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Search Results: 1 - 10 of 144461 matches for " F Mulcahy "
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HIV in women
Mulcahy F
Journal of the International AIDS Society , 2012, DOI: 10.7448/ias.15.6.18075
Abstract: Globally over 50% of HIV-infected individuals are women. With the widespread use of HAART, we can expect women to have mortality rates approaching normal. Indeed, studies have shown that women may expect a slower disease progression than men following seroconversion; furthermore, it appears that female who injects drugs can live longer than their male counterparts. However, other studies from cohort analysis have reported worse outcomes in women. In essence, many studies are consistently underpowered to adequately address these questions. The proportion of women in clinical trials remains at 20 to 30%, with pregnancy potential being a major exclusion factor. Hence, many questions remain unanswered. Recent data suggest women are more likely to present late with a new AIDS diagnosis. Why this should be the case is not well understood. In addition, HIV-positive women should have the same access to reproduction health as their negative counterparts, but unfortunately many inequalities remain. Advise on contraception and fertility services are very variable across both the developed and developing world. Data are limited on the most appropriate use of contraceptives in the presence of HAART, the possible drug interactions and possible increased risk of HIV transmission. There remain significant differences in guidelines regarding prevention of mother-to-child transmission (MTCT) across Europe, and implications of stopping and starting HAART for MTCT have not been adequately addressed. The mode of timing of delivery, and the effect of length of time of ruptured membranes on this decision is also contentious. Further issues relate to the desire for HIV-positive women to breastfeed in the setting of HIV viral suppression, where some guidelines now support women in this situation and others categorically would inform child protection authorities. Finally as women age it is more difficult to separate the effect of the menopause and its symptoms from the increased HIV-related cardiovascular and bone fracture risk. This presentation aims to discuss key issues which conflicting or inadequate data fail to resolve.
Bevacizumab in the therapy for refractory metastatic colorectal cancer
Mary F Mulcahy
Biologics: Targets and Therapy , 2008,
Abstract: Mary F MulcahyNorthwestern University, Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago IL, USAAbstract: Colorectal cancer is the second most common cause of cancer related deaths in the United States. Recent developments have led to prolonged survival with the use of sequential lines of chemotherapy agents. The addition of bevacizumab to active chemotherapy has further improved survival when used in the first and second lines of therapy for metastatic colorectal cancer. Evidence supporting the continued use of bevacizumab throughout lines of therapy is accumulating. Clinical trials are underway in which bevacizumab is continued beyond the first line of a chemotherapy and bevacizumab combination regimen. The mechanism by which colorectal cancer may become resistant to bevacizumab is poorly understood. Molecular and biochemical correlates which may identify bevacizumab resistance are an important component in the design of these clinical trials.Keywords: colorectal cancer, bevacizumab, refractory
Pregnant women with HIV on ART in Europe: how many achieve the aim of undetectable viral load at term and are able to deliver vaginally?
Aebi-Popp K,Mulcahy F,Glass T,Rudin C
Journal of the International AIDS Society , 2012, DOI: 10.7448/ias.15.6.18141
Abstract: Purpose of the study Mother-to-child transmission rates in Europe are below 1% in HIV-infected women on successful combined antiretroviral therapy (cART) irrespective of mode of delivery. Consequently, most national guidelines updated between 2001 and 2009 recommended vaginal deliveries for women with undetectable or very low viral load (VL). The aim of this study was to explore the impact of these new guidelines on the rates of vaginal deliveries following complete viral suppression on cART. Methods A pooled analysis of data on HIV-1-positive women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study with a live birth between 2000 and 2010 was carried out. Deliveries were classified as occurring pre- or post-publication of national guidelines recommending vaginal delivery in women with low/ undetectable VL for each country. Summary of results Overall, 2527 mothers, 2848 deliveries and 2903 births were included from 10 countries. The women were mostly Caucasian (44%) or black (47%) and had a median age of 31 at the time of delivery. They were diagnosed with HIV a median of 3.3 years before pregnancy and 84% were CDC stage A with a median CD4 cell count of 450 cells/mm3. 17% reported a history of injecting-drug use (IDU) and 3% current IDU. 29% of women conceived on cART, 63% started in pregnancy and 8% received no antenatal ART. The most common regimen used was PI based cART (50%). Of the deliveries, elective caesarean section (CS) was carried out in 58%, emergency CS in 17% and vaginal delivery in 23%. Of 1869 women with a VL measure within the last trimester of pregnancy, only 65% had undetectable HIV-RNA. Overall, 21% of all deliveries occurring before the guideline change were vaginal, increasing to 48% subsequently. The proportion of women with undetectable VL having a CS decreased from 29% before to 13% after the guidelines update. Conclusions Nearly half of all deliveries subsequent to European guideline changes were vaginal. Nevertheless, there are missed opportunities to achieve fully suppressed viral load at time of delivery and to deliver vaginally in HIV infected women. Further evaluation of treatment regimens, adherence data and barriers to treatment is planned within these cohorts.
