tbuckley/cabot-search huggingface dataset:
The role of patient care teams in chronic disease management
Authors: E. H Wagner
Journal: BMJ (2000)

> “In the gradual division of labor, by which civilization has emerged from barbarism, the doctor and nurse have been evolved”
> 
> Sir William Osler (1891)

The delivery of health care by a coordinated team of individuals has always been assumed to be a good thing. Patients reap the benefits of more eyes and ears, the insights of different bodies of knowledge, and a wider range of skills. Thus team care has generally been embraced by most as a criterion for high quality care. Despite its appeal, team care, especially in the primary care setting, remains a source of confusion and some scepticism.1 Which disciplines are essential on the team? What do the team members other than the doctor do to support patient care?

With the ageing of the population and the advances in the treatment of chronic diseases, teamwork in the context of chronic diseases needs to be re-examined. Successful chronic disease interventions usually involve a coordinated multidisciplinary care team.2–5

In this article I consider the implications of these observations for the structure and functioning of patient care teams in primary care. My work is rooted in US health care, and the references and roles described largely reflect that perspective. I performed a Medline search for randomised controlled trials of team care using the MeSH heading “patient care team.”

#### Summary points

Effective chronic illness interventions generally rely on multidisciplinary care teams

Successful teams often include nurses and pharmacists with clinical and behavioural skills

Such teams ensure that critical elements of care that doctors may not have the training or time to do well are competently performed

These elements include population management, protocol based regulation of medication, self management support, and intensive follow up

The participation of medical specialists in consultative and educational roles outside conventional referrals may contribute to …
Spatial regulation of intracellular pH in multicellular strands of neonatal rat cardiomyocytes
Authors: Pawel Swietach, Patrizia Camelliti, Alzbeta Hulikova, Peter Kohl, Richard D. Vaughan-Jones
Journal: Cardiovascular Research (2009)

Intracellular pH (pHi), an important modulator of cardiac function, is normally regulated to within narrow limits (7.1–7.2). In adult ventricular cell pairs, localized cellular pHi disturbances are removed by sarcolemmal acid/base transporters, but can also be dissipated (diluted) across gap junctions, aboard mobile buffers such as CO2/HCO3− and histidine-containing dipeptides (HCDPs). In the present work, we test this model of spatial pHi regulation in multicellular strands of neonatal rat ventricular myocytes. We confocally image pHi (intracellular fluorescence emitted from the pH dye carboxy-SNARF-1) in multicellular (>500 µm long, ∼30 µm wide) cultured strands of electrically coupled, neonatal rat ventricular myocytes. Activity of sarcolemmal Na+/H+ exchange and Na+-HCO3− co-transport resembles that in adult cells. Localized photolytic H+ uncaging from intracellular 2-nitrobenzaldehyde, in the presence of CO2/HCO3− buffer, triggers considerable passive H+ spread along a strand, thus helping to dissipate the acid load. Inhibition of gap junctions (with α-glycyrrhetinic acid) truncates the spread, indicating they are conduits for local intracellular H+ flux. Without CO2/HCO3− buffer, longitudinal H+ mobility is reduced by ∼90%, indicating that intracellular and cell-to-cell H+ flux relies far less on intrinsic mobile buffers (e.g. HCDPs) in neonates than in adults. This is consistent with five-fold lower HCDP levels in neonatal, compared to adult, ventricular tissue, and also with measurements of a lower intrinsic (non-CO2/HCO3−) H+ buffering capacity in neonatal strands compared with freshly isolated adult cells. We conclude that mobile buffers and gap junctions are key spatial controllers of pHi in cardiac tissue, helping to maintain a myocardial pHi syncitium. In neonatal tissue, intracellular H+ movement is CO2/HCO3− dependent, while adult tissue relies increasingly on intrinsic dipeptides that provide additional spatial pHi control, appropriate for the developmental increase in myocyte size.
Ocular Olopatadine Treatment of Seasonal Allergic Conjunctivitis Decreases the Ability of Tears to Promote In Vitro Eosinophil Adhesion to Tear-Stimulated Conjun ctival Epithelial Cells
Authors: E.B. Cook, J.L. Stahl, J.B. Sedgwick, A.M. Brooks, F.M. Graziano, N.P. Barney
Journal: Journal of Allergy and Clinical Immunology (2006)
D-dimer Testing for Suspected Pulmonary Embolism in Outpatients
Authors: ARNAUD PERRIER, SYLVIE DESMARAIS, CATHERINE GOEHRING, PHILIPPE de MOERLOOSE, ALFREDO MORABIA, PIERRE-FRANÇOIS UNGER, DANIEL SLOSMAN, ALAIN JUNOD, HENRI BOUNAMEAUX
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The plasma level of D-dimer, a fibrin degradation product (FDP), is nearly always increased in the presence of acute pulmonary embolism (PE). Hence, a normal D-dimer level (below a cutoff value of 500 μ g/L by enzyme-linked immunosorbent assay [ELISA]) may allow the exclusion of PE. To assess the negative predictive value of a D-dimer concentration below 500 μ g/L in outpatients with suspected PE, and the safety of withholding anticoagulant treatment from such patients, we performed D-dimer assays, lower limb venous compression ultrasonography, and lung scans in 671 consecutive outpatients presenting in the Emergency Center of the Geneva University Hospital with suspected PE. Pulmonary angiography was reserved for patients with an inconclusive noninvasive workup. Patients with a normal D-dimer concentration were discharged without anticoagulant treatment and followed for 3 mo. The prevalence of PE was 29%, and D-dimer (using a cutoff of 500 μ g/L) had a diagnostic sensitivity for PE of 99.5%. Overall diagnostic specificity of D-dimer was 41%, but it was lower among older patients. Of the 198 patients with a D-dimer concentration below the cutoff value, 196 were free of PE, one had a PE, and one had incomplete information because of loss to follow-up. Thus, the negative predictive value of D-dimer concentration fell between 197 of 198 and 196 of 198 cases of PE (99% [95% CI: 96.4 to 99.9]). Using a cutoff value of 4,000 μ g/L, the overall specificity of D-dimer concentration for PE was 93.1%. In conclusion, a plasma D-dimer concentration below 500 μ g/L allows the exclusion of PE in 29% of outpatients suspected of having PE. Withholding anticoagulation from such patients is associated with a conservative 1% risk of thromboembolic events during follow-up.
STAT3 Is Necessary for Proliferation and Survival in Colon Cancer–Initiating Cells
Authors: Li Lin, Aiguo Liu, Zhengang Peng, Huey-Jen Lin, Pui-Kai Li, Chenglong Li, Jiayuh Lin
Journal: Cancer Research (2011)

