Demographic and epidemiological characteristics of major regions, 1990-2001

In an era when most societies are coping with greater demand for health resources, choices will have to be made about the provision of health services. Strategic health planning must take into account the comparative burden of diseases and injuries, and the risk factors that cause them, and how this burden is likely to change under various policies and interventions. The Global Burden of Disease (GBD) framework is the principal, if not the only, framework for integrating and analyzing information on population health and making it more relevant for health policy and planning purposes. The comprehensive findings of the 2001 GBD study represent a major update of the effort launched with the 1990 GBD study. The 1990 GBD study was a major advance in the quantification of the impact of diseases, injuries, and risk factors on population health globally and by region. Government and nongovernmental agencies alike have used its results to argue for more strategic allocation of health resources to programs that are likely to yield the greatest gains in population health. Publication of the 1990 results led to improvements in analytical methods and mortality data in a number of countries. In addition, critiques of methodological approaches used in the 1990 study prompted a new framework for risk factor assessment along with systematic attempts to quantify some of the uncertainty in national and global assessments of disease burden. The 2001 GBD provides a new and improved baseline for measuring progress in global health

Effects of a multi-faceted program to increase influenza vaccine coverage among health care workers:A hospital-based cluster randomized controlled trial

Background: Immunizing health care workers (HCWs) against influenza has proven to protect their patients. Despite recommentations of the World Health Organization and the Dutch Health Council, influenza vaccine uptake among hospital HCWs remains low in the Netherlands Objectives: To assess the effects of implementing a hospital- based multi-faceted influenza immunization program on vaccine coverage in health care workers (HCW) and on patient morbidity. Methods: We conducted a cluster randomized controlled trial among all eight University Medical Centers (UMC) of The Netherlands during the influenza seasons of 2009- 2010 and 2010-2011. Participants were hospital staff of three intervention (n = 27,900 in 2009), three control (n = 22,451) and two external non-randomized intervention UMCs (n = 16,893), and 3,367 patients admitted to the departments of pediatrics and internal medicine during both influenza epidemics. We offered a vaccination implementation progran to staff of intervention and external UMCs, but not to control UMCs. The primary outcome measure was influenza vaccine coverage among HCW. Secondary outcome measures were work absenteeism and patient morbidity. Results: In 2009, the coverage of seasonal, first pandemic and second pandemic vaccine was 32.3%, 61.7% and 45.8% in the intervention UMCs. Corresponding figures for control UMCs were significantly lower at 20.4%, 38.0%, and 17.8%, respectively (p <0.05). In 2010, the coverage of the seasonal vaccine was 28.6% and 17.8% in intervention and control UMCs, respectively (p <0.05). During their stay, influenza and/or pneumonia was reduced in patients of intervention UMCs compared to control UMCs (work in progress). Rates of HCWs' absenteeism and influenza testing rates during epidemics were higher in intervention than control UMCs. Conclusions: Adoption of the program improved the influenza vaccine coverage among hospital staff. An increase in coverage was associated with decreased patient morbidity from influenza and/or pneumonia

Leukapheresis increases circulating tumour cell yield in non-small cell lung cancer, counts related to tumour response and survival

Background: Circulating tumour cells (CTCs) can be used to monitor cancer longitudinally, but their use in non-small cell lung cancer (NSCLC) is limited due to low numbers in the peripheral blood. Through diagnostic leukapheresis (DLA) CTCs can be obtained from larger blood volumes. Methods: Patients with all stages of NSCLC were selected. One total body blood volume was screened by DLA before and after treatment. Peripheral blood was drawn pre- and post DLA for CTC enumeration by CellSearch. CTCs were detected in the DLA product (volume equalling 2 × 108 leucocytes) and after leucocyte depletion (RosetteSep, 9 mL DLA product). Single-cell, whole-genome sequencing was performed on isolated CTCs. Results: Fifty-six patients were included. Before treatment, CTCs were more often detected in DLA (32/55, 58%) than in the peripheral blood (pre-DLA: 18/55, 33%; post DLA: 13/55, 23%, both at p < 0.01). CTCs per 7.5 mL DLA product were median 9.2 times (interquartile range = 5.6–24.0) higher than CTCs in 7.5 mL blood. RosetteSEP did not significantly improve CTC detection (pretreatment: 34/55, 62%, post treatment: 16/34, 47%) and CTCs per mL even decreased compared to DLA (p = 0.04). Patients with advanced-stage disease with DLA-CTC after treatment showed fewer tumour responses and shorter progression-free survival (PFS) than those without DLA-CTC (median PFS, 2.0 vs 12.0 months, p < 0.01). DLA-CTC persistence after treatment was independent of clinical factors associated with shorter PFS (hazard ratio (HR) = 5.8, 95% confidence interval (CI), 1.4–35.5, p = 0.02). All evaluable CTCs showed aneuploidy. Conclusions: DLA detected nine times more CTCs than in the peripheral blood. The sustained presence of CTCs in DLA after treatment was associated with therapy failure and shortened PFS. Trial registration: The study was approved by the Medical Ethical Committee (NL55754.042.15) and was registered in the Dutch trial register (NL5423)

