Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial

Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs). Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results: In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers. Conclusions: Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

How can onchocerciasis elimination in Africa be accelerated? Modelling the impact of increased ivermectin treatment frequency and complementary vector control

Background: Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. Methods: We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Results: Areas with 40%–50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%–80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Conclusions: Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful

Hyaluronan concentration and size distribution in human knee synovial fluid: variations with age and cartilage degeneration.

BackgroundOne potential mechanism for early superficial cartilage wear in normal joints is alteration of the lubricant content and quality of synovial fluid. The purpose of this study was to determine if the concentration and quality of the lubricant, hyaluronan, in synovial fluid: (1) was similar in left and right knees; (2) exhibited similar age-associated trends, whether collected postmortem or antemortem; and (3) varied with age and grade of joint degeneration.MethodsHuman synovial fluid of donors (23-91 years) without osteoarthritis was analyzed for the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, 0.5-1 MDa, and 0.03-0.5 MDa. Similarity of data between left and right knees was assessed by reduced major axis regression, paired t-test, and Bland-Altman analysis. The effect of antemortem versus postmortem collection on biochemical properties was assessed for age-matched samples by unpaired t-test. The relationships between age, joint grade, and each biochemical component were assessed by regression analysis.ResultsJoint grade and the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, and 0.5-1 MDa in human synovial fluid showed good agreement between left and right knees and were similar between age-matched patient and cadaver knee joints. There was an age-associated decrease in overall joint grade (-15 %/decade) and concentrations of hyaluronan (-10.5 %/decade), and hyaluronan in the molecular weight ranges of 2.5-7 MDa (-9.4 %/decade), 1-2.5 MDa (-11.3 %/decade), 0.5-1 MDa (-12.5 %/decade), and 0.03-0.5 MDa (-13.0 %/decade). Hyaluronan concentration and quality was more strongly associated with age than with joint grade.ConclusionsThe age-related increase in cartilage wear in non-osteoarthritic joints may be related to the altered hyaluronan content and quality of synovial fluid

An ontology-based MDA framework for service-based software systems architecting

Model-driven Architecture (MDA) is a software architecture framework proposed by the Object Management Group OMG. MDA emphasises the importance of modelling in the architectural design of software systems. Ontologies are can enhance the modelling aspects here. We present a layered MDA-based modelling approach. We focus on servicebased software and the Web Services platform

A review of factors that influence individual compliance with mass drug administration for elimination of lymphatic filariasis.

BACKGROUND: The success of programs to eliminate lymphatic filariasis (LF) depends in large part on their ability to achieve and sustain high levels of compliance with mass drug administration (MDA). This paper reports results from a comprehensive review of factors that affect compliance with MDA. METHODOLOGY/PRINCIPAL FINDINGS: Papers published between 2000 and 2012 were considered, and 79 publications were included in the final dataset for analysis after two rounds of selection. While results varied in different settings, some common features were associated with successful programs and with compliance by individuals. Training and motivation of drug distributors is critically important, because these people directly interact with target populations, and their actions can affect MDA compliance decisions by families and individuals. Other important programmatic issues include thorough preparation of personnel, supplies, and logistics for implementation and preparation of the population for MDA. Demographic factors (age, sex, income level, and area of residence) are often associated with compliance by individuals, but compliance decisions are also affected by perceptions of the potential benefits of participation versus the risk of adverse events. Trust and information can sometimes offset fear of the unknown. While no single formula can ensure success MDA in all settings, five key ingredients were identified: engender trust, tailor programs to local conditions, take actions to minimize the impact of adverse events, promote the broader benefits of the MDA program, and directly address the issue of systematic non-compliance, which harms communities by prolonging their exposure to LF. CONCLUSIONS/SIGNIFICANCE: This review has identified factors that promote coverage and compliance with MDA for LF elimination across countries. This information may be helpful for explaining results that do not meet expectations and for developing remedies for ailing MDA programs. Our review has also identified gaps in understanding and suggested priority areas for further research

Multi-micronutrient supplementation in HIV-infected South African children : effect on nutritional s tatus, diarrhoea and respiratory infections

