tbuckley/cabot-search huggingface dataset:
Constipation, deficit in colon contractions and alpha-synuclein inclusions within the colon precede motor abnormalities and neurodegeneration in the central nervous system in a mouse model of alpha-synucleinopathy
Authors: Lucia Rota, Carolina Pellegrini, Laura Benvenuti, Luca Antonioli, Matteo Fornai, Corrado Blandizzi, Antonino Cattaneo, Emanuela Colla
Journal: Translational Neurodegeneration (2019)

Gastrointestinal dysfunction can affect Parkinson's disease (PD) patients long before the onset of motor symptoms. However, little is known about the relationship between gastrointestinal abnormalities and the development of PD. Contrary to other animal models, the human A53T alpha-synuclein (αS) transgenic mice, Line G2–3, develops αS-driven neurological and motor impairments after 9 months of age, displaying a long presymptomatic phase free of central nervous system (CNS) dysfunction. To determine whether this line can be suitable to study constipation as it occurs in prodromal PD, gastrointestinal functionality was assessed in young mice through a multidisciplinary approach, based on behavioral and biochemical analysis combined with electrophysiological recordings of mouse intestinal preparations. We found that the A53T αS mice display remarkable signs of gastrointestinal dysfunction that precede motor abnormalities and αS pathology in the CNS by at least 6 months. Young αS mice show a drastic delay in food transit along the gastrointestinal tract, of almost 2 h in 3 months old mice that increased to more than 3 h at 6 months. Such impairment was associated with abnormal formation of stools that resulted in less abundant but longer pellets excreted, suggesting a deficit in the intestinal peristalsis. In agreement with this, electrically evoked contractions of the colon, but not of the ileum, showed a reduced motor response in both longitudinal and circular muscle layers in αS mice already at 3 months of age, that was mainly due to an impaired cholinergic transmission of the underlying enteric nervous system. Interestingly, the presence of insoluble and aggregated αS was found in enteric neurons in both myenteric and submucosal plexi only in the colon of 3 months old αS mice, but not in the small intestine, and exacerbated with age, mimicking the increase in transit delay and the contraction deficit showed by behavioral and electrical recordings data. Gastrointestinal dysfunction in A53T αS mice represents an early sign of αS-driven pathology without concomitant CNS involvement. We believe that this model can be very useful to study disease-modifying strategies that could extend the prodromal phase of PD and halt αS pathology from reaching the brain.
Phase 2 Study of Pembrolizumab during Lymphodepleted State after Autologous Hematopoietic Cell Transplantation in Multiple Myeloma Patients
Authors: Attaphol Pawarode, Anita D'Souza, Marcelo C. Pasquini, Bryon Johnson, Thomas Braun, Binod Dhakal, Mehdi Hamadani, John M. Magenau, Nirav N Shah, Mary Mansour Riwes, Brian Parkin, Pavan Reddy, Parameswaran Hari
Journal: Blood (2017)
Abstract P354: Impact of a Single Mixed Mediterranean-type Meal Compared to a High-Saturated Fat Meal on Postprandial Endothelial Function and Metabolic Markers
Authors: Sebastien Lacroix, Christine DesRosiers, Mathieu Gayda, Anil Nigam
Journal: Circulation (2012)

