tbuckley/cabot-search huggingface dataset:
Hip Fracture Risk among Hemodialysis-Dependent Patients Prescribed Opioids and Gabapentinoids
Authors: Chandan Vangala, Jingbo Niu, Maria E. Montez-Rath, Jingyin Yan, Sankar D. Navaneethan, Aanand D. Naik, Wolfgang C. Winkelmayer
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Among the general population, use of opioids have generated concern regarding their effect on fall risk and bone metabolism. Also, association of opioids or gabapentinoid use with fractures has been described in the general population. Patients with ESKD on hemodialysis are at high risk for falls and retain unique bone pathology related to renal osteodystrophy; consequently, they are about four times more likely than individuals in the general population to experience a hip fracture. In a case-control study involving 4912 patients who are dependent on hemodialysis and experience a first-time hip fracture and 49,120 controls, the authors reported an association between hip fractures and opioid use, but not gabapentinoid use. Increasing cumulative opioid exposure conferred a stepwise increase in hip fracture risk. These findings highlight potential detriment with opioid use in this high-risk subpopulation. Background Despite opioids’ known association with hip fracture risk in the general population, they are commonly prescribed to patients with ESKD. Whether use of opioids or gabapentinoids (also used to treat pain in patients with ESKD) contributes to hip fracture risk in patients with ESKD on hemodialysis remains unknown. Methods In a case-control study nested within the US Renal Data System, we identified all hip fracture events recorded among patients dependent on hemodialysis from January 2009 through September 2015. Eligible cases were risk-set matched on index date with ten eligible controls. We required &gt;1 year of Medicare Parts A and B coverage and &gt;3 years of part D coverage to study cumulative longer-term exposure. To examine new, short-term exposure, we selected individuals with &gt;18 months of Part D coverage and no prior opioid or gabapentinoid use between 18 and 7 months before index. We used conditional logistic regression to estimate unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI). Results For the longer-term analyses, we identified 4912 first-time hip fracture cases and 49,120 controls. Opioid use was associated with increased hip fracture risk (adjusted OR, 1.39; 95% CI, 1.26 to 1.53). Subgroups of low, moderate, and high use yielded adjusted ORs of 1.33 (95% CI, 1.20 to 1.47), 1.53 (95% CI, 1.36 to 1.72), and 1.66 (95% CI, 1.45 to 1.90), respectively. The association with hip fractures was also elevated with new, short-term use (adjusted OR, 1.38; 95% CI, 1.25 to 1.52). There were no associations between gabapentinoid use and hip fracture. Conclusions Among patients dependent on hemodialysis in the United States, both short-term and longer-term use of opioid analgesics were associated with hip fracture events.
Abstract 17935: Regenerative Potential of Pluripotent Stem Cell-Derived PDGFRα+ Cardiac Lineage Committed Cells in Infarcted Myocardium
Authors: Sung Woo Cho, Seon Pyo Hong, Sukhyun Song, Jae-Hyeong Park
Journal: Circulation (2017)

Background: Pluripotent stem cell (PSC)-derived cardiomyocytes have become one of the most attractive cellular resources for cell-based therapy to rescue damaged hearts. We newly generated PSC-deri...
How to Examine for Life Insurance.
Journal: JAMA (1890)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Tuberculosis bacillary load, an early marker of disease severity: the utility of tuberculosis Molecular Bacterial Load Assay
Authors: Wilber Sabiiti, Khalide Azam, Eoghan Charles William Farmer, Davis Kuchaka, Bariki Mtafya, Ruth Bowness, Katarina Oravcova, Isobella Honeyborne, Dimitrios Evangelopoulos, Timothy Daniel McHugh, Celso Khosa, Andrea Rachow, Norbert Heinrich, Elizabeth Kampira, Geraint Davies, Nilesh Bhatt, Elias N Ntinginya, Sofia Viegas, Ilesh Jani, Mercy Kamdolozi, Aaron Mdolo, Margaret Khonga, Martin J Boeree, Patrick P J Phillips, Derek Sloan, Michael Hoelscher, Gibson Kibiki, Stephen H Gillespie
Journal: Thorax (2020)

