tbuckley/cabot-search huggingface dataset:
A phase II trial of epigenetic therapy with hydralazine and magnesium valproate associated to doxorubicin and cyclophosphamide for locally advanced breast cancer
Authors: C. Arce-Salinas, B. Segura-Pacheco, T. Vela-Chavez, E. Bargallo-Rocha, E. Pérez-Cárdenas, L. Taja-Chayeb, C. Trejo-Becerril, A. Revilla-Vazquez, A. Dueñas-González
Journal: Journal of Clinical Oncology (2006)

13147 Background: DNA methylation and histone deacetylation are the most studied epigenetic alterations in cancer. Hydralazine and magnesium valproate are proven DNA methylation and histone deacetylase inhibitors respectively that in combination exert antitumor effects by their own and potentate the effect of chemotherapy. Methods: Open label two-stage design phase II trial to evaluate safety and efficacy of hydralazine and magnesium valproate plus chemotherapy in terms of pathologic complete response as neoadjuvant treatment. A total of 42 patients will be accrued. Untreated patients with histological confirmation of breast cancer in clinical stage IIb-IIIa, and hematological, renal and hepatic normal function are elegible. Patients with any collagen disease and any cardiovascular condition were excluded. Treatment consisted on four 21-day courses of doxorubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 plus epigenetic therapy starting 7 days before the first cycle of chemotherapy and continued until the end of chemotherapy. Oral hydralazine dosed according to acetylator phenotype and magnesium valproate at 30mg/Kg. After chemotherapy patients were evaluated with mammography and then submitted to surgical resection. Results: 17 patients in the first-stage have been accrued. Their characteristics are as follows: Median age 45-y (39–67), 67% were stage IIIa, median size of tumor was 5 cm (3–10 cm). All patients had clinically positive axillary nodes, with median size of 2 cm (1–5 cm), 80% were ductal carcinomas and 80% had either intermediate or high grade; 77% were ER-positive and 30% over-expressed HER2. Hematological toxicity was the most common side effect, neutropenia grade 3/4 was found in 35% of cases, anemia grade 3/4 was present in 15% of cases and most presented transient grade 2 depressed level of consciousness. Seven patients have completed planned treatment, clinical responses were CR 2, PR 4 and SD 1; in 1 of 7 a pathological complete response was seen. Conclusions: Epigenetic therapy with hydralazine and magnesium valproate associated to conventional chemotherapy is well tolerated. Its antitumor efficacy is pending to evaluate. No significant financial relationships to disclose.
Variation in the Assessment of Immune-Related Adverse Event Occurrence, Grade, and Timing in Patients Receiving Immune Checkpoint Inhibitors
Authors: David Hsiehchen, Mary K. Watters, Rong Lu, Yang Xie, David E. Gerber
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Toxic effects of conventional chemotherapy and molecularly targeted cancer therapies are generally well defined and occur at predictable points. By contrast, owing to their heterogeneous manifestations, unpredictable timing, and clinical overlap with other conditions, immune-related adverse events (irAE) may be more difficult to diagnose and characterize. <h3>Objective</h3> To determine concordance of algorithm-driven medical record review by medical oncologists for the characterization of 8 irAE in patients treated with immune checkpoint inhibitors. <h3>Design, Setting, and Participants</h3> Cross-sectional study of patients treated with immune checkpoint inhibitors at a National Cancer Institute–designated comprehensive cancer center from November 30, 2015, to March 7, 2018. A sample size of 52 patients provided 80% power to distinguish substantial agreement (κ = 0.85) from poor agreement (κ = 0.5) based on the Cohen κ. <h3>Main Outcomes and Measures</h3> Interrater agreement of 2 observers in the occurrence and grade of irAE. <h3>Results</h3> Of 52 patients (32 [61.5%] male; mean [SD] age, 69 [9] years) analyzed, 42 (80.8%) had non–small cell lung cancer and all received anti–programmed cell death 1 or anti–programmed cell death ligand 1 antibodies, with 3 patients (5.8%) receiving combinations with anti–cytotoxic T-lymphocyte antigen 4 antibodies. A median (interquartile range) of 82 (47-180) documents were reviewed per case. There was limited or poor interrater agreement on irAE occurrence (Cohen κ, 0.37-0.64), with the exception of hypothyroidism (κ = 0.8). Weighted κ similarly showed limited or poor agreement for irAE grade (κ = 0.31-0.75). Differences in assessed time of onset ranged from 5 to 188 days. As a control for data availability and access, observers had a high degree of agreement for the exact start date (98%) and end date (96%) of immunotherapy administration, suggesting that information interpretation rather than identification largely accounted for assessment differences. In multivariable analysis, therapy duration (adjusted odds ratio, 4.80; 95% CI, 1.34-17.17;<i>P</i> = .02) and Charlson Comorbidity Index (adjusted odds ratio, 4.09; 95% CI, 1.10-15.18;<i>P</i> = .03) were significantly associated with discordant irAE assessment. <h3>Conclusions and Relevance</h3> These findings underscore critical challenges in assessing the occurrence, type, timing, and severity of irAE. Apart from hypothyroidism (a condition that has a discrete diagnostic laboratory test and few other likely etiologies during immunotherapy treatment), interobserver agreement was poor. Given the importance of accurate and timely assessment of toxic effects for clinical trials and real-world disease management, efforts to improve irAE diagnosis and characterization are needed.
Burnout in healthcare: a sign of death by overwork for doctors in China
Authors: C Yang, Z-L Chen, L-Y Chen, J-X Jiang
Journal: BMJ (2019)

