tbuckley/cabot-search huggingface dataset:
Management for Doctors: Making finance work for you--strategic issues in clinical directorates
Authors: J. Stuart, P. C Spurgeon, A. Cook
Journal: BMJ (1995)

The NHS has a long history of underinvestment interspersed with periodic bouts of overspending to relieve the ensuing crises. Strict cash limits make it unlikely that funding will match the multiple demands of an increasingly aging population, rising drug prices, and advancing technology. In this context it is difficult to perceive the finance function as a “flexible friend.”

The restructuring of the NHS, with the formation of budget holding clinical teams (directorates) and self governing (trust) status for hospitals, and especially contracting, which brings together activity and financial data, means that clinicians now have the opportunity to influence the use of revenue funds in a more imaginative way than before, to improve patient care. Yet, many doctors view financial management as yet another mechanism for restricting clinical freedom. But doctors who participate actively in financial management within a sufficiently large clinical directorate can make finance work to achieve a clinical service of more uniform quality.

To illustrate the point, we have compiled a case history (box) which is not based on any one hospital or health authority. We begin with a clinical service directorate (surgery) and follow with a support service directorate (laboratory medicine).

Bottomless Memorial Hospital is a large district general hospital in an urban health authority which also contains one other general hospital and a specialist hospital for the elderly. The three hospitals have recently amalgamated to achieve self governing NHS trust status (Bottomless Trust Hospitals). There has been little or no collaboration between the hospitals in the past, but a new management structure with clinical directorates extending across all three hospitals has now been established by a new chief executive. A computerised clinical information system is also being developed as part of the NHS resource management initiative. Serious financial difficulties in both clinical and support services have …
Polybrominated diphenyl ethers and their hydroxylated metabolites in serum in humans in Nicaragua
Authors: M Athanasiadou, S N Cuadra, G Marsh, Åke Bergman, Kristina Jakobsson
Journal: Environmental Health Perspectives (2008)

OBJECTIVE: Our aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected.

METHODS: We assessed PBDEs in pooled serum samples obtained in 2002 from children 11-15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15-44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances.

RESULTS: The children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites.

CONCLUSIONS: Unexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum.
Methods are changing rapidly
Authors: F C Hamdy, D E Neal
Journal: BMJ (1995)

Thus most cancers detected were aggressive, and only a small number of men with prostate specific antigen concentrations >4 0 ng/ml would have a diagnosis of a non-aggressive cancer preceded by a long disease free interval.This was also true for the subset of men who were aged under 70 when the diagnosis was made.Compared with men with antigen concentrations of < 1 0 ng/ml, those with concentrations of 2-0-3-0 ng/ml had a relative risk of all prostate cancer of 5-5 and a relative risk of aggressive cancer of 6-8.It is important to note that this was a once only test, and the potential benefit of repeat screening or the addition of other screening modalities was not available.For men older than 70 watchful waiting may be appropriate management.This new study shows, however, that in this population of American doctors the mean age at diagnosis of prostate cancer was 68-7 years, most of the cancers detected were aggressive, and three quarters of deaths in the cases were directly related to the diagnosis.Thus in younger men screening for prostate specific antigens may be justified, particularly for those in higher risk groups, such as those with a family history ofprostate cancer.45
Physical status and dependence levels in patients with COPD exacerbation
Authors: Paz Moreno-Ramirez, Irene Torres-Sánchez, Ana Romero-Ortiz, Belén Gallego-Ariza, Sara Mateos-Toset, Marie Carmen Valenza
Journal: European Respiratory Journal (2014)

Introduction:  Chronic obstructive pulmonary disease (COPD) is often associated with loss of functional capacity and high levels of dependence. Few studies have been focused on physical status and dependency in hospitalized patients due to COPD exacerbation. The aim of this study was to evaluate the relationship between physical measures and the degree of dependence in COPD exacerbation.   Methods:  Patients hospitalized due to a COPD (GOLD stage III-IV) exacerbation were included in this study. The degree of dependence was measured by Barthel Index. Variables assessing physical function were: upper and lower limb strength and aerobic endurance.   Results: 32 COPD patients were included in the study, GOLD stage III and IV were included in our sample. Mean age was 71 years old and all of them were men.  Barthel index values of dependence were 63,21± 5.62. Physical status of upper limbs, measured with hand grip strength showed significant correlation with independence levels (dominant hand: r= 0.260**; non-dominant hand: 0.222** ).  Physical status of lower limbs, measured with quadriceps hand held dynamometry showed significant correlation with independence levels (right leg: r= 0.229**; left leg: 0.239**).  Aerobic endurance, measured with 2 minutes step test shows significant correlation with independence levels(r=0.463**).   Conclusion:  The study revealed that exist a relationship between physical status and the degree of dependence in patients with acute COPD exacerbation.
Pre-medications of weekly taxanes in advanced non-small cell lung cancer
Authors: X. Huang, Z. Ye, Y. Lin
Journal: Journal of Clinical Oncology (2007)

