tbuckley/cabot-search huggingface dataset:
'Treat to target': moving targets from hypertension, hyperlipidaemia and diabetes to rheumatoid arthritis
Authors: D. Atar, K. I. Birkeland, T. Uhlig
Journal: Annals of the Rheumatic Diseases (2010)

The principle of ‘treat to target’ embraces an indispensable approach to the prevention of some of the most prevalent diseases: diabetes, arterial hypertension and coronary heart disease. These highly ubiquitous disorders account for most deaths and disabilities worldwide. Preventive treatment is thus a matter of paramount priority.

How did ‘treat to target’ come about? The rationale for this therapeutic paradigm is based on a comprehensive evidence base that is—fair to say—unique to cardiovascular medicine. Few areas in contemporary medicine have investigated hundreds of thousands of patients with a given condition just to scrutinise one particular therapeutic intervention, such as the lowering of blood pressure with a given agent, or such as low-density lipoprotein (LDL)-cholesterol lowering by a statin.

What do we mean by ‘comprehensive evidence base’? Clinical trials demonstrate that to reduce cardiovascular events in individuals with hypertension, blood pressure lowering (eg, to <150/100 mm Hg) is effective, and more intensive blood pressure lowering (eg, to <140/90 mm Hg) is more effective.1 Likewise, to reduce cardiovascular events in patients with established ischaemic heart disease through lipid lowering, a statin is more effective than placebo, aggressive statin therapy is more effective than lenient statin therapy, and in patients receiving aggressive statin therapy the lowest risk is associated with the lowest LDL-cholesterol levels.2 This preventive treatment strategy aiming at lowering LDL-cholesterol has been coined as the concept of ‘the lower the better’. Incidentally, the aphorism ‘the lower the better’ is just a linguistic corollary to the dictum ‘treat to target’. Taken together, this evidence base essentially teaches us that treating patients to goal confers the …
A6.4 Induction of TH2 cells and eosinophil by infection with<i>nippostrongylus brasiliensis</i>protects against rheumatoid arthritis
Authors: Zhu Chen, Katharina Oeser, Wolfgang Baum, David Voehringer, Georg Schett, Aline Bozec
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objective</h3> Infection with helminth triggers strong Th2 immune response, which modulates the development of systemic autoimmune diseases. The aim of this study was to investigate whether infection with <i>Nippostrongylus brasiliensis</i> influence rheumatoid arthritis development as well as the molecular mechanism from Th2 and eosinophil cells in this effect. <h3>Materials and Methods</h3> 5 to 7 weeks old human TNF transgenic (hTNFtg) mice were infected with <i>Nippostrongylus brasiliensis</i> subcutaneously. Moreover, wild-type, IL-4<sup>-/-</sup>IL-13<sup>-/-</sup> and CD4-Cre IL-4<sup>-/-</sup>IL-13<sup>-/</sup>mice were infected with <i>Nippostrongylus brasiliensis</i> subcutaneously 6 days before induction of experimental arthritis through injection of 150 µl K/BxN serum intraperitoneally. Clinical arthritis score and histomorphometric analysis in the inflammatory hind paw were evaluated. <h3>Results</h3> Infection with <i>Nippostrongylus brasiliensis</i> alleviated spontaneous chronic arthritis in hTNFtg mice accompanied with a reduction of the systemic and local bone loss. Moreover, wild-type and CD4cre IL-4<sup>-/-</sup>IL-13<sup>-/</sup>mice infected with <i>Nippostrongylus brasiliensis</i> have a reduction of the arthritis score whereas arthritis in IL-4<sup>-/-</sup>IL-13<sup>-/-</sup> mice with infection remained comparable to the non-infected control mice. Histomorphometric analyses revealed that inflammation area and bone erosion were decreased in wild-type and CD4cre IL-4<sup>-/-</sup>IL-13<sup>-/</sup>mice with infection compared with IL-4<sup>-/-</sup>IL-13<sup>-/-</sup> or noninfected wild-type control. Consistently, osteoclast marker such as <i>Trap, RANK</i> and <i>CathepsinK</i> mRNA expression levels in the inflammatory joint were lower in wild-type mice with infection than control. In order to define the role of eosinophil, induction of K/BxN serum transfer arthritis in delta-dblGATA mice was performed. Interestingly genetically lack of eosinophil showed increased inflammation and bone erosion than wild-type control. <h3>Conclusions</h3> Infection with <i>Nippostrongylus brasiliensis</i> significantly alleviated bone erosion in experimental arthritis models, which is dependent of IL-4 and IL-13. In addition, eosinophils might play a crucial role in arthritis protection induced by <i>Nippostrongylus brasiliensis</i> infection.
Evaluation of a multiplex PCR for bacterial pathogens applied to bronchoalveolar lavage
Authors: K. Strålin, J. Korsgaard, P. Olcén
Journal: European Respiratory Journal (2006)

