Effectiveness of an influenza vaccine programme for care home staff to prevent death, morbidity, and health service use among residents: cluster randomised controlled trial

Objective To determine whether vaccination of care home staff against influenza indirectly protects residents.Design Pair matched cluster randomised controlled trial.Setting Large private chain of UK care homes during the winters of 2003-4 and 2004-5.Participants Nursing home staff (n = 1703) and residents (n = 2604) in 44 care homes (22 intervention homes and 22 matched control homes).Interventions Vaccination offered to staff in intervention homes but not in control homes.Main outcome measures The primary outcome was all cause mortality of residents. Secondary outcomes were influenza-like illness and health service use in residents.Results In 2003-4 vaccine coverage in full time staff was 48.2% (407/884) in intervention homes and 5.9% (51/859) in control homes. In 2004-5 uptake rates were 43.2% (365/844) and 3.5% (28/800). National influenza rates were substaritially below average in 2004-5. In the 2003-4 period of influenza activity significant decreases were found in mortality of residents in intervention homes compared with control homes (rate difference - 5.0 per 100 residents, 95% confidence interval - 7.0 to - 2.0) and in influenza-like illness (P = 0.004), consultations with general practitioners for influenza-like illness (P = 0.008), and admissions to hospital with influenza-like illness (P = 0.009). No significant differences were found in 2004-5 or during periods of no influenza activity in 2003-4.Conclusions Vaccinating care home staff against influenza can prevent deaths, health service use, and influenza-like illness in residents during periods of moderate influenza activity

The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer

Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (£2132) and tegafur with uracil (£3385) were lower than costs for the intravenous Mayo regimen (£3593) and infusional regimens on the de Gramont (£6255) and Modified de Gramont (£3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens

Business opportunities analysis using GIS: the retail distribution sector

[EN] The retail distribution sector is facing a difficult time as the current landscape is characterized by ever-increasing competition. In these conditions, the search for an appropriate location strategy has the potential to become a differentiating and competitive factor. Although, in theory, an increasing level of importance is placed on geography because of its key role in understanding the success of a business, this is not the case in practice. For this reason, the process outlined in this paper has been specifically developed to detect new business locations. The methodology consists of a range of analyzes with Geographical Information Systems (GISs) from a marketing point of view. This new approach is called geomarketing. First, geodemand and geocompetition are located on two separate digital maps using spatial and non-spatial databases. Second, a third map is obtained by matching this information with the demand not dealt with properly by the current commercial offer. Third, the Kernel density allows users to visualize results, thus facilitating decision-making by managers, regardless of their professional background. The advantage of this methodology is the capacity of GIS to handle large amounts of information, both spatial and non-spatial. A practical application is performed in Murcia (Spain) with 100 supermarkets and data at a city block level, which is the highest possible level of detail. This detection process can be used in any commercial distribution company, so it can be generalized and considered a global solution for retailers.Roig Tierno, H.; Baviera-Puig, A.; Buitrago Vera, JM. (2013). Business opportunities analysis using GIS: the retail distribution sector. Global Business Perspectives. 1(3):226-238. doi:10.1007/s40196-013-0015-6S22623813Alarcón, S. (2011). The trade credit in the Spanish agrofood industry. Mediterranean Journal of Economics, Agriculture and Environment (New Medit), 10(2), 51–57.Alcaide, J. 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Changing methods of location planning for retail companies. GeoJournal, 45, 289–298.Clarkson, R. M., Clarke-Hill, C. M., & Robinson, T. (1996). UK supermarket location assessment. International Journal of Retail and Distribution Management, 24(6), 22–33.Davis, P. (2006). Spatial competition in retail markets: Movie theaters. The RAND Journal of Economics, 37(4), 964–982.Ghosh, A., & McLafferty, S. L. (1982). Locating stores in uncertain environments: A scenario planning approach. Journal of Retailing, 58(4), 5–22.Härdle, W. (1991). Smoothing techniques with implementation in S. Nueva York, NY: Springer.Harris, B., & Batty, M. (1993). Locational models, geographical information, and planning support systems. Journal of Planning Education and Research, 12, 184–198.Hernandez, T. (2007). Enhancing retail location decision support: The development and application of geovisualization. Journal of Retailing and Consumer Services, 14, 249–258.Hernandez, T., & Bennison, D. (2000). The art and science of retail location decisions. International Journal of Retail and Distribution Management, 28(8), 357–367.Huff, D. (1963). Defining and estimating a trade area. Journal of Marketing, 28, 34–38.Instituto Nacional de Estadística (INE). (2011). Padrón de habitantes 2011. http://www.ine.es . Accessed 9 Oct 2012.Kelly, J. P., Freeman, D. C., & Emlen, J. M. (1993). Competitive impact model for site selection: The impact of competition, sales generators and own store cannibalization. The International Review of Retail, Distribution and Consumer Research, 3, 237–259.Latour, P., & Le Floc’h, J. (2001). Géomarketing: Principes, méthodes et applications. París: Éditions d’Organisation.Mendes, A. B., & Themido, I. H. (2004). Multi-outlet retail site location assessment. International Transactions in Operational Research, 11, 1–18.Moreno, A. (1991). Modelización cartográfica de densidades mediante estimadores Kernel. Treballs de la Societat Catalana de Geografia, 6(30), 155–170.Moreno, A. (2007). Obtención de capas raster de densidad. In A. Moreno (Coord.), Sistemas y Análisis de la información Geográfica. Manual de autoaprendizaje con ArcGIS (pp. 685–691). Madrid: Editorial RA-MA.Murad, A. A. (2003). Creating a GIS application for retail centers in Jeddah City. International Journal of Applied Earth Observation and Geoinformation, 4, 329–338.Murad, A. A. (2007). Using GIS for retail planning in Jeddah City. American Journal of Applied Sciences, 4(10), 820–826.Musyoka, S. M., Mutyauvyu, S. M., Kiema, J. B. K., Karanja, F. N., & Siriba, D. N. (2007). Market segmentation using geographic information systems (GIS). A case study of the soft drink industry in Kenya. Marketing Intelligence and Planning, 25(6), 632–642.Nielsen Database. (2012). Retailers Database. http://www.nielsen.com/global/en.html . Accessed 12 Oct 2012.Ozimec, A. M., Natter, M., & Reutterer, T. (2010). 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A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer

BACKGROUND: Many emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines. METHODS: A phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines. RESULTS: Twenty-five patients received paclitaxel (150 mg/mq) by 3-hours infusion, followed by gemcitabine (2000 mg/mq) given as a 60 min i.v. infusion (day 1–14) for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16%) achieved a complete response, 12 (48%) a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20%) and progressive disease occurred in 4 patients (16%). CONCLUSION: The schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines

Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy.

Autoimmune destruction of the pancreatic islets in Type 1 diabetes is mediated by both increased proinflammatory (Teff) and decreased regulatory (Treg) T lymphocytes resulting in a significant decrease in the Treg:Teff ratio. The non-obese diabetic (NOD) mouse is an excellent in vivo model for testing potential therapeutics for attenuating the decrease in the Treg:Teff ratio and inhibiting disease pathogenesis. Here we show for the first time that a bioreactor manufactured therapeutic consisting of a complex of miRNA species (denoted as TA1) can effectively reset the NOD immune system from a proinflammatory to a tolerogenic state thus preventing or delaying autoimmune diabetes. Treatment of NOD mice with TA1 resulted in a systemic broad-spectrum upregulation of tolerogenic T cell subsets with a parallel downregulation of Teff subsets yielding a dramatic increase in the Treg:Teff ratio. Moreover, the murine-derived TA1 was highly effective in the inhibition of allorecognition of HLA-disparate human PBMC. TA1 demonstrated dose-responsiveness and exhibited equivalent or better inhibition of allorecognition driven proliferation than etanercept (a soluble TNF receptor). These findings demonstrate that miRNA-based therapeutics can effectively attenuate or arrest autoimmune disease processes and may be of significant utility in a broad range of autoimmune diseases including Type 1 diabetes

Should the Arteriovenous Fistula Be Created before Starting Dialysis?: A Decision Analytic Approach

Background: An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the\ud optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access\ud referral strategy for stage 4 (glomerular filtration rate ,30 ml/min/1.73 m2) chronic kidney disease patients using a decision\ud analytic framework.\ud Methods: A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an\ud AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the\ud probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy\ud and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were\ud performed using Monte Carlo simulation.\ud Results: The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy\ud (38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except\ud at higher rates of progression and lower rates of ischemic steal syndrome.\ud Conclusions: Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all predialysis\ud patients. Further research on cost implications and patient preferences for treatment options needs to be done\ud before recommending early AVF creation

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

The Protein Kinase Tor1 Regulates Adhesin Gene Expression in Candida albicans

Eukaryotic cell growth is coordinated in response to nutrient availability, growth factors, and environmental stimuli, enabling cell–cell interactions that promote survival. The rapamycin-sensitive Tor1 protein kinase, which is conserved from yeasts to humans, participates in a signaling pathway central to cellular nutrient responses. To gain insight into Tor-mediated processes in human fungal pathogens, we have characterized Tor signaling in Candida albicans. Global transcriptional profiling revealed evolutionarily conserved roles for Tor1 in regulating the expression of genes involved in nitrogen starvation responses and ribosome biogenesis. Interestingly, we found that in C. albicans Tor1 plays a novel role in regulating the expression of several cell wall and hyphal specific genes, including adhesins and their transcriptional repressors Nrg1 and Tup1. In accord with this transcriptional profile, rapamycin induced extensive cellular aggregation in an adhesin-dependent fashion. Moreover, adhesin gene induction and cellular aggregation of rapamycin-treated cells were strongly dependent on the transactivators Bcr1 and Efg1. These findings support models in which Tor1 negatively controls cellular adhesion by governing the activities of Bcr1 and Efg1. Taken together, these results provide evidence that Tor1-mediated cellular adhesion might be broadly conserved among eukaryotic organisms

Combination therapy with docetaxel and S-1 as a first-line treatment in patients with advanced or recurrent gastric cancer: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>We performed a single-institution retrospective study to evaluate the efficacy and toxicities of combination therapy with docetaxel and S-1 in patients with advanced or recurrent gastric cancer.</p> <p>Methods</p> <p>Eighty-six patients with advanced or recurrent gastric cancer were enrolled. Patients received docetaxel, 40 mg/m², on day 1 and oral S-1, 80 mg/m²/day, on days 1 to 14 every 3 weeks.</p> <p>Results</p> <p>All 84 patients were assessable for response. The overall response rate was 52.4% (44/84) and the disease control rate was 96.4% (81/84). Median time to progression (TTP) and overall survival (OS) were 6.5 (95% CI, 4.8-8.1 months) and 15.1 months (95% CI, 11.7-18.5 months), respectively. The major toxicities were neutropenia, leukopenia, alopecia and anorexia. Grade 3 or 4 hematologic toxicities included neutropenia in 31 patients (36.0%), leukopenia in 27 (31.7%), febrile neutropenia in four (4.7%), and anemia in one (1.2%). Other grade 3 toxicities included anorexia in five patients (5.8%), and stomatitis, diarrhea and nausea in one each (1.2%). There was one treatment-related death (1.2%).</p> <p>Conclusion</p> <p>The combination of docetaxel and S-1 had good clinical activity with acceptable toxicity in patients with advanced or recurrent gastric cancer.</p