tbuckley/cabot-search huggingface dataset:
Assessing the effect of drought severity on height-for-age z-score in Kenyan children: a secondary analysis
Authors: Kate Lillepold, Ashley Aimone, Susan Keino, Paula Braitstein
Journal: The Lancet Planetary Health (2018)

BackgroundGlobally, droughts are occurring more regularly and are having negative effects on population health, particularly in countries such as Kenya, where agriculture is a primary driver of the economy and a source of subsistence for many communities. Children are particularly susceptible to weather-related shocks. Previous research has shown an association between drought and cross-sectional indicators of malnutrition, such as stunting. In this study, we explored various longitudinal and spatial analysis approaches to evaluating the effect of drought on height-for-age z-scores (HAZ) over time and space among young children in Kenya.MethodsUsing anthropometric data from three georeferenced Kenyan Demographic and Health Surveys (KDHS) and the self-calibrated Palmer Drought Severity Index, we developed multivariate linear regression and spatial lag and error models (with Moran's I calculations) to investigate the association between drought severity and HAZ in children aged 0–5 years. Initial covariates included age of the child, sex, maternal age, height and education, wealth index, urban or rural location, and size at birth. We then did multilevel and geographically weighted regression modelling using frequentist or Bayesian methods and with inclusion of household-level covariates, such as livelihood zones. To assess the effect of changes in drought severity on child HAZ over time, KDHS data from 2003, 2008–09, and 2014 were analysed with spatiotemporal modelling.FindingsPreliminary results from the multivariate linear model showed a negative, non-significant association between drought severity and HAZ among Kenyan children in 2014 (β=0·033, p=0·101); however, there was a significant interaction between drought severity and age (β=–0·002, p<0·0007). The spatial lag model gave similar results. Other variables associated with HAZ included wealth index, age, sex, maternal education, and maternal height. Global Moran's I calculations indicated that there was a slight positive spatial autocorrelation across child HAZ (I=0·047, p<0·0001).InterpretationIncreased drought severity was associated with a non-significant decrease in HAZ among Kenyan children. However, a significant interaction between age and drought severity indicates that the effect of drought on HAZ varies by age. Findings from this study will help to inform the development of methodological approaches for improving understanding of the effects of climate change on child health. Expanding these analyses to other east-African countries will also contribute to the development of national adaptation strategies and planning in anticipation of increased climate variability.FundingCanadian Institutes of Health Research (Institute of Public and Population Health).
Multifactorial Brugada Phenocopy
Authors: Javier García-Niebla, Antonio Bayés de Luna, Adrian Baranchuk
Journal: JAMA Internal Medicine (2018)

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
Margaret McCartney: We must look at the whole impact of revalidation
Authors: Margaret McCartney
Journal: BMJ (2018)

The UK Medical Revalidation Collaboration (Umbrella) has reported on the impact of introducing revalidation.

“Expecting appraisers to consistently evaluate doctors’ fitness to practise, based on appraisal, is unlikely to be reliable,” it says, adding that, “if the main impact is simply to document professional practice it might explain the significant concerns expressed about the time and resources required, with frequent statements in interviews and survey responses that it took doctors away from their patients.”1

Contrast this with (Health Education England chair) Keith Pearson’s 2017 review of revalidation. He wrote that most …
Epithelial and Endothelial Pannexin1 Channels Mediate AKI
Authors: Jakub Jankowski, Heather M. Perry, Christopher B. Medina, Liping Huang, Junlan Yao, Amandeep Bajwa, Ulrike M. Lorenz, Diane L. Rosin, Kodi S. Ravichandran, Brant E. Isakson, Mark D. Okusa
Journal: Journal of the American Society of Nephrology (2018)

Background Pannexin1 (Panx1), an ATP release channel, is present in most mammalian tissues, but the role of Panx1 in health and disease is not fully understood. Panx1 may serve to modulate AKI; ATP is a precursor to adenosine and may function to block inflammation, or ATP may act as a danger-associated molecular pattern and initiate inflammation. Methods We used pharmacologic and genetic approaches to evaluate the effect of Panx1 on kidney ischemia-reperfusion injury (IRI), a mouse model of AKI. Results Pharmacologic inhibition of gap junctions, including Panx1, by administration of carbenoxolone protected mice from IRI. Furthermore, global deletion of Panx1 preserved kidney function and morphology and diminished the expression of proinflammatory molecules after IRI. Analysis of bone marrow chimeric mice revealed that Panx1 expressed on parenchymal cells is necessary for ischemic injury, and both proximal tubule and vascular endothelial Panx1 tissue-specific knockout mice were protected from IRI. In vitro , Panx1 -deficient proximal tubule cells released less and retained more ATP under hypoxic stress. Conclusions Panx1 is involved in regulating ATP release from hypoxic cells, and reducing this ATP release may protect kidneys from AKI.
Timing of initiation of neratinib after trastuzumab-based adjuvant therapy in early-stage HER2+ hormone receptor (HR)-negative breast cancer: Exploratory analyses from the phase III ExteNET trial.
Authors: Bent Ejlertsen, Carlos H. Barrios, Erhan Gokmen, Nicholas Robert, Noelia Martinez, John S. Link, Serafin Morales, Manuel Ruiz Borrego, Manish Bhandari, Yoshiaki Rai, Adam Luczak, Takashi Fujita, Alvin Wong, Bin Yao, Miguel Martin
Journal: Journal of Clinical Oncology (2018)