In this comparative biomarker study, we analysed 1768 serial sputum samples from 178 patients at 4 sites in Southeast Africa. We show that tuberculosis Molecular Bacterial Load Assay (TB-MBLA) reduces time-to-TB-bacillary-load-result from days/weeks by culture to hours and detects early patient treatment response. By day 14 of treatment, 5% of patients had cleared bacillary load to zero, rising to 58% by 12th week of treatment. Fall in bacillary load correlated with mycobacterial growth indicator tube culture time-to-positivity (Spearmans r=−0.51, 95% CI (−0.56 to −0.46), p&lt;0.0001). Patients with high pretreatment bacillary burdens (above the cohort bacillary load average of 5.5log 10 eCFU/ml) were less likely to convert-to-negative by 8th week of treatment than those with a low burden (below cohort bacillary load average), p=0.0005, HR 3.1, 95% CI (1.6 to 5.6) irrespective of treatment regimen. TB-MBLA distinguished the bactericidal effect of regimens revealing the moxifloxacin—20 mg rifampicin regimen produced a shorter time to bacillary clearance compared with standard-of-care regimen, p=0.008, HR 2.9, 95% CI (1.3 to 6.7). Our data show that the TB-MBLA could inform clinical decision making in real-time and expedite drug TB clinical trials.
Finding Cures for Tropical Diseases: Is Open Source an Answer?
Authors: Stephen M Maurer, Arti Rai, Andrej Sali
Journal: PLoS Medicine (2004)

Only about 1% of newly developed drugs are for tropical diseases, such as African sleeping sickness, dengue fever, and leishmaniasis [1].While patent incentives and commercial pharmaceutical houses have made Western health care the envy of the world, the commercial model only works if companies can sell enough patented products to cover their research and development (R&D) costs.The model fails in the developing world, where few patients can afford to pay patented prices for drugs.It is easy and correct to say that Western governments could solve this problem by paying existing institutions to focus on cures for tropical diseases.But sadly, there does not appear to be enough political will for this to happen.In any case, grants and patent incentives were never designed with tropical diseases in mind.Two main kinds of proposals have been suggested for tackling the problem.The fi rst is to ask sponsorsgovernments and charities-to subsidize developing-country purchases at a guaranteed price [2,3,4].The second involves charities creating nonprofi t venture-capital fi rms ("Virtual Pharmas"), which look for promising drug candidates and then push drug development through contracts with corporate partners.In this article, we discuss the limitations of these two approaches and suggest a third, "open source," approach to drug development, called the Tropical Diseases Initiative (TDI).We envisage TDI as a decentralized, Web-based, community-wide effort where scientists from laboratories, universities, institutes, and corporations could work together for a common cause (see www.tropicaldisease.org).
A Genome Wide Approach to Identify Genetic Determinants of Asthma Traits Related to Airway Function in Two Populations of African Descent
Authors: Y.J. Tsai, R. Mathias, A. Grant, N. Rafaels, T. Hand, A. Togias, N. Hansel, G. Diette, N.F. Adkinson Jr., M.C. Liu
Journal: Journal of Allergy and Clinical Immunology (2009)
Letter to the Editor: Blocking Sodum‐Taurocholate Cotransporting Polypeptide Stimulates Biliary Cholesterol and Phospholipid Secretion in Mice
Authors: Norman B. Javitt
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. TO THE EDITOR: The recent report(1) that the increased cholesterol and lecithin content of hepatic bile after administration of the complex lipopeptide, myrcludex B, is attributable to its binding to the sodium taurocholate cotransporting polypeptide (NTCP), which causes a redistribution of canalicular bile transport to the pericentral zone, appears to conflict with a previous study.(2) After partial hepatectomy, NTCP expression significantly decreases in the remaining liver along with increased in hepatic bile flow and no change in cholesterol or lecithin output, findings that were also attributed to a shift in bile acid transport to the pericentral zone of the canaliculus. Given that in the earlier study(2) no drugs were administered, it seems more likely that myrcludex B also affects other aspects of cholesterol and lecithin transport, including not only the carriers, but also pertubations in the canalicular membrane that affect paracellular and/or transmembrane water flow. Currently, very little data exist on the metabolism and excretion of this potentially very useful drug for the management of hepatitis B. Although bile acid excretion is essential for the generation of cholesterol‐lecithin vesicles(3) and their transition to mixed micelles, a second requirement is their canalicular concentration, which is regulated by the rate of trans‐ or paracellular water flow(4) as evident from the findings in the Claudin‐2 knockout mouse(5) Thus, canalicular concentration of bile acids, rather than residence time within the canaliculus, is probably the major determinant of cholesterol and lecithin concentration in canalicular fluid.
Letter to the Editor: Radiation for Prior DCIS is a Risk Factor for Death From Invasive Breast Cancer
Authors: Victoria Sopik, Vasily Giannakeas, Steven Narod
Journal: Journal of the National Comprehensive Cancer Network (2020)

