Development of abbreviated measures to assess patient trust in a physician, a health insurer, and the medical profession

BACKGROUND: Despite the recent proliferation in research on patient trust, it is seldom a primary outcome, and is often a peripheral area of interest. The length of our original scales to measure trust may limit their use because of the practical needs to minimize both respondent burden and research cost. The objective of this study was to develop three abbreviated scales to measure trust in: (1) a physician, (2) a health insurer, and (3) the medical profession. METHODS: Data from two samples were used. The first was a telephone survey of English-speaking adults in the United States (N = 1117) and the second was a telephone survey of English-speaking adults residing in North Carolina who were members of a health maintenance organization (N = 1024). Data were analyzed to examine data completeness, scaling assumptions, internal consistency properties, and factor structure. RESULTS: Abbreviated measures (5-items) were developed for each of the three scales. Cronbach's alpha was 0.87 for trust in a physician (test-retest reliability = 0.71), 0.84 for trust in a health insurer (test-retest reliability = 0.73), and 0.77 for trust in the medical profession. CONCLUSION: Assessment of data completeness, scale score dispersion characteristics, reliability and validity test results all provide evidence for the soundness of the abbreviated 5-item scales

Dental Amalgam Restorations and Children’s Neuropsychological Function: The New England Children’s Amalgam Trial

BACKGROUND: A concern persists that children’s exposure to mercury vapor from dental amalgams produces neurotoxicity. OBJECTIVE: Our goal was to compare the neuropsychological function of children, without prior exposure to dental amalgam, whose caries were repaired using either dental amalgam or mercury-free composite materials. METHODS: We conducted a randomized controlled trial involving 534 6- to 10-year-old urban and rural children who were assessed yearly for 5 years using a battery of tests of intelligence, achievement, language, memory, learning, visual–spatial skills, verbal fluency, fine motor function, problem solving, attention, and executive function. RESULTS: Although the mean urinary mercury concentration was greater among children in the amalgam group than the composite group (0.9 vs. 0.6 μg/g creatinine), few significant differences were found between the test scores of children in the two groups. The differences found were inconsistent in direction. Analyses using two cumulative exposure indices—surface years of amalgam and urinary mercury concentration—produced similar results. CONCLUSIONS: Exposure to elemental mercury in amalgam at the levels experienced by the children who participated in the trial did not result in significant effects on neuropsychological function within the 5-year follow-up period

Changes in Urinary Bisphenol A Concentrations Associated with Placement of Dental Composite Restorations in Children and Adolescents

BACKGROUND: Bisphenol A-glycidyl methacrylate (bis-GMA)-based dental composite restorations may release bisphenol A (BPA). The authors assessed changes in urinary BPA concentrations over a 6-month follow-up period in children and adolescents who received bis-GMA-based restorations. METHODS: The authors collected data from 91 study participants aged 3 to 17 years who needed composite restorations. Participants provided urine samples and information on BPA-related exposures before and at approximately 1 day, 14 days, and 6 months after treatment. The authors used multivariable linear regression models to test associations between the number of surface restorations placed and the changes in urinary BPA concentrations. RESULTS: Participants had a mean (standard deviation [SD]) of 1.4 (1.0) for surfaces restored with composite at the first treatment visit and 2.3 (1.6) for surfaces restored during the entire study period. Mean (SD) change in urinary BPA concentrations between pretreatment and day 1 was 1.71 (9.94) nanograms per milliliter overall and 0.87 (5.98) after excluding 1 participant who had 8 surfaces restored at the visit. Overall, the authors observed an association between a greater number of composite surface restorations placed and higher urinary BPA concentrations in the 1-day sample (posterior-occlusal exponentiated coefficients [e(β)] = 1.47; 95% confidence interval [CI], 1.18-1.83; P \u3c .001), but the association was attenuated after the authors restricted the sample to the 88 participants who had up to 4 restorations (e(β) = 1.19; 95% CI, 0.86-1.64), and they did not observe any association using 14-day (e(β) = 0.94; 95% CI, 0.75-1.18) or 6-month (e(β) = 0.88; 95% CI, 0.74-1.04) samples. CONCLUSIONS: Placement of bis-GMA-based restorations in children and adolescents may produce transient increases in urinary BPA concentrations that are no longer detectable in urine samples taken approximately 14 days or 6 months after treatment. After placement of a few restorations, increases in urinary BPA concentrations may not be detectable, owing to a high level of variation in background BPA exposure. PRACTICAL IMPLICATIONS: These results suggest that leaching of BPA from newly placed composite restorations ceases to be detectable in urine within 2 weeks after restoration placement. The potential human health impact of such short-term exposure remains uncertain

