tbuckley/cabot-search huggingface dataset:
Abstract 9871: Utility of Electronic Health Records in Predicting 30-Day Readmission After Heart Failure Hospitalization
Authors: Philip H Schmidt, Preeti Kansal, Gregory Wozniak, Keri Christensen, Liviu Klein, Peter S Pang, Jeffrey H Barsuk, Mark V Williams, Stephanie Kitt, Danny Sama, Steven A Farmer, Mihai Gheorghiade, Robert O Bonow
Journal: Circulation (2011)

Introduction: Hospitalizations for heart failure (HF) represent a growing healthcare burden and are a major focus for quality improvement and payment reform. Prior studies have evaluated predictors of readmission after hospitalization for HF, but few have examined consecutive patients at a single medical center using electronic health records (EHRs). Objectives: (1) Determine predictors of 30 day readmission in patients with a HF discharge diagnosis and (2) evaluate relationship between 30 day readmission and 1 year mortality using the Social Security Death Index. Methods: We analyzed outcomes of 1,417 consecutive patients with a primary discharge diagnosis of HF for years 2008 and 2009 in an urban, tertiary-care hospital using a unique EHR system integrating inpatient and outpatient data. Outcomes included 30 day all-cause hospital readmissions and all-cause mortality from 30 days to 1 year. Results: The 30-day readmission rate was 24.8%. Factors associated with readmission included weight, BNP, creatinine, and BUN at both admission and discharge, as well as systolic blood pressure and ejection fraction (Table). Readmitted patients had higher BNP, creatinine, and BUN at the time of discharge compared to corresponding admission data in patients not readmitted (p &lt;0.01). Age, gender, and length of stay (7.3±7.5 vs 7.3±7.6 days, respectively) did not differ between the 2 groups. Readmitted patients were less likely to have hypertension, but other comorbidities did not differ between the 2 groups. Readmission within 30 days was not associated with all-cause mortality at 30, 60, 90, 180 days or 1-year post-discharge. Conclusion: Patients with HF at risk for 30 day readmission are readily identified by EHR data during the index hospitalization. Real time utilization of EHRs provides potential to detect patients who may benefit most from targeted interventions at discharge to reduce rehospitalization. Short-term readmissions are not related to long-term mortality.
Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs
Authors: M H Chakos, J A Lieberman, R M Bilder, M Borenstein, G Lerner, B Bogerts, H Wu, B Kinon, M Ashtari
Journal: American Journal of Psychiatry (1994)

This study examined the pathomorphology of the caudate nuclei in first-episode schizophrenic patients with minimal previous neuroleptic exposure.Magnetic resonance imaging (MRI) of the brain was used to examine longitudinally the caudate pathomorphology in 29 first-episode schizophrenic patients and 10 healthy comparison subjects. MRI scans were obtained after the subjects entered the study and at 18-month follow-up. The patients were treated with standardized neuroleptic regimens during the 18-month period. Volumetric assessments of the cerebral cortex, lateral ventricles, and caudate nuclei were performed on T1-weighted coronal brain sections. In addition, the patients were systematically evaluated for psychopathology at baseline and during treatment.Caudate volumes increased 5.7% in the patients during the 18-month treatment interval, whereas they decreased 1.6% in the comparison subjects over the same time period. Greater amounts of antipsychotic medication received by patients before the first scan and younger age at the time of the first scan were associated with larger increases in caudate volume.Caudate enlargement occurs early in the course of treatment in young first-episode schizophrenic patients. This may be a result of an interaction between neuroleptic treatment and the plasticity of dopaminergic neuronal systems in young patients.
Evaluation of selective biomarkers of the broad spectrum CDK inhibitor: RGB-286199
Authors: Shaoshan Wang, Eman Ayyub, Lou Lamphere
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4428 