We read with interest the article by Li et al 1 regarding the impact of prior radiotherapy (RT) for ductal carcinoma in situ (DCIS) on the prognosis of women with invasive breast cancer.The authors report that the risk of breast cancer mortality following invasive breast cancer among women with a prior diagnosis of DCIS is 1.7 times higher if the DCIS was treated with lumpectomy 1 RT versus lumpectomy alone (adjusted hazard ratio [HR], 1.70; 95% CI, 1.18-2.45;P5.005).The authors suggest that this finding may have implications for the use of RT in the initial treatment of DCIS.However, we propose another interpretation.Treatment of DCIS with lumpectomy 1 RT, compared with lumpectomy alone, is associated with a large reduction in the risk of subsequent ipsilateral invasive breast cancer but little or no reduction in the risk of breast cancer mortality. 2,3 In SEER, we compared the risks of ipsilateral invasive recurrence and of breast cancer-specific mortality among patients with DCIS treated with lumpectomy 6 RT using one-to-one matching. 2 In this analysis (including 29,465 propensitymatched pairs of patients), the use of RT after lumpectomy was associated with a 36% reduction in the 15-year risk of ipsilateral invasive breast cancer (8.1% vs 5.2%; absolute reduction of 2.9%) and a small reduction in the risk of breast cancer mortality (2.0% vs. 1.8%; absolute reduction of 0.2%).The ratio of deaths to recurrences increased from 0.25 in patients treated with lumpectomy alone to 0.35 in patients treated with lumpectomy 1 RT; therefore, for every 10,000 patients treated with lumpectomy alone, we would expect approximately 810 ipsilateral invasive recurrences and 200 breast cancer deaths, whereas for every 10,000 patients treated with lumpectomy 1 RT, we would expect 520 ipsilateral invasive recurrences and 180 breast cancer deaths.These numbers correspond to a HR for death associated with RT of approximately 1.40, suggesting that the HR of 1.70 generated by Li et al 1 may in part be explained by a reduction in the number of cases (ie, patients with recurrence after DCIS) but no reduction in the number of deaths.
Living on a farm protects from allergic rhinitis at school age
Authors: Bernt Alm, Emma Goksör, Nils Åberg, Per Möllborg, Rolf Pettersson, Laslo Erdes, Göran Wennergren
Journal: European Respiratory Journal (2013)

Background  Family history plays a major role in the development of allergic rhinitis. External influences, such as a farm childhood and fish introduction have been suggested to play a protective role. The aim was to analyse early risk factors and protective factors for allergic rhinitis at school age.  Methods  The material is a prospective, longitudinal study of a cohort of children born in the region of western Sweden in 2003 where 8,176 families (50% of the birth cohort) were randomly selected. The parents answered questionnaires at 6 months, 12 months, 4½ years and 8 years of age. The response rate at eight years was 80% (4,051 of 5,044 questionnaires distributed).  Results  At eight years of age, 441 children (11.3%) had used medicines for allergic rhinitis the past twelve months. The mean onset age was 5.1 year and 61.9% were boys. In a multivariate analysis of factors associated with allergic rhinitis with p  Conclusion  In conclusion, we found that a family history of rhinitis, early food allergy, early eczema and male gender increased the risk of rhinitis at school age. Furthermore, we found a protective effect of living on a farm at preschool age, and that antibiotics neonatally increased the risk. Both findings are compatible with the hygiene hypothesis.
Analysis of lung cancer risk model (PLCO<sub>M2012</sub> and LLP<sub>v2</sub>) performance in a community-based lung cancer screening programme
Authors: Mikey B Lebrett, Haval Balata, Matthew Evison, Denis Colligan, Rebecca Duerden, Peter Elton, Melanie Greaves, John Howells, Klaus Irion, Devinda Karunaratne, Judith Lyons, Stuart Mellor, Amanda Myerscough, Tom Newton, Anna Sharman, Elaine Smith, Ben Taylor, Sarah Taylor, Anna Walsham, James Whittaker, Phil V Barber, Janet Tonge, Hilary A Robbins, Richard Booton, Philip A J Crosbie
Journal: Thorax (2020)

