tbuckley/cabot-search huggingface dataset:
Clinical Documentation in the 21st Century: Executive Summary of a Policy Position Paper From the American College of Physicians
Authors: Thomson Kuhn, Peter Basch, Michael Barr, Thomas Yackel
Journal: Annals of Internal Medicine (2015)

Clinical documentation was developed to track a patient's condition and communicate the author's actions and thoughts to other members of the care team. Over time, other stakeholders have placed additional requirements on the clinical documentation process for purposes other than direct care of the patient. More recently, new information technologies, such as electronic health record (EHR) systems, have led to further changes in the clinical documentation process. Although computers and EHRs can facilitate and even improve clinical documentation, their use can also add complexities; new challenges; and, in the eyes of some, an increase in inappropriate or even fraudulent documentation. At the same time, many physicians and other health care professionals have argued that the quality of the systems being used for clinical documentation is inadequate. The Medical Informatics Committee of the American College of Physicians has undertaken this review of clinical documentation in an effort to clarify the broad range of complex and interrelated issues surrounding clinical documentation and to suggest a path forward such that care and clinical documentation in the 21st century best serve the needs of patients and families.
Effect of immersion, submersion, and scuba diving on heart rate variability: Figure 1
Authors: J D Schipke, M Pelzer
Journal: British Journal of Sports Medicine (2001)

Background —Heart rate variability (HRV) describes the cyclic variations in heart rate and offers a non-invasive tool for investigating the modulatory effects of neural mechanisms elicited by the autonomic nervous system on intrinsic heart rate. Objective —To introduce the HRV concept to healthy volunteers under control conditions and during scuba diving. In contrast with more established manoeuvres, diving probably activates both the sympathetic and parasympathetic nervous system through various stimuli—for example, through cardiac stretch receptors, respiration pattern, psychological stress, and diving reflex. A further aim of the study was to introduce a measure for determining a candidate's ability to scuba dive by providing ( a ) standard values for HRV measures (three from the time domain and three from the frequency domain) and ( b ) physiological responses to a strenuous manoeuvre such as scuba diving. Methods —Twenty five trained scuba divers were investigated while diving under pool conditions (27°C) after the effects of head out immersion and submersion on HRV had been studied. Results and conclusions —( a ) Immersion under pool conditions is a powerful stimulus for both the sympathetic and parasympathetic nervous system. ( b ) As neither the heart rate nor the HRV changed on going from immersion to submersion, the parasympathetic activation was probably due to haemodynamic alterations. ( c ) All HRV measures showed an increase in the parasympathetic activity. ( d ) If a physiological HRV is a mechanism for providing adaptability and flexibility, diving should not provoke circulatory problems in healthy subjects. ( e ) Either a lower than normal HRV under control conditions or a reduction in HRV induced by diving would be unphysiological, and a scuba diving candidate showing such characteristics should be further investigated.
Effect of recombinant human erythropoietin on platelet production in dialysis patients.
Authors: C J Kaupke, G C Butler, N D Vaziri
Journal: Journal of the American Society of Nephrology (1993)

