursement rates, the additional costs of DBT screening are likely high relative to the benefits gained; however, DBT could be cost-effective at lower screening costs.
National Trends in Utilization and 1-Year Outcomes with Transplantation of HCV-Viremic Kidneys
Authors: Vishnu S. Potluri, David S. Goldberg, Sumit Mohan, Roy D. Bloom, Deirdre Sawinski, Peter L. Abt, Emily A. Blumberg, Chirag R. Parikh, James Sharpe, K. Rajender Reddy, Miklos Z. Molnar, Meghan Sise, Peter P. Reese
Journal: Journal of the American Society of Nephrology (2019)

Recent pilot trials have demonstrated the safety of transplanting HCV-viremic kidneys into HCV-seronegative recipients. However, it remains unclear if allograft function is impacted by donor HCV-viremia or recipient HCV-serostatus.We used national United States registry data to examine trends in HCV-viremic kidney use between 4/1/2015 and 3/31/2019. We applied advanced matching methods to compare eGFR for similar kidneys transplanted into highly similar recipients of kidney transplants.Over time, HCV-seronegative recipients received a rising proportion of HCV-viremic kidneys. During the first quarter of 2019, 200 HCV-viremic kidneys were transplanted into HCV-seronegative recipients, versus 69 into HCV-seropositive recipients, while 105 HCV-viremic kidneys were discarded. The probability of HCV-viremic kidney discard has declined over time. Kidney transplant candidates willing to accept a HCV-seropositive kidney increased from 2936 to 16,809 from during this time period. When transplanted into HCV-seronegative recipients, HCV-viremic kidneys matched to HCV-non-viremic kidneys on predictors of organ quality, except HCV, had similar 1-year eGFR (66.3 versus 67.1 ml/min per 1.73 m2, P=0.86). This was despite the much worse kidney donor profile index scores assigned to the HCV-viremic kidneys. Recipient HCV-serostatus was not associated with a clinically meaningful difference in 1-year eGFR (66.5 versus 71.1 ml/min per 1.73 m2, P=0.056) after transplantation of HCV-viremic kidneys.By 2019, HCV-seronegative patients received the majority of kidneys transplanted from HCV-viremic donors. Widely used organ quality scores underestimated the quality of HCV-viremic kidneys based on 1-year allograft function. Recipient HCV-serostatus was also not associated with worse short-term allograft function using HCV-viremic kidneys.
Genetic underpinnings of recovery after stroke: an opportunity for gene discovery, risk stratification, and precision medicine
Authors: Julián N. Acosta, Stacy C. Brown, Guido J. Falcone
Journal: Genome Medicine (2019)

As the number of stroke survivors continues to increase, identification of therapeutic targets for stroke recovery has become a priority in stroke genomics research. The introduction of high-throughput genotyping technologies and novel analytical tools has significantly advanced our understanding of the genetic underpinnings of stroke recovery.
Pharmacokinetic (PK) and pharmacodynamics (PD) properties of SC-PEG <i>e. coli </i>L-asparaginase (EZN-2285) in the treatment of patients with acute lymphoblastic leukemia (ALL): Results from Children's Oncology Group (COG) study AALL07P4.
Authors: Anne L. Angiolillo, Reuven J. Schore, Gregory H. Reaman, Naomi Joan Winick, Meenakshi Devidas, Hao W. Zheng, Charlotte Wood, Ashley R. Lane, Elizabeth A. Raetz, William L. Carroll, Stephen Hunger
Journal: Journal of Clinical Oncology (2012)

9543 Background: Asparaginase is a critical therapeutic agent in the treatment of childhood ALL, and pegaspargase (Oncospar, ONC) is now the preferred product in COG frontline ALL trials. EZN-2285 replaces the succinimidyl succinate linker in ONC with a succinimidyl carbamate linker creating a more stable molecule. AALL07P4 was designed to determine the PK comparability of EZN-2285 to ONC when given intravenously in newly diagnosed patients with NCI high-risk (HR) B-precursor ALL. Methods: 162 eligible patients were randomized to receive EZN-2285 at 2100 (LD, n=66) or 2500 (HD, n=42) IU/m 2 vs. 2500 IU/m 2 of ONC (n=51) in a 2:1 manner based on the prednisone/Capizzi methotrexate arm of COG AALL0232. All groups were similar demographically with the exception of number of patients over the age of 16 years were 6, 5, and 19 in the ONC, HD and LD, respectively. Results: PK, PD and targeted AEs (Gr 3-5) after the first doses of study drug are presented in the table below. Adverse events in induction were not significantly different between arms with the exception of a higher incidence of hyperglycemia (p=0.042). Conclusions: Based on C max , AUC 0-25d , and asparaginase activity 25 days post drug, EZN-2285 2500 IU/m 2 appears to have an improved PK/PD profile compared to pegaspargase 2500 IU/m 2 and a comparable toxicity profile in children with HR ALL. [Table: see text]
Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: a randomised, open-label, phase 1–2 trial
Authors: Paul G Corn, Elisabeth I Heath, Amado Zurita, Naveen Ramesh, Lianchun Xiao, Emi Sei, Elsa Li-Ning-Tapia, Shi-Ming Tu, Sumit K Subudhi, Jennifer Wang, Xuemei Wang, Eleni Efstathiou, Timothy C Thompson, Patricia Troncoso, Nicholas Navin, Christopher J Logothetis, Ana M Aparicio
Journal: The Lancet Oncology (2019)
DNA methylation-regulated QPCT promotes sunitinib resistance by increasing HRAS stability in renal cell carcinoma
Authors: Tangliang Zhao, Yi Bao, Xinxin Gan, Jie Wang, Qiong Chen, Zhihui Dai, Bing Liu, Anbang Wang, Shuhan Sun, Fu Yang, Linhui Wang
Journal: Theranostics (2019)

: Although sunitinib has been shown to improve the survival rate of advanced renal cell carcinoma (RCC) patients, poor drug response is a major challenge that reduces patient benefit. It is important to elucidate the underlying mechanism so that the therapeutic response to sunitinib can be restored.