Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA): protocol for a prospective observational study

Background: Pain and fatigue are persistent problems in people with rheumatoid arthritis. Central sensitisation (CS) may contribute to pain and fatigue, even when treatment has controlled inflammatory disease. This study aims to validate a self-report 8-item questionnaire, the Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) questionnaire, developed to measure central pain mechanisms in RA, and to predict patient outcomes and response to treatment. A secondary objective is to explore mechanisms linking CS, pain and fatigue in people with RA. Methods/design: This is a prospective observational cohort study recruiting 250 adults with active RA in secondary care. The CAP-RA questionnaire, demographic data, medical history, and patient reported outcome measures (PROMs) of traits associated with central sensitization will be collected using validated questionnaires. Quantitative sensory testing modalities of pressure pain detection thresholds, temporal summation and conditioned pain modulation will be indices of central sensitization, and blood markers, swollen joints and ultrasound scans will be indices of inflammation. Primary data collection will be at baseline and 12 weeks. The test-retest reliability of CAP-RA questionnaire will be determined 1 week after the baseline visit. Pain and fatigue data will be collected weekly via text messages for 12 weeks. CAP-RA psychometric properties, and predictive validity for outcomes at 3 months will be evaluated. Discussion: This study will validate a simple self-report questionnaire against psychophysical indices of central sensitization and patient reported outcome measures of traits associated with CS in a population of individuals with active RA. The application of this instrument in the clinical environment could provide a mechanism-based stratification tool to facilitate the provision of targeted therapy to individuals with pain and fatigue in RA, alongside treatments that target joint inflammation. Trial registration: Clinicaltrials.gov NCT04515589. Date of registration 17 August 2020

The feasibility and clinical utility of microsphere contrast-enhanced transthoracic echocardiography in adult congenital heart disease

Background: Transthoracic echocardiography (TTE) plays a key role in adult congenital heart disease (ACHD). However, a significant number of studies are nondiagnostic due to poor image quality. Enhancement of the blood pool-tissue interface with contrast-enhanced TTE (CE-TTE) can improve image quality in suboptimal studies. The aim of this analysis was to evaluate feasibility and clinical utility of CE-TTE in the assessment of patients with ACHD. Methods: A retrospective analysis of all CE-TTE performed in ACHD patients at our institution from August 2007 to May 2014 was performed. Endocardial definition scores (EDS) for each segment in the right and left ventricles were graded pre- and postcontrast imaging, as 1 = good, 2 = suboptimal, 3 = not seen. The endocardial border definition score index (EBDSI) was also calculated pre- and postcontrast imaging. Results: Twenty patients with ACHD had 24 CE. Summation data for all ventricular EDS for unenhanced TTE vs. CE-TTE imaging was: EDS 1 = 136 vs. 314, EDS 2 = 119 vs. 72, EDS 3 = 162 vs. 31, respectively. Wilcoxon matched-pairs rank-signed test showed a significant ranking difference (improvement) pre- and postcontrast for the combined ventricular data (P < .0001) and the individual left and right ventricular data (all P < .0001). The EBDSI for combined ventricular data using CE-TTE was significantly lower than for noncontrast imaging (1.23 ± 0.49 vs. 2.06 ± 0.62, P < .0001). There was one minor contrast adverse reaction. Conclusions: CE-TTE resulted in significantly improved right and left ventricular endocardial definition and improved EDBSI. CE-TTE should be viewed as an additional imaging technique that is available to help assess patients with ACHD, especially those with nondiagnostic images

Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

AbstractBackgroundOral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated.MethodsIn urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea.ResultsCampylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (−0.08 change in log titer per tenfold increase in quantity; P=0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64–0.96; P=0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05–1.71; P=0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity.ConclusionIn this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses.ClinicalTrials.gov Identifier: NCT01375647