Too little but not too late: Results of a literature review to improve routine immunization programs in developing countries

<p>Abstract</p> <p>Background</p> <p>Globally, immunization services have been the center of renewed interest with increased funding to improve services, acceleration of the introduction of new vaccines, and the development of a health systems approach to improve vaccine delivery. Much of the credit for the increased attention is due to the work of the GAVI Alliance and to new funding streams. If routine immunization programs are to take full advantage of the newly available resources, managers need to understand the range of proven strategies and approaches to deliver vaccines to reduce the incidence of diseases. In this paper, we present strategies that may be used at the sub-national level to improve routine immunization programs.</p> <p>Methods</p> <p>We conducted a systematic review of studies and projects reported in the published and gray literature. Each paper that met our inclusion criteria was rated based on methodological rigor and data were systematically abstracted. Routine-immunization – specific papers with a methodological rigor rating of greater than 60% and with conclusive results were reported.</p> <p>Results</p> <p>Greater than 11,000 papers were identified, of which 60 met our inclusion criteria and 25 papers were reported. Papers were grouped into four strategy approaches: bringing immunizations closer to communities (n = 11), using information dissemination to increase demand for vaccination (n = 3), changing practices in fixed sites (n = 4), and using innovative management practices (n = 7).</p> <p>Conclusion</p> <p>Immunization programs are at a historical crossroads in terms of developing new funding streams, introducing new vaccines, and responding to the global interest in the health systems approach to improving immunization delivery. However, to complement this, actual service delivery needs to be strengthened and program managers must be aware of proven strategies. Much was learned from the 25 papers, such as the use of non-health workers to provide numerous services at the community level. However it was startling to see how few papers were identified and in particular how few were of strong scientific quality. Further well-designed and well-conducted scientific research is warranted. Proposed areas of additional research include integration of additional services with immunization delivery, collaboration of immunization programs with new partners, best approaches to new vaccine introduction, and how to improve service delivery.</p

A genome-wide expression analysis identifies a network of EpCAM-induced cell cycle regulators

Expression of the epithelial cell adhesion molecule EpCAM is upregulated in a variety of carcinomas. This antigen is therefore explored in tumour diagnosis, and clinical trials have been initiated to examine EpCAM-based therapies. Notably, the possible intracellular effects and signalling pathways triggered by EpCAM-specific antibodies are unknown. Here, we show treatment of the mouse lung carcinoma cell line A2C12, of the human lung carcinoma cell line A549 and the human colorectal cell line Caco-2 with the monoclonal EpCAM antibody G8.8 to cause dose dependently an increase in cell proliferation, as determined by the MTS and the 5′-bromo-2′-deoxyuridine (BrdU) labelling assay. Furthermore, a genome-wide approach identified networks of regulated genes, most notably cell cycle regulators, upon treatment with an EpCAM-specific antibody. Indeed, changes in the expression of cell cycle regulators agreed well with the BrdU labelling data, and an analysis of differentially expressed genes revealed the processes with the strongest over-representation of modulated genes, for example, cell cycle, cell death, cellular growth and proliferation, and cancer. These data suggest that EpCAM is involved in signal transduction triggering several intracellular signalling pathways. Knowing EpCAM signalling pathways might lead to a reassessment of EpCAM-based therapies

Effectiveness of photodynamic therapy for mammary and extra-mammary Paget's disease: a state of the science review

<p>Abstract</p> <p>Background</p> <p>Paget's disease is a rare skin disorder occurring in the breast (mammary) or in the groin, genital, peri-anal and axillary regions (extra-mammary). Typical treatment involves surgical excision, which in the case of extra-mammary Paget's disease, can lead to significant morbidity. Photodynamic therapy (PDT) which uses a topical or intravenous photosensitizing agent that is activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to assess the effectiveness of photodynamic therapy in the treatment of Paget's disease.</p> <p>Methods</p> <p>Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for mammary and extra-mammary Paget's disease was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale.</p> <p>Results</p> <p>21 retrospective and 2 prospective non-comparative studies were identified and included in the review: 9 case reports with 1-2 patients and 14 case series with 1-16 patients. These reports totalled 99 patients with 133 extra-mammary Paget's lesions and 3 patients (with 3 lesions) with mammary Paget's disease. Follow-up periods were typically one year or less, with 77/133 extra-mammary lesions exhibiting complete response to PDT. One recurrent mammary skin lesion and two mammary lesions treated concomitantly with surgery also exhibited complete responses.</p> <p>Conclusions</p> <p>Evidence of the effectiveness of PDT for Paget's disease is promising, but limited. This may, in part, be explained by the rarity of the condition, making controlled comparative clinical trials challenging.</p