Dysregulated Arginine Metabolism and Cardiopulmonary Dysfunction in Patients with Thalassaemia

Pulmonary hypertension (PH) commonly develops in thalassaemia syndromes, but is poorly characterized. The goal of this study was to provide a comprehensive description of the cardiopulmonary and biological profile of patients with thalassaemia at risk for PH. A case-control study of thalassaemia patients at high versus low PH-risk was performed. A single cross-sectional measurement for variables reflecting cardiopulmonary status and biological pathophysiology were obtained, including Doppler-echocardiography, 6-min-walk-test, Borg Dyspnoea Score, New York Heart Association functional class, cardiac magnetic resonance imaging (MRI), chest-computerized tomography, pulmonary function testing and laboratory analyses targeting mechanisms of coagulation, inflammation, haemolysis, adhesion and the arginine-nitric oxide pathway. Twenty-seven thalassaemia patients were evaluated, 14 with an elevated tricuspid-regurgitant-jet-velocity (TRV) ≥ 2·5 m/s. Patients with increased TRV had a higher frequency of splenectomy, and significantly larger right atrial size, left atrial volume and left septal-wall thickness on echocardiography and/or MRI, with elevated biomarkers of abnormal coagulation, lactate dehydrogenase (LDH) levels and arginase concentration, and lower arginine-bioavailability compared to low-risk patients. Arginase concentration correlated significantly to several echocardiography/MRI parameters of cardiovascular function in addition to global-arginine-bioavailability and biomarkers of haemolytic rate, including LDH, haemoglobin and bilirubin. Thalassaemia patients with a TRV ≥ 2·5 m/s have additional echocardiography and cardiac-MRI parameters suggestive of right and left-sided cardiac dysfunction. In addition, low arginine bioavailability may contribute to cardiopulmonary dysfunction in β-thalassaemia

Dentate gyrus abnormalities in sudden unexplained death in infants: morphological marker of underlying brain vulnerability

Sudden unexplained death in infants, including the sudden infant death syndrome, is likely due to heterogeneous causes that involve different intrinsic vulnerabilities and/or environmental factors. Neuropathologic research focuses upon the role of brain regions, particularly the brainstem, that regulate or modulate autonomic and respiratory control during sleep or transitions to waking. The hippocampus is a key component of the forebrain–limbic network that modulates autonomic/respiratory control via brainstem connections, but its role in sudden infant death has received little attention. We tested the hypothesis that a well-established marker of hippocampal pathology in temporal lobe epilepsy—focal granule cell bilamination in the dentate, a variant of granule cell dispersion—is associated with sudden unexplained death in infants. In a blinded study of hippocampal morphology in 153 infants with sudden and unexpected death autopsied in the San Diego County medical examiner’s office, deaths were classified as unexplained or explained based upon autopsy and scene investigation. Focal granule cell bilamination was present in 41.2 % (47/114) of the unexplained group compared to 7.7 % (3/39) of the explained (control) group (p < 0.001). It was associated with a cluster of other dentate developmental abnormalities that reflect defective neuronal proliferation, migration, and/or survival. Dentate lesions in a large subset of infants with sudden unexplained death may represent a developmental vulnerability that leads to autonomic/respiratory instability or autonomic seizures, and sleep-related death when the infants are challenged with homeostatic stressors. Importantly, these lesions can be recognized in microscopic sections prepared in current forensic practice. Future research is needed to determine the relationship between hippocampal and previously reported brainstem pathology in sudden infant death. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1357-0) contains supplementary material, which is available to authorized users