STAT3 is constitutively activated in colon cancer but its contributions in cancer-initiating cells have not been explored. In this study, we characterized STAT3 in aldehyde dehydrogenase (ALDH)-positive (ALDH(+)) and CD133-positive (CD133(+)) subpopulations of human colon tumor cells that exhibited more potent tumor-initiating ability than ALDH(-)/CD133(-) cells in tumor xenograft assays in mice. We found that ALDH(+)/CD133(+) cells expressed higher levels of the active phosphorylated form of STAT3 than either ALDH(-)/CD133(-) or unfractionated colon cancer cells. STAT3 inhibition by RNA interference-mediated knockdown or small-molecule inhibitors LLL12 or Stattic blocked downstream target gene expression, cell viability, and tumorsphere-forming capacity in cancer-initiating cells. Similarly, treatment of mouse tumor xenografts with STAT3 short hairpin RNA (shRNA), interleukin 6 shRNA, or LLL12 inhibited tumor growth. Our results establish that STAT3 is constitutively activated in colon cancer-initiating cells and that these cells are sensitive to STAT3 inhibition. These findings establish a powerful rationale to develop STAT3 inhibitory strategies for treating advanced colorectal cancers.
Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies
Authors: T. Moore, E. M. Hennessy, J. Myles, S. J. Johnson, E. S. Draper, K. L. Costeloe, N. Marlow
Journal: BMJ (2012)