549 Background: ExteNET, an international, randomized, placebo-controlled phase III trial, showed that neratinib given for 1 year after trastuzumab-based adjuvant therapy significantly improved 2- (HR 0.67, p = 0.009) and 5-year (HR 0.73, p = 0.008) invasive disease-free survival (iDFS) in early-stage HER2+ breast cancer [Chan et al. 2016; Martin et al. 2017]. Prespecified subgroup analyses showed greater benefit with neratinib in HR+ than HR tumors, and in patients who initiated neratinib ≤12 months of completing trastuzumab. To better understand the effects of neratinib in patients with HR disease, we examined the impact on efficacy of the interval from prior trastuzumab to start of neratinib in the HR subpopulation. Methods: Patients with early-stage HER2+ breast cancer received oral neratinib 240 mg/day or placebo for 1 year after standard trastuzumab-based (neo)adjuvant therapy. iDFS, the primary study endpoint, was examined in subgroups categorized according to the interval between completing trastuzumab and randomization (i.e. 06, 612 and > 12 months). Data cut-off: March 1, 2017. Clinicaltrials.gov: NCT00878709. Results: The ITT population comprised 2840 patients; 1209 (43%) had HR disease (neratinib, n = 604; placebo, n = 605). Results after a median of 5.2 years in the HR subgroup are shown below. Conclusions: Patients with HER2+ HR tumors tend to recur early. The risk of recurrence is higher in patients who have recently completed trastuzumab-based therapy (reflected in the iDFS rates of the placebo group). Consistent with these observations, our analyses suggest that the benefits of neratinib in HR disease are greater when treatment is started closer to completion of trastuzumab (i.e. ≤6 months). Clinical trial information: NCT00878709.Interval between prior trastuzumab and randomization, months n 5-year iDFS rate, % Hazard ratio (95% CI)a Neratinib Placebo 06 695 88.9 86.1 0.73 (0.471.14) 612 268 86.1 91.7 1.61 (0.733.70) > 12 246 91.3 93.7 1.39 (0.523.90) Overall 1209 88.8 88.9 0.95 (0.661.35) aNeratinib vs placebo
Stratifying Risk for Men With Low-Volume Intermediate-Risk Prostate Cancer
Authors: Laurence Klotz
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
A 9-year summary of a mentor-based 5K training program for childhood cancer survivors.
Authors: Diana Lone, Caitlin Agrawal, Linda Rivard, Julia Stepenske, Lisa Boland
Journal: Journal of Clinical Oncology (2018)

96 Background: 5-year survival rate for childhood cancers significantly improved leading to increased awareness to long-term effects associated with these diseases. Many childhood cancer survivors have significantly lower exercise capacity. The POST (Pediatric Oncology Survivorship in Transition) team at Advocate Children’s Hospital created a 5k Program to encourage survivors to return to physical activity. Participants were childhood cancer survivors who had been off therapy or cleared by their oncologist to participate, and who were greater than 9 years old. The Program had weekly 1 hour supervised training sessions and home physical activity assignments over 8-12 weeks in preparation for the 5K. Each participant invited a friend/family member to partner in training and on race day. Methods: The purpose of this study is to evaluate the strengths and weaknesses of the 5K Program in promoting physical activity and to validate its continuation and expansion. All participants who finished the 5K (n = 68) from 2009-2017 were included in our retrospective chart review. Data collected from the medical records included diagnoses and number of times of participation. An online Qualtrics survey inquired about barriers encountered, subjective experience of having a personal coach and training partner, and additional personal comments. The IRB approved this study. Results: The survey was distributed in October 2017 and complete data collection is anticipated in November 2017. The primary outcome will reflect the effectiveness of the Program in promoting return to physical activity, measured by descriptive survey responses. Secondary outcomes include data collected by retrospective chart review. 44 of 68 (65%) participants completed the 5K multiple times. The majority of these were survivors of leukemia (31) followed by lymphoma (13), solid tumors (9), bone marrow transplant (9), brain tumors (5) and histiocytosis (1). Conclusions: While the 8-12 week program is likely too short to measure physical changes, the high percentage of participants completing multiple 5Ks demonstrates its effectiveness in improving physical endurance. Additional conclusions with full data analysis will be completed by February 2018.
ABC trial (A011502): A randomized phase III double-blinded placebo-controlled trial of aspirin as adjuvant therapy breast cancer.
Authors: Wendy Y. Chen, Eric P. Winer, Karla V. Ballman, Ann H. Partridge, Lisa A. Carey, Margaret Carvan, Carol Matyka, Thomas H. Openshaw, Kala Visvanathan, Banu Symington, Michelle D. Holmes
Journal: Journal of Clinical Oncology (2020)