The present study assessed the diagnostic usefulness of a multiplex PCR (mPCR) for Streptococcus pneumoniae , Haemophilus influenzae , Mycoplasma pneumoniae and Chlamydophila pneumoniae applied to bronchoalveolar lavage (BAL). Fibreoptic bronchoscopy was performed on 156 hospitalised adult patients with lower respiratory tract infection (LRTI) and 36 controls. BAL fluid was analysed with bacterial culture and mPCR. By conventional diagnostic methods, S. pneumoniae , H. influenzae , M. pneumoniae and C. pneumoniae were aetiological agents in 14, 21, 3.2 and 0% of the LRTI patients, respectively. These pathogens were identified by BAL mPCR in 28, 47, 3.2 and 0.6% of cases, respectively, yielding sensitivities of 86% for S. pneumoniae , 88% for H. influenzae , 100% for M. pneumoniae and 0% for C. pneumoniae , and specificities of 81, 64, 100 and 99% for S. pneumoniae , H. influenzae , M. pneumoniae and C. pneumoniae , respectively. Of the 103 patients who had taken antibiotics prior to bronchoscopy, S. pneumoniae was identified by culture in 2.9% and by mPCR in 31%. Among the controls, mPCR identified S. pneumoniae in 11% and H. influenzae in 39%. In lower respiratory tract infection patients, bronchoalveolar lavage multiplex PCR can be useful for identification of Streptococcus pneumoniae , Mycoplasma pneumoniae and Chlamydophila pneumoniae . The method appears to be particularly useful in patients treated with antibiotics.
Mobile Large Left Atrial Thrombus
Authors: Manish Bansal, Ravi R. Kasliwal
Journal: New England Journal of Medicine (2014)

A 58-year-old obese woman with rheumatic heart disease presented with progressively increasing dyspnea on exertion for the past month. Transesophageal echocardiography revealed a mass, freely floating within the left atrial cavity, shown in a video.
Combination of NK cells therapy and oral administration of entinostat as an approach for osteosarcoma lung metastasis treatment
Authors: Simin Kiany, Ling Yu, Eugenie S Kleinerman
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The goal of this study is to find an alternate therapy for osteosarcoma (OS) lung metastasis. Previously we showed that NK cell therapy significantly decreased OS lung metastasis in a mouse model; however, the therapy was not effective enough to cure OS lung metastasis. To augment
A case for serial examination of sputum inflammatory cells
Authors: AG Wong, ID Pavord, MR Sears, FE Hargreave
Journal: European Respiratory Journal (1996)

In the case reported, serial evaluation of sputum inflammatory cell counts made it possible to identify an unusual series of events in a man with eosinophilic bronchitis. The patient initially presented with a productive cough, which did not respond to treatment with antibiotics or high-dose inhaled corticosteroids. A diagnosis of eosinophilic bronchitis was made after demonstration of intense sputum eosinophilia. When inhaled corticosteroids were stopped, symptoms and sputum eosinophilia became worse and airway hyperresponsiveness developed. Both abnormalities were reversed by a course of prednisone. When the prednisone was stopped the productive cough recurred but on this occasion sputum examination suggested a different disease process and the symptoms resolved after a course of co-trimoxazole. The patient has subsequently remained well on no treatment with little or no sputum eosinophilia.
Human dendritic cells. Enrichment and characterization from peripheral blood
Authors: WC Van Voorhis, LS Hair, RM Steinman, G Kaplan
Journal: The Journal of Experimental Medicine (1982)