Management of dyslipidaemia in an HIV-positive cohort
A Loy,L Townsend,S O'Dea,F Mulcahy
Journal of the International AIDS Society , 2012, DOI: 10.7448/ias.15.6.18128
Abstract: Background: Dyslipidaemia, secondary to both HIV and the use of antiretroviral therapy (ART) is well recognised, with HIV replication and immune status also thought to contribute to the risk. Traditionally the HIV physician has looked after HIV with primary care physicians (GP) managing non-HIV-related medical issues. However with the ageing population and the effectiveness of ART the HIV physician is diversifying to focus management strategies on preventative measures also. Method: 127 subjects were recruited. All subjects were HIV-positive males without any traditional cardiovascular disease symptoms or history. Details of patients demographics, family history, statin therapy, and primary care physician contact were collected. Baseline parameters were recorded and fasting bloods taken. Results: 127 asymptomatic HIV-positive males were recruited. 74/127 (58.3%) met the EACS criteria for statin prescription. 33/74 (44.6%) were on a statin. There was no significant difference between the class of antiretroviral prescribed, (NNRTI v PI) and lipid abnormalities (p=0.628). Hypertension and increased waist:hip ratio significantly increased the chances of the patient being hyperlipidaemic. Patients were more likely to be prescribed a statin if they were older, had hypertension, an increased waist circumference, increased Framingham risk, increased brain natriuretic peptide (BNP), or were diagnosed HIV-positive for longer (p<0.05). Pravastatin (21/33 [63.6%]), was most commonly prescribed statin. 24.2% received their statin prescription from their HIV physician, with 75.8% receiving their prescription from their GP. 5/21 (23.8%) on pravastatin met the target verses 7/7 (100%) on atorvastatin verses 2/2 (100%) on simvastatin versus 1/3 (33.3%) on rosuvastatin (p=0.02). Meeting lipid targets was less successful in the protease inhibitor group (1/9) 11.1% versus 11/21 (52.4%) in the NNRTI group (p=0.16). Conclusion: The majority met criteria for lipid management but less than half of those were prescribed it. Of those, most received treatment from their GP. Nearly half of those on statins did not meet lipid targets. HIV physicians were most likely to prescribe pravastatin and those on pravastatin were the least likely to achieve lipid targets when compared to the other statins. HIV physicians need to diversify their knowledge base and have clearly defined management strategies for the management of dyslipidaemia.
Magnesium Limitation Is an Environmental Trigger of the Pseudomonas aeruginosa Biofilm Lifestyle
Heidi Mulcahy, Shawn Lewenza
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023307
Abstract: Biofilm formation is a conserved strategy for long-term bacterial survival in nature and during infections. Biofilms are multicellular aggregates of cells enmeshed in an extracellular matrix. The RetS, GacS and LadS sensors control the switch from a planktonic to a biofilm mode of growth in Pseudomonas aeruginosa. Here we detail our approach to identify environmental triggers of biofilm formation by investigating environmental conditions that repress expression of the biofilm repressor RetS. Mg2+ limitation repressed the expression of retS leading to increased aggregation, exopolysaccharide (EPS) production and biofilm formation. Repression of retS expression under Mg2+ limitation corresponded with induced expression of the GacA-controlled small regulatory RNAs rsmZ and rsmY and the EPS biosynthesis operons pel and psl. We recently demonstrated that extracellular DNA sequesters Mg2+ cations and activates the cation-sensing PhoPQ two-component system, which leads to increased antimicrobial peptide resistance in biofilms. Here we show that exogenous DNA and EDTA, through their ability to chelate Mg2+, promoted biofilm formation. The repression of retS in low Mg2+ was directly controlled by PhoPQ. PhoP also directly controlled expression of rsmZ but not rsmY suggesting that PhoPQ controls the equilibrium of the small regulatory RNAs and thus fine-tunes the expression of genes in the RetS pathway. In summary, Mg2+ limitation is a biologically relevant environmental condition and the first bonafide environmental signal identified that results in transcriptional repression of retS and promotes P. aeruginosa biofilm formation.