<b>Objective</b> To determine outcomes at age 3 years in babies born before 27 completed weeks’ gestation in 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks’ gestation. <b>Design</b> Prospective national cohort studies, EPICure and EPICure 2. <b>Setting</b> Hospital and home based evaluations, England. <b>Participants</b> 1031 surviving babies born in 2006 before 27 completed weeks’ gestation. Outcomes for 584 babies born at 22-25 weeks’ gestation were compared with those of 260 surviving babies of the same gestational age born in 1995. <b>Main outcome measures</b> Survival to age 3 years, impairment (2008 consensus definitions), and developmental scores. Multiple imputation was used to account for the high proportion of missing data in the 2006 cohort. <b>Results</b> Of the 576 babies evaluated after birth in 2006, 13.4% (n=77) were categorised as having severe impairment and 11.8% (n=68) moderate impairment. The prevalence of neurodevelopmental impairment was significantly associated with length of gestation, with greater impairment as gestational age decreased: 45% at 22-23 weeks, 30% at 24 weeks, 25% at 25 weeks, and 20% at 26 weeks (P&lt;0.001). Cerebral palsy was present in 83 (14%) survivors. Mean developmental quotients were lower than those of the general population (normal values 100 (SD 15)) and showed a direct relation with gestational age: 80 (SD 21) at 22-23 weeks, 87 (19) at 24 weeks, 88 (19) at 25 weeks, and 91 (18) at 26 weeks. These results did not differ significantly after imputation. Comparing imputed outcomes between the 2006 and 1995 cohorts, the proportion of survivors born between 22 and 25 weeks’ gestation with severe disability, using 1995 definitions, was 18% (95% confidence interval 14% to 24%) in 1995 and 19% (14% to 23%) in 2006. Fewer survivors had shunted hydrocephalus or seizures. Survival of babies admitted for neonatal care increased from 39% (35% to 43%) in 1995 to 52% (49% to 55%) in 2006, an increase of 13% (8% to 18%), and survival without disability increased from 23% (20% to 26%) in 1995 to 34% (31% to 37%) in 2006, an increase of 11% (6% to 16%). <b>Conclusion</b> Survival and impairment in early childhood are both closely related to gestational age for babies born at less than 27 weeks’ gestation. Using multiple imputation to account for the high proportion of missing values, a higher proportion of babies admitted for neonatal care now survive without disability, particularly those born at gestational ages 24 and 25 weeks.
Molecular Precision Chemotherapy: Overcoming Resistance to Targeted Therapies?
Authors: Stefan Burdach
Journal: Clinical Cancer Research (2014)

Cytotoxic drugs may have specific effects on oncogenes and their downstream targets. Increase of cancer cell sensitivity due to repression of an oncogene downstream target can be specifically addressed by combined precision chemotherapy, increasing the therapeutic index of chemotherapy and overcoming resistance to highly selective targeted therapies.
Lymphomas can develop from B cells chronically helped by idiotype-specific T cells
Authors: Michael M. Zangani, Marianne Frøyland, Gao Yue Qiu, Leonardo A. Meza-Zepeda, Jeffery L. Kutok, Keith M. Thompson, Ludvig A. Munthe, Bjarne Bogen
Journal: The Journal of Experimental Medicine (2007)

B cell lymphomas have been associated with chronic infections and autoimmunity. However, most lymphomas develop in the absence of any known chronic antigenic stimulation. B cells process their highly diversified endogenous immunoglobulin and present clonally unique variable-region idiotypic (Id) peptides on their major histocompatibility complex (MHC) class II molecules to Id-specific T cells. We show that B cells chronically helped by Id-specific Th2 cells developed into large B cell lymphomas with cytogenetic DNA aberrations. The lymphomas expressed high amounts of Id, MHC class II, CD80/86, and CD40 and bidirectionally collaborated with Th2 cells. Thus, MHC class II–presented Id peptides may represent a chronic self-antigenic stimulus for T cell–dependent lymphomagenesis. Eventually, B lymphomas grew independent of T cells. Thus, T cells do not only eliminate cancers as currently believed. In fact, Id-specific Th2 cells can induce B lymphomas.
Challenge model for Helicobacter pylori infection in human volunteers
Authors: D Y Graham
Journal: Gut (2004)

<b>Background:</b> A reliable challenge model is needed to evaluate <i>Helicobacter pylori</i> vaccine candidates. <b>Methods:</b> A <i>cag</i> pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of <i>H pylori</i> obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers. Volunteers received 40 mg of famotidine at bedtime and 10<sup>4</sup>–10<sup>10</sup> cfu of <i>H pylori</i> in beef broth the next morning. Infection was confirmed by <sup>13</sup>C urea breath test (<sup>13</sup>C-UBT), culture, and histology. Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology. <b>Results:</b> Twenty subjects (nine women and 11 men; aged 23–33 years) received a <i>H pylori</i> challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained &gt;10<sup>3</sup> viable/ml <i>H pylori</i>. By two weeks post challenge gastric histology showed typical chronic <i>H pylori</i> gastritis with intense acute and chronic inflammation. The density of <i>H pylori</i> (as assessed by cfu/biopsy) was similarly independent of the challenge dose. A minimal infectious dose was not found. Gastric mucosal interleukin 8 levels increased more than 20-fold by two weeks after the challenge. <b>Conclusion:</b> Challenge reliably resulted in <i>H pylori</i> infection. Infection was associated with typical <i>H pylori</i> gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the <i>cag</i> pathogenicity island. Experimental <i>H pylori</i> infection is one of the viable approaches to evaluate vaccine candidates.
Fluorescence endoscopy for the detection of low and high grade dysplasia in ulcerative colitis using systemic or local 5-aminolaevulinic acid sensitisation
Authors: H Messmann
Journal: Gut (2003)

<b>Background and aims:</b> Longstanding ulcerative colitis (UC), especially in the presence of epithelial dysplasia, is associated with an increased risk of developing cancer. As dysplasia is not visible during routine endoscopy, at least 40–50 random biopsies in four quadrants every 10 cm are recommended. Fluorescence endoscopy after sensitisation with 5-aminolaevulinic acid (5-ALA) was assessed for the detection of dysplasia in ulcerative colitis by taking optical guided biopsies. 5-ALA is converted intracellularly into the sensitiser protoporphyrin IX which accumulates selectively in neoplastic tissue allowing the detection of dysplasia by typical red fluorescence after illumination with blue light. <b>Methods:</b> In 37 patients with UC, 54 examinations were performed with fluorescence endoscopy after oral (20 mg/kg) or local (either with an enema or by spraying the mucosa with a catheter) sensitisation with 5-ALA. A total of 481 biopsies of red fluorescent (n=218) and non-fluorescent (n=263) areas of the colonic mucosa were taken. <b>Results:</b> Forty two biopsies in 12 patients revealed either low grade (n=40) or high grade (n=2) dysplasia. Sensitivity of fluorescence for dysplastic lesions was excellent and ranged from 87% (95% confidence interval (CI) 0.73–1.00) to 100% (95% CI 1.00–1.00) after local sensitisation, in contrast with only 43% (95% CI 0.17–0.69) after systemic administration. Specificity did not differ for both forms of local sensitisation (enema 51% (95% CI 0.44–0.57) and spray catheter 62% (95% CI 0.51–0.73)); after systemic sensitisation specificity was 73% (95% CI 0.69–0.83). Negative predictive values of non-fluorescent mucosa for exclusion of dysplasia were very high; 89% after systemic sensitisation and 98–100% after local sensitisation. Positive predictive values were 13% and 14% after local sensitisation with enema and spray catheter, and 21% after oral sensitisation with 20 mg/kg ALA. The overall number of biopsies per examination was less than five from fluorescent positive areas. <b>Conclusion:</b> Fluorescence endoscopy after 5-ALA sensitisation is a possible tool to visualise dysplastic lesions in ulcerative colitis using 5-ALA sensitisation. Local sensitisation is a promising alternative approach compared with systemic administration of 5-ALA. A randomised controlled study is now indicated to compare the efficacy of endoscopic fluorescence detection with the standard technique of four quadrant random biopsies.
Structural and Evolutionary Analyses of the Ty3/gypsy Group of LTR Retrotransposons in the Genome of Anopheles gambiae
Authors: Jose Manuel C. Tubío, Horacio Naveira, Javier Costas
Journal: Molecular Biology and Evolution (2004)

