Intracluster correlation coefficients and coefficients of variation for perinatal outcomes from five cluster-randomised controlled trials in low and middle-income countries: results and methodological implications

Background: Public health interventions are increasingly evaluated using cluster-randomised trials in which groups rather than individuals are allocated randomly to treatment and control arms. Outcomes for individuals within the same cluster are often more correlated than outcomes for individuals in different clusters. This needs to be taken into account in sample size estimations for planned trials, but most estimates of intracluster correlation for perinatal health outcomes come from hospital-based studies and may therefore not reflect outcomes in the community. In this study we report estimates for perinatal health outcomes from community-based trials to help researchers plan future evaluations.Methods: We estimated the intracluster correlation and the coefficient of variation for a range of outcomes using data from five community-based cluster randomised controlled trials in three low-income countries: India, Bangladesh and Malawi. We also performed a simulation exercise to investigate the impact of cluster size and number of clusters on the reliability of estimates of the coefficient of variation for rare outcomes.Results: Estimates of intracluster correlation for mortality outcomes were lower than those for process outcomes, with narrower confidence intervals throughout for trials with larger numbers of clusters. Estimates of intracluster correlation for maternal mortality were particularly variable with large confidence intervals. Stratified randomisation had the effect of reducing estimates of intracluster correlation. The simulation exercise showed that estimates of intracluster correlation are much less reliable for rare outcomes such as maternal mortality. The size of the cluster had a greater impact than the number of clusters on the reliability of estimates for rare outcomes.Conclusions: The breadth of intracluster correlation estimates reported here in terms of outcomes and contexts will help researchers plan future community-based public health interventions around maternal and newborn health. Our study confirms previous work finding that estimates of intracluster correlation are associated with the prevalence of the outcome of interest, the nature of the outcome of interest ( mortality or behavioural) and the size and number of clusters. Estimates of intracluster correlation for maternal mortality need to be treated with caution and a range of estimates should be used in planning future trials

Socioeconomic and physical distance to the maternity hospital as predictors for place of delivery: an observation study from Nepal

BACKGROUND: Although the debate on the safety and women's right of choice to a home delivery vs. hospital delivery continues in the developed countries, an undesirable outcome of home delivery, such as high maternal and perinatal mortality, is documented in developing countries. The objective was to study whether socio-economic factors, distance to maternity hospital, ethnicity, type and size of family, obstetric history and antenatal care received in present pregnancy affected the choice between home and hospital delivery in a developing country. METHODS: This cross-sectional study was done during June, 2001 to January 2002 in an administratively and geographically well-defined territory with a population of 88,547, stretching from urban to adjacent rural part of Kathmandu and Dhading Districts of Nepal with maximum of 5 hrs of distance from Maternity hospital. There were no intermediate level of private or government hospital or maternity homes in the study area. Interviews were carried out on 308 women who delivered within 45 days of the date of the interview with a pre-tested structured questionnaire. RESULTS: A distance of more than one hour to the maternity hospital (OR = 7.9), low amenity score status (OR = 4.4), low education (OR = 2.9), multi-parity (OR = 2.4), and not seeking antenatal care in the present pregnancy (OR = 4.6) were statistically significantly associated with an increased risk of home delivery. Ethnicity, obstetric history, age of mother, ritual observance of menarche, type and size of family and who is head of household were not statistically significantly associated with the place of delivery. CONCLUSIONS: The socio-economic standing of the household was a stronger predictor of place of delivery compared to ethnicity, the internal family structure such as type and size of family, head of household, or observation of ritual days by the mother of an important event like menarche. The results suggested that mothers, who were in the low-socio-economic scale, delivered at home more frequently in a developing country like Nepal

Rationale and study design of the prospective, longitudinal, observational cohort study “rISk strAtification in end-stage renal disease” (ISAR) study

