tbuckley/cabot-search huggingface dataset:
Implications of incidental germline findings identified in the context of clinical whole exome sequencing (WES) for guiding cancer therapy.
Authors: Bryan P. Schneider, Leigh Anne Stout, Santosh Philips, Cynthia Hunter, Patrick Kiel, Milan Radovich
Journal: Journal of Clinical Oncology (2019)

1581 Background: The identification of incidental germline mutations in the context of next-generation sequencing to guide therapy for cancer patients has become an unintended consequence of advancing technologies. While not the primary goal, additional information buried within the genomic data generated could be important for family members to better understand inherited disease risks and take action. While targeted gene panels are predominantly used in practice, comprehensive WES is becoming increasingly more common. The broader use of WES increases the complexity and scope of potential cancer and non-cancer pathogenic germline variation. Methods: 582 adult metastatic cancer patients from the Indiana University Health Precision Genomics Program were sequenced with tumor and germline CLIA-based WES. The primary intent was for guiding cancer therapy. Germline variant call files were mined for pathogenic/likely pathogenic (P/LP) variants using the ClinVar database. Clinvar classifications were narrowed only to high quality submitters. Results: We identified 1,454 P/LP variants in 209 genes. 92% of patients harbored at least one variant. 72 P/LP variants were identified in 19 cancer predisposition genes with BRCA2 being the most common. 63 patients (10.8%) carried a P/LP variant in a gene that would be recommended by the ACMG to be reported due to clinical actionability with the most common being ATP7B (N = 17), BRCA2 (n = 13), MUTYH (n = 8), and BRCA1 (n = 5). We observed a preponderance of patients who carried autosomal recessive non-cancer pathogenic mutations of varying penetrance. Notable mutated genes included CFTR (cystic fibrosis, n = 16), BTD (biotinidase deficiency, n = 43), and CBS (homocystinuria, n = 90). Of 209 mutated genes, 173 genes had mutations present in less than 1% of our population, demonstrating significant genetic heterogeneity. Conclusions: The majority of patients undergoing clinical cancer WES harbor pathogenic germline variation. Identification of clinically actionable germline findings will create additional burden on oncology clinics as broader WES becomes commonplace.
Association of Differing Dietary, Metabolic, and Clinical Risk Factors with Microvascular Complications of Diabetes: A Prevalence Study of 503 Mexican Type II Diabetic Subjects. II
Authors: R B Paisey, G Arredondo, A Villalobos, O Lozano, L Guevara, S Kelly
Journal: Diabetes Care (1984)

The overall prevalences of microvascular complications and their association with dietary, clinical, and metabolic characteristics have been studied in 503 Mexican type II diabetic subjects. Average daily dietary intakes were 1866 kcal, 46.5% as carbohydrate, 13.7 mmol cholesterol, 8.7 g fiber, and a polyunsaturated/saturated fat ratio of 0.98. Prevalence rates of microvascular and metabolic complications were as follows: background retinopathy 12.3%, exudative retinopathy 24.2%, proliferative retinopathy 8.1% (1% blind, 4% able to read large print only), 9.1% of patients had cataract, 15.9% nephropathy, and 40.8% peripheral neuropathy. In addition, 3.6% had experienced transient lower motor neuron facial paralysis and 0.2% oculomotor paralysis. Patients with retinopathy had a longer mean duration of diabetes, were less obese at the time of examination, and had higher initial and mean blood pressures and higher mean fasting blood glucose levels when compared with those without retinopathy. Similar differences were observed between groups with and without nephropathy except that mean blood glucose levels were similar in the two groups. The presence of peripheral neuropathy was associated with longer duration of diabetes, less obesity, higher mean blood pressure and mean blood glucose levels, and lower hemoglobin concentration. Patients treated with diet alone had significantly lower prevalences of all three microvascular complications but they also had significantly shorter duration of diabetes and lower mean blood glucose levels. However, multivariate analyses on the subgroup of 360 patients who had repeated fasting blood glucose measurements for at least 5 yr demonstrated associations between retinopathy and duration of diabetes, mean blood pressure and mean blood glucose, and percent calories from carbohydrate. Nephropathy was associated with duration, percent calories from carbohydrate, and mean blood pressure. Neuropathy was related to duration, hemoglobin concentration, and mean blood glucose. The significance of these results and dissociation of risk factors for macro- and microvascular disease in this group of patients is discussed.
ISIS-4
Authors: WilliamR. Herzog, HenrikO. Lagerhöf, CarlG. Nilsson, JohnG.F. Cleland, J.L. Morris, J.C. Cowan, Gianni Tognoni, MariaGrazia Franzosi, Roberto Latini, AldoP. Maggioni, Giulio Zuanetti, P. Chaturvedi, Rory Collins, Richard Peto, Peter Sleight
Journal: The Lancet (1995)
A sharper focus for psychotherapy
Authors: M. F. Goldsmith
Journal: JAMA (1984)