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t1/2 ∼1 h), or a slow, zero-order release rate (t1/2 ∼ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies

Update of complications and functional outcome of the ileo-pouch anal anastomosis: overview of evidence and meta-analysis of 96 observational studies

Item does not contain fulltextOBJECTIVE: The objective of this study is to provide a comprehensive update of the outcome of the ileo-pouch anal anastomosis (IPAA). DATA SOURCES: An extensive search in PubMed, EMBASE, and The Cochrane Library was conducted. STUDY SELECTION AND DATA EXTRACTION: All studies published after 2000 reporting on complications or functional outcome after a primary open IPAA procedure for UC or FAP were selected. Study characteristics, functional outcome, and complications were extracted. DATA SYNTHESIS: A review with similar methodology conducted 10 years earlier was used to evaluate developments in outcome over time. Pooled estimates were compared using a random-effects logistic meta-analyzing technique. Analyses focusing on the effect of time of study conductance, centralization, and variation in surgical techniques were performed. RESULTS: Fifty-three studies including 14,966 patients were included. Pooled rates of pouch failure and pelvic sepsis were 4.3% (95% CI, 3.5-6.3) and 7.5% (95% CI 6.1-9.1), respectively. Compared to studies published before 2000, a reduction of 2.5% was observed in the pouch failure rate (p = 0.0038). Analysis on the effect of the time of study conductance confirmed a decline in pouch failure. Functional outcome remained stable over time, with a 24-h defecation frequency of 5.9 (95% CI, 5.0-6.9). Technical surgery aspects did not have an important effect on outcome. CONCLUSION: This review provides up to date outcome estimates of the IPAA procedure that can be useful as reference values for practice and research. It is also shows a reduction in pouch failure over time.1 juli 201

Are vaccination programmes delivered by lay health workers cost-effective? A systematic review

<p>Abstract</p> <p>Background</p> <p>A recently updated Cochrane systematic review on the effects of lay or community health workers (LHWs) in primary and community health care concluded that LHW interventions could lead to promising benefits in the promotion of childhood vaccination uptake. However, understanding of the costs and cost-effectiveness of involving LHWs in vaccination programmes remains poor. This paper reviews the costs and cost-effectiveness of vaccination programme interventions involving LHWs.</p> <p>Methods</p> <p>Articles were retrieved if the title, keywords or abstract included terms related to 'lay health workers', 'vaccination' and 'economics'. Reference lists of studies assessed for inclusion were also searched and attempts were made to contact authors of all studies included in the Cochrane review. Studies were included after assessing eligibility of the full-text article. The included studies were then reviewed against a set of background and technical characteristics.</p> <p>Results</p> <p>Of the 2616 records identified, only three studies fully met the inclusion criteria, while an additional 11 were retained as they included some cost data. Methodologically, the studies were strong but did not adequately address affordability and sustainability and were also highly heterogeneous in terms of settings and LHW outcomes, limiting their comparability. There were insufficient data to allow any conclusions to be drawn regarding the cost-effectiveness of LHW interventions to promote vaccination uptake. Studies focused largely on health outcomes and did illustrate to some extent how the institutional characteristics of communities, such as governance and sources of financial support, influence sustainability.</p> <p>Conclusion</p> <p>The included studies suggest that conventional economic evaluations, particularly cost-effectiveness analyses, generally focus too narrowly on health outcomes, especially in the context of vaccination promotion and delivery at the primary health care level by LHWs. Further studies on the costs and cost-effectiveness of vaccination programmes involving LHWs should be conducted, and these studies should adopt a broader and more holistic approach.</p

Emerging roles of ATF2 and the dynamic AP1 network in cancer

Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. The AP1 complex exemplifies a network of transcription factors that function in unison under normal circumstances and during the course of tumour development and progression. This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis.Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Lau, Eric . Burnham Institute for Medical Research; Estados UnidosFil: Ronai, Zeev . Burnham Institute for Medical Research; Estados Unido