Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST—Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab. METHODS: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg). DISCUSSION: This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov NCT03816397. Registered on 25 January 2019. EudraCT 2019-000412-29. Registered on 17 January 201

A Randomized Controlled Trial to Measure Spillover Effects of a Combined Water, Sanitation, and Handwashing Intervention in Rural Bangladesh.

Water, sanitation, and handwashing interventions may confer spillover effects on intervention recipients' neighbors by interrupting pathogen transmission. We measured geographically local spillovers in the Water Quality, Sanitation, and Handwashing (WASH) Benefits Study, a cluster-randomized trial in rural Bangladesh, by comparing outcomes among neighbors of intervention versus those of control participants. Geographically defined clusters were randomly allocated to a compound-level intervention (i.e., chlorinated drinking water, upgraded sanitation, and handwashing promotion) or control arm. From January 2015 to August 2015, in 180 clusters, we enrolled 1,799 neighboring children who were age matched to trial participants who would have been eligible for the study had they been conceived slightly earlier or later. After 28 months of intervention, we quantified fecal indicator bacteria in toy rinse and drinking water samples and measured soil-transmitted helminth infections and caregiver-reported diarrhea and respiratory illness. Neighbors' characteristics were balanced across arms. Detectable Escherichia coli prevalence in tubewell samples was lower for intervention participants' neighbors than control participants' (prevalence ratio = 0.83; 95% confidence interval: 0.73, 0.95). Fecal indicator bacteria prevalence did not differ between arms for other environmental samples. Prevalence was similar in neighbors of intervention participants versus those of control participants for soil-transmitted helminth infection, diarrhea, and respiratory illness. A compound-level water, sanitation, and handwashing intervention reduced neighbors' tubewell water contamination but did not affect neighboring children's health

Open defecation and childhood stunting in India: an ecological analysis of new data from 112 districts.

Poor sanitation remains a major public health concern linked to several important health outcomes; emerging evidence indicates a link to childhood stunting. In India over half of the population defecates in the open; the prevalence of stunting remains very high. Recently published data on levels of stunting in 112 districts of India provide an opportunity to explore the relationship between levels of open defecation and stunting within this population. We conducted an ecological regression analysis to assess the association between the prevalence of open defecation and stunting after adjustment for potential confounding factors. Data from the 2011 HUNGaMA survey was used for the outcome of interest, stunting; data from the 2011 Indian Census for the same districts was used for the exposure of interest, open defecation. After adjustment for various potential confounding factors--including socio-economic status, maternal education and calorie availability--a 10 percent increase in open defecation was associated with a 0.7 percentage point increase in both stunting and severe stunting. Differences in open defecation can statistically account for 35 to 55 percent of the average difference in stunting between districts identified as low-performing and high-performing in the HUNGaMA data. In addition, using a Monte Carlo simulation, we explored the effect on statistical power of the common practice of dichotomizing continuous height data into binary stunting indicators. Our simulation showed that dichotomization of height sacrifices statistical power, suggesting that our estimate of the association between open defecation and stunting may be a lower bound. Whilst our analysis is ecological and therefore vulnerable to residual confounding, these findings use the most recently collected large-scale data from India to add to a growing body of suggestive evidence for an effect of poor sanitation on human growth. New intervention studies, currently underway, may shed more light on this important issue

Formal modeling and analysis of cognitive agent behavior

From an external perspective, cognitive agent behavior can be described by specifying (temporal) correlations of a certain complexity between stimuli (input states) and (re)actions (output states) of the agent. From an internal perspective the agent’s dynamics can be characterized by direct (causal) temporal relations between internal and mental states of the agent. The latter type of specifications can be represented in a relatively simple, executable format, which enables different types of analysis of the agent’s behavior. In particular, simulations of the agent’s behavior under different (environmental) circumstances can be explored. Furthermore, by applying verification techniques, automated analysis of the consequences of the agent’s behavior can be carried out. To enable such types of analysis when only given an external behavioral specification, this has to be transformed first into some type of executable format. An automated procedure for such a transformation is proposed in this paper. The application of the transformation procedure is demonstrated for a number of cases, showing examples of the types of analysis as mentioned for different forms of behavior

Impact of Indian Total Sanitation Campaign on latrine coverage and use: a cross-sectional study in Orissa three years following programme implementation.

BACKGROUND: Faced with a massive shortfall in meeting sanitation targets, some governments have implemented campaigns that use subsidies focused on latrine construction to overcome income constraints and rapidly expand coverage. In settings like rural India where open defecation is common, this may result in sub-optimal compliance (use), thereby continuing to leave the population exposed to human excreta. METHODS: We conducted a cross-sectional study to investigate latrine coverage and use among 20 villages (447 households, 1933 individuals) in Orissa, India where the Government of India's Total Sanitation Campaign had been implemented at least three years previously. We defined coverage as the proportion of households that had a latrine; for use we identified the proportion of households with at least one reported user and among those, the extent of reported use by each member of the household. RESULTS: Mean latrine coverage among the villages was 72% (compared to <10% in comparable villages in the same district where the Total Sanitation Campaign had not yet been implemented), though three of the villages had less than 50% coverage. Among these households with latrines, more than a third (39%) were not being used by any member of the household. Well over a third (37%) of the members of households with latrines reported never defecating in their latrines. Less than half (47%) of the members of such households reported using their latrines at all times for defecation. Combined with the 28% of households that did not have latrines, it appears that most defecation events in these communities are still practiced in the open. CONCLUSION: A large-scale campaign to implement sanitation has achieved substantial gains in latrine coverage in this population. Nevertheless, gaps in coverage and widespread continuation of open defecation will result in continued exposure to human excreta, reducing the potential for health gains