Background: Endothelial dysfunction is considered to be a precursor of atherosclerosis and is an independent predictor of cardiovascular events. A high-saturated fat meal (HFM) has been shown to induce postprandial endothelial dysfunction. However, no studies have evaluated the acute endothelial effect of a single mixed Mediterranean-type meal (MMM). Our objective was to evaluate postprandial endothelial and metabolic function in response to a MMM in comparison to an isocaloric HFM. Methods: In this ongoing crossover study, 22 of 28 healthy non-smoking males have completed the research protocol. In random order on two separate days during a 1-week interval, subjects were fed two isocaloric meals after a 12-hour overnight fast. The MMM (885 kcal) consisted of fresh salmon, almonds and vegetables baked in olive oil providing 51% of total calories from fat (7.87g SFA and 2.29g of omega-3, 2:1 DHA:EPA). The HFM consisted of a McDonald's sausage, egg and cheese McMuffin and three hashbrowns (858 kcal) providing 58% of total energy from fat (14.78g SFA and no omega-3). Endothelial function was evaluated by measuring brachial artery flow-mediated dilation (%FMD) at baseline and at two (T2) and four (T4) hours postprandial. Results: Mean postprandial %FMD tends to be less impaired following the MMM than the HFM (variation at T4 -0.15±3.6% vs -2.83±3.3% respectively, p&lt;0.1). Postprandial insulin response was less important following the MMM than the HFM (at T2 72.42±94.8% vs 253.89±291.5% respectively, p≤0.1). Postprandial variations of TG and TG/HDL ratio at T4 were also less severe with the MMM than the HFM (p≤0.05). When dividing the subjects on the basis of the median fasting TG levels (0.90 mmol/L), the HFM led to a more severe endothelial impairment in subjects with high (variation in %FMD at T4 -4.36±2.9% p&lt;0.005) vs low fasting TG levels (variation in %FMD at T4 -0.965±2.99%, ns). Conclusion: Our data suggest that a single MMM exerts less of a deleterious effect on postprandial endothelial function and metabolic markers than does a HFM. A single MMM could thus be less atherogenic than a HFM. Moreover, subjects with moderate fasting TG levels (avg. 1.54±0.59 mmol/L, well bellow hypertriglyceridemia threshold) could be at higher risk of endothelial injury following a single HFM. Data on all 28 subjects will be available in March 2012.
Dual Imaging With 68Ga-DOTATOC and 18F-FDG PET for Planning and Follow-up of PRRT in Combination With Temozolomide Treatment in a Patient With a Metastatic Neuroendocrine Tumor
Authors: Xiao Wei, Susanne Hain, Lynn Hartmann, Stefan Hirzebruch, Hojjat Ahmadzadehfar
Journal: Clinical Nuclear Medicine (2019)

A 68-year-old man with a metastatic neuroendocrine tumor with unknown primary was found to have partially dedifferentiated metastases according to F-FDG uptake. He received 3 cycles of radiopeptide therapy using [Lu]Lutetium-DOTATATE combined with temozolomide. Before this treatment, the patient had already undergone a series of therapies, including biotherapy, everolimus, 5 cycles of radiopeptide therapies, radiotherapy, and bone-protecting therapy with bisphosphonate and receptor activator of NF-κB ligand, each of which temporarily stalled the progress of the disease. After combined treatment with radiopeptide therapy and temozolomide, the patient showed a very good response in all tumor lesions, including the FDG-positive ones.
Transfusion Independence in Lower-Risk, Non-del5(q) Myelodysplastic Syndromes (LR-MDS) Among Patients (pts) Initiating Hypomethylating Agents (HMAs) While Receiving Red Blood Cell (RBC) Transfusions
Authors: Amer M. Zeidan, Weiwei Zhu, Rong Wang, Maximilian Stahl, Scott F Huntington, Smith Giri, Nikolai A. Podoltsev, Steven D. Gore, Xiaomei Ma, Amy J. Davidoff
Journal: Blood (2018)
Extending models of “How Foraging Works”: Uncertainty, controllability, and survivability
Authors: Oliver J. Hulme, Duda Kvitsiani
Journal: Behavioral and Brain Sciences (2019)

Abstract We argue that How Foraging Works sketches a good foundational model, but it needs expanding to incorporate hierarchical and multiscale conceptions of uncertainty and to incorporate inference of environmental controllability. Most pressingly, its algorithmic implementation needs to be better justified in terms of its functional forms and, ultimately, to be more heavily constrained by survival optimality.
Group opposed to RCP assisted dying poll lacks transparency, claims report
Authors: Bryan Christie
Journal: BMJ (2019)

The row over a poll on assisted dying being conducted by the Royal College of Physicians has reached a new level of acrimony, with claims that opposition to the poll is been orchestrated by conservative Christian groups.

A report from the Dignity in Dying campaign group, which wants a change in the law to legalise assisted dying, says that attempts are being made to deny doctors a say by networks linked to pro-life, faith based organisations.1

The RCP is polling its 35 000 members and fellows on the issue and has ruled that it will adopt a “neutral” position unless at least 60% vote either in favour of or against a change in the law, effectively ending its opposition to legalisation.2 The college is due to announce the results of the poll on Thursday 21 March.

