tbuckley/cabot-search huggingface dataset:
Global implementation of WHO's multimodal strategy for improvement of hand hygiene: a quasi-experimental study
Authors: Benedetta Allegranzi, Angèle Gayet-Ageron, Nizam Damani, Loséni Bengaly, Mary-Louise McLaws, Maria-Luisa Moro, Ziad Memish, Orlando Urroz, Hervé Richet, Julie Storr, Liam Donaldson, Didier Pittet
Journal: The Lancet Infectious Diseases (2013)

BackgroundHealth-care-associated infections are a major threat to patient safety worldwide. Transmission is mainly via the hands of health-care workers, but compliance with recommendations is usually low and effective improvement strategies are needed. We assessed the effect of WHO's strategy for improvement of hand hygiene in five countries.MethodsWe did a quasi-experimental study between December, 2006, and December, 2008, at six pilot sites (55 departments in 43 hospitals) in Costa Rica, Italy, Mali, Pakistan, and Saudi Arabia. A step-wise approach in four 3–6 month phases was used to implement WHO's strategy and we assessed the hand-hygiene compliance of health-care workers and their knowledge, by questionnaire, of microbial transmission and hand-hygiene principles. We expressed compliance as the proportion of predefined opportunities met by hand-hygiene actions (ie, handwashing or hand rubbing). We assessed long-term sustainability of core strategy activities in April, 2010.FindingsWe noted 21 884 hand-hygiene opportunities during 1423 sessions before the intervention and 23 746 opportunities during 1784 sessions after. Overall compliance increased from 51·0% before the intervention (95% CI 45·1–56·9) to 67·2% after (61·8–72·2). Compliance was independently associated with gross national income per head, with a greater effect of the intervention in low-income and middle-income countries (odds ratio [OR] 4·67, 95% CI 3·16–6·89; p<0·0001) than in high-income countries (2·19, 2·03–2·37; p<0·0001). Implementation had a major effect on compliance of health-care workers across all sites after adjustment for main confounders (OR 2·15, 1·99–2·32). Health-care-workers' knowledge improved at all sites with an increase in the average score from 18·7 (95% CI 17·8–19·7) to 24·7 (23·7–25·6) after educational sessions. 2 years after the intervention, all sites reported ongoing hand-hygiene activities with sustained or further improvement, including national scale-up.InterpretationImplementation of WHO's hand-hygiene strategy is feasible and sustainable across a range of settings in different countries and leads to significant compliance and knowledge improvement in health-care workers, supporting recommendation for use worldwide.FundingWHO, University of Geneva Hospitals, the Swiss National Science Foundation, Swiss Society of Public Health Administration and Hospital Pharmacists.
HIV Prevalence, Risk, and Partner Serodiscordance Among Pregnant Women in Bangkok
Authors: Wimol Siriwasin
Journal: JAMA (1998)

Context.—Most prior studies of the human immunodeficiency virus (HIV) epidemic in Thailand have focused on commercial sex encounters; however, because the epidemic increasingly concerns stable heterosexual relationships, determining risk factors for this form of transmission is warranted.Objectives.—To determine temporal trends in HIV prevalence, risk factors for HIV seropositivity, and rates of partner serodiscordance for pregnant women in Bangkok, Thailand.Design.—Retrospective review of hospital antenatal clinic HIV test results from 1991 through 1996. Baseline demographic and behavioral risk factors for HIV were assessed for subjects enrolled from November 1992 through March 1994.Setting.—Two Bangkok hospitals with routine antenatal clinic HIV counseling and testing.Participants.—The HIV-positive pregnant women enrolled in a perinatal HIV transmission study and their partners and HIV-negative pregnant controls.Results.—From 1991 through 1996, antenatal clinic HIV seroprevalence increased from 1.0% to 2.3%. On multivariate analysis of data from 342 HIV-positive and 344 HIV-negative pregnant women, more than 1 lifetime sex partner, history of a sexually transmitted disease, and a high-risk sex partner were the most important factors for seropositivity (all P&lt;.001). Twenty-six percent of partners of HIV-positive women were HIV negative. Women reporting more than 1 lifetime sex partner were more likely to have an HIV-negative partner than women reporting only 1 (45% vs 8%; relative risk, 5.5; 95% confidence interval, 3.2-9.5; P&lt;.001); women reporting no high-risk behaviors were less likely to have an HIV-negative partner (10% vs 44%; relative risk, 0.2; 95% confidence interval, 0.1-0.4; P &lt;.001).Conclusions.—Prevalence of HIV in pregnant women has increased steadily in Bangkok from 1991 through 1996. Sex with current partners was the only identified risk exposure for about half (52%) of the HIV-positive women. Although few HIV-positive pregnant women reported high-risk behaviors, more than 1 lifetime partner and a partner with high-risk behavior were strong risk factors for seropositivity. Together with the unexpected finding that one fourth of partners of seropositive pregnant women were seronegative, these data emphasize that women in the general population are at risk for HIV because of the risk behavior of both current and previous partners.
Functional impairment in fibrosing alveolitis: relationship to reversible disease on thin section computed tomography
Authors: AU Wells, MB Rubens, RM du Bois, DM Hansell
Journal: European Respiratory Journal (1997)

