tbuckley/cabot-search huggingface dataset:
Confounding by indication and ethnicity difference? Comment on ‘Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data’
Authors: Po-Ke Hsu, Yung-Heng Lee, James Cheng Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

Confounding by indication and ethnicity difference?Comment on 'Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data'We read with great interest the study by Singh and Cleveland 1 that investigated the risk of hypersensitivity reactions (HRs) with allopurinol and febuxostat using Medicare claims data.These authors analysed a national cohort in the 5% Medicare beneficiary sample randomised from 2006 to 2012 of adults older than 65 years who experienced a new treatment episode with allopurinol, febuxostat or colchicine.They reported the following incidence rates for HRs: allopurinol, 23.9; febuxostat, 30.5; and colchicine, 25.7 cases per 1000 person-years.Combination treatments of febuxostat+colchicine, allopurinol+colchicine and febuxostat+colchicine+allopurinol increased the incidence of HRs to 56.8, 27.4 and 89.1 per 1000 person-years, respectively.Based on a propensity-matched analyses of allopurinol versus febuxostat (5:1), which showed febuxostat with an HR of 1.25 (95% CI 0.93 to -1.67), the study concluded there was no difference between the HRs for allopurinol versus febuxostat.However, some study results and aspects of these findings must be clarified.First, Lin et al 2 reported a higher incidence rate of HRs with allopurinol versus febuxostat (15.37 vs 3.48 per 1000 personyears, respectively), which differs from the conclusion reached by Singh et al.In clinical practice, physicians are generally concerned about the potential adverse effects of allopurinol, such as Steven-Johnson syndrome for their older adult patients or those who have chronic kidney disease, leading them to choose febuxostat versus allopurinol.This choice may cause an overestimation of the rate of HRs with febuxostat and even doubts of confounding by indication.Regarding ethnicity, Lu et al 3 found that white patients have lower frequencies of human leucocyte antigen-B*5801 in the USA compared with Asian patients, which correlates with a lower risk for Stevens-Johnson syndrome in white patients and may result in the study showing a lower incidence of HRs in a predominantly white population.Another key issue for the study by Singh et al is that several numeric discrepancies appear in the text versus the abstract.For example, the abstract stated the crude incidence rates of HRs by drug as follows: allopurinol, 23.7; febuxostat, 30.7; and colchicine, 25.6 cases per 1000 person-years.However, the Results section and table 2 in the text by Singh et al, these values are listed as 23.9, 30.5 and 25.7, respectively.Finally, the discussion about the safety of allopurinol, febuxostat and colchicine is an important issue that must be addressed by further research.
Prehabilitation vs Postoperative Rehabilitation for Frail Patients
Authors: Lisa Cooper, Laura Frain, Michael T. Jaklitsch
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal
Reconsidering the scope of US state laws allowing pharmacist substitution of generic drugs
Authors: Jonathan J Darrow, Jessica E Chong, Aaron S Kesselheim
Journal: BMJ (2020)

Despite high rates of generic prescribing, branded medicines still account for most drug costs. Amending the law to provide pharmacists with greater authority to substitute clinically similar alternatives has the potential to cut spending, <b>say Jonathan Darrow and colleagues</b>
Characteristics of 1573 healthcare workers who underwent nasopharyngeal swab testing for SARS-CoV-2 in Milan, Lombardy, Italy
Authors: A. Lombardi, D. Consonni, M. Carugno, G. Bozzi, D. Mangioni, A. Muscatello, V. Castelli, E. Palomba, A.P. Cantù, F. Ceriotti, B. Tiso, A.C. Pesatori, L. Riboldi, A. Bandera, G. Lunghi, A. Gori
Journal: Clinical Microbiology and Infection (2020)
Investigating coeliac disease in adults
Authors: James J Ashton, Rebecca Smith, Trevor Smith, R Mark Beattie
Journal: BMJ (2020)

### What you need to know

A 29 year old white woman presents to her general practitioner with a 12 month history of borderline anaemia (diagnosed when she tried to donate blood) alongside increasing bloating at the end of every day. On direct questioning, she has slightly looser stools compared with 5-10 years ago, but this has been attributed to irritable bowel syndrome by both the patient and previous GPs. She has no other medical history, including normal menarche. The GP decides to order some blood tests including a tissue transglutaminase (TTG) IgA test, which gives a result of 78.4 U/mL (normal range 0.0-4.5 U/mL), with normal total IgA (normal range 0.80-2.8 g/L). 

