Anti-angiogenic therapies for metastatic colorectal cancer.

BACKGROUND: Angiogenesis inhibitors have been developed to block tumour angiogenesis and target vascular endothelial cells. While some of them have already been approved by the health authorities and are successfully integrated into patient care, many others are still under development, and the clinical value of this approach has to be established. OBJECTIVES: To assess the efficacy and toxicity of targeted anti-angiogenic therapies, in addition to chemotherapy, in patients with metastatic colorectal cancer. Primary endpoints are both progression-free and overall survival. Response rates, toxicity and secondary resectability were secondary endpoints. Comparisons were first-line chemotherapy in combination with angiogenesis inhibitor, to the same chemotherapy without angiogenesis inhibitor; and second-line chemotherapy, to the same chemotherapy without angiogenesis inhibitor. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, as well as proceedings from ECCO, ESMO and ASCO until November 2008. In addition, reference lists from trials were scanned, experts in the field and drug manufacturers were contacted to obtain further information. SELECTION CRITERIA: Randomized controlled trials on targeted anti-angiogenic drugs in metastatic colorectal cancer (MCRC). DATA COLLECTION AND ANALYSIS: Data collection and analysis was performed, according to a previously published protocol. Because individual patient data was not provided, aggregate data had to be used for the analysis. Summary statistics for the primary endpoints were hazard ratios (HR's) and their 95% confidence intervals. MAIN RESULTS: At present, eligible first line trials for this meta-analysis were available for bevacizumab (5 trials including 3101 patients) and vatalanib (1 trial which included 1168 patients). The overall HR s for PFS (0.61, 95% CI 0.45 - 0.83) and OS (0.81, 95% 0.73 - 0.90) for the comparison of first-line chemotherapy, with or without bevacizumab, confirms significant benefits in favour of the patients treated with bevacizumab. However, the effect on PFS shows significant heterogeneity. For second-line chemotherapy, with or without bevacizumab, a benefit in both PFS (HR 0.61, 95% CI 0.51 - 0.73) and OS (HR 0.75, 95% CI 0.63-0.89) was demonstrated in a single, randomized trial. While differences in treatment-related deaths and 60-day mortality were not significant, higher incidences in grade III/IV hypertension, arterial thrombembolic events and gastrointestinal perforations were observed in the patients treated with bevacizumab. For valatanib, currently available data showed a non-significant benefit in PFS and OS. AUTHORS' CONCLUSIONS: The addition of bevacizumab to chemotherapy of metastatic colorectal cancer prolongs both PFS and OS in first-and second-line therapy.

Selecting control genes for RT-QPCR using public microarray data.

Background: Gene expression analysis has emerged as a major biological research area, with real-time quantitative reverse transcription PCR (RT-QPCR) being one of the most accurate and widely used techniques for expression profiling of selected genes. In order to obtain results that are comparable across assays, a stable normalization strategy is required. In general, the normalization of PCR measurements between different samples uses one to several control genes (e. g. housekeeping genes), from which a baseline reference level is constructed. Thus, the choice of the control genes is of utmost importance, yet there is not a generally accepted standard technique for screening a large number of candidates and identifying the best ones. Results: We propose a novel approach for scoring and ranking candidate genes for their suitability as control genes. Our approach relies on publicly available microarray data and allows the combination of multiple data sets originating from different platforms and/or representing different pathologies. The use of microarray data allows the screening of tens of thousands of genes, producing very comprehensive lists of candidates. We also provide two lists of candidate control genes: one which is breast cancer-specific and one with more general applicability. Two genes from the breast cancer list which had not been previously used as control genes are identified and validated by RT-QPCR. Open source R functions are available at http://www.isrec.isb-sib.ch/similar to vpopovic/research/ Conclusion: We proposed a new method for identifying candidate control genes for RT-QPCR which was able to rank thousands of genes according to some predefined suitability criteria and we applied it to the case of breast cancer. We also empirically showed that translating the results from microarray to PCR platform was achievable.