"To separate psychological distress into psychiatric problems caused by chemical and structural defects in the brain and `problems of living' is an unwarranted dichotomy," according to Michael F. Basch, MD, professor of psychiatry, Rush Medical College of Rush University, Chicago. Considering the brain as analogous to a computer— a reasonable analogy, in Basch's view—"you have hardware and software. What the psychopharmacologic discoveries of the past 20 years or so have done is enable us to begin to deal with the hardware problems, or brain itself. The so-called problems of living are part of the software, the programs people develop to cope with life. "If that development has been interfered with by significant failures in empathy and communication, then people develop ways to protect themselves by adaptations that are ultimately counterproductive. "But where do these `problems of living' come from?" asks Basch, who is also author of<i>Doing Psychotherapy</i>(New York,
El libro del hospital moderno
Journal: JAMA (1941)

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
EARLY AMERICAN PHARMACOPEIAS AND THEIR AUTHORS.
Journal: JAMA (1896)

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Errors in Figures 1 and 2
Authors: David Li, Arash Mostaghimi
Journal: JAMA Dermatology (2019)

out of in vivo bioequivalence testing in 5 cases, while recommending comparative physicochemical characterization in the final case. 5 Given these requirements, it is likely that existing FDA requirements may dissuade manufacturers from entering these restricted markets.Although we are in complete support of efforts to streamline drug approval, variations between topical medications may render in vitro evaluation unsuitable for some medications.For example, differences in vehicle can potentially alter the performance of a generic formulation in a manner that may not be captured by in vitro studies alone. 3,6Additionally, the intrinsic properties of select topical drugs may interfere with the reliability of in vitro testing.One recent study illustrated the difficulty of standardizing the in vitro release test for betamethasone valerate owing to its high solubility in hydrophobic barriers. 3espite these differences, the FDA's rationale for mandating in vivo studies for some drugs while allowing the in vitro option in others is not fully elucidated.Development and validation of criteria to identify topical drugs that can be granted an in vitro testing option may improve throughput of new medications without compromising trust in the equivalent performance of generic medications entering the market.While these criteria are being developed, short-term improvements in market competition may be realized by subsidizing a portion of costs associated with clinical trials for generic drug manufacturers entering restricted markets.Although we agree that the current recommendations for bioequivalence studies may discourage drug manufacturers, a rapid transition toward in vitro testing may compromise the integrity of topical dermatology generic drugs reaching the market.Until researchers and regulators can decide on a transparent and standardized framework for the design of bioequivalence studies, barriers to entry will continue to limit the impact of competition on keeping topical drug prices in check.
Factors Potentially Associated With Reductions in Alcohol-Related Traffic Fatalities—1990 and 1991
Journal: JAMA (1993)

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Rationing Resources While Improving Quality
Authors: Louis C. Waddell
Journal: JAMA (1995)

<h3>To the Editor.</h3> —In the most recent of a series of articles by Dr Eddy<sup>1</sup>featuring the merits of clinical decision analysis, he claims to offer what many may think impossible: to contain medical costs while increasing quality. However, to do this, "quality" has to be defined in a particular way and his proposals involve major and dramatic changes. The following appear to be required: (1) acceptance of the utilitarian philosophy by a society in which to date no particular secular philosophy is dominant, (2) widespread acceptance of decision analysis in clinical medicine, and (3) a complete reversal and denial of the major tenet of medical ethics—the primacy of the individual patient's well-being. Utilitarian philosophy becomes the controlling principle in health care decisions. Eddy states that the goal of a health care system should be the maximization of the health of the group, ie, the greatest good for the
Abstract 12334: How Much Exposure to Resuscitation Do Emergency Medical Service Personnel Get?
Authors: Kylie Dyson, Janet Bray, Karen Smith, Stephen Bernard, Lahn Straney, Finn Judith
Journal: Circulation (2014)