Two hundred forty-four anemic hemodialysis patients were randomized into recombinant erythropoietin and placebo-treated groups during a 12-wk double-blind phase, followed by a 24-wk open-label period. Mean platelet count rose from the baseline value of 242 x 10(9)/L to 264 x 10(9)/L on day 5 of epoetin therapy (P < 0.001, paired t test). Mean platelet count peaked at 290 x 10(9)/L on day 40 and remained at a significantly elevated level below the peak thereafter. The peak platelet count did not exceed the normal range in a majority of cases. Platelet count was unaffected by placebo. Patients without an erythropoietic response during the first few weeks of therapy exhibited a rise in platelet count comparable to that in patients with a satisfactory erythropoiesis. Patients with low initial serum ferritin concentrations had baseline platelet counts comparable to those with normal or high ferritin values and showed a similar rise in platelet count during therapy. As a group, patients with baseline platelet counts above 400 x 10(9)/L showed no rise in platelet count, whereas those with normal or reduced platelet counts showed a marked thrombopoietic response to epoetin. Erythropoietin therapy did not significantly alter the incidence of blood access thrombosis when compared with placebo treatment.
Metabolic Inflexibility Impairs Insulin Secretion and Results In MODY-like Diabetes in Triple FoxO-Deficient Mice
Authors: Ja Young Kim-Muller, Shangang Zhao, Shekhar Srivastava, Yves Mugabo, Hye-Lim Noh, YoungJung R. Kim, S.R. Murthy Madiraju, Anthony W. Ferrante, Edward Y. Skolnik, Marc Prentki, Domenico Accili
Journal: Cell Metabolism (2014)
Transforming Growth Factor β (TGF-β)-dependent Inhibition of T Helper Cell 2 (Th2)-induced Autoimmunity by Self–Major Histocompatibility Complex (MHC) Class II–specific, Regulatory CD4+ T Cell Lines
Authors: Frank Bridoux, Abdallah Badou, Abdelhadi Saoudi, Isabelle Bernard, Elvira Druet, Régine Pasquier, Philippe Druet, Lucette Pelletier
Journal: The Journal of Experimental Medicine (1997)

Autoreactive anti–MHC class II T cells are found in Brown Norway (BN) and Lewis (LEW) rats that receive either HgCl2 or gold salts. These T cells have a T helper cell 2 (Th2) phenotype in the former strain and are responsible for Th2-mediated autoimmunity. In contrast, T cells that expand in LEW rats produce IL-2 and prevent experimental autoimmune encephalomyelitis, a cell-mediated autoimmune disease. The aim of this work was to investigate, using T cell lines derived from HgCl2-injected LEW rats (LEWHg), the effect of these autoreactive T cells on the development of Th2-mediated autoimmunity. The five LEWHg T cell lines obtained protect against Th2-mediated autoimmunity induced by HgCl2 in (LEW × BN)F1 hybrids. The lines produce, in addition to IL-2, IFN-γ and TGF-β, and the protective effect is TGF-β dependent since protection is abrogated by anti-TGF-β treatment. These results identify regulatory, TGF-β–producing, autoreactive T cells that are distinct from classical Th1 or Th2 and inhibit both Th1- and Th2-mediated autoimmune diseases.
Dosage-sensitive network in polycystic kidney and liver disease: Multiple mutations cause severe hepatic and neurological complications
Authors: Jens Kleffmann, Valeska Frank, Andreas Ferbert, Carsten Bergmann
Journal: Journal of Hepatology (2012)

Single kidney and liver cysts are common. If cysts occur multiply and earlier in life, they are mostly inherited. Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic disorders with mutations in PKD1 or PKD2 and affects 10–15million individuals worldwide [1]. Variable disease expression even in the same family is incompletely understood, some have intracranial aneurysms and most elderly patients show liver cysts. Polycystic liver disease (ADPLD) is caused by a dominant mutation in PRKCSH or SEC63, involved in posttranslational translocation and quality control of proteins (such as the ADPKD proteins) [2].
Secondary recurrent miscarriage and H-Y immunity
Authors: H. S. Nielsen
Journal: Human Reproduction Update (2011)