Background: The nutritional status of HIV-infected children is reported to be poor. Diarrhoea and acute respiratory infections tend to be more common and severe in HIV-infected children than in uninfected ones. Deficiencies of micronutrients may result in poor growth and increased risk of diarrhoea and respiratory infections. Micronutrient deficiencies are common in HIV-infected children. The poor growth, diarrhoea and respiratory infections seen in HIV-infected children may be partly due to micronutrient deficiencies. The studies in this thesis had two main objectives: (1) to evaluate the effect of short-term (during hospitalization) and long-term (6 months) multi-micronutrient supplementation on episodes of diarrhoea and respiratory infections in HIV-infected children who are not yet on antiretroviral therapy (ART), and (2) to assess the effects of long-term multi-micronutrient supplementation on appetite and growth performance of HIV-infected who are not on ART. Methods and results: Four studies were conducted. Initially a cross-sectional study was performed in which the duration of hospitalization, weight, length, micronutrient status and appetite of HIV-infected children admitted with diarrhoea or pneumonia was compared with the results of HIV-uninfected children. Duration of hospitalization was 2.8 days (52%) longer in HIV-infected children. Appetite as measured by amount of test food eaten (g per kg body weight) was 26% poorer in HIV-infected children. Mean length-for-age Z-scores were lower in HIV-infected children; there was no difference in level of wasting. Subsequently multi-micronutrient supplementation studies were performed, one short-term and two long-term studies. The effect of supplementation on the duration of hospitalization in HIV-infected children with diarrhoea or pneumonia was assessed in the short-term study. One long-term study assessed the supplement’s impact on growth and frequency of episodes of diarrhoea and of pneumonia in HIV-infected children. The other evaluated the effect of the supplement on the appetite of these children. The supplement contained vitamins A, B complex, C, D, E and folic acid, and the minerals copper, iron, selenium and zinc at levels based on recommended dietary allowances. In the short-term supplementation study HIV-infected children aged 4-24 months who were hospitalized with pneumonia or diarrhoea received the supplement or a placebo until discharge from hospital. The duration of hospitalization was 1.7 days (19%) shorter in the supplement group. Long-term multi-micronutrient supplementation improved the weight-for-age and weight-for-height Z-scores of HIV-infected children aged 4-24 months by 0.4 over the 6-month period. There was no improvement in stunting. Children in the supplement group had substantially fewer episodes of respiratory symptoms per month than the placebo group (0.66 ± 0.51) per month vs (1.01 ± 0.67) (P P = 0.09). There was no effect on CD4 lymphocytes. Long-term supplementation with micronutrients had benefits on the appetite of HIV-infected children aged 6-24 months as well. Improvements in amount of test food eaten over the 6-month period were much higher among children who received the supplement (4.7 ± 14.7 g/kg body weight) than the changes in those who received the placebo (-1.4 ± 11.6 g/kg body weight). Conclusion: Multi-micronutrient supplementation reduces the duration of diarrhoea and of pneumonia and incidence of diarrhoea and of respiratory symptoms in HIV-infected children who are not yet on ART. Multi-micronutrient supplementation also improves appetite and weight in these children but not height. The results of these studies indicate that multi-micronutrient supplementation should be considered in HIV-infected infant and young children who have not commenced ART. </p

The use of Multiple Displacement Amplification to increase the detection and genotyping of <i>Trypanosoma</i> samples immobilised on FTA filters.

Whole genome amplification methods are a recently developed tool for amplifying DNA from limited template. We report its application in trypanosome infections, characterized by low parasitemias. Multiple displacement amplification (MDA) amplifies DNA with a simple in vitro step and was evaluated on mouse blood samples on FTA filter cards with known numbers of Trypanosoma brucei parasites. The data showed a 20-fold increase in the number of PCRs possible per sample, using primers diagnostic for the multicopy ribosomal ITS region or 177-bp repeats, and a 20-fold increase in sensitivity over nested PCR against a single-copy microsatellite. Using MDA for microsatellite genotyping caused allele dropout at low DNA concentrations, which was overcome by pooling multiple MDA reactions. The validity of using MDA was established with samples from Human African Trypanosomiasis patients. The use of MDA allows maximal use of finite DNA samples and may prove a valuable tool in studies where multiple reactions are necessary, such as population genetic analyses