Detection of Circulating Tumor Cells in the Diagnostic Leukapheresis Product of Non-Small-Cell Lung Cancer Patients Comparing CellSearch® and ISET

Circulating tumor cells (CTCs) detected by CellSearch are prognostic in non-small-cell lung cancer (NSCLC), but rarely found. CTCs can be extracted from the blood together with mononuclear cell populations by diagnostic leukapheresis (DLA), therefore concentrating them. However, CellSearch can only process limited DLA volumes (≈2 mL). Therefore, we established a protocol to enumerate CTCs in DLA products with Isolation by SizE of Tumor cells (ISET), and compared CTC counts between CellSearch® and ISET. DLA was performed in NSCLC patients who started a new therapy. With an adapted protocol, ISET could process 10 mL of DLA. CellSearch detected CTCs in a volume equaling 2 × 108 leukocytes (mean 2 mL). CTC counts per mL were compared. Furthermore, the live cell protocol of ISET was tested in eight patients. ISET successfully processed all DLA products—16 with the fixed cell protocol and 8 with the live cell protocol. In total, 10–20 mL of DLA was processed. ISET detected CTCs in 88% (14/16), compared to 69% (11/16, p < 0.05) with CellSearch. ISET also detected higher number of CTCs (ISET median CTC/mL = 4, interquartile range [IQR] = 2–6, CellSearch median CTC/mL = 0.9, IQR = 0–1.8, p < 0.01). Cells positive for the epithelial cell adhesion molecule (EpCAM+) per mL were detected in similar counts by both methods. Eight patients were processed with the live cell protocol. All had EpCAM+, CD45−, CD235- cells isolated by fluorescence-activated cell sorting (FACS). Overall, ISET processed larger volumes and detected higher CTC counts compared to CellSearch. EpCAM+ CTCs were detected in comparable rates

Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools

BACKGROUND: Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. METHODS: The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. RESULTS: Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. CONCLUSIONS: Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example, incidence of pneumonia, distribution of serotypes causing pneumonia) were influential parameters in the models we compared. Understanding the differences and similarities of such CE tools through regular comparisons could render decision-making processes in different countries more efficient, as well as providing guiding information for further clinical and epidemiological research. A tool comparison exercise using standardized data sets can help model developers to be more transparent about their model structure and assumptions and provide analysts and decision makers with a more in-depth view behind the disease dynamics. Adherence to the WHO guide of economic evaluations of immunization programs may also facilitate this process. Please see related article: http://www.biomedcentral.com/1741-7007/9/55

Positive Feedbacks in Seagrass Ecosystems – Evidence from Large-Scale Empirical Data

Positive feedbacks cause a nonlinear response of ecosystems to environmental change and may even cause bistability. Even though the importance of feedback mechanisms has been demonstrated for many types of ecosystems, their identification and quantification is still difficult. Here, we investigated whether positive feedbacks between seagrasses and light conditions are likely in seagrass ecosystems dominated by the temperate seagrass Zostera marina. We applied a combination of multiple linear regression and structural equation modeling (SEM) on a dataset containing 83 sites scattered across Western Europe. Results confirmed that a positive feedback between sediment conditions, light conditions and seagrass density is likely to exist in seagrass ecosystems. This feedback indicated that seagrasses are able to trap and stabilize suspended sediments, which in turn improves water clarity and seagrass growth conditions. Furthermore, our analyses demonstrated that effects of eutrophication on light conditions, as indicated by surface water total nitrogen, were on average at least as important as sediment conditions. This suggests that in general, eutrophication might be the most important factor controlling seagrasses in sheltered estuaries, while the seagrass-sediment-light feedback is a dominant mechanism in more exposed areas. Our study demonstrates the potentials of SEM to identify and quantify positive feedbacks mechanisms for ecosystems and other complex systems

Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle

Background: Acetylcholine, the primary parasympathetic neurotransmitter in the airways, plays an important role in bronchoconstriction and mucus production. Recently, it has been shown that acetylcholine, by acting on muscarinic receptors, is also involved in airway inflammation and remodelling. The mechanism(s) by which muscarinic receptors regulate inflammatory responses are, however, still unknown. Methods: The present study was aimed at characterizing the effect of muscarinic receptor stimulation on cytokine secretion by human airway smooth muscle cells (hASMc) and to dissect the intracellular signalling mechanisms involved. hASMc expressing functional muscarinic M(2) and M(3) receptors were stimulated with the muscarinic receptor agonist methacholine, alone, and in combination with cigarette smoke extract (CSE), TNF-alpha, PDGF-AB or IL-1 beta. Results: Muscarinic receptor stimulation induced modest IL-8 secretion by itself, yet augmented IL-8 secretion in combination with CSE, TNF-alpha or PDGF-AB, but not with IL-1 beta. Pretreatment with GF109203X, a protein kinase C (PKC) inhibitor, completely normalized the effect of methacholine on CSE-induced IL-8 secretion, whereas PMA, a PKC activator, mimicked the effects of methacholine, inducing IL-8 secretion and augmenting the effects of CSE. Similar inhibition was observed using inhibitors of I kappa B-kinase-2 (SC514) and MEK1/2 (U0126), both downstream effectors of PKC. Accordingly, western blot analysis revealed that methacholine augmented the degradation of I kappa B alpha and the phosphorylation of ERK1/2 in combination with CSE, but not with IL-1b in hASMc. Conclusions: We conclude that muscarinic receptors facilitate CSE-induced IL-8 secretion by hASMc via PKC dependent activation of I kappa B alpha and ERK1/2. This mechanism could be of importance for COPD patients usin