But the RCP is facing a legal challenge to the decision to seek a supra-majority.3 A crowdfunding campaign has been set up by a group of doctors …
Thrombolysis Works in Lacunar Infarct, Complicating Imaging Selection
Authors: Pooja Khatri
Journal: JAMA Neurology (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 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
Association of Characteristics of Psychiatrists With Use of Telemental Health Visits in the Medicare Population
Authors: Suyoung Choi, Andrew D. Wilcock, Alisa B. Busch, Haiden A. Huskamp, Lori Uscher-Pines, Zhuo Shi, Ateev Mehrotra
Journal: JAMA Psychiatry (2019)

Emergency departments most commonly assessed patients who present with self-harm for current suicidal intent/plans (2156 [97.6%]), past suicidal thoughts/behaviors (1989 [90.6%]), and access to lethal means (1708 [77.7%]) (Figure).Provision of individual safety planning elements ranged from 24.8% (n = 492) to 79.2% (n = 1710), with 2 of 6 elements being routinely provided more than 50% of the time: lists of professionals or agencies to contact in a crisis (1710 [79.2%]) and helping patients to recognize warning signs of suicide (1075 [52.2%]).Only 15.3% (n = 342) routinely provided all recommended safety planning elements.There were no significant differences in emergency self-harm management practices by urban/rural status, mental health staff availability, or hospital volume.However, EDs associated with teaching hospitals were significantly more likely than EDs affiliated with nonteaching hospitals to provide professional contact lists (791 [86.5%] vs 909 [73.7%];P = .004)(Table ).Discussion | Most EDs in the United States routinely assess patients who present with deliberate self-harm for suicidal thoughts/ behaviors and access to lethal means, but relatively few routinely act to provide basic aspects of safety planning, such as creating individualized plans to restrict access to lethal means, helping patients to use internal coping strategies, or accessing available social supports/activities.Emerging research indicates that safety planning in combination with structured telephone follow-up can significantly reduce suicidal behaviors after ED discharge compared with usual care. 6 Because provision of these services in our study was largely independent of ED characteristics, there are widespread opportunities for improvement.Study limitations include use of self-report rather than an audit, the possibility that our ED sample may not generalize to all US EDs, and an inability to know whether social workers have mental health specialty training or which professionals provide the services.The study also was not designed to assess the effect of severity of the self-harm incident or recognition of a mental disorder in the ED on self-harm management practices.
Locum GPs must have same death in service benefits as other doctors, say LMCs
Authors: Abi Rimmer
Journal: BMJ (2019)

The BMA’s General Practitioners Committee must actively seek changes to the NHS pension scheme to make it fairer for all GPs, local medical committees (LMCs) have urged.

On 20 March the annual LMC conference in Belfast unanimously called for sessional GPs to have the same death in service benefits as the rest of the GP workforce.

The NHS pension scheme provides a lump sum and pension benefits to a doctor’s dependants in the event of his or her death.1 However, some locum GPs are not eligible for this benefit.2

Speaking at the conference, Andrew Parkin, a locum GP …
Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-2016
Authors: Mikael Norman, Boubou Hallberg, Thomas Abrahamsson, Lars J. Björklund, Magnus Domellöf, Aijaz Farooqi, Cathrine Foyn Bruun, Christian Gadsbøll, Lena Hellström-Westas, Fredrik Ingemansson, Karin Källén, David Ley, Karel Maršál, Erik Normann, Fredrik Serenius, Olof Stephansson, Lennart Stigson, Petra Um-Bergström, Stellan Håkansson
Journal: JAMA (2019)

Importance Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown. Objective To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016. Design, Setting and Participants All births at 22-26 weeks’ gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. Exposures Delivery at 22-26 weeks’ gestational age. Main Outcomes and Measures The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia). Results During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks’ gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 ( P = .61). One-year survival among live-born infants at 22-26 weeks’ gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, −7% [95% CI, −11% to −2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks’ gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, −6% [95% CI, −11% to −1.7%], P = .008). Conclusions and Relevance Among live births at 22-26 weeks’ gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.
Abstract 18440: Low Ferritin Levels are Associated With Increased Risk of Heart Failure - The Atherosclerosis Risk in Communities Study
Authors: Odilson M Silvestre, Alexandra Gonçalves, Wilson Nadruz, Brian Claggett, John H Eckfeldt, James S Pankow, Scott D Solomon
Journal: Circulation (2015)