RGB-286199 is a novel broad spectrum CDK (cyclin dependent kinases) inhibitor currently under development as an anticancer agent. Its antiproliferative activity in vitro is characterized by both cell cycle arrest and loss of viability through apoptosis. These effects are due to CDK inhibition, as confirmed by loss of phosphorylation of Rb protein, accompanied by loss of cyclin A protein, in the human colon carcinoma cell line HCT-116 treated in vitro with RGB-286199 50 nM. RGB-286199 has significant antitumor efficacy in vivo against several human xenograft models at tolerated doses. Intravenous (iv) administration of RGB-286199 to mice bearing the human ovarian tumor xenograft A2780 results in tumor regressions and a tumor growth delay equivalent to > 3.5 log cell kill. The goal of the present study was to confirm RGB-286199 as a negative regulator of CDK activity in vivo , and to identify one or more quantitative biomarkers that could be used to monitor its pharmacodynamic effects. Nude mice bearing 300 mg A2780 tumors were treated iv with RGB-286199, and sacrificed at different times after treatment. Tumors were collected and examined by immunohistochemistry for the following biomarkers: BrdU incorporation as indicator of cell proliferation; levels of pRb and cyclin A as indicators of CDK inhibition; and PARP 89 kDa cleavage product (as well as TUNEL assay) as measure of cell proliferation and apoptosis. A2780 tumor-bearing mice treated with 60 mg/kg RGB-286199 were examined at 3, 6, 12 and 24 hr after treatment. In a second experiment, mice were treated iv daily for 5 days with RGB-286199 at 20, 40 or 60 mg/kg and tumors were collected at 24 and 96 hrs after the last treatment. A single dose of RGB-286199 was sufficient to inhibit BrdU incorporation, Rb phosphorylation and to reduce the protein level of cyclin A in a time-dependent manner. A time-dependent increase in the percentage of apoptotic cells, as revealed by the accumulation of the PARP 89 kDA cleavage product and by the appearance of TUNEL-positive cells, was also observed. These results confirm that RGB-286199 acts as a CDK inhibitor in vivo , and suggests that the biomarkers identified in this study could be used to monitor the antitumor effect of RGB-286199 in clinical studies.
The burden of chronic obstructive pulmonary disease (COPD) in Taiwan
Authors: Chieh-Mo Lin, Tsung-Ming Yang, Shu-yi Huang, Yen-Li Chou, Ying Huang Tsai
Journal: European Respiratory Journal (2013)

Introduction:  The prevalence of chronic obstructive pulmonary disease (COPD) in Taiwan was estimated to be 7.8% for adults aged 40 years and over. The current disease burden of COPD is still not well-understood.   Aims:  To evaluate the economic burden of COPD and the time trends of cost structure in COPD management and health-care utilization in Taiwan.   Methods:  Patients aged 40 years and older, who had medical claims with primary diagnoses of COPD (ICD-9-CM code: 491, 492, and 496) from 2004 to 2010, were included from the National Health Insurance Research Database (NHIRD) of Taiwan. Annual costs of COPD according to the utilization of healthcare resources were analyzed.   Results:  The annual total costs of COPD declined from €87 million in 2004 to €68 million in 2010 in the administrative claims. Between 2004 and 2010, the annual costs of intensive care unit (ICU) and non-ICU admission for each COPD patient declined from €65 to €48 and €80 to €69, respectively. Over the same time frame, the annual outpatient costs for each COPD patient increased from €88 to €106. Despite the increase of COPD-related pharmacy costs for each patient (from €22 in 2004 to €36 in 2010), the total pharmacy costs did not change across years. The total COPD-related costs per patient-year was €232 by 2010, and the estimated annual total burden of COPD in Taiwan is around €200 million according to the prevalence of COPD in Taiwan.   Conclusions:  Over the past years, the hospitalization costs involving ICU and non-ICU admissions for COPD are decreasing in spite of the increase of the COPD-related pharmacy costs. Optimization of use of COPD-related medications may be an important strategy to reduce the hospitalization costs and total COPD burden.
The use of benzodiazepines in COPD: A population-based study of Norway
Authors: Pål Erling Martinussen, Thomas Halvorsen
Journal: European Respiratory Journal (2013)

Background: Due to the great sufferings and high mortality risk associated with COPD, such patients tend to have a higher risk of anxiety and depression. Given that benzodiazepines (BZD) may cause respiratory depression they should be used with caution among COPD patients. Aims: We investigated the use of BZD among persons suffering from COPD by analysing 3 relevant indicators: a) the sum of defined daily doses (DDD), b) the number of prescribers involved, and c) the number of different types of BZDs used. Methods: The study builds on a linkage of national prescription data and patient-administrative data, which includes all Norwegian drug prescriptions during 2009, amounting to a total of 595,333 observations. This allowed us to compare the COPD population with other chronic patient groups and the general patient population. Regression techniques were used to identify patient and clinical characteristics associated with BZD use. Results: BZD use was 81.64 DDDs higher in COPD than in the average patient, while the difference between COPD and other chronic illnesses (cancer, stroke, heart disease and diabetes) ranged from 72.46 to 87.42 DDDs. COPD patients furthermore used more prescribers and combined more medication types than both the average patient and other chronic patients. Conclusions: While the association between COPD and anxiety or depression has been well established, the research has almost exclusively dealt with patients actively seeking health care. This study suggests a high prevalence of depression and anxiety in persons with COPD outside of the clinic or inpatient setting. The results give cause for concern because of the potential adverse respiratory effects of BZD in COPD.
A phase I and pharmacodynamic study of a 7 day infusion schedule of the DNMT1 antisense compound MG98
Authors: L. Vidal, M. Leslie, J. Sludden, M. G. Griffin, R. Plummer, I. Judson, C. Lee, A. Greystoke, A. H. Calvert, A. V. Boddy
Journal: Journal of Clinical Oncology (2005)