Positive Feedbacks in Seagrass Ecosystems – Evidence from Large-Scale Empirical Data

Positive feedbacks cause a nonlinear response of ecosystems to environmental change and may even cause bistability. Even though the importance of feedback mechanisms has been demonstrated for many types of ecosystems, their identification and quantification is still difficult. Here, we investigated whether positive feedbacks between seagrasses and light conditions are likely in seagrass ecosystems dominated by the temperate seagrass Zostera marina. We applied a combination of multiple linear regression and structural equation modeling (SEM) on a dataset containing 83 sites scattered across Western Europe. Results confirmed that a positive feedback between sediment conditions, light conditions and seagrass density is likely to exist in seagrass ecosystems. This feedback indicated that seagrasses are able to trap and stabilize suspended sediments, which in turn improves water clarity and seagrass growth conditions. Furthermore, our analyses demonstrated that effects of eutrophication on light conditions, as indicated by surface water total nitrogen, were on average at least as important as sediment conditions. This suggests that in general, eutrophication might be the most important factor controlling seagrasses in sheltered estuaries, while the seagrass-sediment-light feedback is a dominant mechanism in more exposed areas. Our study demonstrates the potentials of SEM to identify and quantify positive feedbacks mechanisms for ecosystems and other complex systems

Feasibility and impact of providing feedback to vaccinating medical clinics: evaluating a public health intervention

<p>Abstract</p> <p>Background</p> <p>Vaccine coverage (VC) at a given age is a widely-used indicator for measuring the performance of vaccination programs. However, there is increasing data suggesting that measuring delays in administering vaccines complements the measure of VC. Providing feedback to vaccinators is recognized as an effective strategy for improving vaccine coverage, but its implementation has not been widely documented in Canada. The objective of this study was to evaluate the feasibility of providing personalized feedback to vaccinators and its impact on vaccination delays (VD).</p> <p>Methods</p> <p>In April and May 2008, a one-hour personalized feedback session was provided to health professionals in vaccinating medical clinics in the Quebec City region. VD for vaccines administered at two and twelve months of age were presented. Data from the regional vaccination registry were analysed for participating clinics. Two 12-month periods before and after the intervention were compared, namely from April 1^st, 2007 to March 31^st, 2008 and from June 1^st, 2008 to May 31^st, 2009.</p> <p>Results</p> <p>Ten medical clinics out of the twelve approached (83%), representing more than 2500 vaccinated children, participated in the project. Preparing and conducting the feedback involved 20 hours of work and expenses of $1000 per clinic. Based on a delay of one month, 94% of first doses of DTaP-Polio-Hib and 77% of meningococcal vaccine doses respected the vaccination schedule both before and after the intervention. Following the feedback, respect of the vaccination schedule increased for vaccines planned at 12 months for the four clinics that had modified their vaccination practices related to multiple injections (depending on the clinic, VD decreased by 24.4%, 32.0%, 40.2% and 44.6% respectively, p < 0.001 for all comparisons).</p> <p>Conclusions</p> <p>The present study shows that it is feasible to provide personalized feedback to vaccinating clinics. While it may have encouraged positive changes in practice concerning multiple injections, this intervention on its own did not impact vaccination delays of the clinics visited. It is possible that feedback integrated into other types of effective interventions and sustained over time may have more impact on VD.</p

Estimation of Pap-test coverage in an area with an organised screening program: challenges for survey methods

BACKGROUND: The cytological screening programme of Viterbo has completed the second round of invitations to the entire target population (age 25–64). From a public health perspective, it is important to know the Pap-test coverage rate and the use of opportunistic screening. The most commonly used study design is the survey, but the validity of self-reports and the assumptions made about non respondents are often questioned. METHODS: From the target population, 940 women were sampled, and responded to a telephone interview about Pap-test utilisation. The answers were compared with the screening program registry; comparing the dates of Pap-tests reported by both sources. Sensitivity analyses were performed for coverage over a 36-month period, according to various assumptions regarding non respondents. RESULTS: The response rate was 68%. The coverage over 36 months was 86.4% if we assume that non respondents had the same coverage as respondents, 66% if we assume they were not covered at all, and 74.6% if we adjust for screening compliance in the non respondents. The sensitivity and specificity of the question, "have you ever had a Pap test with the screening programme" were 84.5% and 82.2% respectively. The test dates reported in the interview tended to be more recent than those reported in the registry, but 68% were within 12 months of each other. CONCLUSION: Surveys are useful tools to understand the effectiveness of a screening programme and women's self-report was sufficiently reliable in our setting, but the coverage estimates were strongly influenced by the assumptions we made regarding non respondents