Coeliac disease is a common autoimmune condition, often presenting with vague symptoms triggered by chronic gluten ingestion in genetically predisposed individuals. It is characterised by the presence of specific autoantibodies with a coexisting enteropathy.1 It is more common in females (1.5:1 predominance) and in populations with European ancestry, with an estimated prevalence of 1.4% globally.123 Despite growing recognition of coeliac disease, many cases remain undiagnosed: a North American study spanning 2006 to 2011 of over 30 000 individuals without a known coeliac disease diagnosis demonstrated coeliac-positive serology in 1.1%.4 The classic symptoms usually trigger testing, but patients with less common presentations are often not screened for coeliac disease.1 Timely diagnosis is important, …
RARB Translocations in Acute Promyelocytic Leukemia without Rara translocation
Authors: Motohiro Kato, Tomoo Osumi, Shinichi Tsujimoto, Moe Tamura, Meri Uchiyama, Kazuhiko Nakabayashi, Kohji Okamura, Daisuke Tomizawa, Akihiro Watanabe, Hiroyuki Takahashi, Tsukasa Hori, Shohei Yamamoto, Kazuko Hamamoto, Masahiro Migita, Hiroko Ogata-Kawata, Toru Uchiyama, Hiroe Kizawa, Hitomi Ueno-Yokohata, Ryota Shirai, Masanori Yoshida, Masafumi Seki, Kentaro Oki, Junko Takita, Seishi Ogawa, Toshio Kitamura, Kimikazu Matsumoto, Kenichiro Hata, Susumu Goyama, Nobutaka Kiyokawa
Journal: Blood (2017)
Strategies to Modulate MicroRNA Functions for the Treatment of Cancer or Organ Injury
Authors: Tae Jin Lee, Xiaoyi Yuan, Keith Kerr, Ji Young Yoo, Dong H. Kim, Balveen Kaur, Holger K. Eltzschig
Journal: Pharmacological Reviews (2020)

Cancer and organ injury-such as that occurring in the perioperative period, including acute lung injury, myocardial infarction, and acute gut injury-are among the leading causes of death in the United States and impose a significant impact on quality of life. MicroRNAs (miRNAs) have been studied extensively during the last two decades for their role as regulators of gene expression, their translational application as diagnostic markers, and their potential as therapeutic targets for disease treatment. Despite promising preclinical outcomes implicating miRNA targets in disease treatment, only a few miRNAs have reached clinical trials. This likely relates to difficulties in the delivery of miRNA drugs to their targets to achieve efficient inhibition or overexpression. Therefore, understanding how to efficiently deliver miRNAs into diseased tissues and specific cell types in patients is critical. This review summarizes current knowledge on various approaches to deliver therapeutic miRNAs or miRNA inhibitors and highlights current progress in miRNA-based disease therapy that has reached clinical trials. Based on ongoing advances in miRNA delivery, we believe that additional therapeutic approaches to modulate miRNA function will soon enter routine medical treatment of human disease, particularly for cancer or perioperative organ injury. SIGNIFICANCE STATEMENT: MicroRNAs have been studied extensively during the last two decades in cancer and organ injury, including acute lung injury, myocardial infarction, and acute gut injury, for their regulation of gene expression, application as diagnostic markers, and therapeutic potentials. In this review, we specifically emphasize the pros and cons of different delivery approaches to modulate microRNAs, as well as the most recent exciting progress in the field of therapeutic targeting of microRNAs for disease treatment in patients.
End-of-life planning: ideas are not new but a system is needed to implement them
Authors: Richard Scheffer
Journal: BMJ (2020)

In their editorial Bowers and colleagues highlight two important matters—long recognised by palliative care and primary care teams—in caring for the dying in their own home or a care home.1 Both matters need tackling to reduce delays in getting end-of-life drugs to suffering, dying people. Delays occur while prescriptions are written and processed and drugs delivered, especially after hours and at weekends. Any delay in getting this medication …
Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome
Authors: Alice Gallo de Moraes, Rama El-Yafawi, Richard A Oeckler
Journal: New England Journal of Medicine (2019)

