Ten years of the International Patient Decision Aid Standards Collaboration: evolution of the core dimensions for assessing the quality of patient decision aids

In 2003, the International Patient Decision Aid Standards (IPDAS) Collaboration was established to enhance the quality and effectiveness of patient decision aids by establishing an evidence-informed framework for improving their content, development, implementation, and evaluation. Over this 10 year period, the Collaboration has established: a) the background document on 12 core dimensions to inform the original modified Delphi process to establish the IPDAS checklist (74 items); b) the valid and reliable IPDAS instrument (47 items); and c) the IPDAS qualifying (6 items), certifying (6 items + 4 items for screening), and quality criteria (28 items). The objective of this paper is to describe the evolution of the IPDAS Collaboration and discuss the standardized process used to update the background documents on the theoretical rationales, evidence and emerging issues underlying the 12 core dimensions for assessing the quality of patient decision aids. © 2013 Volk et al; licensee BioMed Central Ltd

The production of Necator americanus larvae for use in experimental human infection

Background: Although there is unprecedented interest in experimental human hookworm infection, details of hookworm manufacture and characterisation have been sparsely reported. In this report, we detail the production and characterisation of Necator americanus larvae for use in a recently published clinical trial. Methods: Faeces was obtained from an experimentally infected donor. Faecal hookworm DNA was determined by quantitative PCR. Paired samples were incubated in either sterile water or sterile water mixed with antimicrobials (amphotericin and gentamicin). Coproculture was performed by modified Harada-Mori method. The harvested larvae were then processed in either sterile water or antiseptic solution. Larval yield was then calculated (larvae per gram), larval viability was determined by thermally induced motility assay and microbial burden was determined at the day of harvest, at 48 h and at 7 days. Results: Twenty-eight faecal cultures were performed over 16 months. The faecal hookworm DNA content was variable over this time. There was no association of larval yield with faecal hookworm DNA content. Pre-treatment of faeces with antimicrobials did not influence larval yield. Larval motility was 85.3% (95% CI 79.3–91.3%). Incubation of larvae in antiseptics did not reduce viability at 14 days with a marginal mean of 68.6% (95% CI 59.1–78.1%) washed in water vs. 63.3% (95% CI 53.8 – 72.9%) when incubated in betadine (p = 0.38). Larvae washed in sterile water did not meet microbial bioburden criteria. Incubation in antiseptic resulted in acceptable microbial bioburden at 48 h but not at 7 days. Although the addition of gentamicin did reduce the microbial bio-burden acceptable levels, it was found to significantly lower larval motility at 7 days compared to incubation in sterile water and motility at 7 days 37.8% (95% CI 4.7–70.9%) vs. 67.3% (95% CI 35.2–99.3%, p < 0.001), respectively. Conclusions: Despite standardised culture methodologies and the use of a single donor, larval yield varied considerably between batches and had no association with faecal hookworm DNA. Larval viability decreases over time and the age of larvae at time of use are likely to be important. Microbial bioburden maybe temporarily reduced by incubation in antiseptics and has little effect on viability. Incubation of larvae in gentamicin is effective at reducing microbial bioburden but is deleterious to larval viability

A Novel, Species-Specific, Real-Time PCR Assay for the Detection of the Emerging Zoonotic Parasite Ancylostoma Ceylanicum in Human Stool

Historically, Ancylostoma ceylanicum has been viewed as an uncommon cause of human hookworm infection, with minimal public health importance. However, recent reports have indicated that this zoonotic hookworm causes a much greater incidence of infection within certain human populations than was previously believed. Current methods for the species-level detection of A. ceylanicum rely on techniques that involve conventional PCR accompanied by restriction enzyme digestions. These PCR-based assays are not only labo- rious but they lack sensitivity as they target suboptimal regions on the DNA. As efforts aimed at the eradication of hookworm disease have grown substantially over the last decade, the need for sensitive and specific tools to monitor and evaluate programmatic successes has correspondingly escalated. Since a growing body of evidence suggests that patient responses to drug treatment can vary based upon the species of hookworm that is causing infection, accurate species-level diagnostics are advantageous. Accordingly, the novel real-time PCR-based assay described here provides a sensitive, species-specific diag- nostic tool that will facilitate the accurate mapping of disease endemicity and will aid in the evaluation of progress of programmatic deworming efforts

An environmental assessment and risk map of Ascaris lumbricoides and Necator americanus distributions in Manufahi District, Timor-Leste