The recent availability of the genome of Anopheles gambiae offers an extraordinary opportunity for comparative studies of the diversity of transposable elements (TEs) and their evolutionary dynamics between two related species, taking advantage of the existing information from Drosophila melanogaster. To this goal, we screened the genome of A. gambiae for elements belonging to the Ty3/gypsy group of long-terminal repeat (LTR) retrotransposons. The A. gambiae genome displays a rich diversity of LTR retrotransposons, clearly greater than D. melanogaster. We have characterized in detail 63 families, belonging to five of the nine main lineages of the Ty3/gypsy group. The Mag lineage is the most diverse and abundant, with more than 30 families. In sharp contrast with this finding, a single family belonging to this lineage has been found in D. melanogaster, here reported for the first time in the literature, most probably consisting of old inactive elements. The CsRn1 lineage is also abundant in A. gambiae but almost absent from D. melanogaster. Conversely, the Osvaldo lineage has been detected in Drosophila but not in Anopheles. Comparison of structural characteristics of different families led to the identification of several lineage-specific features such as the primer-binding site (PBS), the gag-pol translational recoding signal (TRS), which is extraordinarily diverse within the Ty3/gypsy retrotransposons of A. gambiae, or the presence/absence of specific amino acid motifs. Interestingly, some of these characteristics, although in general well conserved within lineages, may have evolved independently in particular branches of the phylogenetic tree. We also show evidence of recent activity for around 75% of the families. Nevertheless, almost all families contain a high proportion of degenerate members and solitary LTRs (solo LTRs), indicative of a lower turnover rate of retrotransposons belonging to the Ty3/gypsy group in A. gambiae than in D. melanogaster. Finally, we have detected significant overrepresentations of insertions on the X chromosome versus autosomes and of putatively active insertions on euchromatin versus heterochromatin.
Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors
Authors: M. Llanos Casanova, Cristina Blázquez, Jesús Martínez-Palacio, Concepción Villanueva, M. Jesús Fernández-Aceñero, John W. Huffman, José L. Jorcano, Manuel Guzmán
Journal: Journal of Clinical Investigation (2003)

Nonmelanoma skin cancer is one of the most common malignancies in humans. Different therapeutic strategies for the treatment of these tumors are currently being investigated. Given the growth-inhibiting effects of cannabinoids on gliomas and the wide tissue distribution of the two subtypes of cannabinoid receptors (CB1 and CB2), we studied the potential utility of these compounds in anti–skin tumor therapy. Here we show that the CB1 and the CB2 receptor are expressed in normal skin and skin tumors of mice and humans. In cell culture experiments pharmacological activation of cannabinoid receptors induced the apoptotic death of tumorigenic epidermal cells, whereas the viability of nontransformed epidermal cells remained unaffected. Local administration of the mixed CB1/CB2 agonist WIN-55,212-2 or the selective CB2 agonist JWH-133 induced a considerable growth inhibition of malignant tumors generated by inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors showed an increased number of apoptotic cells. This was accompanied by impairment of tumor vascularization, as determined by altered blood vessel morphology and decreased expression of proangiogenic factors (VEGF, placental growth factor, and angiopoietin 2). Abrogation of EGF-R function was also observed in cannabinoid-treated tumors. These results support a new therapeutic approach for the treatment of skin tumors.
Trends in consultant clinical activity and the effect of the 2003 contract change: retrospective analysis of secondary data
Authors: Karen Bloor, Nick Freemantle, Alan Maynard
Journal: Journal of the Royal Society of Medicine (2012)

To explore trends in the clinical activity of hospital specialists in English National Health Service (NHS) hospitals, and test the effect of contract reform.Retrospective secondary analysis of hospital episode statistics, describing trends and testing for a contract effect using multilevel interrupted time series analysis.Ten surgical and medical specialties in English NHS hospitals from 1999 to 2009. Participants Hospital consultants on full time or maximum part-time English NHS hospitals.A new contract offered to NHS consultants in October 2003, with higher pay alongside job planning and appraisal.Inpatient finished consultant episodes (FCEs) per consultant per month, with and without accounting for case-mix differences.In most specialties there was a statistically significant downward trend in FCEs per consultant per month. On average in the surgical specialties, FCEs reduced by 0.14 per month (95% CI -0.16 to -0.11) and in medicine there was a smaller reduction of 0.08 FCEs per month (95% CI -0.1 to -0.06). NHS patients symptoms have increased in severity over time, and the downward trend is reduced after case-mix-adjustment, and reversed in general and geriatric medicine. The effect of the contract on clinical activity was minimal. In five specialties there was no statistically significant effect, but in five specialties there was a statistically significant negative effect.Consultant clinical activity, as measured by FCEs per month, has shown a general downward trend from 1999 to 2009. The consultant contract was not associated with an increase in consultant clinical activity rates.