BACKGROUNDApproximately half recurrent miscarriage (RM) cases remain unexplained after standard investigations. Secondary RM (SRM) is, in contrast to primary RM, preceded by a birth, which increases the transfer of fetal cells into the maternal circulation. Mothers of boys are often immunized against male-specific minor histocompatibility (H-Y) antigens, and H-Y immunity can cause graft-versus-host disease after stem-cell transplantation. We proposed the H-Y hypothesis that aberrant H-Y immunity is a causal factor for SRM.
Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer
Authors: Peng Hou, Dingxie Liu, Yuan Shan, Shuiying Hu, Kimberley Studeman, Stephen Condouris, Yangang Wang, Ariel Trink, Adel K. El-Naggar, Giovanni Tallini, Vasily Vasko, Mingzhao Xing
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To investigate the overall occurrence and relationship of genetic alterations in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in thyroid tumors and explore the scope of this pathway as a therapeutic target for thyroid cancer. Experimental Design: We examined collectively the major genetic alterations and their relationship in this pathway, including PIK3CA copy number gain and mutation, Ras mutation, and PTEN mutation, in a large series of primary thyroid tumors. Results: Occurrence of any of these genetic alterations was found in 25 of 81 (31%) benign thyroid adenoma (BTA), 47 of 86 (55%) follicular thyroid cancer (FTC), 21 of 86 (24%) papillary thyroid cancer (PTC), and 29 of 50 (58%) anaplastic thyroid cancer (ATC), with FTC and ATC most frequently harboring these genetic alterations. PIK3CA copy gain was associated with increased PIK3CA protein expression. A mutual exclusivity among these genetic alterations was seen in BTA, FTC, and PTC, suggesting an independent role of each of them through the PI3K/Akt pathway in the tumorigenesis of the differentiated thyroid tumors. However, coexistence of these genetic alterations was increasingly seen with progression from differentiated tumor to undifferentiated ATC. Their coexistence with BRAF mutation was also frequent in PTC and ATC. Conclusions: The data provide strong genetic implication that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate. Progression of PTC to ATC may be facilitated by coexistence of PI3K/Akt pathway–related genetic alterations and BRAF mutation. The PI3K/Akt pathway may thus be a major therapeutic target in thyroid cancers.
Affective Disorders and Cognitive Failures: A Comparison of Seasonal and Nonseasonal Depression
Authors: Brianna Sullivan, Tabitha W Payne
Journal: American Journal of Psychiatry (2007)

Seasonal depression shares certain common symptoms with nonseasonal depression; however, the two disorders have never been examined in a single study, to the authors' knowledge. The goal of this research was to examine the potential similarities in cognitive impairments in seasonal affective disorder and major depressive disorder in college students in the Midwest. Identification of affective disorders was based on participants' self-reported behavior and affect on the Beck Depression Inventory and the Seasonal Pattern Assessment Questionnaire. A group of 93 participants was assessed for major depressive disorder and seasonal affective disorder in late autumn and completed the Cognitive Failures Questionnaire for reported difficulties in everyday activities that correspond to problems with perception, attention, and memory retrieval. The results indicated that seasonal affective disorder was highly prevalent (28.0%), substantially more so than major depressive disorder (8.6%). Similar to previous research on major depressive disorder, gender differences were also evident among participants with seasonal affective disorder, with more women qualifying than men. Both affective disorders were associated with higher reports of cognitive failures in comparison to participants with no depressive symptoms. These results reveal that individuals with seasonal affective disorder showed cognitive impairments similar to those with nonseasonal depression.
Long-term Proton Pump Inhibitor Therapy and Risk of Hip Fracture
Authors: Yu-Xiao Yang, James D. Lewis, Solomon Epstein, David C. Metz
Journal: JAMA (2006)

Context Proton pump inhibitors (PPIs) may interfere with calcium absorption through induction of hypochlorhydria but they also may reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps.Objective To determine the association between PPI therapy and risk of hip fracture. Design, Setting, and PatientsA nested case-control study was conducted using the General Practice Research Database (1987-2003), which contains information on patients in the United Kingdom.The study cohort consisted of users of PPI therapy and nonusers of acid suppression drugs who were older than 50 years.Cases included all patients with an incident hip fracture.Controls were selected using incidence density sampling, matched for sex, index date, year of birth, and both calendar period and duration of up-to-standard follow-up before the index date.For comparison purposes, a similar nested case-control analysis for histamine 2 receptor antagonists was performed. Main Outcome Measure The risk of hip fractures associated with PPI use.Results There were 13 556 hip fracture cases and 135 386 controls.The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30-1.59).The risk of hip fracture was significantly increased among patients prescribed long-term high-dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90;PϽ.001).The strength of the association increased with increasing duration of PPI therapy (AOR for 1 year, 1.22 [95% CI, 1.15-1.30]; 2 years, 1.41 [95% CI, 1.28-1.56];3 years, 1.54 [95% CI, 1.37-1.73];and 4 years, 1.59 [95% CI, 1.39-1.80];PϽ.001 for all comparisons). ConclusionLong-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.
Air pollution and exacerbations of bronchitis
Authors: P. J. Lawther, R. E. Waller, M. Henderson
Journal: Thorax (1970)

A simple `diary9 technique has been used in London and in other large towns to examine the relationship between daily changes in the condition of bronchitic patients and their environment. It has been shown that these changes are closely related to air pollution, as indicated by the concentrations of smoke or sulphur dioxide. There is some evidence that patients are more sensitive to the effects of pollution at the beginning than at the end of each winter. Comparative studies are now being made in London at five-year intervals to study any change in response following the definite reduction in smoke concentrations. Results indicate some decline in the response of patients to specified concentrations of sulphur dioxide, but in recent years there have been few days on which pollution has been high enough to produce any response.
Peginterferon therapy for chronic hepatitis B: one size fits all?
Authors: Henry Lik-Yuen Chan
Journal: Gut (2012)

The disease of chronic hepatitis B hinges on a balance between the virus and the host immune system. Clearance of hepatitis B virus (HBV) relies on the host immunity. On the other hand, liver necroinflammation and cirrhosis occurs when there is persistent, yet unsuccessful, immune clearance of the virus.1 Interferon is the first registered drug for the treatment of chronic hepatitis B. It is an immune modulator with weak antiviral property. Its main function is to augment the host immune clearance of the virus. Hence interferon works best when the host is in the immune clearance phase with elevated liver enzymes and low HBV DNA.2 One major advantage of interferon is the finite treatment course, which can potentially lead to sustained remission of disease in the subsequent decades.3 Long-term follow-up studies have confirmed a reduction in risk of liver-related complications, hepatocellular carcinoma and liver-related mortality among sustained interferon responders.4 ,5

Since the mid-1980s, the standard duration of interferon has been 16–24 weeks. Although some evidence suggested that prolonged interferon to 32 weeks might improve the response,6 24 weeks was still the recommended duration for hepatitis B e antigen (HBeAg)-positive patients in regional guidelines.7 ,8 Early studies of peginterferon have used 32-week peginterferon, with or without lamivudine combination, with satisfactory results.9 ,10 In the pivotal of studies of peginterferon, all patients received 48–52 weeks of treatment.11–13 The standard treatment duration of peginterferon for chronic hepatitis B was then set to 48 weeks in both HBeAg-positive and HBeAg-negative patients.7 ,14 The evidence to support the use of 48-week over 24-week peginterferon was only available half a decade after its global registration for this indication.15 In this study (the NEPTUNE study), peginterferon α-2a at a standard dose of 180 mcg/week for 48 weeks was associated with …
Validation of two predictive models for survival in pulmonary arterial hypertension
Authors: Olivier Sitbon, Raymond L. Benza, David B. Badesch, Robyn J. Barst, C. Gregory Elliott, Virginie Gressin, Jean-Christophe Lemarié, Dave P. Miller, Erwan Muros-Le Rouzic, Gérald Simonneau, Adaani E. Frost, Harrison W. Farber, Marc Humbert, Michael D. McGoon
Journal: European Respiratory Journal (2015)