Background In Timor-Leste there have been intermittent and ineffective soil-transmitted helminth (STH) deworming programs since 2004. In a resource-constrained setting, having information on the geographic distribution of STH can aid in prioritising high risk communities for intervention. This study aimed to quantify the environmental risk factors for STH infection and to produce a risk map of STH in Manufahi district, Timor-Leste. Methodology/Principal findings Georeferenced cross-sectional data and stool samples were obtained from 2,194 participants in 606 households in 24 villages in the Manufahi District as part of cross sectional surveys done in the context of the “WASH for Worms” randomised controlled trial. Infection status was determined for Ascaris lumbricoides and Necator americanus using real-time quantitative polymerase chain reaction. Baseline infection data were linked to environmental data obtained for each household. Univariable and multivariable multilevel mixed-effects logistic regression analysis with random effects at the village and household level were conducted, with all models adjusted for age and sex. For A. lumbricoides, being a school-aged child increased the odds of infection, whilst higher temperatures in the coolest quarter of the year, alkaline soils, clay loam/loam soils and woody savannas around households were associated with decreased infection odds. For N. americanus, greater precipitation in the driest month, higher average enhanced vegetation index, age and sandy loam soils increased infection odds, whereas being female and living at higher elevations decreased the odds of infection. Predictive risk maps generated for Manufahi based upon these final models highlight the high predicted risk of N. americanus infection across the district and the more focal nature of A. lumbricoides infection. The predicted risk of any STH infection is high across the entire district. Conclusions/Significance The widespread predicted risk of any STH infection in 6 to 18 year olds provides strong evidence to support strategies for control across the entire geographical area. As few studies include soil texture and pH in their analysis, this study adds to a growing body of evidence suggesting these factors influence STH infection distribution. This study also further supports that A. lumbricoides prefers acidic soils, highlighting a potential relatively unexplored avenue for control

Development and evaluation of a multiplex quantitative real-time Polymerase Chain Reaction for hookworm species in human stool

Hookworm disease caused by; Necator americanus; ,; Ancylostoma duodenale; , and; Ancylostoma ceylanicum; affects half a billion people worldwide. The prevalence and intensity of infection of individual hookworm species are vital for assessing morbidity and generating targeted intervention programs for their control. The present study aims to evaluate a multiplex real-time quantitative PCR (qPCR) assay to determine the prevalence and egg intensity of all three hookworm species and compare this with standard microscopy and published genus-based conventional and real-time multiplex qPCRs. Performance of the diagnostic assays was evaluated using DNA extracted from 192 fecal samples collected as part of a soil-transmitted helminth (STH) survey in northern Cambodia. The prevalence of hookworms as detected by the multiplex hookworm qPCR of 84/192 (43.8%) was significantly higher than that using microscopy of 49/192 (25.5%). The hookworm multiplex qPCR showed very good agreement for the detection of both; N. americanus; (Kappa 0.943) and; Ancylostoma; spp. (Kappa 0.936) with a multiplex STH qPCR. A strong and moderate quantitative correlation between cycle threshold and eggs per gram (EPG) feces was obtained for the hookworm qPCR for seeded DNA egg extracts (; R; 2; ≥ 0.9004) and naturally egg-infected individuals (; R; 2; = 0.6848), respectively. The newly developed hookworm quantitative multiplex qPCR has the potential for application in anthelmintic efficacy trials and for monitoring the success of mass deworming programs targeting individual species of anthroponotic and zoonotic hookworms

Investigations into the association between soil-transmitted helminth infections, haemoglobin and child development indices in Manufahi District, Timor-Leste

Background: Timor-Leste has a high prevalence of soil-transmitted helminth (STH) infections. High proportions of the population have been reported as being anaemic, and extremely high proportions of children as stunted or wasted. There have been no published analyses of the contributions of STH to these morbidity outcomes in Timor-Leste. Methods: Using baseline cross-sectional data from 24 communities (18 communities enrolled in a cluster randomised controlled trial, and identically-collected data from six additional communities), analyses of the association between STH infections and community haemoglobin and child development indices were undertaken. Stool samples were assessed for STH using qPCR and participant haemoglobin, heights and weights were measured. Questionnaires were administered to collect demographic and socioeconomic data. Intensity of infection was categorised using correlational analysis between qPCR quantification cycle values and eggs per gram of faeces equivalents, with algorithms generated from seeding experiments. Mixed-effects logistic and multinomial regression were used to assess the association between STH infection intensity classes and anaemia, and child stunting, wasting and underweight. Results: Very high stunting (60%), underweight (60%), and wasting (20%) in children, but low anaemia prevalence (15%), were found in the study communities. STH were not significantly associated with morbidity outcomes. Male children and those in the poorest socioeconomic quintile were significantly more likely to be moderately and severely stunted. Male children were significantly more likely than female children to be severely underweight. Increasing age was also a risk factor for being underweight. Few risk factors emerged for wasting in these analyses. Conclusions: According to World Health Organization international reference standards, levels of child morbidity in this population constitute a public health emergency, although the international reference standards need to be critically evaluated for their applicability in Timor-Leste. Strategies to improve child development and morbidity outcomes, for example via nutrition and iron supplementation programmes, are recommended for these communities. Despite the apparent lack of an association from STH in driving anaemia, stunting, wasting and underweight, high endemicity suggests a need for STH control strategies.ACAC is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow (1058878), JSM is an Australian NHMRC Practitioner Fellow, and DJG is an Australian NHMRC Career Development Fellow. This work is funded by an NHMRC Partnership project in collaboration with WaterAid Australia