Improvements to water purification and sanitation infrastructure may reduce the diarrheal burden in a marginalized and flood prone population in remote Nicaragua

<p>Abstract</p> <p>Background</p> <p>The isolated northern region of Nicaragua has one of the highest rates of diarrheal disease in Central America. Political and environmental hardships faced by inhabitants of this region are contributing factors to this health inequity. The aim of this study was to assess the relationship between water and latrine infrastructure and the prevalence of diarrhea in this region.</p> <p>Methods</p> <p>A population-based, cross-sectional survey of women of reproductive age was conducted in the Sahsa region of northern Nicaragua in July, 2009. Households were selected by two stage cluster sampling methodology. A questionnaire was administered in Spanish and Miskito with assessment of household and socioeconomic conditions, sanitation practices, and health care access. Diarrhea prevalence differences at the household level over a two week reporting period were estimated with a standardized instrument which included assessment of water treatment and latrine use and maintenance.</p> <p>Results</p> <p>There were 189 women enrolled in the current study. The use of water purification methods, such as chlorine and filters, and latrine ownership were not associated with reduced prevalence of household diarrhea in the two week reporting period. Latrine overflow, however, was associated with an increased prevalence of diarrhea during the same two week period [adjusted prevalence difference and 95% CI: 0.19 (0.03, 0.36)].</p> <p>Conclusions</p> <p>Simple, low cost interventions that improve water and latrine infrastructure may reduce the prevalence of diarrheal disease in the isolated regions of Nicaragua and Central America.</p

Child feces disposal practices in rural Orissa: a cross sectional study.

BACKGROUND: An estimated 2.5 billion people worldwide lack access to improved sanitation facilities. While large-scale programs in some countries have increased latrine coverage, they sometimes fail to ensure optimal latrine use, including the safe disposal of child feces, a significant source of exposure to fecal pathogens. We undertook a cross-sectional study to explore fecal disposal practices among children in rural Orissa, India in villages where the Government of India's Total Sanitation Campaign had been implemented at least three years prior to the study. METHODS AND FINDINGS: We conducted surveys with heads of 136 households with 145 children under 5 years of age in 20 villages. We describe defecation and feces disposal practices and explore associations between safe disposal and risk factors. Respondents reported that children commonly defecated on the ground, either inside the household (57.5%) for pre-ambulatory children or around the compound (55.2%) for ambulatory children. Twenty percent of pre-ambulatory children used potties and nappies; the same percentage of ambulatory children defecated in a latrine. While 78.6% of study children came from 106 households with a latrine, less than a quarter (22.8%) reported using them for disposal of child feces. Most child feces were deposited with other household waste, both for pre-ambulatory (67.5%) and ambulatory (58.1%) children. After restricting the analysis to households owning a latrine, the use of a nappy or potty was associated with safe disposal of feces (OR 6.72, 95%CI 1.02-44.38) though due to small sample size the regression could not adjust for confounders. CONCLUSIONS: In the area surveyed, the Total Sanitation Campaign has not led to high levels of safe disposal of child feces. Further research is needed to identify the actual scope of this potential gap in programming, the health risk presented and interventions to minimize any adverse effect

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

Psychopharmacological and Other Treatments in Preschool Children with Attention-Deficit/Hyperactivity Disorder: Current Evidence and Practice

Objective: This article reviews rational approaches to treating attention-deficit/hyperactivity disorder (ADHD) in preschool children, including pharmacological and nonpharmacological treatments. Implications for clinical practice are discussed. Data Sources: We searched MEDLINE, PsychINFO, Cumulative Index to Nursing & Allied Health, Educational Resources Information Center, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects for relevant literature published in English from 1967 to 2007 on preschool ADHD. We also reviewed the references cited in identified reports. Study Selection: Studies were reviewed if the sample included at least some children younger than 6 years of age or attending kindergarten, the study participants had a diagnosis of ADHD or equivalent symptoms, received intervention aimed at ADHD symptoms, and included a relevant outcome measure. Data Extraction: Studies were reviewed for type of intervention and outcome relevant to ADHD and were rated for the level of evidence for adequacy of the data to inform clinical practice. Conclusions: The current level of evidence for adequacy of empirical data to inform clinical practice for shortterm treatment of ADHD in preschool children is Level A for methylphenidate and Level B for parent behavior training, child training, and additive-free elimination diet

Enriching Business Process Models with Decision Rules

Making the right decisions in time is one of the key tasks in every business. In this context, decision theory fosters decision-making based on well-defined decision rules. The latter evaluate a given set of input parameters and utilize evidenced data in order to determine an optimal alternative out of a given set of choices. In particular, decision rules are relevant in the context business processes as well. Contemporary process modeling languages, however, have not incorporated decision theory yet, but mainly consider rather simple, guard-based decisions that refer to process-relevant data. To remedy this drawback, this paper introduces an approach that allows embedding decision problems in business process models and applying decision rules to deal with them. As a major benefit, it becomes possible to automatically determine optimal execution paths during run time