18210 Background: Taxane is a widely accepted treatment in advanced non-small cell lung cancer (NSCLC). However, a standard pre-medication for weekly taxane has not been established at present. We conducted this study to evaluate the efficacy,safety and pre-medication of weekly paclitaxel /docetaxel schedule in the treatment of advanced NSCLC and to obtain an optimal pre-medication protocol for weekly paclitaxel /docetaxel. Methods: From December 2001 to June 2006, 78 patients with advanced NSCLC (Stage III, IV) were recruited from Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute. Eleven cases were treated with paclitaxel 80–100 mg/m 2 by intravenous infusion(ivi)on days 1 and 8, 23 cases were treated with paclitaxel 50–80 mg/m 2 ivi on days 1, 8 and 15, 14 cases were treated with docetaxel 25–35 mg/m 2 ivi on days 1,8 and 15,30 cases were treated with docetaxel 35–45 mg/m 2 ivi on days 1 and 8, all combined with a platinum(cisplatin, oxaliplatin or carboplatin), followed by 1 week rest. Four pre-medications were attempted. Results: All 78 patients received a total of 202 courses of treatment. Dose limiting toxicity was myelosuppression. Grade 3 and 4 leukopenia occurred in 19.2% (15/78) of patients. Of the 56 eligible patients who completed at least 2 courses, no patient had a complete response, 20 achieved a partial response and 5 patients showed progression. Toxicity profile of pre-medications included: hypersensitivity (1 case), hypopotassemia (8 cases), myasthenia (5 cases), hiccup (1 case), infection (2 cases). No treatment related death occurred in this study. Conclusions: Weekly administration of paclitaxel/docetaxel is a safe and active protocol for Chinese patients with advanced NSCLC. Our recommendations for weekly pre-medication of taxane are: dexamethasone 2.25 mg-7.5 mg orally 12 h and 2 h before, promethazine 25 mg intramuscularly and cimetidine 600 mg ivi 30 min before paclitaxel; oral dexamethasone 4.5 mg-7.5 mg twice daily for three consecutive days (the day before, the day of, and the day after docetaxel), promethazine 25 mg intramuscularly and cimetidine 600 mg ivi 30 min before docetaxel. No significant financial relationships to disclose.
Abstract 16184: Impact of Aortorenal Morphology in Renal Artery Intervention: Procedural Significance of Abdominal Aorta Tortuosity and Renal Artery Derivation
Authors: Osami Kawarada, Yoshiaki Yokoi, Shingo Sakamoto, Koichiro Harada, Masaharu Ishihara, Satoshi Yasuda, Hisao Ogawa
Journal: Circulation (2013)

Objectives: There has been limited information of classification of aortorenal morphology and its impact on renal artery interventional procedures. Methods: This study included a total of 142 conse...
Survival predictors of severe community-acquired pneumonia (CAP): Multivariate analysis of immunological and inflammatory parameters
Authors: Tetyana Kireeva, Tetyana Pertseva, Kseniia Bielosludtseva
Journal: European Respiratory Journal (2014)

Aim:  to determine the significance of immunological (CD4, CD8) and inflammatory (procalcitonin (PCT)) markers as predictors of survival in patients with severe CAP.   Methods:  51 patients with verified severe CAP without HIV (age – 57,50±4,31 years, men – 37 (72,5%), women – 14 (27,5%)). General analysis, determination of serum PCT, blood CD4, CD8 prior antibacterial treatment (ABT) (visit 1), on 8–10 day of ABT (visit 2), cluster analysis.   Results:  in 6 (11,7%) patients with severe CAP, despite adequate ABT, lethal end of disease was determined. All patients were divided into 3 classes: 1) whose PCT at visit 2 decreased by more than 95,6% and CD4 increased significantly (by more than 335,7%) we can predict recovery with a maximal probability; 2) patients whose PCT at visit 2 decreased by more than 95,3% and CD4 increased by more than 4,7%, have a chance to recover, although the risk of death and pulmonary complications is high; 3) patients whose PCT decreased very slightly (by 1%) or significantly increased (by more than 11,460%) and CD4 decreased by more than 50% have a maximum risk of death.   Conclusions:  with a substantial decrease of PCT and increase of CD4 during the adequate ABT a favorable outcome of severe CAP can expect, whereas at the increasing of PCT and decreasing of CD4 the survival is unfavorable.
Consequences of chronic pulmonary TLR9 activation in the lung and beyond
Authors: Gillina Bezemer, Dmitri Fillipov, Esmaeil Mortaz, Ingrid van Ark, Johan Garssen, Aletta Kraneveld, Ferry Ossendorp, Gert Folkerts
Journal: European Respiratory Journal (2011)

Background: Toll like receptor 9 (TLR9) agonist CpG-ODN is being explored as an anti-allergic drug for asthma. However TLR9 could play a role in COPD. Cigarette smoke induced IL-8 production is partly TLR9 mediated.