Previous studies demonstrated that lymphoid tissues of mice and rats contain small numbers (less than 1 percent of nucleated cells) of dendritic cells (DC) with special cytologic, surface, and functional properties. We show here that similar DC represent 0.1-0.5 percent of human peripheral blood mononuclear cells. DC can be enriched to 20-60 percent purity by a multistep procedure analogous to that used in mice. Adherent peripheral blood mononuclear cells are cultured overnight, and the released cells are depleted of monocytes and B cells by readherence to plastic, rosetting with erythrocytes coated with anti-human IgG, and centrifugation in dense albumin columns. Enriched DC have similar cytologic features to rodent DC by light and electron microscopy. DC express HLA, and HLA-DR and the leukocyte-common antigens. They lack phagocytic capacity, receptors for antibody-coated and neuraminidase-treated erythrocytes, surface and intracellular Ig, esterase, peroxidase, and azurophilic granules. DC do not react with several monoclonal antibodies directed to phagocytes (OKM 1, "mac-1," 63D3, and 61D3) and T cells (OKT 3, 6, 8). Unlike the mouse, human DC express complement receptors. When maintained in culture for 4 d, human DC did not give rise to either B cells or monocytes. Therefore, DC identified by cytologic criteria are distinct from other leukocytes. Enriched populations of DC have been compared to fractions enriched in monocytes, B cells, and T cells in three functional assays: stimulation of the primary allogeneic mixed leukocyte reaction, stimulation of the primary syngeneic MLR, and accessory function for the proliferation of periodate- modified T cells. In each case, the DC fraction was 10-fold or more active than other cell fractions. We conclude that DC circulate in man, and represent the principal cell type required for the initiation of several immune responses.
Bifid Uvula and Aortic Aneurysm
Authors: Isidre Vilacosta, Victoria Cañadas Godoy
Journal: New England Journal of Medicine (2008)

This 24-year-old man had a family history of aortic disease. The triad of craniofacial abnormalities, aortic aneurysm, and bifid uvula suggested a diagnosis of Loeys–Dietz syndrome.
c-kit+ stem cells and thymocyte precursors in the livers of adult mice.
Authors: H Watanabe, C Miyaji, S Seki, T Abo
Journal: The Journal of Experimental Medicine (1996)

Livers of the adult mice contain c-kit+ stem cells that can reconstitute thymocytes, multiple lineage cells, and bone marrow (BM) stem cells. Transfer of 1 x 10(7) hepatic mononuclear cells (MNC) and 5 x 10(4) hepatic c-kit+ cells of BALB/c mice induced DP thymocytes within a week in four Gy-irradiated CB17/-SCID mice, but 2 wk were required for BM cells or BM c-kit+ cells to produce DP thymocytes. Moreover, B cell-depleted BM cells or liver MNC of SCID mice that had been rescued by hepatic MNC of BALB/c mice again reconstituted thymus and B cells of other irradiated SCID mice. CD3- IL-2R beta- populations of both BM cells and hepatic MNC of C57BL/6 (B6) mice could generate T cells with intermediate TCR (mostly NK1.1-) in the liver of irradiated B6 SCID mice before thymic reconstitution (extrathymic T cells). Furthermore, transfer of liver c-kit+ cells of B6-Ly 5.1 mice into irradiated B6 SCID (Ly5.2) mice revealed that liver c-kit+ cells can reconstitute myeloid and erythroid lineage cells. These results strongly suggest that the liver contains pluripotent stem cells and serves an important hematopoietic organ even into adulthood.
Lessons from the withdrawal of rofecoxib: Observational studies should not be forgotten
Authors: Godfrey Oakley
Journal: BMJ (2004)

EDITOR—In their editorial Dieppe et al describe the lessons from the withdrawal of rofecoxib.1

Randomised controlled trials are not the usual way in which serious, uncommon adverse effects of a new drug are discovered. They are usually discovered in observational studies, often case-control studies. Using randomised controlled trials to find adverse effects is dangerous. It would feed on the current vogue from trialists that the …
The Influence of Boundary Conditions on the Amplitude of R and Other Accession Potentials in Leads from the Ventricular Wall
Authors: LOYAL L. CONRAD, T. EDWARD CUDDY
Journal: Circulation Research (1960)

