Interobserver and Intraobserver Reliability of Hepatic Shear Wave Elastography and the Influence of Fasted Versus Nonfasted States in Healthy Volunteers.

OBJECTIVES: The primary objective of this study was to assess the effect of fasting versus ingestion of food and water on hepatic measurements by shear wave elastography (SWE) in healthy participants. The secondary objective was to assess inter- and intra-reader reliability of hepatic elastography in healthy participants. METHODS: Twenty healthy participants were enrolled in this prospective study and underwent quantitative SWE under fasting conditions and after the ingestion of water and food and water. Two blinded sonographers each independently performed a total of 6 sessions of hepatic SWE in each participant. Sessions 1 to 3 were performed on day 0 and sessions 4 to 6 on day 7. Statistical tests used included the Wilcoxon signed ranks test, the intraclass correlation coefficient, and Bland-Altman plots. RESULTS: There were no significant differences in hepatic SWE measurements after the ingestion of water versus the fasting state. Statistical significance was assessed as P < 0.05. The postprandial status had a statistically significant effect on hepatic SWE measurements at 1 hour (P = .04) but not at 3 hours (P = .08). By the intraclass correlation coefficient, there was poor-to-moderate inter-reader agreement and minimal-to-moderate intra-reader agreement. The median inter-reader difference in SWE measurements ranged from 0.66 to 0.96 kPa. The median intra-reader difference ranged from 0.43 to 0.55 kPa. CONCLUSIONS: Our study shows that the ingestion of water has no effect on hepatic SWE measurements in healthy participants. The postprandial state had a significant effect on SWE measurements at 1 hour after ingestion but not at 3 hours. The inter-reader and intra-reader agreements were variable and moderate at best.

Investigating the effectiveness of an online acceptance and commitment therapy (ACT) intervention versus a waiting list control condition on pain interference and quality of life in adults with chronic pain and multimorbidity: protocol for a randomised controlled trial.

INTRODUCTION: Multimorbidity refers to the presence of two or more chronic health conditions within one person, where no one condition is primary. Research suggests that multimorbidity is highly correlated with chronic pain, which is pain lasting longer than 3 months. Psychotherapeutic interventions for people living with chronic illness have resulted in reduced symptom reporting and improved psychological well-being. There is a dearth of research, however, using online psychotherapy for people living with multimorbidity where chronic pain is a central condition. This study will compare the effectiveness of an online acceptance and commitment therapy (ACT) intervention with a waiting list control condition in terms of improving health-related quality of life (HRQoL) and reducing levels of pain interference in people with chronic pain and at least one other condition. METHODS AND ANALYSIS: 192 adult participants with non-malignant pain that persists for at least 3 months and at least one other medically diagnosed condition will be randomised to one of two study conditions. The experimental group will undergo an eight-session internet-delivered ACT programme over an 8-week period. A waiting list group will be offered the ACT intervention after the 3-month follow-up period. HRQoL and pain interference will act as the primary outcomes. Data will be analysed using a linear mixed model and adjusted to account for demographic and clinical variables as necessary. A Study Within a Trial will be incorporated to examine the effect on recruitment and retention of showing participants an animated educational video. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Research Ethics Committee of the National University of Ireland, Galway. Dissemination of results will be via peer reviewed journal articles and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN22343024.

Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Elderly Volunteers.

BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated the pharmacokinetics, safety, and tolerability of cromolyn and ibuprofen co-administration in healthy elderly adult volunteers. METHODS: In this open-labeled study, 26 subjects, aged 55-75 years, received co-administration of inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral ibuprofen (single dose 10 mg; double dose 20 mg total). Blood sampling was performed for 6 h after co-administration in all subjects; cerebrospinal fluid (CSF) was collected in three to four subjects per cohort for 4 h following co-administration. Safety parameters, including adverse events (AEs), were monitored throughout the study. RESULTS: For cromolyn, the mean (±SD) maximum observed concentration (C max) in plasma was 46.69 ± 32.97 and 96.75 ± 46.22 ng/ml after single- and double-dose inhalation, respectively [time to C max (t max) ~22 min for each; terminal elimination half-life (t ½) ~1.8 h for each]. For ibuprofen, the plasma C max was 1090.98 ± 474.64 ng/ml and 2062.96 ± 655.13 ng/ml after single- and double-dose oral administration, respectively (t max ~1.6-1.8 h; t ½ ~1.9 h for each). For cromolyn, the CSF C max was 0.24 ± 0.08 ng/ml at 3.72 ± 0.70 h after single-dose administration and 0.34 ± 0.17 ng/ml at 3.45 ± 0.95 h after double-dose administration, and for ibuprofen, the CSF C max was 3.94 ± 1.29 ng/ml at 2.55 ± 0.96 h after single-dose administration and 8.93 ± 3.29 ng/ml at 3.15 ± 1.05 h after double-dose administration. Three (12%) subjects reported mild or moderate AEs which were unlikely to be related to study drug. CONCLUSIONS: The combination of cromolyn and ibuprofen was safe and well tolerated. The concentrations of cromolyn and ibuprofen observed in the CSF are considered sufficient to titrate the estimated daily amyloid production and the associated inflammatory response in patients with AD.