Montgomery and colleagues say that burnout is associated with sleep deprivation, medical errors, poor quality of care, and low ratings of patient satisfaction.1 It is a sophisticated social problem and a sign of karoshi (death by overwork) for exhausted doctors, especially in China. 

Growing evidence shows the escalation of karoshi in Chinese doctors. Between …
Ushering in Liquid Biopsy for the Microsatellite Status: Advantages and Caveats
Authors: Linghua Wang, Jaffer A. Ajani
Journal: Clinical Cancer Research (2019)

Microsatellite instable tumors often respond to immune checkpoint blockade (ICB), however, tumor tissue is unavailable/insufficient in some patients. Two groups are reporting a blood-based assessment of the microsatellite status validated in tumor tissue and by clinical benefit in patient receiving ICB. Both approaches are highly appealing with a few caveats.See related articles by Georgiadis et al., p. 7024, and Willis et al., p. 7035.
Risk Analysis for the Carcinogen Pulegone in Mint- and Menthol-Flavored e-Cigarettes and Smokeless Tobacco Products
Authors: Sairam V. Jabba, Sven-Eric Jordt
Journal: JAMA Internal Medicine (2019)

Risk Analysis for the Carcinogen Pulegone in Mint-and Menthol-Flavored e-Cigarettes and Smokeless Tobacco ProductsPulegone, a constituent of oil extracts prepared from mint plants, including peppermint, spearmint and pennyroyal, is a carcinogen that causes hepatic carcinomas, pulmonary metaplasia, and other neoplasms on oral administration in rodents. 1 In 2018, the US Food and Drug Administration (FDA) banned synthetic pulegone as a food additive. 2 Studies by the Centers for Disease Control and Prevention (CDC) detected substantial amounts of pulegone in mint-and menthol-flavored e-cigarette liquids and smokeless tobacco products marketed in the United States. 3,4 The tobacco industry has minimized pulegone levels in cigarette flavorings because of toxicity concerns.Mint-and menthol-flavored e-cigarettes may be exempt from proposed federal regulations; therefore, the health risk associated with pulegone in these products should be considered.
Maribavir for Preemptive Treatment of Cytomegalovirus Reactivation
Authors: Johan Maertens, Catherine Cordonnier, Peter Jaksch, Xavier Poiré, Marc Uknis, Jingyang Wu, Anna Wijatyk, Faouzi Saliba, Oliver Witzke, Stephen Villano
Journal: New England Journal of Medicine (2019)

Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known.In a phase 2, open-label, maribavir dose-blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment.Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available - 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir.Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events - notably dysgeusia - and a lower incidence of neutropenia were found in the maribavir group. (Funded by ViroPharma/Shire Development; EudraCT number, 2010-024247-32.).
Cost-effectiveness and budget impact of the community-based management of hypertension in Nepal study (COBIN): a retrospective analysis
Authors: Anirudh Krishnan, Eric Andrew Finkelstein, Per Kallestrup, Arjun Karki, Michael Hecht Olsen, Dinesh Neupane
Journal: The Lancet Global Health (2019)

The greatest risk factor for cardiovascular disease is hypertension, which can be alleviated via diet, exercise, and adherence to medication. Yet, blood pressure control in Nepal is inadequate, which is partly hindered by a lack of evidence-based, low-cost, scalable, and cost-effective cardiovascular disease prevention programmes. The the community-based management of hypertension in Nepal (COBIN) study was a 12-month community-based hypertension management programme of blood pressure monitoring and lifestyle counselling intervention undertaken by female community health volunteers (FCHVs) in Nepal, against usual care, which showed success in reducing blood pressure. Here we aimed to retrospectively quantify the budget impact and cost-effectiveness of the scale-up of the programme.In this retrospective analysis, we collected participant-level data from the COBIN study; programme delivery cost data from programme administrators from the COBIN study group; and popualtion and other data from WHO, the World Bank, and the Nepalese Government. We estimated costs per participant and total costs of a national scale-up of the COBIN programme focusing on two scenarios: scenario A, delivery of the intervention to only people aged 25-65 years with hypertension; and scenario B, delivery of the intervention to all adults aged 25-65 years regardless of hypertension status. Effectiveness was based on in-trial blood pressure reductions converted to cardiovascular disease disability-adjusted life-years (DALYs) averted. The primary cost-effectiveness measure was incremental cost per averted cardiovascular disease DALY (calculated using the incremental cost-effectiveness ratio [ICER]) from a health system perspective, including programme delivery and incremental medication costs. We did univariate sensitivity analyses of scenario B to assess the effect of uncertainty in key parameter values in our calculations.From a health system perspective, the first-year budget impact was US$7·1 million in scenario A and $10·8 million in scenario B. With each subsequent year, the costs decreased by approximately 50%. In the base-case cost-effectiveness analysis, from the health system perspective, scenario A resulted in an ICER of $582 per DALY averted and scenario B resulted in an ICER of $411 per DALY averted. The ICER was most sensitive to uncertainty in the number of total avertable cardiovascular disease DALYs in the eligible population.The programme is projected to be highly cost-effective in both scenarios compared with the WHO thresholds for cost-effectiveness for Nepal. For policy makers intending to meet the UN Sustainable Development Goal of reducing premature mortality from non-communicible diseases, this intervention should be considered.Duke-NUS Medical School, Singapore.
Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy
Authors: Jenica N. Upshaw, Brian Finkelman, Rebecca A. Hubbard, Amanda M. Smith, Hari K. Narayan, Linzi Arndt, Susan Domchek, Angela DeMichele, Kevin Fox, Payal Shah, Amy Clark, Angela Bradbury, Jennifer Matro, Srinath Adusumalli, Joseph R. Carver, Bonnie Ky
Journal: JACC. Cardiovascular imaging (2019)
Diversity, Mechanisms, and Significance of Macrophage Plasticity
Authors: Massimo Locati, Graziella Curtale, Alberto Mantovani
Journal: Annual Review of Pathology Mechanisms of Disease (2019)