The effects of altering the conductivities of the boundary media at the endocardial and epicardial surfaces of the ventricle on accession potentials in the ventricular wall and at its surfaces were studied in dogs. The amplitude of R at all points in the wall was decreased by any measure which increased the conductivity of the medium surrounding the heart or which decreased the conductivity of the medium in the ventricular cavity. The progression of R in the ventricular wall observed experimentally results, at least in part, from the differing conductivities of intracavitary blood, myocardium, and the medium surrounding the heart.
Early Treatment with Prednisolone or Acyclovir in Bell's Palsy
Authors: Frank M. Sullivan, Iain R.C. Swan, Peter T. Donnan, Jillian M. Morrison, Blair H. Smith, Brian McKinstry, Richard J. Davenport, Luke D. Vale, Janet E. Clarkson, Victoria Hammersley, Sima Hayavi, Anne McAteer, Ken Stewart, Fergus Daly
Journal: New England Journal of Medicine (2007)

Corticosteroids and antiviral agents are widely used to treat the early stages of idiopathic facial paralysis (i.e., Bell's palsy), but their effectiveness is uncertain.We conducted a double-blind, placebo-controlled, randomized, factorial trial involving patients with Bell's palsy who were recruited within 72 hours after the onset of symptoms. Patients were randomly assigned to receive 10 days of treatment with prednisolone, acyclovir, both agents, or placebo. The primary outcome was recovery of facial function, as rated on the House-Brackmann scale. Secondary outcomes included quality of life, appearance, and pain.Final outcomes were assessed for 496 of 551 patients who underwent randomization. At 3 months, the proportions of patients who had recovered facial function were 83.0% in the prednisolone group as compared with 63.6% among patients who did not receive prednisolone (P<0.001) and 71.2% in the acyclovir group as compared with 75.7% among patients who did not receive acyclovir (adjusted P=0.50). After 9 months, these proportions were 94.4% for prednisolone and 81.6% for no prednisolone (P<0.001) and 85.4% for acyclovir and 90.8% for no acyclovir (adjusted P=0.10). For patients treated with both drugs, the proportions were 79.7% at 3 months (P<0.001) and 92.7% at 9 months (P<0.001). There were no clinically significant differences between the treatment groups in secondary outcomes. There were no serious adverse events in any group.In patients with Bell's palsy, early treatment with prednisolone significantly improves the chances of complete recovery at 3 and 9 months. There is no evidence of a benefit of acyclovir given alone or an additional benefit of acyclovir in combination with prednisolone. (Current Controlled Trials number, ISRCTN71548196 [controlled-trials.com].).
Assessing the Reproducibility of Asthma Candidate Gene Associations, Using Genome-wide Data
Authors: Angela J. Rogers, Benjamin A. Raby, Jessica A. Lasky-Su, Amy Murphy, Ross Lazarus, Barbara J. Klanderman, Jody S. Sylvia, John P. Ziniti, Christoph Lange, Juan C. Celedón, Edwin K. Silverman, Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Association studies have implicated many genes in asthma pathogenesis, with replicated associations between single-nucleotide polymorphisms (SNPs) and asthma reported for more than 30 genes. Genome-wide genotyping enables simultaneous evaluation of most of this variation, and facilitates more comprehensive analysis of other common genetic variation around these candidate genes for association with asthma.To use available genome-wide genotypic data to assess the reproducibility of previously reported associations with asthma and to evaluate the contribution of additional common genetic variation surrounding these loci to asthma susceptibility.Illumina Human Hap 550Kv3 BeadChip (Illumina, San Diego, CA) SNP arrays were genotyped in 422 nuclear families participating in the Childhood Asthma Management Program. Genes with at least one SNP demonstrating prior association with asthma in two or more populations were tested for evidence of association with asthma, using family-based association testing.We identified 39 candidate genes from the literature, using prespecified criteria. Of the 160 SNPs previously genotyped in these 39 genes, 10 SNPs in 6 genes were significantly associated with asthma (including the first independent replication for asthma-associated integrin beta(3) [ITGB3]). Evaluation of 619 additional common variants included in the Illumina 550K array revealed additional evidence of asthma association for 15 genes, although none were significant after adjustment for multiple comparisons.We replicated asthma associations for a minority of candidate genes. Pooling genome-wide association study results from multiple studies will increase the power to appreciate marginal effects of genes and further clarify which candidates are true "asthma genes."
TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function
Authors: Jochen Reiser, Krishna R Polu, Clemens C Möller, Peter Kenlan, Mehmet M Altintas, Changli Wei, Christian Faul, Stephanie Herbert, Ivan Villegas, Carmen Avila-Casado, Mary McGee, Hikaru Sugimoto, Dennis Brown, Raghu Kalluri, Peter Mundel, Paula L Smith, David E Clapham, Martin R Pollak
Journal: Nature Genetics (2005)
Association of Changes in Clinical Characteristics and Management With Improvement in Survival Among Patients With ST-Elevation Myocardial Infarction
Authors: Etienne Puymirat
Journal: JAMA (2012)

