Dementia care initiative in primary practice – study protocol of a cluster randomized trial on dementia management in a general practice setting

<p>Abstract</p> <p>Background</p> <p>Current guidelines for dementia care recommend the combination of drug therapy with non-pharmaceutical measures like counselling and social support. However, the scientific evidence concerning non-pharmaceutical interventions for dementia patients and their informal caregivers remains inconclusive. Targets of modern comprehensive dementia care are to enable patients to live at home as long and as independent as possible and to reduce the burden of caregivers. The objective of the study is to compare a complex intervention including caregiver support groups and counselling against usual care in terms of time to nursing home placement. In this paper the study protocol is described.</p> <p>Methods/Design</p> <p>The IDA (Initiative Demenzversorgung in der Allgemeinmedizin) project is designed as a three armed cluster-randomized trial where dementia patients and their informal caregivers are recruited by general practitioners. Patients in the study region of Middle Franconia, Germany, are included if they have mild or moderate dementia, are at least 65 years old, and are members of the German AOK (Allgemeine Ortskrankenkasse) sickness fund. In the control group patients receive regular treatment, whereas in the two intervention groups general practitioners participate in a training course in evidence based dementia treatment, recommend support groups and offer counseling to the family caregivers either beginning at baseline or after the 1-year follow-up. The study recruitment and follow-up took place from July 2005 to January 2009. 303 general practitioners were randomized of which 129 recruited a total of 390 patients. Time to nursing home admission within the two year intervention and follow-up period is the primary endpoint. Secondary endpoints are cognitive status, activities of daily living, burden of care giving as well as healthcare costs. For an economic analysis from the societal perspective, data are collected from caregivers as well as by the use of routine data from statutory health insurance and long-term care insurance.</p> <p>Discussion</p> <p>From a public health perspective, the IDA trial is expected to lead to evidence based results on the community effectiveness of non-pharmaceutical support measures for dementia patients and their caregivers in the primary care sector. For health policy makers it is necessary to make their decisions about financing new services based on strong knowledge about the acceptance of measures in the population and their cost-effectiveness.</p> <p>Trial registration</p> <p>ISRCTN68329593</p

Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa

Lujo virus (LUJV), a new member of the family Arenaviridae and the first hemorrhagic fever–associated arenavirus from the Old World discovered in three decades, was isolated in South Africa during an outbreak of human disease characterized by nosocomial transmission and an unprecedented high case fatality rate of 80% (4/5 cases). Unbiased pyrosequencing of RNA extracts from serum and tissues of outbreak victims enabled identification and detailed phylogenetic characterization within 72 hours of sample receipt. Full genome analyses of LUJV showed it to be unique and branching off the ancestral node of the Old World arenaviruses. The virus G1 glycoprotein sequence was highly diverse and almost equidistant from that of other Old World and New World arenaviruses, consistent with a potential distinctive receptor tropism. LUJV is a novel, genetically distinct, highly pathogenic arenavirus

Adoption of an “Open” Envelope Conformation Facilitating CD4 Binding and Structural Remodeling Precedes Coreceptor Switch in R5 SHIV-Infected Macaques

A change in coreceptor preference from CCR5 to CXCR4 towards the end stage disease in some HIV-1 infected individuals has been well documented, but the reasons and mechanisms for this tropism switch remain elusive. It has been suggested that envelope structural constraints in accommodating amino acid changes required for CXCR4 usage is an obstacle to tropism switch, limiting the rate and pathways available for HIV-1 coreceptor switching. The present study was initiated in two R5 SHIVSF162P3N-infected rapid progressor macaques with coreceptor switch to test the hypothesis that an early step in the evolution of tropism switch is the adoption of a less constrained and more “open” envelope conformation for better CD4 usage, allowing greater structural flexibility to accommodate further mutational changes that confer CXCR4 utilization. We show that, prior to the time of coreceptor switch, R5 viruses in both macaques evolved to become increasingly sCD4-sensitive, suggestive of enhanced exposure of the CD4 binding site and an “open” envelope conformation, and this correlated with better gp120 binding to CD4 and with more efficient infection of CD4low cells such as primary macrophages. Moreover, significant changes in neutralization sensitivity to agents and antibodies directed against functional domains of gp120 and gp41 were seen for R5 viruses close to the time of X4 emergence, consistent with global changes in envelope configuration and structural plasticity. These observations in a simian model of R5-to-X4 evolution provide a mechanistic basis for the HIV-1 coreceptor switch

Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity

Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the “intrinsic reactivity” of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant (“Tier 2-like”) viruses, globally sensitive (“Tier 1”) viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of inhibitor/antibody binding to the envelope glycoprotein trimer and by envelope glycoprotein reactivity to the inhibitor/antibody binding event. Quantitative differences in intrinsic reactivity contribute to HIV-1 strain variability in global susceptibility to neutralization and explain the long-observed relationship between increased inhibitor sensitivity and decreased entry requirements for target cell CD4

Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in Gambian case contacts.

BACKGROUND: Studies of Tuberculosis (TB) case contacts are increasingly being utilised for understanding the relationship between M. tuberculosis and the human host and for assessing new interventions and diagnostic tests. We aimed to identify the incidence rate of new TB cases among TB contacts and to relate this to their initial Mantoux and ELISPOT test results. METHODS AND FINDINGS: After initial Mantoux and ELISPOT tests and exclusion of co-prevalent TB cases, we followed 2348 household contacts of sputum smear positive TB cases. We visited them at 3 months, 6 months, 12 months, 18 months and 24 months, and investigated those with symptoms consistent with TB. Those who were diagnosed separately at a government clinic had a chest x-ray. Twenty six contacts were diagnosed with definite TB over 4312 person years of follow-up (Incidence rate 603/100,000 person years; 95% Confidence Interval, 370-830). Nine index and secondary case pairs had cultured isolates available for genotyping. Of these, 6 pairs were concordant and 3 were discordant. 2.5% of non-progressors were HIV positive compared to 12% of progressors (HR 6.2; 95% CI 1.7-22.5; p = 0.010). 25 secondary cases had initial Mantoux results, 14 (56%) were positive ; 21 had initial ELISPOT results, 11 (52%) were positive; 15 (71%) of 21 tested were positive by one or the other test. Of the 6 contacts who had concordant isolates with their respective index case, 4 (67%) were Mantoux positive at recruitment, 3 (50%) were ELISPOT positive; 5 (83%) were positive by one or other of the two tests. ELISPOT positive contacts, and those with discordant results, had a similar rate of progression to those who were Mantoux positive. Those negative on either or both tests had the lowest rate of progression. CONCLUSIONS: The incidence rate of TB disease in Gambian TB case contacts, after screening for co-prevalent cases, was 603/100,000 person years. Since initial ELISPOT test and Mantoux tests were each positive in only just over half of cases, but 71% were positive by one or other test, positivity by either might be the best indication for preventive treatment. These data do not support the replacement of the Mantoux test by an ELISPOT test in The Gambia or similar settings

Gravidez na adolescência e baixo peso ao nascer: existe associação? Embarazo en la adolescencia y bajo peso al nacer: ¿existe asociación? Pregnancy in teenagers and low birthweight infant: is there an association?