Thin-section computed tomography (CT) provides a reproducible method of quantifying global disease extent and can also discriminate between fibrotic disease, with predominance of reticular abnormalities, and reversible inflammatory cell infiltration, shown as ground-glass attenuation. The aim of this study was to determine whether functional impairment varied according to the presence of ground-glass attenuation on CT, independently of extent of disease on CT, demographic factors, smoking history, therapeutic status, and the type of fibrosing alveolitis (lone cryptogenic fibrosing alveolitis (CFA) versus fibrosing alveolitis associated with systemic sclerosis (FASSc)). Patients with concurrent emphysema on CT (n = 16) and FASSc patients with end-stage pulmonary hypertension (n = 5) were excluded. One hundred and eleven patients were studied (CFA, n = 54; FASSc, n = 57). The severity of functional impairment did not vary independently with the presence of predominant ground-glass attenuation, mixed appearance and predominant reticulation on CT. In 34 treated patients undergoing serial CT scanning, the severity of functional impairment did not differ independently between patients with and without regression of ground-glass attenuation at follow-up. We conclude that the severity of functional impairment does not discriminate between inflammatory and fibrotic disease in fibrosing alveolitis, as judged by initial and serial computed tomographic scanning, after adjustment for the morphological extent of disease on computed tomography.
Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells
Authors: Cindy G. Leung, Yanfei Xu, Bretton Mularski, Hui Liu, Sandeep Gurbuxani, John D. Crispino
Journal: The Journal of Experimental Medicine (2007)

Survivin, which is the smallest member of the inhibitor of apoptosis protein (IAP) family, is a chromosomal passenger protein that mediates the spindle assembly checkpoint and cytokinesis, and also functions as an inhibitor of apoptosis. Frequently overexpressed in human cancers and not expressed in most adult tissues, survivin has been proposed as an attractive target for anticancer therapies and, in some cases, has even been touted as a cancer-specific gene. Survivin is, however, expressed in proliferating adult cells, including human hematopoietic stem cells, T-lymphocytes, and erythroid cells throughout their maturation. Therefore, it is unclear how survivin-targeted anticancer therapies would impact steady-state blood development. To address this question, we used a conditional gene-targeting strategy and abolished survivin expression from the hematopoietic compartment of mice. We show that inducible deletion of survivin leads to ablation of the bone marrow, with widespread loss of hematopoietic progenitors and rapid mortality. Surprisingly, heterozygous deletion of survivin causes defects in erythropoiesis in a subset of the animals, with a dramatic reduction in enucleated erythrocytes and the presence of immature megaloblastic erythroblasts. Our studies demonstrate that survivin is essential for steady-state hematopoiesis and survival of the adult, and further, that a high level of survivin expression is critical for proper erythroid differentiation.
Meiotic Recombination Dramatically Decreased in Thelytokous Queens of the Little Fire Ant and Their Sexually Produced Workers
Authors: O. Rey, A. Loiseau, B. Facon, J. Foucaud, J. Orivel, J.-M. Cornuet, S. Robert, G. Dobigny, J. H. C. Delabie, C. D. S. F. Mariano, A. Estoup
Journal: Molecular Biology and Evolution (2011)