The contemporary decline in mortality reported in patients with ST-segment elevation myocardial infarction (STEMI) has been attributed mainly to improved use of reperfusion therapy.To determine potential factors-beyond reperfusion therapy-associated with improved survival in patients with STEMI over a 15-year period.Four 1-month French nationwide registries, conducted 5 years apart (between 1995, 2000, 2005, 2010), including a total of 6707 STEMI patients admitted to intensive care or coronary care units.Changes over time in crude 30-day mortality, and mortality standardized to the 2010 population characteristics.Mean (SD) age decreased from 66.2 (14.0) to 63.3 (14.5) years, with a concomitant decline in history of cardiovascular events and comorbidities. The proportion of younger patients increased, particularly in women younger than 60 years (from 11.8% to 25.5%), in whom prevalence of current smoking (37.3% to 73.1%) and obesity (17.6% to 27.1%) increased. Time from symptom onset to hospital admission decreased, with a shorter time from onset to first call, and broader use of mobile intensive care units. Reperfusion therapy increased from 49.4% to 74.7%, driven by primary percutaneous coronary intervention (11.9% to 60.8%). Early use of recommended medications increased, particularly low-molecular-weight heparins and statins. Crude 30-day mortality decreased from 13.7% (95% CI, 12.0-15.4) to 4.4% (95% CI, 3.5-5.4), whereas standardized mortality decreased from 11.3% (95% CI, 9.5-13.2) to 4.4% (95% CI, 3.5-5.4). Multivariable analysis showed a consistent reduction in mortality from 1995 to 2010 after controlling for clinical characteristics in addition to the initial population risk score and use of reperfusion therapy, with odds mortality ratios of 0.39 (95%, 0.29-0.53, P <.001) in 2010 compared with 1995.In France, the overall rate of cardiovascular mortality among patients with STEMI decreased from 1995 to 2010, accompanied by an increase in the proportion of women younger than 60 years with STEMI, changes in other population characteristics, and greater use of reperfusion therapy and recommended medications.
The challenges of quality improvement reports and the urgent need for more of them
Authors: K. McIntyre, K. G. Shojania
Journal: Thorax (2011)

Healthcare quality has received sustained attention since the release of To Err is Human by the US Institute of Medicine in late 1999.1 This report captured widespread interest with the oft-quoted estimate that medical errors annually cause 44 000–98 000 deaths in US hospitals alone. This period also coincided with publication of ‘An organisation with a memory’,2 which described the scale and nature of serious failures in the UK National Health Service.

A widely accepted definition describes quality as the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge.3 4 This definition further characterised quality in terms of six dimensions: safety, effectiveness, patient centeredness, timeliness, efficiency and equitability.

Numerous studies document major shortcomings in each of these dimensions across a range of clinical settings.3 One illustrative study5 showed that only 55% of Americans with chronic medical conditions received basic aspects of acute, chronic and preventive care.5 For example, only 50% of patients with asthma received chronic inhaled corticosteroids and a similarly low percentage of patients with chronic obstructive pulmonary disease (COPD) received influenza vaccination. These major shortfalls in effective healthcare do not simply reflect access issues, as comparable data from Canada (with universal public healthcare) show that only 56% of patients with COPD had undergone spirometry as recommended by guidelines and only 34% received guideline-concordant treatment.6 Given that COPD will become the third leading cause of death by 20307 and represents the one common cause of death for which mortality rates continue to climb, we must improve adherence to evidence-based aspects of COPD management.8

Quality improvement (QI) is a science9 and includes numerous distinct strategies for changing patient and provider behaviour, as well …