OBJETIVO: Verificar a associação entre gravidez na adolescência (dez a 19 anos) e baixo peso ao nascer. MÉTODOS: Estudo transversal realizado em maternidade terciária entre junho de 2000 a junho de 2001. Por sorteio aleatório simples, foram selecionadas mães adolescentes e não adolescentes entrevistadas no primeiro dia após o parto. Aplicou-se a análise multivariada por meio de regressão logística das variáveis implicadas com o baixo peso ao nascer. RESULTADOS: Foram selecionadas 539 duplas (mães e seus respectivos recém-nascidos), sendo 331 (61,4%) mulheres com 20 anos ou mais e 208 (38,5%) abaixo de 20 anos. Entre as adolescentes, 50 bebês (24%) tiveram idade gestacional <37 semanas, enquanto entre as mães acima de 20 anos, 52 (15,7%) eram prematuros (OR 1,58; IC95% 1,00-2,51). Entre as adolescentes, ocorreram 52 (25%) recém-nascidos com peso <2500g e, entre as adultas, 56 (16,9%) tinham baixo peso (OR 1,64; IC95% 1,05-2,56). Entre as que realizaram pré-natal adequado, a ocorrência de baixo peso foi de 12,3% e de 22,1% no grupo cuja assistência foi inadequada. Nesta casuística, a associação encontrada na análise univariada entre baixo peso e mãe adolescente não se manteve na análise multivariada. CONCLUSÕES: Baixo peso ao nascer em gestações na adolescência não pode ser atribuído isoladamente à idade materna.<br>OBJETIVO: Verificar la asociación entre embarazo en la adolescencia (10 a 19 años) y bajo peso al nacer. MÉTODOS: Estudio transversal realizado en maternidad terciaria entre junio de 2000 a junio de 2001. Por sorteo aleatorio simple, se seleccionaron madres adolescentes y no adolescentes entrevistadas en el primer día después del parto. Se aplicó el análisis multivariado mediante regresión logística de las variables implicadas con el bajo peso al nacer. RESULTADOS: Se seleccionaron 539 parejas (madres y sus respectivos recién-nacidos), siendo 331 (61,4%) mujeres con 20 años o más y 208 (38,5%) abajo de los 20 años. Entre las adolescentes, 50 bebés (24%) tuvieron edad gestacional <37 semanas, mientras que entre las madres con más de 20 años, 52 (15,7%) eran prematuros (OR 1,58; IC95% 1,00-2,51). Entre las adolescentes, ocurrieron 52 (25%) recién nacidos con peso <2.500g entre las adultas, 56 (16,9%) tenían bajo peso (OR 1,64; IC95% 1,05-2,56). Entre las que realizaron prenatal adecuado, la ocurrencia de bajo peso fue de 12,3% y de 22,1% en el grupo cuya asistencia fue inadecuada. En esa casuística, la asociación encontrada en el análisis bivariado entre bajo peso y madre adolescente no se mantuvo en el análisis multivariado. CONCLUSIONES: Bajo peso al nacer en gestaciones en la adolescencia no puede ser atribuido aisladamente a la edad materna.<br>OBJECTIVE: To study the association between teenage pregnancy (ten to 19 years old) and low birthweight. METHODS: Cross-sectional study carried out at a tertiary center from June 2000 to June 2001. A simple random drawing selected teenagers and adult mothers who were interviewed during the first day after birth. Multivariate analysis using logistic regression of variables related to low birthweight was applied. RESULTS: 539 pairs (mothers and their newborns) were studied - 331 (61.4%) women with 20 years old or more and 208 (38.5%) <20 years old. Among the adolescents, 50 (24%) infants had gestational age <37 weeks, whereas among mothers over 20 years old, 52 (15.7%) were preterm (OR 1.58; 95%CI 1.00-2.51). Among the adolescent and adult women, there were respectively 52 (25%) and 56 (16.9%) newborns <2500g (OR 1.64; 95%CI 1.05-2.56). Among those who had adequate prenatal care, low birth weight was detected in 12.3 and 22.1% of mothers with adequate and inadequate prenatal care, respectively. The association found in the univariate analysis between low birth weight and maternal age was not sustained in the multivariate analysis. CONCLUSIONS: Low birth weight in teenage pregnancies can not be attributed only to maternal age

Gangs, Migration and Crime; The changing landscape in Europe and the United States

The history of gangs is intertwined with migration. In America, a number of classic studies have reported on the possible causal link between immigration, socio-economic position, social disorganization, and gang formation. More recently in Europe, the impact of migration on gangs reflects a complex mix of factors that also includes cultural and media influences. In addition, there are other contextual factors such as immigration and population movement that have received less attention, yet condition the relationship between structural factors and the formation of gangs. Processes such as immigration, migration, and resettlement have had an important impact on the transmission of gangs on an international, national, and local scale, often enhanced by the impact of immigration. This article examines the relationship between immigration, culture, and gangs and contrasts European and US research

The impact of national culture and economic ideology on managerial work values: a study of the United States, Russia, Japan, and China

This study assesses the impact of economic ideology and national culture on the individual work values of managers in the United States, Russia, Japan, and China. The convergence–divergence–crossvergence (CDC) framework was used as a theoretical framework for the study, while the Schwartz Value Survey (SVS) was used to operationalize our investigation of managerial work values across these four countries. The findings largely support the crossvergence perspective, while also confirming the role of national culture. Implications from the findings are drawn for the convergence–divergence–crossvergence of values, as well as for the feasibility of multidomestic or global strategies for a corporate culture. Journal of International Business Studies (2008) 39, 8–26. doi:10.1057/palgrave.jibs.8400330