Evaluation of SMN Protein, Transcript, and Copy Number in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study

BACKGROUND: The universal presence of a gene (SMN2) nearly identical to the mutated SMN1 gene responsible for Spinal Muscular Atrophy (SMA) has proved an enticing incentive to therapeutics development. Early disappointments from putative SMN-enhancing agent clinical trials have increased interest in improving the assessment of SMN expression in blood as an early "biomarker" of treatment effect. METHODS: A cross-sectional, single visit, multi-center design assessed SMN transcript and protein in 108 SMA and 22 age and gender-matched healthy control subjects, while motor function was assessed by the Modified Hammersmith Functional Motor Scale (MHFMS). Enrollment selectively targeted a broad range of SMA subjects that would permit maximum power to distinguish the relative influence of SMN2 copy number, SMA type, present motor function, and age. RESULTS: SMN2 copy number and levels of full-length SMN2 transcripts correlated with SMA type, and like SMN protein levels, were lower in SMA subjects compared to controls. No measure of SMN expression correlated strongly with MHFMS. A key finding is that SMN2 copy number, levels of transcript and protein showed no correlation with each other. CONCLUSION: This is a prospective study that uses the most advanced techniques of SMN transcript and protein measurement in a large selectively-recruited cohort of individuals with SMA. There is a relationship between measures of SMN expression in blood and SMA type, but not a strong correlation to motor function as measured by the MHFMS. Low SMN transcript and protein levels in the SMA subjects relative to controls suggest that these measures of SMN in accessible tissues may be amenable to an "early look" for target engagement in clinical trials of putative SMN-enhancing agents. Full length SMN transcript abundance may provide insight into the molecular mechanism of phenotypic variation as a function of SMN2 copy number. TRIAL REGISTRY: Clinicaltrials.gov NCT00756821

Predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome

Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36months read in the core laboratory of 608 trial subjects, aged 6months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz)>3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year>90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R-2=0.01) or by change in AoR diameter (AoRd)/year>90th percentile with higher sinotubular junction z-score and non-white race (R-2=0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R-2=0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364

Design and Rationale of the Fontan Udenafil Exercise Longitudinal (FUEL) Trial

The Fontan operation creates a circulation characterized by elevated central venous pressure and low cardiac output. Over time, these characteristics result in a predictable and persistent decline in exercise performance that is associated with an increase in morbidity and mortality. A medical therapy that targets the abnormalities of the Fontan circulation might, therefore, be associated with improved outcomes. Udenafil, a phosphodiesterase type 5 inhibitor, has undergone phase I/II testing in adolescents who have had the Fontan operation and has been shown to be safe and well tolerated in the short-term. However, there are no data regarding the long-term efficacy of udenafil in this population. The Fontan Udenafil Exercise Longitudinal (FUEL) Trial is a randomized, double blind, placebo controlled phase III clinical trial being conducted by the Pediatric Heart Network in collaboration with Mezzion Pharma Co., Ltd. This trial is designed to test the hypothesis that treatment with udenafil will lead to an improvement in exercise capacity in adolescents who have undergone the Fontan operation. A safety extension trial, the FUEL Open-Label Extension Trial (FUEL OLE), offers the opportunity for all FUEL subjects to obtain open-label udenafil for an additional 12 months following completion of FUEL, and evaluates the long-term safety and tolerability of this medication. This manuscript describes the rationale and study design for FUEL and FUEL OLE. Together, these trials provide an opportunity to better understand the role of medical management in the care of those who have undergone the Fontan operation