Introduction: While severe iron overload has been associated with cardiac damage, iron deficiency is related to worse outcomes in subjects with heart failure (HF).This study investigated the relationship between ferritin, a marker of iron status, and the incidence of HF in a general population based sample. Methods: We examined 1,063 participants from the Atherosclerosis Risk in Communities (ARIC) study, mean age 52±5 years, 62% women, free of heart failure, in whom ferritin serum levels were measured at baseline (1987-1989). The participants were categorized in low (200 ng/mL in women and &gt;300 ng/mL in men; n=247) ferritin levels. Multivariable Cox proportional hazards models were used to evaluate the relationship between ferritin and incident HF. Results: At 20.9±4.6 years of follow-up, HF occurred in 144 (13.5%) participants. When compared with participants with normal ferritin, those with low level had a higher risk of HF (HR 2.10, 95%CI 1.27-3.47; p=0.004), while there was no significant difference between those with normal and high ferritin levels (HR= 1.07, 95%CI= 0.71-1.63, p=0.7), after adjusting for potential confounders. Low ferritin levels remained associated with incident HF in subjects without anemia (HR= 2.06, 95%CI= 1.18-3.61, p=0.01). (Figure) Conclusion: Low ferritin levels are associated with a higher risk of incident HF. These findings suggest that iron deficiency might play a role in the development of HF.
A Stem Cell-Based Epigenetic Memory Mediates Interferon Response-Heterogeneity within the Hematopoietic System
Authors: Simon Haas, Christoph Hirche, Alexandra Schnell, Can Sönmezer, Jens Langstein, Stephan Wurzer, Marc Thier, Sandra Blaszkiewicz, Franziska Pilz, Michael D. Milsom, Andreas Trumpp, Daniel Lipka, Ulrich Kalinke, Marieke A. G. Essers
Journal: Blood (2017)
PD-L1 gene alterations identify a subset of diffuse large B-cell lymphoma harboring a T-cell–inflamed phenotype
Authors: James Godfrey, Sravya Tumuluru, Riyue Bao, Michael Leukam, Girish Venkataraman, John Phillip, Carrie Fitzpatrick, James McElherne, Brendan W. MacNabb, Robert Orlowski, Sonali M. Smith, Justin Kline
Journal: Blood (2019)
Macular Ganglion Cell–Inner Plexiform Layer Loss Precedes Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma with Lower Intraocular Pressure
Authors: Henry N. Marshall, Nicholas H. Andrew, Mark Hassall, Ayub Qassim, Emmanuelle Souzeau, Bronwyn Ridge, Thi Nguyen, Jude Fitzgerald, Mona S. Awadalla, Kathryn P. Burdon, Paul R. Healey, Ashish Agar, Anna Galanopoulos, Alex W. Hewitt, Stuart L. Graham, John Landers, Robert J. Casson, Jamie E. Craig
Journal: Ophthalmology (2019)
CLO19-033: Afatinib Followed by Osimertinib in EGFR Mutation-Positive (EGFRm+) Advanced NSCLC: Subgroup Analyses of the GioTag Study by ECOG PS, Age, and Ethnicity
Authors: Balazs Halmos, Maximilian J. Hochmair, Alessandro Morabito, Desiree Hao, Cheng-Ta Yang, Ross A. Soo, James C-H Yang, Rasim Gucalp, Lara Wang, Angela Märten, Tanja Cufer
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: EGFR TKIs have shown first-line efficacy in EGFR m+ NSCLC but acquired resistance is inevitable; with afatinib, this is predominantly through the emergence of T790M. Therefore, a key consideration when assessing therapeutic choices is the availability of subsequent treatment options. The GioTag study (NCT03370770) is the first to assess outcomes of real-world patients (Pts) who received first-line afatinib followed by osimertinib; for pts with EGFR m+ NSCLC and acquired T790M this sequence resulted in a median time on treatment (ToT) of 27.6 months, which did not include chemotherapy. We present subgroup analyses of pts from the GioTag study who are under-represented in randomized controlled trials (RCTs) and assess the impact of afatinib treatment on ECOG PS. Methods: The GioTag study is an observational, multicenter study. Data were collected retrospectively (Dec 2017–May 2018). Pts had EGFR m+ (Del19/L858R) advanced NSCLC and acquired T790M after first-line afatinib. Pts completed afatinib and started osimertinib treatment ≥10 months before data entry to avoid early censoring