The French Pulmonary Hypertension Network (FPHN) registry and the Registry to Evaluate Early And Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) have developed predictive models for survival in pulmonary arterial hypertension (PAH). In this collaboration, we assess the external validity (or generalisability) of the FPHN ItinérAIR-HTAP predictive equation and the REVEAL risk score calculator. Validation cohorts approximated the eligibility criteria defined for each model. The REVEAL cohort comprised 292 treatment-naïve, adult patients diagnosed &lt;1 year prior to enrolment with idiopathic, familial or anorexigen-induced PAH. The FPHN cohort comprised 1737 patients with group 1 PAH. Application of FPHN parameters to REVEAL and REVEAL risk scores to FPHN demonstrated estimated hazard ratios that were consistent between studies and had high probabilities of concordance (hazard ratios of 0.72, 95% CI 0.64–0.80, and 0.73, 95% CI 0.70–0.77, respectively). The REVEAL risk score calculator and FPHN ItinérAIR-HTAP predictive equation showed good discrimination and calibration for prediction of survival in the FPHN and REVEAL cohorts, respectively, suggesting prognostic generalisability in geographically different PAH populations. Once prospectively validated, these may become valuable tools in clinical practice.
Ambient polycyclic aromatic hydrocarbons and pulmonary function in children
Authors: Amy Padula, John Balmes, Ellen Eisen, Jennifer Mann, Elizabeth Noth, Boriana Pratt, Fred Lurmann, S. Katharine Hammond
Journal: European Respiratory Journal (2013)

Background: Polycyclic aromatic hydrocarbons (PAHs) are a key component of traffic emissions. Exposure to PAHs has been associated with wheezing and impaired T regulatory cell function in a cohort of asthmatic children in Fresno, CA.  Objective: To assess whether exposure to PAHs is associated with lower lung function in children, with and without asthma.  Methods: Children age 9-18 living in Fresno were recruited (n=297; 135 with asthma, 162 without asthma) for respiratory health evaluation including pre- and post-bronchodilator spirometry. Exposure to 4, 5, and 6-member ring PAHs (PAH456) based on a previously published land-use regression model was estimated for each child. Linear regression was used to evaluate the association between annual mean PAH456 exposure in the year prior to testing and maximum post-bronchodilator FEV1. The analysis was restricted to participants with acceptable spirometry and non-missing covariates and stratified by asthma status.  Results: Mean 1-year PAH456 exposure was 2.99 ng/m3 (IQR 1.03). In a model adjusted for age, sex, African-American race, height and socioeconomic status (rented or owned home), a 1 ng/m3 increase in PAH456 was associated with a 0.11 L decrease in FEV1 (95% confidence interval (CI): -0.21, -0.02) among non-asthmatic children. Among asthmatic children, a 1 ng/m3 increase in PAH456 was also associated with a 0.01 L decrease in FEV1, although this result was not statistically significant (95% CI: -0.12, 0.09).  Conclusion: This is the first study to assess the effect of individual PAH exposure estimates on lung function in children or adults. Somewhat surprisingly, we found a significant effect in non-asthmatic children, but not in asthmatic children.
Paracetamol-Induced Renal Tubular Injury
Authors: Corina Lorz, Pilar Justo, Ana Sanz, Dolores Subirá, Jesús Egido, Alberto Ortiz
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Paracetamol (also known as acetaminophen) causes acute and chronic renal failure. While the mechanisms leading to hepatic injury have been extensively studied, the molecular mechanisms of paracetamol-induced nephrotoxicity are poorly defined. Paracetamol induced cell death with features of apoptosis in murine proximal tubular epithelial cells. While paracetamol increased the expression of the death receptor Fas on the cell surface, the Fas pathway was not involved in the paracetamol-induced apoptosis of tubular cells. The mitochondrial pathway was not activated during paracetamol-induced apoptosis; there was no dissipation of mitochondrial potential or release of apoptogenic factors such as cytochrome c or Smac/DIABLO. However, paracetamol-induced apoptosis is a caspase-dependent process that involves activation of caspase-9 and caspase-3 in the absence of cytosolic cytochrome c or Smac/DIABLO. The authors also detected induction of endoplasmic reticulum (ER) stress, characterized by GADD153 upregulation and translocation to the nucleus, as well as caspase-12 cleavage. Interestingly, after treatment of murine tubular cells with paracetamol and calpain inhibitors, the caspase-12 cleavage product was still detectable, and calpain inhibitors were unable to protect tubular cells from paracetamol-induced apoptosis. The results suggest that induction of apoptosis may underlie the nephrotoxic potential of paracetamol and identify ER stress as a therapeutic target in nephrotoxicity.