Macrophages are a diverse set of cells present in all body compartments. This diversity is imprinted by their ontogenetic origin (embryonal versus adult bone marrow-derived cells); the organ context; by their activation or deactivation by various signals in the contexts of microbial invasion, tissue damage, and metabolic derangement; and by polarization of adaptive T cell responses. Classic adaptive responses of macrophages include tolerance, priming, and a wide spectrum of activation states, including M1, M2, or M2-like. Moreover, macrophages can retain long-term imprinting of microbial encounters (trained innate immunity). Single-cell analysis of mononuclear phagocytes in health and disease has added a new dimension to our understanding of the diversity of macrophage differentiation and activation. Epigenetic landscapes, transcription factors, and microRNA networks underlie the adaptability of macrophages to different environmental cues. Macrophage plasticity, an essential component of chronic inflammation, and its involvement in diverse human diseases, most notably cancer, is discussed here as a paradigm.
Escape Hematopoiesis By HLA-B5401-Lacking Hematopoietic Stem Progenitor Cells in Male Patients with Acquired Aplastic Anemia
Authors: Kohei Hosokawa, Mahmoud Ibrahim Elbadry, Hiroki Mizumaki, Luis Espinoza, Noriharu Nakagawa, Kazuhisa Chonabayashi, Yoshinori Yoshida, Takamasa Katagiri, Yoshitaka Zaimoku, Tatsuya Imi, Nguyen Thi Mai Anh, Yoichi Fujii, Seishi Ogawa, Katsuto Takenaka, Koichi Akashi, Shinji Nakao
Journal: Blood (2018)
Walter Sefton Suffern
Authors: Alisdair Stewart, Hilary Fyson, Diana Page, Richard Suffern
Journal: BMJ (2019)

Walter Sefton Suffern was born in Belfast and educated at Leeds Grammar School and Leeds University Medical School. He spent six months as a house physician at St James’s Hospital, Leeds, which was a steep learning curve.

In December 1942, he married a fellow medic, Alison Palmer, and within weeks set sail on an Atlantic convoy to North Africa and the Royal Army Medical Corps. …
Healthcare Costs in Elderly Patients with Acute Myeloid Leukemia (AML) in Routine Clinical Care in the United States (US)
Authors: Jill A Bell, Aaron Galaznik, Sharanya Murty, Megan Pollack, Augustina Ogbonnaya, Michael T. Eaddy, Robert J. Fram, Douglas V. Faller, Vamsi Kota
Journal: Blood (2017)
Sertraline is better at reducing anxiety than depressive symptoms
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The selective serotonin reuptake inhibitor (SSRI) sertraline reduces anxiety and improves quality of life and self rated mental health in patients with depression, according to a study which suggests the drug is effective, but not in the way the researchers had expected.1

The researchers from University College London said that all previous studies on sertraline had been conducted by pharmaceutical companies and included patients with severe depression recruited from specialist mental health services. As antidepressants are now mostly prescribed in general practice to people with varying severity of symptoms, they wanted to update the current evidence to reflect that.

They found that sertraline was more effective at reducing anxiety symptoms—such as nervousness, irritability, and restlessness—with improvements showing after six weeks, while it took 12 weeks for modest changes in depressive symptoms—such as low mood—to show.

The study, published …
Optimizing Postoperative Opioid Prescribing Through Quality-Based Reimbursement
Authors: Ryan Howard, Alexander Hallway, Jessica Santos-Parker, Joceline Vu, Jennifer Waljee, Chad M. Brummett, Michael Englesbe
Journal: JAMA Network Open (2019)

represent an effective strategy to immediately affect the opioid crisis by reducing excessive opioid prescribing after surgical operations.
Association Between a Polymorphism in MBOAT7 and Chronic Kidney Disease in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease
Authors: Bo Kyung Koo, Jung Nam An, Sae Kyung Joo, Donghee Kim, Seonhwa Lee, Jeong Mo Bae, Jeong Hwan Park, Jung Ho Kim, Mee Soo Chang, Won Kim
Journal: Clinical Gastroenterology and Hepatology (2019)
Association of Vessel-Sealant Devices vs Conventional Hemostasis With Postoperative Neck Hematoma After Thyroid Operations
Authors: Jennifer M. Siu, Justin C. McCarty, Shekhar Gadkaree, Edward J. Caterson, Gregory Randolph, Ian J. Witterick, Antoine Eskander, Regan W. Bergmark
Journal: JAMA Surgery (2019)

<h3>Importance</h3> Vessel-sealant devices (VSDs) have been popularized for use in thyroid operations; however, the association of their use with postoperative neck hematoma, a rare but potentially fatal complication, has not been well studied. <h3>Objective</h3> To examine the association of VSDs vs conventional hemostasis (CH) in thyroid operations with the development of neck hematoma. <h3>Design, Setting, and Participants</h3> This retrospective cohort study evaluated 10 903 patients in the Thyroid Procedure–Targeted Database of the National Surgical Quality Improvement Program from January 1, 2016, to December 31, 2017. One-to-one nearest-neighbor propensity score matching was conducted to adjust for differences in baseline covariates, including demographics, comorbidities, indications for thyroid procedure (goiter, Graves disease, malignant and benign thyroid nodule), and several other thyroid-specific characteristics, between the VSD and CH groups. <h3>Main Outcomes and Measures</h3> The primary outcome was postoperative hematoma requiring intervention with open evacuation, return to the operating room, tracheostomy, additional observation, or extended length of stay. Secondary outcomes include recurrent laryngeal nerve injury, operative duration, and hospital length of stay. <h3>Results</h3> One-to-one propensity score matching yielded 6522 patients (mean [SD] age, 52 [15] years; 8544 [78.4%] female) with 3261 in each exposure group such that distribution of observed baseline covariates was not different between groups of the same propensity score. Within the matched cohort, CH was associated with higher odds of neck hematoma compared with VSD (odds ratio, 2.33; 95% CI, 1.55-3.49;<i>P</i> &lt; .001), with 34 (1.0%) hematomas in the VSD group and 78 (2.4%) in the CH group. On the basis of this analysis, the number needed to treat with a VSD to prevent 1 postoperative hematoma was 74. Secondary outcomes included longer length of hospital stay (incidence rate ratio, 1.29; 95% CI, 1.23-1.36;<i>P</i> &lt; .001]) in the CH group compared with the VSD group but no difference in the odds of recurrent laryngeal nerve injury (odds ratio, 0.90; 95% CI, 0.73-1.11;<i>P</i> = .32) or operative duration (incidence rate ratio, 0.99; 95% CI, 0.96-1.01;<i>P</i> = .24). <h3>Conclusions and Relevance</h3> Use of VSDs during thyroid operations was associated with reduced odds of neck hematoma compared with CH techniques without increasing odds of nerve injury. The results suggest that postoperative neck hematoma rates after thyroid surgery may differ based on the hemostasis technique and that these differences should be considered when developing strategies for quality improvement of postoperative outcomes.
Recent drug approvals for acute myeloid leukemia
Authors: Catherine Lai, Kimberley Doucette, Kelly Norsworthy
Journal: Journal of Hematology & Oncology (2019)

Abstract Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, with an incidence that increases with age, and a generally poor prognosis. The disease is clinically and genetically heterogeneous, and recent advances have improved our understanding of the cytogenetic abnormalities and molecular mutations, aiding in prognostication and risk stratification. Until recently, however, therapeutic options were mostly limited to cytotoxic chemotherapy. Since 2017, there has been an explosion of newly approved treatment options both nationally and internationally, with the majority of new drugs targeting specific gene mutations and/or pivotal cell survival pathways. In this review article, we will discuss these new agents approved for the treatment of AML within the last 2 years, and will outline the mechanistic features and clinical trials that led to their approvals.
Optimal Gestational Weight Gain
Authors: Lisa M. Bodnar, Katherine P. Himes, Jennifer A. Hutcheon
Journal: JAMA (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 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