and ensure mature data collection. Patient subgroups were defined based on baseline characteristics (eg, ECOG PS, age, ethnicity). The primary outcome was ToT from afatinib initiation to osimertinib discontinuation. Results: A total of 204 pts were included in the GioTag study: 15.2% had ECOG PS ≥2; 7.4% were aged ≥75 years; 8.8% were African-American. Pts generally considered to have a poor prognosis derived clinical benefit from the afatinib–osimertinib sequence: median ToT for pts with ECOG PS ≥2 (n=31) was 22.2 months (90%CI 16.0–27.0; vs pts with ECOG PS 0/1 [n=153; 31.3 months; 27.6–44.5] P &lt;.001); and for pts aged ≥75 years (n=15), ToT was 19.9 months (9.7–not evaluable [NE]; vs pts aged &lt;75 years [n=189; 28.1 months; 26.6–31.3] P =.382). In African-American pts, median ToT was 27.6 months (90%CI 24.7–NE). Of 180 pts with available data, 75.0% had no change or an improvement in ECOG PS from the start of afatinib to the start of osimertinib treatment; 24.4% of pts had a deterioration in ECOG PS by 1 step and 0.6% of pts had a deterioration by 2 steps. Conclusions: First-line afatinib followed by osimertinib is a feasible therapeutic strategy in pts with EGFR m+ NSCLC and acquired T790M, including those who are often under-represented in RCTs. Clinical benefit (measured by ToT) was seen among pts with poor prognosis (ECOG PS ≥2), pts aged ≥75 years, and African-American pts.
HSR19-096: The Impact of New Oncology Drugs on Disability and Health Care Spending: An Assessment of Real-World Evidence
Authors: Razelle Kurzrock, Robert Goldberg, Alice C. Ceacareanu, Zachary A. P. Wintrob
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: It is sometimes suggested that newly-approved cancer treatments have only marginal effectiveness, which raises questions concerning their cost-vs-benefit ratio. Such concerns appear at odds with the lower cancer-related hospitalization rate and improved survival. However, such cost-effectiveness analyses rely on population-based averages obtained from the analysis of clinical trial data. By failing to analyze data from longitudinal datasets, such assessments are unable to account for real-world patient conditions and treatment patterns in evaluating clinical and cost-effectiveness. Longitudinally surveyed clinical data has the potential to objectively reveal any association between patient outcomes and new cancer treatment utilization. Methods: We investigated the effect of being prescribed a higher proportion of new oncology drugs on quality of life, medical services use, and productivity measures as reported by the Medical Expenditure Panel Survey (MEPS, 1996–2015). General linear models with Taylor series variance estimation were applied. New oncology drugs were defined as cancer treatments marketed after the year 2000. Included subjects (N=16,677) had a solid or hematologic malignancy diagnosis (CCCodex 11–47) and available prescription data. Individual age and employment status were accounted for as covariates. All analyses were performed using SAS version 9.4 (Cary, NC). Results: Unadjusted regression data show that individuals using newer oncology treatments missed on average 2.5 (±0.3 SE) fewer days of work or school per year as compared to patients using older drugs (43% improved productivity, P &lt;.0001). The effect persisted even after adjusting for the magnitude of the effect ( P &lt;.0001). Accounting for age, the use of newer drugs was, on average, associated with ∼35% fewer missed work or school days. Cancer patients using newer treatments had 0.06 (±0.01 SE) fewer hospital admissions/year compared to patients using older treatments ( P &lt;.0001) and spent less time in the emergency room ( P &lt;.0411) with ∼45% fewer hospitalizations. Patients using newer medicines also had fewer health-related visits ( P &lt;.0001). Conclusion: Analysis of longitudinal real-world evidence gives a more comprehensive and reliable view of the clinical and economic impact of new oncology treatments. Our data suggests significant reductions in lost work/school days, hospitalizations, and use of medical services in general.