Introduction Low-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the performance of two risk prediction models (PLCO M2012 and Liverpool Lung Project model (LLP v2 )) and National Lung Screening Trial (NLST) eligibility criteria in a community-based screening programme. Methods Ever-smokers aged 55–74, from deprived areas of Manchester, were invited to a Lung Health Check (LHC). Individuals at higher risk (PLCO M2012 score ≥1.51%) were offered annual LDCT screening over two rounds. LLP v2 score was calculated but not used for screening selection; ≥2.5% and ≥5% thresholds were used for analysis. Results PLCO M2012 ≥1.51% selected 56% (n=1429) of LHC attendees for screening. LLP v2 ≥2.5% also selected 56% (n=1430) whereas NLST (47%, n=1188) and LLP v2 ≥5% (33%, n=826) selected fewer. Over two screening rounds 62 individuals were diagnosed with LC; representing 87% (n=62/71) of 6-year incidence predicted by mean PLCO M2012 score (5.0%). 26% (n=16/62) of individuals with LC were not eligible for screening using LLP v2 ≥5%, 18% (n=11/62) with NLST criteria and 7% (n=5/62) with LLP v2 ≥2.5%. NLST eligible Manchester attendees had 2.5 times the LC detection rate than NLST participants after two annual screens (≈4.3% (n=51/1188) vs 1.7% (n=438/26 309); p&lt;0.0001). Adverse measures of health, including airflow obstruction, respiratory symptoms and cardiovascular disease, were positively correlated with LC risk. Coronary artery calcification was predictive of LC ( adj OR 2.50, 95% CI 1.11 to 5.64; p=0.028). Conclusion Prospective comparisons of risk prediction tools are required to optimise screening selection in different settings. The PLCO M2012 model may underestimate risk in deprived UK populations; further research focused on model calibration is required.
Low-Dose Sorafenib Acts as a Mitochondrial Uncoupler and Ameliorates Nonalcoholic Steatohepatitis
Authors: Chongshu Jian, Jiajun Fu, Xu Cheng, Li-Jun Shen, Yan-Xiao Ji, Xiaoming Wang, Shan Pan, Han Tian, Song Tian, Rufang Liao, Kehan Song, Hai-Ping Wang, Xin Zhang, Yibin Wang, Zan Huang, Zhi-Gang She, Xiao-Jing Zhang, Lihua Zhu, Hongliang Li
Journal: Cell Metabolism (2020)
13q12.2 deletions in acute lymphoblastic leukemia lead to upregulation of FLT3 through enhancer hijacking
Authors: Minjun Yang, Setareh Safavi, Eleanor L. Woodward, Nicolas Duployez, Linda Olsson-Arvidsson, Jonas Ungerbäck, Mikael Sigvardsson, Marketa Zaliova, Jan Zuna, Thoas Fioretos, Bertil Johansson, Karolin H. Nord, Kajsa Paulsson
Journal: Blood (2020)
Cognition After Lowering LDL-Cholesterol With Evolocumab
Authors: Baris Gencer, François Mach, Jianping Guo, KyungAh Im, Andrea Ruzza, Huei Wang, Christopher E. Kurtz, Terje Rolf Pedersen, Anthony C. Keech, Brian R. Ott, Marc S. Sabatine, Robert P. Giugliano
Journal: Journal of the American College of Cardiology (2020)
Molecular variances between rectal and left-sided colon cancers.
Authors: John Marshall, Heinz-Josef Lenz, Joanne Xiu, Wafik S. El-Deiry, Jeffrey Swensen, Hesham El Ghazaly, Zoran Gatalica, Jimmy J. Hwang, Philip Agop Philip, Anthony Frank Shields, Mohamed E. Salem
Journal: Journal of Clinical Oncology (2017)