Healthy child, healthy future: speech and language therapy for children

This resource is designed to reinforce a collaborative approach between speech and language therapists, referrers and parents in the identification and management of children with developmental speech and language and communication needs (including children with feeding and/or swallowing difficulties). It includes a comprehensive key skills section, which provides details on the communication-related skills a child should have acquired at each stage in his/her early years development. It also includes specific criteria and guidelines for referral, should there be concern about whether the child has a significant problem. The resource provides additional guidance on: • communication and child play; • speech sound development; • dummies; • stammering; • dysphonia; • bilingualism; • feeding and swallowing difficulties. Lists of supplementary leaflets, handouts and websites, as well as a bibliography, are also included.

Comparison of indices proposed as criteria for assigning skin notation

OBJECTIVES: Skin notations are used as a hazard identification tool to flag chemicals associated with a potential risk related to transdermal penetration. The transparency and rigorousness of the skin notation assignment process have recently been questioned. We compared different approaches proposed as criteria for these notations as a starting point for improving and systematizing current practice. METHODS: In this study, skin notations, dermal acute lethal dose 50 in mammals (LD(50)s) and two dermal risk indices derived from previously published work were compared using the lists of Swiss maximum allowable concentrations (MACs) and threshold limit values (TLVs) from the American Conference of Governmental Industrial Hygienists (ACGIH). The indices were both based on quantitative structure-activity relationship (QSAR) estimation of transdermal fluxes. One index compared the cumulative dose received through skin given specific exposure surface and duration to that received through lungs following inhalation 8 h at the MAC or TLV. The other index estimated the blood level increase caused by adding skin exposure to the inhalation route at kinetic steady state. Dermal-to-other route ratios of LD(50) were calculated as secondary indices of dermal penetrability. RESULTS: The working data set included 364 substances. Depending on the subdataset, agreement between the Swiss and ACGIH skin notations varied between 82 and 87%. Chemicals with a skin notation were more likely to have higher dermal risk indices and lower dermal LD(50) than chemicals without a notation (probabilities between 60 and 70%). The risk indices, based on cumulative dose and kinetic steady state, respectively, appeared proportional up to a constant independent of chemical-specific properties. They agreed well with dermal LD(50)s (Spearman correlation coefficients -0.42 to -0.43). Dermal-to-other routes LD(50) ratios were moderately associated with QSAR-based transdermal fluxes (Spearman correlation coefficients -0.2 to -0.3). CONCLUSIONS: The plausible but variable relationship between current skin notations and the different approaches tested confirm the need to improve current skin notations. QSAR-based risk indices and dermal toxicity data might be successfully integrated in a systematic alternative to current skin notations for detecting chemicals associated with potential dermal risk in the workplace. [Authors]

454 Users Successfully 'weaned off' Methadone

A total of 454 methadone users successfully completed treatment programmes aimed at weaning them off the heroin substitute last year - but more than 2,000 others left the state's maintenance programme during the same period for a variety of reasons, new figures have revealed. According to statistics released under the Freedom of Information Act, there were 9,760 methadone users around the country last year, with the majority in the Dublin area. However, over 2,778 clients of the methadone maintenance service left the HSE's central treatment lists during the year. A summary of the reasons reveals that in 1,268 instances, they did so after either being released or committed to prison.This resource was contributed by The National Documentation Centre on Drug Use.

The effectiveness of brief alcohol interventions in primary care settings: A systematic review

Numerous studies have reported that brief interventions delivered in primary care are effective in reducing excessive drinking. However, much of this work has been criticised for being clinically unrepresentative. This review aimed to assess the effectiveness of brief interventions in primary care and determine if outcomes differ between efficacy and effectiveness trials. Approach. A pre-specified search strategy was used to search all relevant electronic databases up to 2006. The authors also hand-searched the reference lists of key articles and reviews. They included randomised controlled trials (RCT) involving patients in primary care who were not seeking alcohol treatment and who received brief intervention. Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, subgroup and sensitivity analyses and meta-regression were conducted.This resource was contributed by The National Documentation Centre on Drug Use.

A brief cognitive behavioural intervention for regular amphetamine users. A treatment guide.