Protocol for a systematic review with network meta-analysis of the modalities used to deliver eHealth interventions for chronic pain.

BACKGROUND: As eHealth interventions prove both efficacious and practical, and as they arguably overcome certain barriers encountered by traditional face-to-face treatment for chronic pain, their number has increased dramatically in recent times. However, there is a dearth of research that focuses on evaluating and comparing the different types of technology-assisted interventions. This is a protocol for a systematic review that aims to evaluate the eHealth modalities in the context of psychological and non-psychological (other than non-drug) interventions for chronic pain. METHODS/DESIGN: We will search the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library), MEDLINE, Embase and PsycINFO. Randomised controlled trials (RCTs) with more than 20 participants per trial arm that have evaluated non-drug psychological or non-psychological interventions delivered via an eHealth modality and have pain as an outcome measure will be included. Two review authors will independently extract data and assess the study suitability in accordance with the Cochrane Collaboration Risk of Bias Tool. Studies will be included if they measure at least one outcome variable in accordance with the IMMPACT guidelines (i.e. pain severity, pain interference, physical functioning, symptoms, emotional functioning, global improvement and disposition). Secondary outcomes will be measures of depression and health-related quality of life (HRQoL). A network meta-analysis will be conducted based on direct comparisons to generate indirect comparisons of modalities across treatment trials, which will return rankings for the eHealth modalities in terms of their effectiveness. DISCUSSION: Most trials that use an eHealth intervention to manage chronic pain typically use one modality. As a result, little evidence exists to support which modality type is the most effective. The current review will address this gap in the literature and compare the different eHealth modalities used for technology-assisted interventions for chronic pain. With the growing reliance and use of technology as a medium for delivering treatment for chronic conditions more generally, it is imperative that research identify the most efficacious eHealth modalities and systematically identify the most important features of such treatment types, so they may be replicated and used for research and in the provision of care. TRIAL REGISTRATION: PROSPERO, CRD42016035595.

Results of an international ring test with the dung fly Musca autumnalis in support of a new OECD test guideline.

A standardized bioassay using the face fly, Musca autumnalis L. (Diptera: Muscidae), was developed to test the lethal and sublethal toxicity of parasiticide residues in livestock dung. The repeatability of this test was assessed for the parasiticide ivermectin in seven tests performed in four laboratories in Germany and France. Additional results of limit tests were provided by two laboratories from the UK. Test results had an acceptable range of heterogeneity. The calculated effect concentration at which 50% emergence was observed (EC50) averaged 4.65+/-2.17 (Standard Deviation (SD) microg ivermectin/kg fresh dung (range: 1.20-7.7)). Effects on emergence were, with one exception, not observed below the No Observed Effect Concentration (NOEC) ranging between 1.11 and 3.33microg ivermectin/kg. No effect on development time was observed. We conclude that the face fly is suitably sensitive, and the methods sufficiently repeatable, to support use of this standardized bioassay by the international community in the registration of new veterinary pharmaceuticals. Following these considerations, this species was accepted as a possible test organism in a recently published OECD Guideline (No. 228).

Higher-tier laboratory methods for assessing the aquatic toxicity of pesticides.

Registration schemes for plant-protection products require applicants to assess the potential ecological risk of their products using a tiered approach. Standard aquatic ecotoxicity tests are used at lower tiers and clearly defined methodologies are available for assessing the potential environmental risks. Safety factors are incorporated into the assessment process to account for the uncertainties associated with the use of lower-tier single-species ecotoxicity studies. If lower-tier assessments indicate that a substance may pose a risk to the environment, impacts can be assessed using more environmentally realistic conditions through the use of either pond mesocosms, artificial streams or field monitoring studies. Whilst these approaches provide more realistic assessments, the results are difficult to interpret and extrapolation to other systems is problematic. Recently it has been recognised that laboratory approaches that are intermediate between standard aquatic toxicity tests and field/mesocosm studies may provide useful data and help reduce the uncertainties associated with standard single-species tests. However, limited guidance is available on what tests are available and how they can be incorporated into the risk-assessment process. This paper reviews a number of these higher-tier laboratory techniques, including modified exposure studies, species sensitivity studies, population studies and tests with sensitive life stages. Recommendations are provided on how the approaches can be incorporated into the risk-assessment process.