Water, Sanitation and Hygiene (WASH) and environmental risk factors for soil-transmitted helminth intensity of infection in Timor-Leste, using real time PCR

Background: No investigations have been undertaken of risk factors for intensity of soil-transmitted helminth (STH) infection in Timor-Leste. This study provides the first analysis of risk factors for intensity of STH infection, as determined by quantitative PCR (qPCR), examining a broad range of water, sanitation and hygiene (WASH) and environmental factors, among communities in Manufahi District, Timor-Leste. Methods: A baseline cross-sectional survey of 18 communities was undertaken as part of a cluster randomised controlled trial, with additional identically-collected data from six other communities. qPCR was used to assess STH infection from stool samples, and questionnaires administered to collect WASH, demographic, and socioeconomic data. Environmental information was obtained from open-access sources and linked to infection outcomes. Mixed-effects multinomial logistic regression was undertaken to assess risk factors for intensity of Necator americanus and Ascaris infection. Results: 2152 participants provided stool and questionnaire information for this analysis. In adjusted models incorporating WASH, demographic and environmental variables, environmental variables were generally associated with infection intensity for both N. americanus and Ascaris spp. Precipitation (in centimetres) was associated with increased risk of moderate-intensity (adjusted relative risk [ARR] 6.1; 95% confidence interval [CI] 1.9–19.3) and heavy-intensity (ARR 6.6; 95% CI 3.1–14.1) N. americanus infection, as was sandy-loam soil around households (moderate-intensity ARR 2.1; 95% CI 1.0–4.3; heavy-intensity ARR 2.7; 95% CI 1.6–4.5; compared to no infection). For Ascaris, alkaline soil around the household was associated with reduced risk of moderate-intensity infection (ARR 0.21; 95% CI 0.09–0.51), and heavy-intensity infection (ARR 0.04; 95% CI 0.01–0.25). Few WASH risk factors were significant. Conclusion: In this high-prevalence setting, strong risk associations with environmental factors indicate that anthelmintic treatment alone will be insufficient to interrupt STH transmission, as conditions are favourable for ongoing environmental transmission. Integrated STH control strategies should be explored as a priorityACAC is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow (1058878), JSM is an Australian NHMRC Practitioner Fellow, and DJG is an Australian NHMRC Career Development Fellow. This work is funded by an NHMRC Partnership project in collaboration with WaterAid Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Randomized, placebo controlled trial of experimental hookworm infection for improving gluten tolerance in Celiac disease

INTRODUCTION: Celiac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled. METHODS: We undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease. The 94-week study involved treatment with either 20 or 40 Necator americanus third-stage larvae (L3-20 or L3-40) or placebo, followed by escalating gluten consumption (50 mg/d for 12 weeks, 1 g intermittent twice weekly for 12 weeks, 2 g/d sustained for 6 weeks, liberal diet for 1 year). RESULTS: Successful study completion rates at week 42 (primary outcome) were similar in each group (placebo: 57%, L3-20: 37%, and L3-40: 44%; P = 0.61), however gluten-related adverse events were significantly reduced in hookworm-treated participants: Median (range) adverse events/participant were as follows: placebo, 4 (1–9); L3-20, 1 (0–9); and L3-40, 0 (0–3) (P = 0.019). Duodenal villous height:crypt depth deteriorated similarly compared with their enrolment values in each group (mean change [95% confidence interval]: placebo, −0.6 [−1.3 to 0.2]; L3-20, −0.5 [−0.8 to 0.2]; and L3-40, −1.1 [−1.8 to 0.4]; P = 0.12). A retrospective analysis revealed that 9 of the 40 L3-treated participants failed to establish hookworm infections. Although week 42 completion rates were similar in hookworm-positive vs hookworm-negative participants (48% vs 44%, P = 0.43), quality of life symptom scores were lower in hookworm-positive participants after intermittent gluten challenge (mean [95% confidence interval]: 38.9 [33.9–44] vs 45.9 [39.2–52.6]). DISCUSSION: Hookworm infection does not restore tolerance to sustained moderate consumption of gluten (2 g/d) but was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses

Preliminary assessment of the feasibility of using AB words to assess candidacy in adults

Background: Adult cochlear implant (CI) candidacy is assessed in part by the use of speech perception measures. In the United Kingdom the current cut-off point to fall within the CI candidacy range is a score of less than 50% on the BKB sentences presented in quiet (presented at 70 dBSPL). Goal: The specific goal of this article was to review the benefit of adding the AB word test to the assessment test battery for candidacy. Results: The AB word test scores showed good sensitivity and specificity when calculated based on both word and phoneme scores. The word score equivalent for 50% correct on the BKB sentences was 18.5% and it was 34.5% when the phoneme score was calculated; these scores are in line with those used in centres in Wales (15% AB word score). Conclusion: The goal of the British Cochlear Implant Group (BCIG) service evaluation was to determine if the pre-implant assessment measures are appropriate and set at the correct level for determining candidacy, the future analyses will determine whether the speech perception cut-off point for candidacy should be adjusted and whether other more challenging measures should be used in the candidacy evaluation