A brief intervention using motivational and cognitive behavioural approaches to help change drug use. Also offer alternative brief interventions for clients not suited to the current approach. This manual is divided into five sections: Section 1. Context Key points from the National Drug Strategy Monograph No 51. Models of Intervention and Care for Psychostimulant Users are included to present the evidence supporting this type of intervention for regular amphetamine users.  A flow-chart to place the intervention in a treatment context. Section 2. Brief background to the study and summary of results of evaluation A brief description of how the study was developed, undertaken and evaluated. A brief description of the evaluation outcome data (detailed results will be published separately). Section 3. The intervention The CBT intervention is presented in a clear and easy to use format for practitioners. Section 4. Suggested alternative brief interventions for those not suitable for the current intervention This section provides an overview of recommendations for alternative interventions for psychostimulant users who are unsuitable for the CBT intervention (e.g. those who are not considering change, experimental users etc). Section 5. Other available resources This section lists a range of other resources that are currently available for practitioners working with psychostimulant users. This treatment guide has not been designed to stand alone. Rather, practitioners are encouraged to: 1. Acquaint themselves with the current research and clinical literature. The recently completed monograph Models of Intervention and Care for Psychostimulant Users is an excellent resource for current evidence supporting practice in this area. 2. Undertake training in CBT and motivational enhancement techniques if unfamiliar with these approaches. 3. Obtain ongoing clinical supervision.This resource was contributed by The National Documentation Centre on Drug Use.

Delivering Choosing Health: Making healthier choices easier

This delivery plan outlines the key steps that will be taken over the next three years to deliver the Governnment White Paper Choosing Health: making healthier choices easier. This delivery plan highlights how the DH and the NHS, within the framework of government policies, will help more people make more healthy choices and reduce health inequalities. It outlines clearly the priorities for delivery at national, regional and local levels and what will be done by whom and when. It brings into one place all of the actions on the White Paper commitments, alongside related Public Service Agreements and local targets to improve health. It lists 45 'big wins' - key interventions which the evidence and expert advice suggest will make the greatest impact on health in the shortest period of time It explains how new policies and programmes will be developed and implemented. It describes how Government will drive forward delivery through Government targets to improve health new partnerships

Estructura de datos avanzadas : clases disjuntas, montículos, árboles de búsqueda

En aquest treball s'amplia la implementació en Java de les estructures de dades iniciada per Esteve Mariné, utilitzant el seu disseny bàsic. Concretament, s'ha fet la programació de les estructures de a) classes disjuntes, utilitzant els algorismes de llistes encadenades i amb estructura d'arbre, b) monticles, amb els algorismes binari, binomial i de Fibonacci, i c) arbres de recerca basats en l'algorisme d'arbre binari vermell-negre, el qual complementa els dos ja existents amb algorismes d'encadenaments i AVL. Per a examinar l'evolució de les estructures, s'ha preparat un visualitzador gràfic interactiu amb l'usuari que permet fer les operacions bàsiques de l'estructura. Amb aquest entorn és possible desar les estructures, tornar a reproduir-les i desfer i tornar a repetir les operacions fetes sobre l'estructura. Finalment, aporta una metodologia, amb visualització mitjançant gràfics, de l'avaluació comparativa dels algorismes implementats, que permet modificar els paràmetres d'avaluació com ara nombre d'elements que s'han de tractar, algorismes que s'han de comparar i nombre de repeticions. Les dades obtingudes es poden exportar per a analitzar-les posteriorment.

Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer.