TPS600 Background: In-vitro and in-vivo evidence suggest that aspirin may have an anti-tumor effect. Multiple epidemiologic studies have reported improved breast cancer survival among regular aspirin users compared to non-users. Pooled data from randomized trials of aspirin for cardiovascular disease have also reported a decreased risk of metastatic cancer among aspirin users. However, the exact benefits and risks for breast cancer survivors need to be confirmed in a randomized controlled trial. Even if the clinical effect were modest, the global impact would be substantial since aspirin is inexpensive and widely available. Methods: The primary objective is to compare the effect of 300 mg daily aspirin versus placebo upon invasive disease-free survival (iDFS) in high risk HER2 negative breast cancer patients. Secondary objectives include effects on overall survival, cardiovascular disease, toxicity, and adherence. A biospecimen repository will be created for correlative analyses including tumor collection at baseline and blood and urine samples and questionnaires assessing lifestyle factors associated with inflammation (pain, sleep, stress, and depression) at baseline and 2 years. Study design: Subjects will be randomized (1:1) to aspirin 300 mg vs placebo daily for 5 years in a double-blinded fashion. Stratification factors include hormone receptor (HR) status (positive vs negative), body mass index ( &lt; or ≥ 30 kg/m2), and stage (II vs III). Subjects will be followed every 6 six months while on study drug, then annually for 10 years. Accrual goal is 2936 patients to reach 381 iDFS events. We have 80% power to detect HR 0.75 assuming 5-year iDFS on placebo of 77%. Eligibility: Eligible subjects include patients aged 18-70 diagnosed with a primary invasive HER2 negative breast cancer. If HR positive, tumors need to be node positive and diagnosed within the past 10 years. If HR negative, tumor can be node positive or T2-4N0 within 18 months of diagnosis. Subjects who are currently anticoagulated or those with a prior history of GI bleeding, atrial fibrillation, or myocardial infarction are excluded. Subjects who regularly use aspirin (defined as ≥ 5 days per week) need to stop 30 days prior to enrollment. Updated accrual numbers will be given at the time of presentation. Clinical trial information: NCT02927249 .
T Cells Genetically Modified to Express an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma
Authors: Jennifer N. Brudno, Irina Maric, Steven D. Hartman, Jeremy J. Rose, Michael Wang, Norris Lam, Maryalice Stetler-Stevenson, Dalia Salem, Constance Yuan, Steven Pavletic, Jennifer A. Kanakry, Syed Abbas Ali, Lekha Mikkilineni, Steven A. Feldman, David F. Stroncek, Brenna G. Hansen, Judith Lawrence, Rashmika Patel, Frances Hakim, Ronald E. Gress, James N. Kochenderfer
Journal: Journal of Clinical Oncology (2018)

Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA). Patients and Methods Sixteen patients received 9 × 10 6 CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients. The patients had a median of 9.5 prior lines of MM therapy. Sixty-three percent of patients had MM refractory to the last treatment regimen before protocol enrollment. T cells were transduced with a γ-retroviral vector encoding CAR-BCMA. Patients received CAR-BCMA T cells after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. Results The overall response rate was 81%, with 63% very good partial response or complete response. Median event-free survival was 31 weeks. Responses included eradication of extensive bone marrow myeloma and resolution of soft-tissue plasmacytomas. All 11 patients who obtained an anti-MM response of partial response or better and had MM evaluable for minimal residual disease obtained bone marrow minimal residual disease–negative status. High peak blood CAR + cell levels were associated with anti-MM responses. Cytokine-release syndrome toxicities were severe in some cases but were reversible. Blood CAR-BCMA T cells were predominantly highly differentiated CD8 + T cells 6 to 9 days after infusion. BCMA antigen loss from MM was observed. Conclusion CAR-BCMA T cells had substantial activity against heavily treated relapsed/refractory MM. Our results should encourage additional development of CAR T-cell therapies for MM.
Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars
Authors: Panu K. Luukkonen, Sanja Sädevirta, You Zhou, Brandon Kayser, Ashfaq Ali, Linda Ahonen, Susanna Lallukka, Véronique Pelloux, Melania Gaggini, Ching Jian, Antti Hakkarainen, Nina Lundbom, Helena Gylling, Anne Salonen, Matej Orešič, Tuulia Hyötyläinen, Marju Orho-Melander, Aila Rissanen, Amalia Gastaldelli, Karine Clément, Leanne Hodson, Hannele Yki-Järvinen
Journal: Diabetes Care (2018)