Background: The ISAR study is a prospective, longitudinal, observational cohort study to improve the cardiovascular risk stratification in endstage renal disease (ESRD). The major goal is to characterize the cardiovascular phenotype of the study subjects, namely alterations in micro-and macrocirculation and to determine autonomic function. Methods/design: We intend to recruit 500 prevalent dialysis patients in 17 centers in Munich and the surrounding area. Baseline examinations include: (1) biochemistry, (2) 24-h Holter Electrocardiography (ECG) recordings, (3) 24-h ambulatory blood pressure measurement (ABPM), (4) 24 h pulse wave analysis (PWA) and pulse wave velocity (PWV), (5) retinal vessel analysis (RVA) and (6) neurocognitive testing. After 24 months biochemistry and determination of single PWA, single PWV and neurocognitive testing are repeated. Patients will be followed up to 6 years for (1) hospitalizations, (2) cardiovascular and (3) non-cardiovascular events and (4) cardiovascular and (5) all-cause mortality. Discussion/conclusion: We aim to create a complex dataset to answer questions about the insufficiently understood pathophysiology leading to excessively high cardiovascular and non-cardiovascular mortality in dialysis patients. Finally we hope to improve cardiovascular risk stratification in comparison to the use of classical and non-classical (dialysis-associated) risk factors and other models of risk stratification in ESRD patients by building a multivariable Cox-Regression model using a combination of the parameters measured in the study

Detection of conjugation related type four secretion machinery in Aeromonas culicicola

BACKGROUND: Aeromonas sp. can now be considered relatively common enteropathogens due to the increase of diseases in humans. Aeromonas culicicola is a gram negative rod-shaped bacterium isolated for the first time from the mosquito mid-gut, but subsequently detected in other insects and waters also. Our previous study discovered that A. culicicola harbors three plasmids, which we designated as pAc3249A, pAc3249B and pAc3249C. We investigated and report here the existence and genetic organization of a Conjugal Type IV Secretion System (TFSS) in pAc3249A. METHODOLOGY/PRINCIPLE FINDING: The complete operon is 11,061 bp in length and has G+C content of 47.20% code for 12 ORFs. The gene order and orientation were similar to those found in other bacteria with some differences. We have designated this system as AcTra for Aeromonas culicicola transfer system. BLAST results of ORFs and phylogenetic analysis showed significant similarity towards the respective proteins of the IncI2 plasmid R721 of E. coli. Other bioinformatics studies have been performed to predict conserved motifs/domains, signal peptides, transmembrane helices, etc. of the ORFs. CONCLUSIONS/SIGNIFICANCE: BLAST results of ORFs and phylogenetic analysis showed significant similarity towards the respective proteins of the IncI2 plasmid R721 of E. coli

S-D logic-informed customer engagement: Integrative framework, revised fundamental propositions, and application to CRM

Advance online in 2016</p

Dual Drug Conjugate Loaded Nanoparticles for the Treatment of Cancer

Two antineoplastic agents, Imatinib (IM) and 5-Fluorouracil (FU) were conjugated by hydrolysable linkers through an amide bond and entrapped in polymeric Human Serum Albumin (HSA) nanoparticles. The presence of dual drugs in a common carrier has the advantage of reaching the site of action simultaneously and acting at different phases of the cell cycle to arrest the growth of cancer cells before they develop chemoresistance. The study has demonstrated an enhanced anticancer activity of the conjugate, and conjugate loaded stealth HSA nanoparticles (NPs) in comparison to the free drug in A-549 human lung carcinoma cell line and Zebra fish embryos (Danio rerio). Hydrolysability of the conjugate has also been demonstrated with complete hydrolysis being observed after 12 h. In vivo pharmacodynamics study in terms of tumor volume and pharmacokinetics in mice for conjugate (IM-SC-FU) and conjugate loaded nanoparticles showed significant anti-cancer activity. The other parameters evaluated were particle size (86nm), Poly Dispersive Index (PDI) (0.209), zeta potential (-49mV), drug entrapment efficiency (96.73%) and drug loading efficiency (89%). Being in stealth mode gives the potential for the NPs to evade Reticulo-Endothelial system (RES), achieve passive targeting by Enhanced Permeation Retention (EPR) effect with controlled release of the therapeutic agent. As the conjugate cleaves into individual drugs in the tumor environment, this promises better suppression of cancer chemoresistance by delivering dual drugs with different modes of action at the same site, thereby synergistically inhibiting the growth of cancerous tissue