The little fire ant, Wasmannia auropunctata, displays a peculiar breeding system polymorphism. Classical haplo-diploid sexual reproduction between reproductive individuals occurs in some populations, whereas, in others, queens and males reproduce clonally. Workers are produced sexually and are sterile in both clonal and sexual populations. The evolutionary fate of the clonal lineages depends strongly on the underlying mechanisms allowing reproductive individuals to transmit their genomes to subsequent generations. We used several queen-offspring data sets to estimate the rate of transition from heterozygosity to homozygosity associated with recombination events at 33 microsatellite loci in thelytokous parthenogenetic queen lineages and compared these rates with theoretical expectations under various parthenogenesis mechanisms. We then used sexually produced worker families to define linkage groups for these 33 loci and to compare meiotic recombination rates in sexual and parthenogenetic queens. Our results demonstrate that queens from clonal populations reproduce by automictic parthenogenesis with central fusion. These same parthenogenetic queens produce normally segregating meiotic oocytes for workers, which display much lower rates of recombination (by a factor of 45) than workers produced by sexual queens. These low recombination rates also concern the parthenogenetic production of queen offspring, as indicated by the very low rates of transition from heterozygosity to homozygosity observed (from 0% to 2.8%). We suggest that the combination of automixis with central fusion and a major decrease in recombination rates allows clonal queens to benefit from thelytoky while avoiding the potential inbreeding depression resulting from the loss of heterozygosity during automixis. In sterile workers, the strong decrease of recombination rates may also facilitate the conservation over time of some coadapted allelic interactions within chromosomes that might confer an adaptive advantage in habitats disturbed by human activity, where clonal populations of W. auropunctata are mostly found.
Collaborative Care Versus Screening and Follow-up for Patients With Diabetes and Depressive Symptoms: Results of a Primary Care–Based Comparative Effectiveness Trial
Authors: Jeffrey A. Johnson, Fatima Al Sayah, Lisa Wozniak, Sandra Rees, Allison Soprovich, Weiyu Qiu, Constance L. Chik, Pierre Chue, Peter Florence, Jennifer Jacquier, Pauline Lysak, Andrea Opgenorth, Wayne Katon, Sumit R. Majumdar
Journal: Diabetes Care (2014)