BACKGROUND: Vascular-endothelial-growth-factor (VEGF) is a key mediator of angiogenesis. VEGF-targeting therapies have shown significant benefits and been successfully integrated in routine clinical practice for other types of cancer, such as metastatic colorectal cancer. By contrast, individual trial results in metastatic breast cancer (MBC) are highly variable and their value is controversial. OBJECTIVES: To evaluate the benefits (in progression-free survival (PFS) and overall survival (OS)) and harms (toxicity) of VEGF-targeting therapies in patients with hormone-refractory or hormone-receptor negative metastatic breast cancer. SEARCH METHODS: Searches of CENTRAL, MEDLINE, EMBASE, the Cochrane Breast Cancer Group's Specialised Register, registers of ongoing trials and proceedings of conferences were conducted in January and September 2011, starting in 2000. Reference lists were scanned and members of the Cochrane Breast Cancer Group, experts and manufacturers of relevant drug were contacted to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) to evaluate treatment benefit and non-randomised studies in the routine oncology practice setting to evaluate treatment harms. DATA COLLECTION AND ANALYSIS: We performed data collection and analysis according to the published protocol. Individual patient data was sought but not provided. Therefore, the meta-analysis had to be based on published data. Summary statistics for the primary endpoint (PFS) were hazard ratios (HRs). MAIN RESULTS: We identified seven RCTs, one register, and five ongoing trials from a total of 347 references. The published trials for VEGF-targeting drugs in MBC were limited to bevacizumab. Four trials, including a total of 2886 patients, were available for the comparison of first-line chemotherapy, with versus without bevacizumab. PFS (HR 0.67; 95% confidence interval (CI) 0.61 to 0.73) and response rate were significantly better for patients treated with bevacizumab, with moderate heterogeneity regarding the magnitude of the effect on PFS. For second-line chemotherapy, a smaller, but still significant benefit in terms of PFS could be demonstrated for patients treated with bevacizumab (HR 0.85; 95% CI 0.73 to 0.98), as well as a benefit in tumour response. However, OS did not differ significantly, neither in first- (HR 0.93; 95% CI 0.84 to 1.04), nor second-line therapy (HR 0.98; 95% CI 0.83 to 1.16). Quality of life (QoL) was evaluated in four trials but results were published for only two of these with no relevant impact. Subgroup analysis stated a significant greater benefit for patients with previous (taxane) chemotherapy and patients with hormone-receptor negative status. Regarding toxicity, data from RCTs and registry data were consistent and in line with the known toxicity profile of bevacizumab. While significantly higher rates of adverse events (AEs) grade III/IV (odds ratio (OR) 1.77; 95% CI 1.44 to 2.18) and serious adverse events (SAEs) (OR 1.41; 95% CI 1.13 to 1.75) were observed in patients treated with bevacizumab, rates of treatment-related deaths were lower in patients treated with bevacizumab (OR 0.60; 95% CI 0.36 to 0.99). AUTHORS' CONCLUSIONS: The overall patient benefit from adding bevacizumab to first- and second-line chemotherapy in metastatic breast cancer can at best be considered as modest. It is dependent on the type of chemotherapy used and limited to a prolongation of PFS and response rates in both first- and second-line therapy, both surrogate parameters. In contrast, bevacizumab has no significant impact on the patient-related secondary outcomes of OS or QoL, which indicate a direct patient benefit. For this reason, the clinical value of bevacizumab for metastatic breast cancer remains controversial.

MisListas : aplicació per a la creació de llistes

El projecte "MisListas" està dissenyat especialment per a usuaris domèstics, permetent a aquests construir llistes amb diferents continguts com: Llista de la compra, de tasques, cites, aniversaris, reunions, arbres genealògics i en definitiva qualsevol tipus de llista jeràrquica que desitgin guardar nostra aplicació.

Three points for speed

This poster focuses on the effects of speed. The poster message is 'Three points for speed' and then lists three of the effects: 1. Extreme tiredness 2. Disturbed sleep 3. Paranoia. It also provides contact details for the National Drugs Helpline. Tel: 0800 776600.

Look after yourself and others - Promoting mental health and suicide prevention within the Northern area

This leaflet lists the wide range of local support available in the Northern area to help improve mental health and emotional wellbeing and reduce the number of deaths by suicide. This leaflet is aimed at individuals and organisations to raise awareness of the support for individuals and communities.

Director of Public Health Annual Report 2014

This is the sixth Director of Public Health Annual Report, detailing the main public health challenges in Northern Ireland. It also provides information on the wide variety of work undertaken by the PHA and its partners during 2014 to improve the health and social wellbeing of the population. Each year, the report focuses on an overarching area, which this year is ‘Adults aged 18–64 years’. The report structure reflects the main areas of public health action: improving health and reducing inequalities; improving health through early detection; improving health through high quality services; improving health through research; protecting health. For ease of reference, the sections are colour coded. On page 94, the report also lists core tables for 2013 relating to key statistical data on, among others, population, birth and death rates, mortality by cause, life expectancy, immunisation and screening. The PDF document of the Core tables is available below. In addition to the core tables, a specific set of tables relating to various aspects of adults aged 18–64 years are published alongside this report.

Smoking: know the facts

This leaflet outlines the health and financial benefits of stopping smoking. It provides key facts on the health dangers associated with smoking, information on second-hand smoke, information on the dangers of smoking to babies, and contact details for help and support available. It also lists the various forms of nicotine replacement therapy (NRT) and non-nicotine medications available.This poster highlights some of the main health and financial benefits of stopping smoking. An associated A5 leaflet goes into detail on these areas.