Aim: To investigate the (extra)-pulmonary effects of CpG-ODN. We hypothesized that pulmonary TLR9 activation induces neutrophil influx which could lead to adverse effects.

Methods: A single dose of 0.01, 0.05 or 0.25nMol/gBW GpG-ODN was targeted to balb/c mice lungs by aspiration (acute). Next 0.01nMol/gBW GpG-ODN was administered repeatedly for 5 days (subchronic) or 5 weeks (chronic). 24 hours after last exposures, measurements were done: lung function; hypertension and heart hypertrophy; lung weight; blood and bronchoalveolar lavage (BAL) analysis; morphology of unlavaged lungs.

Results: Total BAL cells were increased in all CpG-ODN mice (p<0.05). PMNs were increased in blood (30%) and BAL (39%) acute which persistent upon prolonged exposure duration. Blood lymphocytes were subchronically 19% decreased which was reflected in an abundant pulmonary (sub)- chronic lymphocyte influx. Chronic exposure leads to 21% decreased peak expiratory flow (ml/sec) and 71% increased airway resistance (cm H2O/ml/sec). Right ventricle heart hypertrophy was observed upon chronic exposure; ratio right ventricle weight/total heart weight CpG-ODN=0.23±0.007; control=0.19±0.008. Wet lung weight was 15.2% increased subchronically and 70.8% chronically.

Conclusion: An interplay between neutrophils and lymphocytes could possibly play a role in TLR9 induced adverse pulmonary and cardiovascular effects. Caution is needed when CpG-ODNs are chronically administered for therapeutical purposes.

Acknowledgement TIPharma D1-101
The age factor in Alzheimer’s disease
Authors: Rita Guerreiro, Jose Bras
Journal: Genome Medicine (2015)

Alzheimer's disease is the most common type of dementia, and it is characterized by a decline in memory or other thinking skills. The greatest risk factor for Alzheimer's disease is advanced age. A recent genome-wide study identified a locus on chromosome 17 associated with the age at onset, and a specific variant in CCL11 is probably responsible for the association. The association of a protective haplotype with a 10-year delay in the onset of Alzheimer's disease and the identification of a CCL11 variant with possible functional roles in this association might allow the future development of immunomodulators with the potential to halve disease incidence.
Year one evaluation of regional pay for quality (P4Q) oncology program.
Authors: J. A. Scott, W. Wong, T. Olson, B. V. Fortner
Journal: Journal of Clinical Oncology (2010)

6013 Background: Oncology clinical pathways are common in current practice. However, little information is available evaluating the cost savings of enacting pathways. This study evaluates the potential cost savings of a payer-based P4Q program employing clinical pathways. Methods: A P4Q program was enacted in five northeastern states, USA, beginning August 1, 2008, and consisted of physician generated treatment (i.e., breast, lung, and colon-rectal cancer) and supportive care pathways (i.e., colony-stimulating factors, erythropoietin stimulating agents, and antiemetics). Feedback was provided to participants regarding compliance, and increased fee schedules in year 1 were adjusted in year 2 contingent on compliance in year 1. Savings analysis used the difference in participating and nonparticipating practice growth rates from the year prior to the program (pre) to the first year of the program (Yr 1) to estimate yearly savings for the participating practices. Results: 57 participating practices (176 physicians, 10,432 patients) and 43 nonparticipating practices (194 physicians, 14,137 patients) contributed to the analysis. The pre to Yr 1 growth rate in cost was 7.7%, -3.0%, and 2.8% for antineoplastic drugs, supportive care drugs, and nondrug services respectively in the participating practices and 15.4%, 2.4%, and 19.0% in the nonparticipating practices. Estimated savings were calculated for antineoplastic drugs ($6,766,500), supportive care drugs ($1,427,108), nondrug services ($4,039,359), and total ($12,232,967). When the costs of the Yr 1 fee schedule increase for participating practices were factored out, the total savings were estimated at $8,585,148. Conclusions: This study suggests pathway programs may reduce the costs of cancer care by reducing the growth rate of both drug and nondrug expenses. Further evaluations should explore indications of how these costs were reduced (e.g., drug selection) and consider clinical outcomes and compliance in relation to costs savings. The primary limitations of the study derive from the nonexperimental research design which allows confounds to causal inference. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration P4 Healthcare P4 Healthcare
PROOF-registry: A prospective observational registry to describe the disease course and outcomes of idiopathic pulmonary fibrosis patients in a real-world clinical setting
Authors: Wim Wuyts, Caroline Dahlqvist, Marc Schlesser, Christophe Compere, Hans Slabbynck, Benjamin Bondue, Marianne Berrens, Christophe Giot, Paul DeVuyst
Journal: European Respiratory Journal (2014)