522 Background: Recent analysis of CALGB 80405 showed that left sided colon tumors (LT) respond differently to biologics compared with right-sided tumors, likely due to molecular differences. Molecular variations between LT and rectal tumors remain undefined. Herein, we report our exploration of these variations. Methods: Tumors with origins clearly defined as splenic flexure to descending colon (SFT), sigmoid colon (SgT), or rectum (RT) were included. Protein expression, gene amplification and NextGen sequencing was tested. Microsatellite instability (MSI) was measured by PCR. Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations. Chi-square tests were used for comparative analyses. Results: In total, 1,457 primary tumors (SFT 125; SgT 460, and RT 872) were examined. When compared with SFT, RT had a higher frequency of TP53 (71% vs. 57%, p = 0.03) and APC (66% vs. 49%, p = 0.01); a lower frequency of PIK3CA (11% vs. 22%, p = 0.02), BRAF (3% vs. 15% p = 0.0001), GNAS (0.9% vs. 4%, p = 0.04), HNF1A (0.7% vs. 5%, p = 0.01), and CTNNB1(0.3% vs. 4%, p = 0.003); and a higher expression of TOPO1 (52% vs. 31%, p = 0.0001), ERCC1 (29% vs. 15%, p = 0.03), and MGMT (64% vs. 53%, p = 0.048). When compared with SgT, RT had higher expression of TLE3 (33% vs. 23%, p = 0.007), TOPO1 (52% vs. 35%, p &lt; 0.001), TUBB3 (41% vs. 28%, p = 0.003), and MGMT (64% vs. 54%, p = 0.003). There were no differences between SFT, SgT, and RT in the frequency of PD-L1 expression (5%, 2%, and 2%) on tumor cells, PD-1 expression on tumor-infiltrating lymphocytes (54%, 42%, and 42%), or Her-2 expression (1%, 2%, and 3%) and amplification (3%, 3%, and 5%). MSI was seen in 7% of SFT, 4% of SgT, and 0.7% of RT (total LT vs. RT, p = 0.01). Mean TML was 23, 6.5, and 7 mutations (mut)/MB (332 tumors), and the portion of tumors carrying a TML of &gt; 17mut/MB was 9%, 1.6%, and 4% for SFT, SgT, and RT, respectively. In all 3 cohorts, a TML &gt; 17 mut/MB was highly concordant with MSI. There was a correlation between PD-1 and TML in RT (p = 0.04) but not in SFT or SgT. There were no correlations between PD-L1 and TML. Conclusions: Tumors arising in the rectum may carry genetic alterations that are distinct from LT. A better understanding of disease biology may help to identify therapeutic targets and advance precision medicine
Evaluating the impact of 2020 post-polypectomy surveillance guidelines in the Northern Ireland bowel cancer screening programme
Authors: Maurice B Loughrey, Grace Ings, William Dickey, Tracy A Owen, Helen G Coleman
Journal: Gut (2020)

We note with interest the new postpolypectomy and postcolorectal cancer resection surveillance guidelines by Rutter et al , representing an overdue update on preceding guidelines originally published in 2002 and last revised in 2010.1–3 The new guidelines include evidence from the English bowel cancer screening programme (BCSP) and, for the first time, address risk stratification in individuals found to have both adenomas and serrated polyps. An age cut-off for surveillance is recommended. The overarching guidance is towards more selective and less frequent surveillance, focusing limited resources on those most in need.

We have examined data from the Northern Ireland (NI) BCSP, to ascertain the potential impact of introducing the new guidelines. The NIBCSP has maintained a pathology database of all endoscopic specimens procured at screening-related index and surveillance colonoscopies, since inception of the faecal occult blood (FOB)-based programme in 2010. In parallel, a Bowel Screening Information Management System collates participant level endoscopy findings …
Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells
Authors: Renier Myburgh, Jonathan D. Kiefer, Norman F. Russkamp, Chiara F. Magnani, Nicolás Nuñez, Alexander Simonis, Surema Pfister, C. Matthias Wilk, Donal McHugh, Juliane Friemel, Antonia M. Müller, Burkhard Becher, Christian Münz, Maries van den Broek, Dario Neri, Markus G. Manz
Journal: Leukemia (2020)
P0575 : Liver fibrosis in treatment-naïve HIV-infected and HIV/HBV-coinfected patients: Zambia and Switzerland compared
Authors: G. Wandeler, L. Mulenga, M. Vinikoor, H. Kovari, M. Battegay, A. Calmy, M. Cavassini, E. Bernasconi, P. Schmid, E. Sinkala, B. Chi, M. Egger, A. Rauch
Journal: Journal of Hepatology (2015)