3070 Background: DNA methylation has been postulated to play an important role in tumour progression and increased DNA methyltransferase (DNMT) activity has been observed in many cancer cells. Pharmacological inhibition of DNMT may lead to demethylation of tumour suppressor genes, restoring normal growth control to cancer cells. Pre-clinical data show that MG98, a second generation antisense molecule, possesses antitumour activity and provides sustained reductions in DNMT1 expression. Methods: Patients with advanced solid tumours were enrolled to receive MG98 as a continuous infusion for 7 days followed by 7 days rest, defined as one cycle. Dose levels planned were 100, 125, 160, 200 and 250 mg/m2/day. PK analyses for MG98 and its metabolites and determination of DNMT1 expression in peripheral blood lymphocytes (PBL) were performed during the first two cycles. Results: 23 pts have been treated to date. Median age: 54 yrs. Sex: M 13/F 10. Median PS: 1. Median number of cycles: 2.8 (1–9). All 23 pts were evaluated for toxicity. One DLT consisted in grade 3 transaminitis was seen at 200mg/m2/day. MTD was identified as being either 250mg/m2/day or below with 2/4 pts experiencing DLT (gr. 3 transaminitis, gr. 3 thrombocytopenia). Other treatment related toxicities included fatigue, headache, nausea, anorexia and constipation (all ≤gr. 2). DNMT1 data are available for 12 patients. Pre-treatment DNMT1 expression in PBL varied from 0.024 to 2.19 (arbitrary units). Following MG98 infusion, DNMT1 expression decreased by between 6 and 69% on cycle one, and between 34 and 85% on cycle 2. 2 pts (oesophageal and GIST) presented stable disease for more than 4 months. Conclusions: MG98 is reasonably well-tolerated. The recommended Phase II dose is 200 mg/m2/day. PD studies showed that the expression of DNMT1 is consistently decreased following MG98 infusion. Further investigations should include suppression of DNMT1 protein expression and measurement of subsequent changes in DNA methylation in clinical samples. No significant financial relationships to disclose.
Low‐cost periodontal therapy
Authors: Jørgen Slots
Journal: Periodontology 2000 (2012)

Abstract Periodontitis is a complex infectious disease that affects low‐income individuals disproportionately. Periodontitis is associated with specific bacterial species and herpesviruses, and successful prevention and treatment of the disease is contingent upon effective control of these pathogens. This article presents an efficacious, highly safe, minimally invasive, practical and low‐cost periodontal therapy that involves professional and patient‐administered mechanical therapy and antimicrobial agents. The major components are scaling for calculus removal, periodontal pocket irrigation with potent antiseptics, and treatment with systemic antibiotics for advanced disease. Povidone‐iodine and sodium hypochlorite have all the characteristics for becoming the first‐choice antiseptics in the management of periodontal diseases. Both agents show excellent antibacterial and antiviral properties, are readily available throughout the world, have been safely used in periodontal therapy for decades, offer significant benefits for individuals with very limited financial resources, and are well accepted by most dental professionals and patients. Four per cent chlorhexidine applied with a toothbrush to the most posterior part to the tongue dorsum can markedly reduce or eliminate halitosis in most individuals. Systemic antibiotics are used to treat periodontopathic bacteria that are not readily reached by topical therapy, such as pathogens within gingival tissue, within furcation defects, at the base of periodontal pockets, and on the tongue, tonsils and buccal mucosae. Valuable antibiotic therapies are amoxicillin‐metronidazole (250 mg of amoxicillin and 250 mg of metronidazole, three times daily for 8 days) for young and middle‐aged patients, and ciprofloxacin‐metronidazole (500 mg of each, twice daily for 8 days) for elderly patients and for patients in developing countries who frequently harbor enteric rods subgingivally. Scaling to remove dental calculus and the prudent use of inexpensive antimicrobial agents can significantly retard or arrest progressive periodontitis in the great majority of patients.
Amyloid-β drives a type-1 interferon mediated neuro-inflammatory response in Alzheimer’s disease
Authors: Myles Minter, Juliet Taylor, Moses Zhang, Paul Adlard, Peter Crack
Journal: Molecular Neurodegeneration (2013)