Objectives: The exposure of emergency medical service personnel (paramedics) to out-of-hospital cardiac arrest (OHCA) and resuscitation procedures could be an important factor in skill maintenance and quality of care. This study aims to describe paramedic exposure to OHCA resuscitation in the state of Victoria, Australia (population 5.8 million). Methods: We extracted and linked data from the Victorian Ambulance Cardiac Arrest Registry (VACAR) and Ambulance Victoria’s employment dataset for the period 2003-2012. Paramedics were considered to have ‘exposure’ to OHCA if they attended a case where resuscitation was attempted. Individual rates were calculated for annual exposure (number of OHCA exposures for each paramedic/years employed in study period) and days between exposures (total paramedic days/total number of exposures). Results: Over the 10-year period, there were 49,107 OHCAs and 5,673 paramedics employed. Resuscitation was attempted in 44% of patients. An average of 3.2 (SD±1.1) paramedics attended each case. The median average exposure of paramedics was 2.2 (IQR=1.2-3.5) OHCAs/year. The proportion with no exposures in a year increased from 39% in 2003 to 43% in 2012 ( p =0.036). OHCA exposure was significantly less in those employed part-time or casual ( p &lt;0.001), in a rural area ( p &lt;0.001) or with a lower qualification ( p &lt;0.001) (Table). Annual exposure to pediatric and traumatic OHCAs was particularly low (Table). Paramedics were exposed to an average of 0.006 OHCAs/day, meaning it would take an average of 163 days be exposed to OHCA and up to 12.5 years for rare cases, such as pediatric OHCAs. Conclusion: Our study identified paramedic exposure to resuscitation is low and has decreased over time. This highlights the importance of supplementing paramedic exposure with other methods, such as simulation, to maintain resuscitation skills. This may be particularly important to paramedics with low exposure and for rare case types, such as pediatric OHCA.
Medical Reports for the Half-Year Ended Sept. 30, 1896.
Journal: JAMA (1898)

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
Autoantibody prevalence in chronic hepatitis B virus infection: Effect in interferon alfa
Authors: G Gregorio
Journal: Hepatology (1996)

The most effective treatment of chronic hepatitis B virus (HBV) infection is interferon alfa (IFN-α), a potentially severe side effect of which is the induction of autoimmunity. To assess whether IFN- α causes clinical or serological autoimmune manifestations, we studied 61 children randomized to receive 5 MU/m2 of IFN-α three times per week for 12 weeks, with or without steroid priming or no treatment. Autoantibodies to antinuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC), liver kidney microsomal type 1, mitochondrial, liver cytosolic antigen, thyroid microsomal, and thyroid globulin were detected by standard techniques. Over a median of 4 years (range, 1-5 years) from randomization, no clinical signs of autoimmunity were observed. Autoantibody positivity for nuclei, smooth muscle, and/or gastric parietal cells was observed on at least one occasion in 42 of 61 children (69%), with no overall difference in the prevalence between patients treated with interferon alone (19 of 24 [79%]), steroids plus interferon (13 of 20 [65%]), or untreated controls (10 of 17 [59%]). There was also no difference in the autoantibody prevalence before, during, and at follow-up after cessation of treatment in both interferon-treated and interferon- untreated patients. Autoantibodies are common in chronic HBV infection, and their prevalence is uninfluenced by IFN-α.
Comprehensive drug surveillance
Authors: H. Jick
Journal: JAMA (1970)

The urgent need for information about clinical drug effects may be partially met by a large-scale comprehensive drugsurveillance program designed to permit the detection of unsuspected side effects and drug interactions, the quantitation of known effects, and the evaluation of the role of influencing factors. Such a program, the Boston Collaborative Drug Surveillance Program, now involving eight hospitals, is described, the principles and potential of this type of research are discussed, and data on some broad aspects of drug utilization and effects are presented. An appropriately designed drug-surveillance program can be introduced to hospital wards with a minimum of interference with the ward routine, can be applied in a standardized form in different centers, and is indeed capable of providing valuable information about clinical drug effects.
A Synopsis of Medicine.
Journal: JAMA (1931)

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THE JOURNAL SPECIAL.
Journal: JAMA (1896)

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
Hugh Owen Thomas (1834-1891) rustic orthopedist
Journal: JAMA (1966)

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