BACKGROUND The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. METHODS We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. RESULTS The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. CONCLUSIONS Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).
Measurable residual disease in multiple myeloma: ready for clinical practice?
Authors: Leire Burgos, Noemi Puig, Maria-Teresa Cedena, María-Victoria Mateos, Juan José Lahuerta, Bruno Paiva, Jesús F. San-Miguel
Journal: Journal of Hematology & Oncology (2020)

Abstract The landscape of multiple myeloma (MM) has changed considerably in the past two decades regarding new treatments, insight into disease biology and innovation in the techniques available to assess measurable residual disease (MRD) as the most accurate method to evaluate treatment efficacy. The sensitivity and standardization achieved by these techniques together with unprecedented rates of complete remission (CR) induced by new regimens, raised enormous interest in MRD as a surrogate biomarker of patients’ outcome and endpoint in clinical trials. By contrast, there is reluctance and general lack of consensus on how to use MRD outside clinical trials. Here, we discuss critical aspects related with the implementation of MRD in clinical practice.
Safety of Transesophageal Echocardiography to Guide Structural Cardiac Interventions
Authors: Afonso B. Freitas-Ferraz, Mathieu Bernier, Rosaire Vaillancourt, Paula A. Ugalde, Frédéric Nicodème, Jean-Michel Paradis, Jean Champagne, Gilles O’Hara, Lucia Junquera, David del Val, Guillem Muntané-Carol, Kim O’Connor, Jonathan Beaudoin, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2020)
Covid-19: Ethnic minority doctors feel more pressured and less protected than white colleagues, survey finds
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Ethnic minority doctors feel more pressured and less protected than white colleagues, survey finds Elisabeth MahaseLess than a third (29%) of black, Asian, and other ethnic minority doctors in the UK believe they are fully protected from covid-19 at work, whereas nearly half (46%) of their white colleagues do, shows a BMA survey of around 7500 doctors.3
Association of Prior Left Ventricular Ejection Fraction With Clinical Outcomes in Patients With Heart Failure With Midrange Ejection Fraction
Authors: Alison Brann, Satit Janvanishstaporn, Barry Greenberg
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Patients categorized as having heart failure (HF) with left ventricular ejection fraction (LVEF) in the midrange between 40% and 50% (HFmrEF) are known to be at increased risk of future events. Although patients can transition into the midrange through either improvement or deterioration in their LVEF, there is limited information available assessing the association of directional change in LVEF with future events. Understanding the association between change in LVEF and the clinical course of patients with HFmrEF would be of value in guiding management strategies. <h3>Objective</h3> To determine whether risk of clinical events experienced by patients with HFmrEF varies according to whether LVEF improved or deteriorated into the range of 40% to 50% from previous measurements. <h3>Design, Setting, and Participants</h3> In this retrospective cohort study, patients were identified from the electronic health records at the UC San Diego Health System who had an LVEF measured between 40% and 50% on transthoracic echocardiography (TTE) performed during the calendar year of 2015 and who also had at least 1 prior TTE for comparison. The clinical course of these patients was then followed from the time of the index TTE through December 2018. Data were analyzed from January to March 2019. <h3>Main Outcomes and Measures</h3> The composite of all-cause mortality and all-cause hospitalization, the composite of cardiovascular mortality and HF hospitalization, and each of the individual components. <h3>Results</h3> Of the 448 patients who were identified with HFmrEF, 278 (62.1%) were male, and the mean (SD) age was 67.4 (9.7) years. Left ventricular ejection fraction improved from less than 40% in 157 patients (35.0%), deteriorated from greater than 50% in 224 patients (50.0%), and remained between 40% and 50% over time in 67 patients (15.0%). Compared with patients whose LVEF improved from less than 40% to midrange levels, patients whose LVEF deteriorated from greater than 50% had higher risk of all-cause mortality and hospitalization (hazard ratio, 1.34; 95% CI, 1.10-1.82;<i>P</i> = .03) and of cardiovascular mortality and HF hospitalization (hazard ratio, 1.71; 95% CI, 1.08-2.50;<i>P</i> = .02), and these differences persisted after multivariable analysis. Outcomes did not differ significantly between patients whose LVEF improved and those in whom it remained stable. <h3>Conclusion and Relevance</h3> In a cohort of patients with HFmrEF from a large academic medical center, the clinical course was strongly influenced by the directional change in LVEF from prior study. Patients whose LVEF deteriorated into midrange levels experienced a significantly higher risk of adverse clinical events than patients whose LVEF had improved. These results suggest that directional change in LVEF from prior measurements should be considered when devising management strategies for patients with HFmrEF.
What do medical students actually need to know about artificial intelligence?
Authors: Liam G. McCoy, Sujay Nagaraj, Felipe Morgado, Vinyas Harish, Sunit Das, Leo Anthony Celi
Journal: npj Digital Medicine (2020)