Background Neuro-inflammation has been implicated in the progression of both acute and chronic neurological diseases. Resident cells of the central nervous system (CNS) detect soluble amyloid-b (Ab) through the toll-like receptors (TLRs), involving Myd88 and interferon regulatory factor (IRF) signalling, and triggers pro-inflammatory cytokine release. Type-1 interferons (IFNs) are master regulators of the pro-inflammatory cytokine response, however, their CNS function remains largely unclear. Type-1 IFNs bind their cognate receptor IFNAR1, activating the JAK-STAT signalling pathway. Significantly, this cascade has been implicated as a mediator soluble Ab1-42-induced toxicity [1]. We have previously demonstrated that removal of IFNAR1, contributes to neuro-protection following Ab142 insult, decreasing type-1 IFN production and apoptosis. This study investigated a role for type-1 IFNs in an AD mouse model and utilised an in vitro approach to analyse TLR signalling as a potential production pathway.
Margaret McCartney: Flibanserin for low sexual desire is not feminism
Authors: Margaret McCartney
Journal: BMJ (2015)

The UK Medicines and Healthcare Products Regulatory Agency will neither confirm nor deny it, but flibanserin is likely to be coming to British shores.Its maker, Sprout Pharmaceuticals, told me that it is "committed to working closely with other regulatory bodies outside the US . . . to bring to market a safe and effective treatment for the millions of women around the world affected by distressing low sexual desire.
Economic consequences to society of pandemic H1N1 influenza 2009 – preliminary results for Sweden
Authors: L Brouwers, B Cakici, M Camitz, A Tegnell, M Boman
Journal: Eurosurveillance (2009)

Experiments using a microsimulation platform show that vaccination against pandemic H1N1 influenza is highly cost-effective. Swedish society may reduce the costs of pandemic by about SEK 2.5 billion (approximately EUR 250 million) if at least 60 per cent of the population is vaccinated, even if costs related to death cases are excluded. The cost reduction primarily results from reduced absenteeism. These results are preliminary and based on comprehensive assumptions about the infectiousness and morbidity of the pandemic, which are uncertain in the current situation.
Description of a murine model of acute pneumonitis hypersensitivity to pigeon serum
Authors: Mònica Sánchez Ortiz, Xavier Muñoz, Susana Gómez Ollés, Mª Dolores Untoria Corral, Ferran Morell Brotad, Mª Jesús Cruz
Journal: European Respiratory Journal (2014)