Bottom Line: Defining Success in the Creation of a Business Simulation
Robert Sean Mulcahy
International Journal of Designs for Learning , 2011,
Abstract: This paper describes Bottom Line, a hybrid technology/classroom business simulation designed to help interns at an auditing/tax/consulting firm better understand the industry they are entering and the resource trade-offs that professional services firms make to stay competitive. This paper describes the sim on three different levels, the simulation level, the game level, and the instructional level, and the design choices made at each level, some of which were influenced by significant resource constraints. Bottom Line’s learning gains and ROI were not evaluated objectively—in fact, given objectives more focused on thought provocation than content teaching, it is unlikely it would score well on any level of the Kirkpatrick scale beyond the first. Despite that, and despite significant design and development weaknesses, it was seen as an unqualified success by the sponsoring organization. A discussion of what success means concludes this paper.
Projecte integrat "INCLUD-ED: cohesió social i impacte polític a Europa". Presentació
Rosa Valls,Carmel Mulcahy
Temps d'Educació , 2010,
Health Technology Assessment and patient safety
Andrew Mulcahy,Tom Walley
Italian Journal of Public Health , 2005, DOI: 10.2427/5961
Abstract: Health Technology Assessment (HTA) is a process used to evaluate the clinical effectiveness and costeffectiveness of health technologies by a systematic review of clinical, economic, and utilization research. Despite widespread investment in patient safety technologies in the U.K., U.S., and elsewhere, little HTA has been done to establish the clinical or cost-effectiveness of these technologies. The HTA and patient safety literature suggests there are four categories of patient safety HTA, including HTA for existing safety technologies, underutilized safety technologies, emerging safety technologies, as well as safety aspects of technologies with a non-safety primary purpose. Recent HTA and other research, including a 2002 evidencebased evaluation of patient safety technologies from the U.S. Agency for Health Research and Quality, provide an important foundation for a more comprehensive approach to patient safety HTA. However, HTA programs must address prioritization, methodology, and dissemination challenges introduced by patient safety technologies before significant progress can Te made.
Globalization and Culture: the Case of Canada and the United States
Essachess : Journal for Communication Studies , 2010,
Abstract: With a liberal political culture that is characterized by limited government, internationalism and an open society, Canada stands somewhere between France and the United States in its degree of cultural protectionism and overall intensity of cultural politics. The United States, of course, is the great cultural exception with a regnant popular culture that is able to indemnify its production costs over a populous and prosperous society which is largely immune to cultural expressions that do not project an American sensibility. In effect, the United States can afford to have a “cultural open-door policy” because it has little to fear from foreign competition. For Canada, however, cultural free-trade raises the specter of standing unprotected against the forces of American cultural annexation. This discussion will survey the debate over U.S. cultural imperialism and Canadian concerns for its cultural sovereignty with particular reference to the international trade agreements of the past decade.
Efficacy, adherence and tolerability of once daily tenofovir DF-containing antiretroviral therapy in former injecting drug users with HIV-1 receiving opiate treatment: results of a 48-week open-label study
S Esser, A Haberl, F Mulcahy, J G?lz, A Lazzarin, E Teofilo, J Vera, A K?rber, S Staszewski
European Journal of Medical Research , 2011, DOI: 10.1186/2047-783x-16-10-427
Abstract: European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-na?ve, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment.Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing = failure) at week 48, 34% of patients (23/67; 95% CI: 23%-47%) had plasma HIV-1 RNA < 50 copies/mL. Using an intent-totreat missing = excluded approach, the week 48 proportion of patients with plasma HIV-1 RNA < 50 copies/mL increased to 56% (23/41; 95% CI: 40%-72%). Mean (standard deviation) increase from baseline in CD4+ cell count at week 48 was 176 (242) cells/mm3. Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified.Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients.Managing human immunodeficiency virus (HIV) infection in patients who are current or former injecting drug users poses several challenges that can impair effective clinical management. This population often expresses comorbidites and complicating mental health conditions. A range of viral infections (such as hepatitis B and C) and recurrent bacterial and fungal infections can lead to higher morbidity and mortality in these patients [1,2]. Furthermore, use of illicit drugs is often linked with depression, which is itself associated with reduced levels of adherence that impair disease management [3-5]. There is also the potential for pharmacokinetic interactions between injected or substituted drugs, medication for comorbidities and prescribed antiretroviral therapies, which can further complicate clinical management [6-11]. Toxicities of the various substances taken by these patie
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