OBJECTIVE Depressive symptoms are common and, when coexisting with diabetes, worsen outcomes and increase health care costs. We evaluated a nurse case-manager–based collaborative primary care team model to improve depressive symptoms in diabetic patients. RESEARCH DESIGN AND METHODS We conducted a controlled implementation trial in four nonmetropolitan primary care networks. Eligible patients had type 2 diabetes and screened positive for depressive symptoms, based on a Patient Health Questionnaire (PHQ) score of ≥10. Patients were allocated using an “on-off” monthly time series. Intervention consisted of case-managers working 1:1 with patients to deliver individualized care. The main outcome was improvement in PHQ scores at 12 months. A concurrent cohort of 71 comparable patients was used as nonscreened usual care control subjects. RESULTS Of 1,924 patients screened, 476 (25%) had a PHQ score &amp;gt;10. Of these, 95 were allocated to intervention and 62 to active control. There were no baseline differences between groups: mean age was 57.8 years, 55% were women, and the mean PHQ score was 14.5 (SD 3.7). Intervention patients had greater 12-month improvements in PHQ (7.3 [SD 5.6]) compared with active-control subjects (5.2 [SD 5.7], P = 0.015). Recovery of depressive symptoms (i.e., PHQ reduced by 50%) was greater among intervention patients (61% vs. 44%, P = 0.03). Compared with trial patients, nonscreened control subjects had significantly less improvement at 12 months in the PHQ score (3.2 [SD 4.9]) and lower rates of recovery (24%, P &amp;lt; 0.05 for both). CONCLUSIONS In patients with type 2 diabetes who screened positive for depressive symptoms, collaborative care improved depressive symptoms, but physician notification and follow-up was also a clinically effective initial strategy compared with usual care.
Screening for Depression in Mothers Bringing Their Offspring for Evaluation or Treatment of Depression
Authors: Tova Ferro, Helen Verdeli, Florence Pierre, Myrna M. Weissman
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Numerous studies have shown that the highest risk for first onset of depression occurs in women of childbearing years and that there is a strong association between lifetime rates of depressive disorders in mothers and their offspring. This association is found regardless of whether the mother or child is the targeted patient. However, little is known about rates of current depression in mothers who bring their offspring to outpatient clinics for evaluation and/or treatment of depression. This information might be useful in developing intervention strategies. METHOD: One hundred seventeen mothers bringing their offspring for evaluation or treatment for depression were screened with the Patient Problem Questionnaire to determine current symptoms of depression, anxiety disorders, and substance abuse as well as current psychiatric treatment. RESULTS: Thirty-six (31%) of the mothers screened positive on the Patient Problem Questionnaire for a current psychiatric disorder. Sixteen (14%) screened positive for current major depression, 20 (17%) for panic disorder, 20 (17%) for generalized anxiety disorder, two (2%) for alcohol abuse, and one (1%) for drug abuse. In addition, 50 (43%) of the mothers had psychiatric symptoms that did not meet the diagnostic threshold for any of the above disorders. Twenty-six (22%) of mothers expressed suicidal ideation or intent. Only five (31%) of the 16 mothers diagnosed with major depression were currently receiving any psychiatric treatment. CONCLUSIONS: A substantial number of mothers bringing their offspring for evaluation or treatment of depression were themselves currently depressed and untreated. The treatment of depressed mothers may help both the mothers and their depressed offspring.
Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne
Authors: John J. DiGiovanna, Craig B. Langman, Eduardo H. Tschen, Terry Jones, Alan Menter, Nicholas J. Lowe, Lawrence Eichenfield, Adelaide A. Hebert, David Pariser, Ronald P. Savin, Stacy R. Smith, Michael Jarratt, David Rodriguez, Dan K. Chalker, Steven Kempers, Mark Ling, Elyse S. Rafal, Sabra Sullivan, Sewon Kang, Leena P. Shah, Emily Wu, Julie Newhouse, Jonathan Pak, Douglas R. Eberhardt, Graeme F. Bryce, John A. McLane, Michael Ondovik, Catherine Chin, Ko-Chin Khoo, Phoebe Rich
Journal: Journal of the American Academy of Dermatology (2004)
Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial
Authors: David Malka, Pascale Cervera, Stéphanie Foulon, Tanja Trarbach, Christelle de la Fouchardière, Eveline Boucher, Laetitia Fartoux, Sandrine Faivre, Jean-Frédéric Blanc, Frédéric Viret, Eric Assenat, Thomas Seufferlein, Thomas Herrmann, Julien Grenier, Pascal Hammel, Matthias Dollinger, Thierry André, Philipp Hahn, Volker Heinemann, Vanessa Rousseau, Michel Ducreux, Jean-Pierre Pignon, Dominique Wendum, Olivier Rosmorduc, Tim F Greten
Journal: The Lancet Oncology (2014)
Germ Cell Cancer and Multiple Relapses: Toxicity and Survival
Authors: Jakob Lauritsen, Maria G.G. Kier, Mette S. Mortensen, Mikkel Bandak, Ramneek Gupta, Niels V. Holm, Mads Agerbaek, Gedske Daugaard
Journal: Journal of Clinical Oncology (2015)