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and generally fatal disease. Pirfenidone (PFD) is approved for the treatment of mild-to-moderate IPF in the European Union. An observational registry of IPF patients (pts) (the PROOF registry) was initiated to collect data from routine clinical visits and monitor IPF development. Interim data from the PROOF registry are presented.  Aims and objectives: The PROOF registry aims to describe the disease course and outcomes in IPF pts in a real-world setting.  Methods: The registry is on-going in 6 centres in Belgium and Luxemburg, and will be extended to the Netherlands. Data from IPF pts are collected according to the normal course of pts care and include demographic information, medical history, pulmonary function data, high-resolution computed tomography and previous/current treatments.  Results: Since October 2013, 35 pts (aged 70.2 ± 8.4 years, 89% male) have been enrolled. IPF diagnosis was made during a multidisciplinary discussion and was definite in 91% of cases. IPF symptoms were breathlessness, cough and velcro rales in 77%, 63% and 49% of pts respectively. Surgical lung biopsy was performed in 23% of pts. Pulmonary function tests showed a mean FVC of 80.0 ± 23.6% and a mean FEV1/FVC of 88.4 ± 11.9. Time to IPF diagnosis ranged from 5 days to 8 years. 88% of pts had relevant previous/ongoing co-morbidities and 9% of pts had family history of IPF. 73% of pts received previous IPF treatment; 57% of pts received PFD.  Conclusions: The PROOF registry will provide real-world information and insights on the clinical course of IPF.
Nucleotide sequence analysis of the lemur beta-globin gene family: evidence for major rate fluctuations in globin polypeptide evolution.
Authors: S Harris, J R Thackeray, A J Jeffreys, M L Weiss
Journal: Molecular Biology and Evolution (1986)

Lemur beta-related globin genes have been isolated and sequenced. Orthology of prosimian and human epsilon-, gamma-, and beta-related globin genes was established by dot-matrix analysis. All of these lemur globin genes potentially encode functional beta-related globin polypeptides, though precisely when the gamma-globin gene is expressed remains unknown. The organization of the 18-kb brown lemur beta-globin gene cluster (5' epsilon-gamma-[psi eta-delta]-beta 3') is consistent with its evolution by contraction via unequal crossing-over from the putative ancestral mammalian beta-globin gene cluster (5' epsilon-gamma-eta-delta-beta 3'). The dwarf lemur nonadult globin genes are arranged as in the brown lemur. Similar levels of synonymous (silent) nucleotide substitutions and noncoding DNA sequence differences have accumulated between species in all of these genes, suggesting a uniform rate of noncoding DNA divergence throughout primate beta-globin gene clusters. These differences are comparable with those observed in the nonfunctional psi eta pseudogene and have therefore accumulated at the presumably maximal neutral rate. In contrast, nonsynonymous (replacement) nucleotide substitutions show a significant heterogeneity in distribution for both the same gene in different lineages and different genes in the same lineage. These major fluctuations in replacement but not silent substitution rates cannot be attributed to changes in mutation rate, suggesting that changes in the rate of globin polypeptide evolution in primates is not governed solely by variable mutation rates.
Abstract 15566: Rates of Cardiovascular Events Were Lower in Type 2 Diabetic Patients with Pioglitazone Treatment After Zotarolimus-Eluting Stent Implantation During the Three-Year Follow-Up
Authors: Soon Jun Hong, Je Sang Kim, Jae Hyoung Park, Chul-Min Ahn, Do-Sun Lim
Journal: Circulation (2011)

Background: Recent studies highlight the beneficial effect of pioglitazone in reducing major adverse cardiovascular events (MACEs) in type 2 diabetic patients. We prospectively investigated the eff...
The temporal dynamics of resilience: Neural recovery as a biomarker
Authors: Henrik Walter, Susanne Erk, Ilya M. Veer
Journal: Behavioral and Brain Sciences (2015)

Resilience can be defined as the capability of an individual to maintain health despite stress and adversity. Here we suggest to study the temporal dynamics of neural processes associated with affective perturbation and emotion regulation at different time scales to investigate the mechanisms of resilience. Parameters related to neural recovery might serve as a predictive biomarker for resilience.
Monoclonal antibodies to αVβ3 (7E3 and LM609) inhibit sickle red blood cell–endothelium interactions induced by platelet-activating factor
Authors: D. K. Kaul, H. M. Tsai, X. D. Liu, M. T. Nakada, R. L. Nagel, B. S. Coller
Journal: Blood (2000)