Introduction:  The immunopathological mechanisms of hypersensitivity pneumonitis (HP) are not well known. Animal models with different forms of HP are essential for the study of these mechanisms.   Methods:  C57Bl/6 mice were used. Two intraperitoneal injections of 100µL of pigeon serum (200µg protein/ml) or saline solution were administered, separated by an interval of 48h. Subsequently, 40 µL intranasal instillations of pigeon serum (200µg protein/ml) or saline solution were performed three days a week for three weeks. Pulmonary inflammation in bronchoalveolar lavage (BAL) was evaluated and histological studies were performed 24 hours, seven days, and 14 days after the last exposure.   Results:  Histological studies showed changes consistent with HP using this model, with pericentrolobular inflammation and mixed infiltrate with polymorphonuclear predominance. In the BAL a significant increase was observed in the number of neutrophils, mean (SD) = 2.11 (3.25) cells (x10 4 ), and the number of lymphocytes, mean (SD) = 2.5 (2.02) cells (x10 4 ), 24h after inhalation (p = 0.004 and 0.017 respectively). This increase persisted until a week after inhalation. An increase in the number of eosinophils, 28.69 (17.50) cells (x 10 4 ) at 24 hours was also observed, with a tendency towards progressive decline a week after exposure. The levels of pigeon serum antigen-specific IgG were higher than in the control group 24 hours after inhalation (p l 0.0001).   Conclusions:  Our results provide evidence of lung inflammation and pathology study are consistent with acute HP. The animal model described may serve as a tool for future studies on the pathogenesis of acute HP.  Study funded by Fis PI 001577, FUCAP and SEPAR.
Declining Cancer Rates in the 1990s
Authors: Roberta McKean-Cowdin, Heather Spencer Feigelson, Ronald K. Ross, Malcolm C. Pike, Brian E. Henderson
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To provide evidence of a substantial decline in cancer rates for the period 1991 through 1995 and characterize major risk factors that seem to be driving secular trends in cancer mortality and incidence. DESIGN: Incidence and mortality rates were calculated using national surveillance data collected through the Surveillance, Epidemiology, and End Results (SEER) program and the National Center for Health Statistics. RESULTS: All-sites cancer incidence and mortality fell in the period 1991 through 1995; this decline is largely attributable to decreases in the smoking-related cancers, especially lung cancer. Of the 20 leading incident cancers today, both incidence and mortality are decreasing among 11 sites for men and 12 for women. In men, the decline in mortality has been notable and is especially apparent for the smoking-related cancers, including those of the lung, oral cavity and pharynx, larynx, and, to a lesser extent, bladder. In women, all-sites mortality decreased only approximately 0.4% from 1991 through 1995. Three cancers continued to show substantial increases in mortality through 1995 for both men and women (liver, multiple myeloma, and non-Hodgkin’s lymphoma), while incidence rates continued to climb for liver cancer, non-Hodgkin’s lymphoma, and melanoma. CONCLUSION: Data from the SEER program on recent trends in cancer incidence and mortality show that cancer rates are generally on the decline, largely because of reductions in smoking-related cancers. A consistent increase in mortality rates due to liver cancer poses a new health care challenge, one that will require the development of an effective treatment for individuals currently infected with hepatitis C or B to prevent mortality rates from continuing to increase.
Effect of the level of volume-targeted ventilation on the spontaneous respiratory activity of infants born at term
Authors: Olie Chowdhury, James Perera, Silke Lee, Simon Hannam, Gerrard Rafferty, Anne Greenough
Journal: European Respiratory Journal (2012)

Prematurely born infants frequently breathe while being mechanically ventilated. The pattern of their respiratory efforts with ventilator inflation influences outcome, in particular active expiration leading to pneumothorax.   Aim:  To compare patient-ventilator interactions in infants born at term at different levels of volume-targeting (VT).   Methods:  15 infants, median gestational age 38 (range 34-41) weeks were studied at a median postnatal age of five days. The infants were studied at VT levels of 0, 4 and 6 ml/kg, applied in random order. Five infants were on conventional ventilation (CMV) and 10 on triggered ventilation (PTV). Oesophageal, gastric and airway pressures, flow and volume were simultaneously recorded for at least five minutes at each VT level; 50 consecutive breaths were analysed at each VT level.   Results:  In the infants studied on CMV, active expiration was more common at a VT level of 4 ml/kg than at VT levels of 0 and 6 ml/kg (p   Conclusion : The underlying mode of ventilation significantly influences whether low compared to higher levels of volume targeting will increase active expiration.
Impaired respiratory function in mice exposed to cigarette smoke
Authors: Sofia Jonasson, Bo Koch, Linda Elfsmark, Christine Akfur, Anders Bucht
Journal: European Respiratory Journal (2011)

Introduction:  We have aimed to develop a mouse model of cigarette smoke (CS)-induced small airway disease and emphysema. This model will be used for studies of pathogenic responses in the development of emphysema and for preclinical evaluation of new drug candidates.   Methods:  BALB/c mice were exposed to CS (nose-only), 5 days a week during 10 weeks (Gr.1: 6 cigarettes during 10 min, twice a day; Gr. 2: 12 cigarettes once a day during 20 min; Gr 3: 12 cigarettes during 20 min, twice a day; Gr 4: control, room air). The experiment ended on day 71-73 and day 85-87 (two additional recovery weeks without CS smoke) with thoroughly investigated lung mechanics (FlexiVent), inflammatory cell counts in bronchoalveolar lavage (BAL) and lung histology.   Results:  CS induced an increased respiratory resistance (p   Conclusion:  In our mouse model there is a marked effect on lung mechanics, suggesting that CS induce small airway inflammation which is not dose dependent. Our result indicates that it is the exposure time, rather than the number of cigarettes, that determines the detrimental effects in the mouse lung. Additionally, this model can be used for combined exposure of allergens and air-borne particulate pollution in order to investigate aggravating effects of inhaled particles on emphysema and COPD.