OBJECTIVE Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG. RESEARCH DESIGN AND METHODS We overfed 38 overweight subjects (age 48 ± 2 years, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia), insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks. RESULTS Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P &amp;lt; 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression. CONCLUSIONS Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced the greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes.
Case 17-2018: A 40-Year-Old Woman with Leg Swelling and Abdominal Distention and Pain
Authors: Charles A. Morris, Midhir J. Patel, Andrew Z. Fenves, Ricard Masia
Journal: New England Journal of Medicine (2018)

A 40-year-old woman presented with a 10-month history of progressive edema of the legs, as well as abdominal distention and pain. CT showed a nonocclusive thrombus in the right renal vein. Diagnostic tests were performed.
PTH-033 Spyglass: a four year experience
Authors: Tom Johnston, Kushala Abeysekera, Ashish Sinha, Ben Arnold, Sarah Welsh, Jim Portal, Andy Strickland
Journal: Endoscopy (2018)

<h3>Introduction</h3> Diagnostic and therapeutic single operator cholangioscopy (SOC) has increased in importance for stricture assessment and management of cholelithiasis. The technique is often employed under general anaesthetic but can be performed using conscious sedation. The primary aim of this study was assessment of diagnostic accuracy of histology taken for stricture assessment and stone clearance rates during SOC. <h3>Methods</h3> A single centre retrospective analysis was performed of consecutive SOCs over 4 years at BRI (tertiary referral centre for South West England and South Wales), including fibreoptic (<i>Spyglass Legacy</i>) and high resolution digital systems (<i>Digital Spyglass</i>). Recorded parameters included sedation/general anaesthetic (GA) dosages, stone clearance, use of electrohydraulic lithotripsy (EHL), histology, complications, final diagnosis and correlation with histology. <h3>Results</h3> Between 2013–2017, 164 patients (mean age 65.4 years (range 22–91); 79 females; 85 males) had 206 SOC procedures, referred from 12 hospitals. 15 SOCs were performed in 2013 compared to 64 in 2017. 54% of patients were referred for stricture assessments, 43% for SOC+EHL; 5 patients had assessment of an indeterminate lesion on imaging. 7 patients had SOC under GA. 97% of patients had conscious sedation: average midazolam dose was 7 mg; fentanyl 141 mcg; buscopan 24 mg. Macroscopic assessment of strictures and indeterminate lesions correlating with malignancy had a sensitivity, specificity and accuracy of 90% (95%CI 79–97), 83% ((95% CI 71–96) and 86% (78.5%–92%) respectively. Histological correlation with final diagnosis increased over the study, from 77% in 2015 to 87% in 2017. Complete stone clearance rose from 50% in 2014 to 85% by 2017. 70% of patients had complete stone clearance at 1 st attempt. 4.3% of patients developed complications post SOC. Post-ERCP pancreatitis (PEP) was the commonest adverse event (2.4%; n=5/206). <h3>Conclusions</h3> The role of SOC in tertiary centres for identification of biliary lesions and management of difficult choledocholithiasis continues to grow. The South West service is centralised to one centre with a clear improvement in diagnostic accuracy for malignancy and stone clearance rates. Diagnostic accuracy rates mirror figures quoted in literature, most recently Japanese data in 2017.<sup>1 2</sup> Adverse events were lower than those widely reported, but PEP remains the commonest cause. SOC under conscious sedation is both safe and effective. <h3>References</h3> . Kalaitzakis E, Webster GJ, Oppong KW, et al. Diagnostic and therapeutic utility of single-operator peroral cholangioscopy for indeterminate biliary lesions and bile duct stones. Eur J Gastroenterol Hepatol2012;24(6):656–664. . Ogura T, Imanishi M, Kurisu Y, et al. Prospective evaluation of digital single-operator cholangioscope for diagnostic and therapeutic procedures (with videos). Dig Endosc2017;29:782–789.