Levels and Correlates of Non-Adherence to WHO Recommended Inter-Birth Intervals in Rufiji, Tanzania.

Poorly spaced pregnancies have been documented worldwide to result in adverse maternal and child health outcomes. The World Health Organization (WHO) recommends a minimum inter-birth interval of 33 months between two consecutive live births in order to reduce the risk of adverse maternal and child health outcomes. However, birth spacing practices in many developing countries, including Tanzania, remain scantly addressed. METHODS: Longitudinal data collected in the Rufiji Health and Demographic Surveillance System (HDSS) from January 1999 to December 2010 were analyzed to investigate birth spacing practices among women of childbearing age. The outcome variable, non-adherence to the minimum inter-birth interval, constituted all inter-birth intervals <33 months long. Inter-birth intervals >=33 months long were considered to be adherent to the recommendation. Chi-Square was used as a test of association between non-adherence and each of the explanatory variables. Factors affecting non-adherence were identified using a multilevel logistic model. Data analysis was conducted using STATA (11) statistical software. RESULTS: A total of 15,373 inter-birth intervals were recorded from 8,980 women aged 15--49 years in Rufiji district over the follow-up period of 11 years. The median inter-birth interval was 33.4 months. Of the 15,373 inter-birth intervals, 48.4% were below the WHO recommended minimum length of 33 months between two live births. Non-adherence was associated with younger maternal age, low maternal education, multiple births of the preceding pregnancy, non-health facility delivery of the preceding birth, being an in-migrant resident, multi-parity and being married. CONCLUSION: Generally, one in every two inter-birth intervals among 15--49 year-old women in Rufiji district is poorly spaced, with significant variations by socio-demographic and behavioral characteristics of mothers and newborns. Maternal, newborn and child health services should be improved with a special emphasis on community- and health facility-based optimum birth spacing education in order to enhance health outcomes of mothers and their babies, especially in rural settings

Preventing Bias in Cluster Randomised Trials

Bruno Giraudeau and Philippe Ravaud discuss the difficulties in preventing selection bias and applying intention-to-treat analysis in cluster randomized trials, and propose some solutions

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

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78-8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80-235.90] and 5.12 [1.45-18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15-17.22).The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.ISRCTN 48133332

Distribuição espacial do baixo peso ao nascer em Sergipe, Brasil, 1995/1998 Space distribution of low birth weight in Sergipe, Brazil, 1995/1998

O estudo analisa a distribuição espacial do baixo peso ao nascer em Sergipe, Brasil, avaliando o evento como indicador de saúde. A análise foi feita a partir de 166.312 nascimentos vivos dos 75 municípios, numa abordagem ecológica. Foram utilizados quatro métodos: clusters analysis, análise de correlação, análise de regressão múltipla e multiple comparisons (Tukey). O estudo evidencia homogeneidade interna dos municípios nos distritos de saúde e nos grupos resultantes do dendrograma. Considerando 10,00% de perda de informação, identifica-se a presença de sete grupos, sendo dois resíduos (Aracaju e Porto da Folha). A evolução do baixo peso ao nascer, em Sergipe, é declinante (média de 6,97% no período) e reflete tímida melhoria da qualidade de vida. As suas causas indicam relações com o ambiente e são influenciadas pelos padrões de ocupação do espaço. O percentual do baixo peso ao nascer é útil como indicador de risco individual, porém, como indicador coletivo de saúde, não parece ser capaz de expressar diferenças entre regiões que não apresentam variabilidade acentuada entre si.<br>This study analyzes the spatial distribution of low birth weight (LBW) in the State of Sergipe, Brazil, evaluating the event as a health indicator. The analysis was based on 166,312 live births in the 75 municipalities in the State, using an ecological approach. Four methods were used: cluster analysis, correlation analysis, multiple regression analysis, and multiple comparisons (Tukey). The study shows internal homogeneity in the municipalities' health districts and in the groups resulting from the cluster analysis. Considering a 10% loss of information, seven groups were identified, two of which were residues (Aracaju and Porto da Folha). There is a downward trend in LBW in Sergipe (with a mean of 6.97% during the period), reflecting a slight improvement in quality of life. The causes suggest relations with the environment and are influenced by spatial occupation patterns. The percentage of LBW is a useful indicator of individual risk, but as a collective health indicator it does not appear capable of expressing differences between regions that do not display strong inter-variability

The Central Atlantic Magmatic Province (CAMP): A Review

The Central Atlantic magmatic province (CAMP) consists of basic rocks emplaced as shallow intrusions and erupted in large lava flow fields over a land surface area in excess of 10 million km2 on the supercontinent Pangaea at about 201 Ma. The peak activity of the CAMP straddled the Triassic-Jurassic boundary and probably lasted less than 1 million years, while late activity went on for several Ma more into the Sinemurian. Emission of carbon and sulfur from the CAMP magmas and from intruded sediments probably caused extinctions at the end-Triassic. Intrusive rocks are represented by isolated dykes up to 800 km-long, by dense dyke swarms and by extremely voluminous sills and a few layered intrusions. Lava fields were erupted as short-lived pulses and can be traced over distances of several hundred km within sedimentary basins. They consist of either compound or simple pahoehoe flows. Globally, the intrusive and effusive rocks are estimated to represent an original magmatic volume of at least 3 million km3. Herein we subdivide the CAMP basalts for the first time into six main geochemical groups, five represented by low-Ti and one by high-Ti rocks. Except for one low-Ti group, which is ubiquitous throughout the entire province, all other groups occur in relatively restricted areas and their compositions probably reflect contamination from the local continental lithosphere. Major and trace elements and Sr-Nd-Pb-Os isotopic compositions indicate that the basaltic magmas had an enriched composition compared to Mid-Ocean Ridge basalts and different from Atlantic Ocean Island basalts. The enriched composition of CAMP basalts is only in part attributable to crustal contamination. It also probably requires subducted upper and lower continental crust material that enriched the shallow upper mantle from which CAMP basalts were generated. A contribution from a deep mantle-plume is not required by geochemical and thermometric data, but it remains unclear what other possible heat source caused mantle melting on the scale required to form CAMP