With emerging innovations in artificial intelligence (AI) poised to substantially impact medical practice, interest in training current and future physicians about the technology is growing. Alongside comes the question of what, precisely, should medical students be taught. While competencies for the clinical usage of AI are broadly similar to those for any other novel technology, there are qualitative differences of critical importance to concerns regarding explainability, health equity, and data security. Drawing on experiences at the University of Toronto Faculty of Medicine and MIT Critical Data's "datathons", the authors advocate for a dual-focused approach: combining robust data science-focused additions to baseline health research curricula and extracurricular programs to cultivate leadership in this space.
Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Production of dexamethasone must be rapidly ramped up to meet global demand for the drug, the World Health Organization has said. 1 The call came as the University of Oxford's RECOVERY trial published its much anticipated preprint paper 2 on the drug's effect on covid-19.The paper states that the drug cuts deaths in ventilated patients by one third and deaths in other admitted patients receiving oxygen by only one fifth.The headline findings of the trial were reported by the investigators on 16 June and were adopted into UK practice the same day through an alert sent to doctors. 3 WHO's director general, Tedros Adhanom Ghebreyesus, said, "The next challenge is to increase production and rapidly and equitably distribute dexamethasone worldwide, focusing on where it is needed most.Demand has already surged following the UK trial results." Ventilation and standard careIn the preprint paper published on 22 June, 2 the study team reported that 454 of 2104 (21.6%) patients allocated to dexamethasone and 1065 of 4321 (24.6%) patients allocated to usual care died within 28 days (age adjusted rate ratio 0.83 (95% confidence interval (0.74 to 0.92); P<0.001).The randomised, controlled, and open label trial began in March 2020 and is investigating a number of potential covid-19 treatments at 176 NHS hospitals.In the dexamethasone arm, which ended recruitment on 8 June, eligible and consenting patients were assigned in a ratio of 2:1 to a usual standard of care or to a usual standard of care plus dexamethasone 6 mg once daily (oral or intravenous) for a maximum of 10 days (or until discharge if sooner).The preprint reported that, among the ventilated patients, 94 of the 324 patients taking dexamethasone died, compared with 278 of the 683 receiving standard care.This is a reduction of around a third, from 40.7% to 29.0% (0.65 (0.51 to 0.82); P<0.001).Among patients receiving oxygen, 275 of the 1279 taking dexamethasone died, compared with 650 of the 2604 receiving standard care.This is a reduction in mortality from 25.0% to 21.5% (0.80 (0.70 to 0.92); P=0.002).However, in the group of admitted patients receiving no respiratory support, 85 of the 501 taking dexamethasone died, compared with 137 of the 1034 allocated to usual care (17.0%v 13.2% (1.22 (0.93 to 1.61); P=0.14).The researchers concluded that the steroid did not reduce mortality in this group.The mean age of study participants in this arm was 66.1 years, and 36% of patients were female.A history of diabetes was present in 24% of patients, heart disease in 27%, and chronic lung disease in 21%, the study found, and 56% had at least one major comorbidity.
Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia
Authors: Basit Salik, Hangyu Yi, Nunki Hassan, Nancy Santiappillai, Binje Vick, Patrick Connerty, Alastair Duly, Toby Trahair, Andrew J. Woo, Dominik Beck, Tao Liu, Karsten Spiekermann, Irmela Jeremias, Jianlong Wang, Maria Kavallaris, Michelle Haber, Murray D. Norris, Dan A. Liebermann, Richard J. D'Andrea, Christopher Murriel, Jenny Y. Wang
Journal: Cancer Cell (2020)
Oral Administration of the LSD1 Inhibitor OG-S1335 Increases Fetal Hemoglobin in Humanized Transgenic Sickle Cell Disease Mice and in Baboons
Authors: Angela Rivers, Kestis Vaitkus, Ramasamy Jagadeeswaran, Vinzon Ibanez, Maria Armila Ruiz, Filippo Ciceri, Fernando Cavalcanti, Robert E. Molokie, Donald Lavelle
Journal: Blood (2017)