Purpose A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment for disseminated disease. Methods From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse and death were identified and compared with the International Prognostic Factors Study Group (IPFSG) classification. Results In total, 268 patients received more than one line of treatment for disseminated GCC. Approximately half of patients (n = 136) died as a result of GCC. The 132 remaining patients, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal impairment (HR, 8.3; 95% CI, 3.0 to 23.2), neurologic disorders (HR, 6.3; 95% CI, 3.1 to 12.6), and death as a result of other causes (HR, 2.6; 95% CI, 1.6 to 4.2). In large part, the IPFSG classification was confirmed in our population; however, we could not confirm the primary site and the level of human chorionic gonadotropin as independent factors. We identified increasing age as a possible new prognostic factor for treatment failure after second-line treatment (HR, 1.2 per 10 years; 95% CI, 1.2 to 15). Conclusion Patients with GCC who survive after more than one line of treatment for disseminated disease have a highly increased risk of late toxicity and death as a result of causes other than GCC. Therefore, they should be candidates for life-long follow-up. The IPFSG classification was confirmed in this unselected population.
Activin Type II Receptor Restoration in <b> <i>ACVR2</i> </b>-Deficient Colon Cancer Cells Induces Transforming Growth Factor-β Response Pathway Genes
Authors: Elena Deacu, Yuriko Mori, Fumiaki Sato, Jing Yin, Andreea Olaru, Anca Sterian, Yan Xu, Suna Wang, Karsten Schulmann, Agnes Berki, Takatsugu Kan, John M. Abraham, Stephen J. Meltzer
Journal: Cancer Research (2004)

Abstract The activin type II receptor (ACVR2) gene is a putative tumor suppressor gene that is frequently mutated in microsatellite-unstable colon cancers (MSI-H colon cancers). ACVR2 is a member of the transforming growth factor (TGF)-β type II receptor (TGFBR2) family and controls cell growth and differentiation. SMAD proteins are major intracellular effectors shared by ACVR2 and TGFBR2 signaling; however, additional shared effector mechanisms remain to be explored. To discover novel mechanisms transmitting the ACVR2 signal, we restored ACVR2 function by transfecting wild-type ACVR2 (wt-ACVR2) into a MSI-H colon cancer cell line carrying an ACVR2 frameshift mutation. The effect of ACVR2 restoration on cell growth, SMAD phosphorylation, and global molecular phenotype was then evaluated. Decreased cell growth was observed in wt-ACVR2 transfectants relative to ACVR2-deficient vector-transfected controls. Western blotting revealed higher expression of phosphorylated SMAD2 in wt-ACVR2 transfectants versus controls, suggesting cells deficient in ACVR2 had impaired SMAD signaling. Microarray-based differential expression analysis revealed substantial ACVR2-induced overexpression of genes implicated in the control of cell growth and tumorigenesis, including the activator protein (AP)-1 complex genes JUND, JUN, and FOSB, as well as the small GTPase signal transduction family members, RHOB, ARHE, and ARHGDIA. Overexpression of these genes is shared with TGFBR2 activation. This observed similarity between the activin and TGF-β signaling systems suggests that activin may serve as an alternative activator of TGF-β effectors, including SMADs, and that frameshift mutation of ACVR2 may contribute to MSI-H colon tumorigenesis via disruption of alternate TGF-β effector pathways.
Assessing the residual antibacterial activity of clinical materials disinfected with glutaraldehyde, o-phthalaldehyde, hydrogen peroxide or 2-bromo-2-nitro-1,3-propanediol by means of a bacterial toxicity assay
Authors: C. Lerones, A. Mariscal, M. Carnero, A. García-Rodríguez, J. Fernández-Crehuet
Journal: Clinical Microbiology and Infection (2004)
The Fetal Mouse Is a Sensitive Genotoxicity Model That Exposes Lentiviral-associated Mutagenesis Resulting in Liver Oncogenesis
Authors: Ali Nowrouzi, Wing T Cheung, Tingting Li, Xuegong Zhang, Anne Arens, Anna Paruzynski, Simon N Waddington, Emma Osejindu, Safia Reja, Christof von Kalle, Yoahe Wang, Faisal Al-Allaf, Lisa Gregory, Matthew Themis, Maxine Holder, Niraja Dighe, Alaine Ruthe, Suzanne MK Buckley, Brian Bigger, Eugenio Montini, Adrian J Thrasher, Robert Andrews, Terry P Roberts, Robert F Newbold, Charles Coutelle, Manfred Schmidt, Mike Themis
Journal: Molecular Therapy (2013)

Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis.