tbuckley/cabot-search huggingface dataset:
Association Between Maternal Perinatal Depression and Anxiety and Child and Adolescent Development
Authors: Alana Rogers, Shelley Obst, Samantha J. Teague, Larissa Rossen, Elizabeth A. Spry, Jacqui A. Macdonald, Matthew Sunderland, Craig A. Olsson, George Youssef, Delyse Hutchinson
Journal: JAMA Pediatrics (2020)

There is widespread interest in associations between maternal perinatal depression and anxiety and offspring development; however, to date, there has been no systematic, meta-analytic review on the long-term developmental outcomes spanning infancy through adolescence. To provide a comprehensive systematic review and meta-analysis of the extant literature on associations between maternal perinatal depression and anxiety and social-emotional, cognitive, language, motor, and adaptability outcomes in offspring during the first 18 years of life. Six databases were searched (CINAHL Complete, Cochrane Library, Embase, Informit, MEDLINE Complete, and PsycInfo) for all extant studies reporting associations between perinatal maternal mental health problems and offspring development to March 1, 2020. Studies were included if they were published in English; had a human sample, quantitative data, a longitudinal design, and measures of perinatal depression and/or anxiety and social-emotional, cognitive, language, motor, and/or adaptability development in offspring; and investigated an association between perinatal depression or anxiety and childhood development. Of 27 212 articles identified, 191 were eligible for meta-analysis. Data were extracted by multiple independent observers and pooled using a fixed- or a random-effects model. A series of meta-regressions were also conducted. Data were analyzed from January 1, 2019, to March 15, 2020. Primary outcomes included social-emotional, cognitive, language, motor, and adaptability development in offspring during the first 18 years of life. After screening, 191 unique studies were eligible for meta-analysis, with a combined sample of 195 751 unique mother-child dyads. Maternal perinatal depression and anxiety were associated with poorer offspring social-emotional (antenatal period, r = 0.21 [95% CI, 0.16-0.27]; postnatal period, r = 0.24 [95% CI, 0.19-0.28]), cognitive (antenatal period, r = -0.12 [95% CI, -0.19 to -0.05]; postnatal period, r = -0.25 [95% CI, -0.39 to -0.09]), language (antenatal period, r = -0.11 [95% CI, -0.20 to 0.02]; postnatal period, r = -0.22 [95% CI, -0.40 to 0.03]), motor (antenatal period, r = -0.07 [95% CI, -0.18 to 0.03]; postnatal period, r = -0.07 [95% CI, -0.16 to 0.03]), and adaptive behavior (antenatal period, r = -0.26 [95% CI, -0.39 to -0.12]) development. Findings extended beyond infancy, into childhood and adolescence. Meta-regressions confirmed the robustness of the results. Evidence suggests that perinatal depression and anxiety in mothers are adversely associated with offspring development and therefore are important targets for prevention and early intervention to support mothers transitioning into parenthood and the health and well-being of next-generation offspring.
Painful perianal ulcers with nicorandil
Authors: Patricia McGettigan, Robin E Ferner
Journal: BMJ (2020)

### What you need to know

A 73 year old man presents with painful ulcers around his anus that have worsened, despite his use of a barrier cream. His bowel habit is unchanged, his weight is stable, he is not anaemic, and he has experienced no rectal bleeding. He has ischaemic heart disease for which he takes aspirin, atorvastatin, bisoprolol, diltiazem, nicorandil, and ramipril. You find extensive perianal ulceration. Rectal examination is painful, but no masses are evident. Since clinical findings do not suggest cancer or inflammatory bowel disease, you consider if this might represent an adverse reaction to nicorandil, recalling a photograph you had seen ( fig 1 ). 



Fig 1 
Perianal ulceration, reproduced from Kulakov E, Baron S BMJ 2013;346:f3686



Nicorandil, a drug occasionally used to treat symptoms of angina, can cause a rare but serious adverse reaction of painful, non-healing ulcers that affect the skin and mucosa.1 Failure to recognise this adverse drug reaction can result in serious harm to some patients.2345 The danger is increased because nicorandil treatment is usually initiated by cardiologists, but this rare adverse reaction usually presents to others, including general practitioners, surgeons, dentists, ophthalmologists, and dermatologists.

Nicorandil is a nicotinamide ester that dilates arteries and veins, reducing after-load and pre-load on the heart.1 Guidelines from the European Society of Cardiology and National Institute for Health and Care Excellence recommend nicorandil as second line treatment in the management of stable angina that is inadequately controlled by …
Type I interferon signaling in fibroblastic reticular cells prevents exhaustive activation of antiviral CD8 <sup>+</sup> T cells
Authors: Christian Perez-Shibayama, Ulrika Islander, Mechthild Lütge, Hung-Wei Cheng, Lucas Onder, Sandra S. Ring, Angelina De Martin, Mario Novkovic, Julia Colston, Cristina Gil-Cruz, Burkhard Ludewig
Journal: Science Immunology (2020)

Programming of lymph node fibroblastic reticular cells by type I interferons is needed for effective antiviral CD8 + T cell responses.
Another Medical Malpractice Crisis?
Authors: William M. Sage, Richard C. Boothman, Thomas H. Gallagher
Journal: JAMA (2020)

Adam C. Schaffer, MD; Anupam B. Jena, MD, PhD; Seth A. Seabury, PhD; Harnam Singh, PhD; Venkat Chalasani, PhD; Allen Kachalia, MD, JD
Abstract #3276: The BH3 mimetic Obatoclax (GX15-070) sensitized B-NHL cells to TRAIL-mediated apoptosis by activating Bak and inhibiting Mcl-1, NF-\#954;B and the DR5 transcription repressor YY1
Authors: Melisa Martinez-Paniagua, Mario Vega, Sara Huerta-Yepez, Stavroula Baritaki, Bernardo Martinez-Miguel, Cesar Gonzalez-Bonilla, Benjamin Bonavida
Journal: Cancer Research (2009)

Novel therapeutic strategies are urgently needed to treat patients with B-NHL that are unresponsive to conventional therapies. TRAIL, a member of the TNF-\#945; family, has been shown to induce apoptosis in transformed cells with minimal toxicity to normal tissues; however, the majority of tumor cell lines and freshly derived tumor cells are resistant to TRAIL-induced apoptosis. Studies by us and others have reported that inhibition of overexpressed anti-apoptotic gene products, such as Bcl-2 and Bcl-XL, can reverse resistance to TRAIL apoptosis. The BH3 mimetic Obatoclax (GX15-070, Gemin X Pharmaceuticals, Malvern, PA) inhibits diverse anti-apoptotic molecules like Bcl-2, Bcl-XL and Mcl-1 through direct binding and can reverse tumor cells resistance to chemotherapeutic drugs. We hypothesized that treatment of B-NHL cell lines with Obatoclax will result in tumor cell sensitization to TRAIL apoptosis. Using the B-NHL Ramos cell line as model, cells were treated with different concentrations of Obatoclax (7-28 nM) and TRAIL (2.5-20 ng/ml, 24 h). Significant potentiating of apoptosis and synergy were achieved by the combination treatment. There was also depolarization of the mitochondrial membrane potential by the combination treatment observed 4 hours after treatment. We then examined the potential underlying mechanism of sensitization by Obatoclax. It has been reported that Mcl-1, an anti-apoptotic protein, confers resistance to TRAIL-mediated apoptosis due to the interaction between Mcl-1 and the truncated Bid protein (Tanai et. al., Can Res 64: 3517, 2004; Clohessy JG, JBC: 5750, 2006). We show here a disruption of the Mcl-1 binding to Bak and to Bid by immunoprecipitation. Further, we also show inhibition of the NF-\#954;B activity and downstream anti-apoptotic gene products regulated by NF-\#954;B (Bcl-XL, Mcl-1 and XIAP) as assessed by western. NF-\#954;B regulates the transcription of the DR5 transcription repressor Yin Yang 1 (YY1). Treatment of Ramos with Obatoclax significantly inhibited YY1 expression and concurrently, upregulated total and surface DR5 expression. In addition to its direct role in inhibiting the Bcl-2 family members, Obatoclax induces gene modification by a different mechanism than that reported by Song et. al. for the ABT-737 inhibitor (JBC, 283:25003, 2008). Present findings demonstrate that Obatoclax sensitizes TRAIL resistant B-NHL cells to TRAIL apoptosis. In addition to its known effect on inhibiting physically Bcl-2 family members, it also inhibits NF-\#954;B activity and downstream gene products that regulate both chemo-resistance and immune-resistance.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3276.
Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States
Authors: Nicole J. Kim, Karine Rozenberg-Ben-Dror, David A. Jacob, Nicole E. Rich, Amit G. Singal, Elizabeth S. Aby, Ju Dong Yang, Veronica Nguyen, Anjana Pillai, Michael Fuchs, Andrew M. Moon, Hersh Shroff, Parul D. Agarwal, Ponni Perumalswami, Shaun Chandna, Kali Zhou, Yuval A. Patel, Nyan L. Latt, Robert Wong, Andres Duarte-Rojo, Christina C. Lindenmeyer, Catherine Frenette, Jin Ge, Neil Mehta, Francis Yao, Jihane N. Benhammou, Patricia P. Bloom, Michael Leise, Hyun-seok Kim, Cynthia Levy, Abbey Barnard, Mandana Khalili, George N. Ioannou
Journal: Clinical Gastroenterology and Hepatology (2020)
Do Pregnancies Forestall the Onset of MS?
Authors: Jennifer S. Graves
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus
Authors: Lennard Ostendorf, Marie Burns, Pawel Durek, Gitta Anne Heinz, Frederik Heinrich, Panagiotis Garantziotis, Philipp Enghard, Ulrich Richter, Robert Biesen, Udo Schneider, Fabian Knebel, Gerd Burmester, Andreas Radbruch, Henrik E. Mei, Mir-Farzin Mashreghi, Falk Hiepe, Tobias Alexander
Journal: New England Journal of Medicine (2020)

Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented. (Supported by the Deutsche Forschungsgemeinschaft and others.).
In ischemic stroke, thrombectomy alone was noninferior to thrombectomy plus alteplase for functional outcome at 90 days
Authors: Mark J. Alberts
Journal: Annals of Internal Medicine (2020)

Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med. 2020;382:1981-93. 32374959.
Cancer statistics for adolescents and young adults, 2020
Authors: Kimberly D. Miller, Miranda Fidler‐Benaoudia, Theresa H. Keegan, Heather S. Hipp, Ahmedin Jemal, Rebecca L. Siegel
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract Cancer statistics for adolescents and young adults (AYAs) (aged 15‐39 years) are often presented in aggregate, masking important heterogeneity. The authors analyzed population‐based cancer incidence and mortality for AYAs in the United States by age group (ages 15‐19, 20‐29, and 30‐39 years), sex, and race/ethnicity. In 2020, there will be approximately 89,500 new cancer cases and 9270 cancer deaths in AYAs. Overall cancer incidence increased in all AYA age groups during the most recent decade (2007‐2016), largely driven by thyroid cancer, which rose by approximately 3% annually among those aged 20 to 39 years and 4% among those aged 15 to 19 years. Incidence also increased in most age groups for several cancers linked to obesity, including kidney (3% annually across all age groups), uterine corpus (3% in the group aged 20‐39 years), and colorectum (0.9%‐1.5% in the group aged 20‐39 years). Rates declined dramatically for melanoma in the group aged 15 to 29 years (4%‐6% annually) but remained stable among those aged 30 to 39 years. Overall cancer mortality declined during 2008 through 2017 by 1% annually across age and sex groups, except for women aged 30 to 39 years, among whom rates were stable because of a flattening of declines in female breast cancer. Rates increased for cancers of the colorectum and uterine corpus in the group aged 30 to 39 years, mirroring incidence trends. Five‐year relative survival in AYAs is similar across age groups for all cancers combined (range, 83%‐86%) but varies widely for some cancers, such as acute lymphocytic leukemia (74% in the group aged 15‐19 years vs 51% in the group aged 30‐39 years) and brain tumors (77% vs 66%), reflecting differences in histologic subtype distribution and treatment. Progress in reducing cancer morbidity and mortality among AYAs could be addressed through more equitable access to health care, increasing clinical trial enrollment, expanding research, and greater alertness among clinicians and patients for early symptoms and signs of cancer. Further progress could be accelerated with increased disaggregation by age in research on surveillance, etiology, basic biology, and survivorship.
Preventing COVID-19 Outbreaks in Long-Term Care Facilities Through Preemptive Testing of Residents and Staff Members — Fulton County, Georgia, March–May 2020
Authors: Carson T. Telford, Udodirim Onwubiko, David P. Holland, Kim Turner, Juliana Prieto, Sasha Smith, Jane Yoon, Wecheeta Brown, Allison Chamberlain, Neel Gandhi, Steve Williams, Fazle Khan, Sarita Shah
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

This report describes an analysis of facility-wide COVID-19 testing at long-term care facilities in Fulton County, Georgia, which found that active testing of staff and residents could help identify cases of COVID-19 early and prevent widespread infection.
Potent Activity of an Anti-ICAM1 Antibody–Drug Conjugate against Multiple Myeloma
Authors: Daniel W. Sherbenou, Yang Su, Christopher R. Behrens, Blake T. Aftab, Olivia Perez de Acha, Megan Murnane, Shelby C. Bearrows, Byron C. Hann, Jeffery L. Wolf, Thomas G. Martin, Bin Liu
Journal: Clinical Cancer Research (2020)

New therapies have changed the outlook for patients with multiple myeloma, but novel agents are needed for patients who are refractory or relapsed on currently approved drug classes. Novel targets other than CD38 and BCMA are needed for new immunotherapy development, as resistance to daratumumab and emerging anti-BCMA approaches appears inevitable. One potential target of interest in myeloma is ICAM1. Naked anti-ICAM1 antibodies were active in preclinical models of myeloma and safe in patients, but showed limited clinical efficacy. Here, we sought to achieve improved targeting of multiple myeloma with an anti-ICAM1 antibody-drug conjugate (ADC).
Human Myocardium-on-a-Chip Enables Mechanistic Studies Into the Effects of Strain on Cardiac Fibrosis
Authors: Thomas C. Bracco Gartner, Ye Wang, Jaap M. den Toonder, Carlijn V. Bouten, Joost P. Sluijter, Willem J. Suyker, Jesper Hjortnaes
Journal: Circulation (2019)
Projected spending for brand-name drugs in English primary care given US prices: a cross-sectional study
Authors: Michael Liu, Brian MacKenna, William B Feldman, Alex J Walker, Jerry Avorn, Aaron S Kesselheim, Ben Goldacre
Journal: Journal of the Royal Society of Medicine (2020)

Summary Objectives To estimate additional spending if NHS England paid the same prices as US Medicare Part D for the 50 single-source brand-name drugs with the highest expenditure in English primary care in 2018. Design Retrospective analysis of 2018 drug prescribing and spending in the NHS England prescribing data and the Medicare Part D Drug Spending Dashboard and Data. We examined the 50 costliest drugs in English primary care available as brand-name-only in the US and England. We performed cost projections of NHS England spending with US Medicare Part D prices. We estimated average 2018 US rebates as 1 minus the quotient of net divided by gross Medicare Part D spending. Setting England and US Participants NHS England and US Medicare systems Main outcome measures Total spending, prescriptions and claims in NHS England and Medicare Part D. All spending and cost measures were reported in 2018 British pounds. Results NHS England spent £1.39 billion on drugs in the cohort. All drugs were more expensive under US Medicare Part D than NHS England. The US–England price ratios ranged from 1.3 to 9.9 (mean ratio 4.8). Accounting for prescribing volume, if NHS England had paid US Medicare Part D prices after adjusting for estimated US rebates, it would have spent 4.6 times as much in 2018 on drugs in the cohort (£6.42 billion). Conclusions Spending by NHS England would be substantially higher if it paid US Medicare Part D prices. This could result in decreased access to medicines and other health services.
Policy Recommendations to Promote Prescription Drug Competition: A Position Paper From the American College of Physicians
Authors: Hilary Daniel, Josh Serchen, Thomas G. Cooney
Journal: Annals of Internal Medicine (2020)

The prescription drug market in the United States relies on competition to keep prices reasonable. Although many policies have been implemented to spur competition and decrease costs for patients, these policies may be outdated and should be redesigned and updated to achieve success in the current prescription drug market. In this paper, the American College of Physicians (ACP) proposes that new policies should be implemented to prevent market manipulation, help lower-cost alternatives make it to the market faster, and ensure a robust and competitive market for generic and biosimilar drugs. The ACP believes these changes will have a meaningful effect on patients without shifting costs to other areas of the health care system.
Reassessment of the risk of narcolepsy in children in England 8 years after receipt of the AS03-adjuvanted H1N1 pandemic vaccine: A case-coverage study
Authors: Julia Stowe, Nick Andrews, Paul Gringras, Timothy Quinnell, Zenobia Zaiwalla, John Shneerson, Elizabeth Miller
Journal: PLoS Medicine (2020)

Background Early studies of narcolepsy after AS03-adjuvanted pandemic A/H1N12009 vaccine (Pandemrix) could not define the duration of elevated risk post-vaccination nor the risk in children aged under 5 years who may not present until much older. Methods/Findings Clinical information and sleep test results, extracted from hospital notes at 3 large pediatric sleep centers in England between September 2017 and June 2018 for narcolepsy cases aged 4–19 years with symptom onset since January 2009, were reviewed by an expert panel to confirm the diagnosis. Vaccination histories were independently obtained from general practitioners (GPs). The odds of vaccination in narcolepsy cases compared with the age-matched English population was calculated after adjustment for clinical conditions that were indications for vaccination. GP questionnaires were returned for 242 of the 244 children with confirmed narcolepsy. Of these 5 were under 5 years, 118 were 5–11 years, and 119 were 12–19 years old at diagnosis; 39 were vaccinated with Pandemrix before onset. The odds ratio (OR) for onset at any time after vaccination was 1.94 (95% confidence interval [CI] 1.30–2.89), The elevated risk period was restricted to onsets within 12 months of vaccination (OR 6.65 [3.44–12.85]) and was highest within the first 6 months. After one year, ORs were not significantly different from 1 up to 8 years after vaccination. The ORs were similar in under five-year-olds and older ages. The estimated attributable risk was 1 in 34,500 doses. Our study is limited by including cases from only 3 sleep centers, who may differ from cases diagnosed in nonparticipating centers, and by imprecision in defining the centers' catchment population. The potential for biased recall of onset shortly after vaccination in cases aware of the association cannot be excluded. Conclusions In this study, we found that vaccine-attributable cases have onset of narcolepsy within 12 months of Pandemrix vaccination. The attributable risk is higher than previously estimated in England because of identification of vaccine-attributable cases with late diagnoses. Absence of a compensatory drop in risk 1–8 years after vaccination suggests that Pandemrix does not trigger onsets in those in whom narcolepsy would have occurred later.
Mortality in Patients With Atrial Fibrillation Receiving Nonrecommended Doses of Direct Oral Anticoagulants
Authors: Alan John Camm, Frank Cools, Saverio Virdone, Jean-Pierre Bassand, David Andrew Fitzmaurice, Keith Alexander Arthur Fox, Samuel Zachary Goldhaber, Shinya Goto, Sylvia Haas, Lorenzo Giovanni Mantovani, Gloria Kayani, Alexander Graham Grierson Turpie, Freek Willem Antoon Verheugt, Ajay Kumar Kakkar
Journal: Journal of the American College of Cardiology (2020)

The recommended doses for direct oral anticoagulants (DOACs) to prevent stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) are described in specific regulatory authority approvals. The impact of DOAC dosing, according to the recommended guidance on all-cause mortality, stroke/SE, and major bleeding, was assessed at 2-year follow-up in patients with newly diagnosed AF. Of a total of 34,926 patients enrolled (2013 to 2016) in the prospective GARFIELD-AF (Global Anticoagulant Registry in the FIELD-AF), 10,426 patients received a DOAC. The majority of patients (72.9%) received recommended dosing, 23.2% were underdosed, and 3.8% were overdosed. Nonrecommended dosing (underdosage and overdosage combined) compared with recommended dosing was associated with a higher risk of all-cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.48); HR: 1.25 (95% CI: 1.04 to 1.50) for underdosing, and HR: 1.19 (95% CI: 0.83 to 1.71) for overdosing. The excess deaths were cardiovascular including heart failure and myocardial infarction. The risks of stroke/SE and major bleeding were not significantly different irrespective of the level of dosing, although underdosed patients had a significantly lower risk of bleeding. A nonsignificant trend to higher risks of stroke/SE (HR: 1.51; 95% CI: 0.79 to 2.91) and major bleeding (HR: 1.29; 95% CI: 0.59 to 2.78) was observed in patients with overdosing. In GARFIELD-AF, most patients received the recommended DOAC doses according to country-specific guidelines. Prescription of nonrecommended doses was associated with an increased risk of death, mostly cardiovascular death, compared with patients on recommended doses, after adjusting for baseline factors. (Global Anticoagulant Registry in the Field-AF [GARFIELD-AF]; NCT01090362)