Utility Assessment of Moderate to Severe Thyroid Eye Disease Health States.

Importance: Thyroid eye disease (TED) results in varying degrees of proptosis and diplopia negatively affecting quality of life (QoL), producing possibly substantial visual changes, disfigurement, and disability. Objective: To determine the association of varying TED severities with QoL in a non-TED population by assessing health state utility scores. Design, Setting, and Participants: This qualitative study, conducted from April 20, 2020, to April 29, 2021, assessed health states for active, moderate-severe TED, and values were elicited using time trade-off methods. Six health states of varying severity were determined from 2 placebo-controlled clinical trials (171 patients with TED and clinical activity score ≥4, ±diplopia/proptosis) and refined using interviews with US patients with TED (n = 6). Each health state description was validated by interviews with additional TED patient advocates (n = 3) and physician experts (n = 3). Health state descriptions and a QOL questionnaire were piloted and administered to a general population. Visual analog scales (VASs) were also administered to detect concurrence of the findings. Main Outcomes and Measures: TED health state utility scores and whether they differ from one another were assessed using Shapiro-Wilk, Kruskal-Wallis, pairwise Wilcoxon rank sum, and paired t tests. Results: A total of 111 participants completed time trade-off interviews. The mean (SD) utility value was 0.44 (0.34). The lowest (worse) mean utility value was observed in the most severe disease state (constant diplopia/large proptosis) with 0.30 (95% CI, 0.24-0.36), followed by constant diplopia/small proptosis (0.34; 95% CI, 0.29-0.40), intermittent or inconstant diplopia/large proptosis (0.43; 95% CI, 0.36-0.49), no diplopia/large proptosis (0.46; 95% CI, 0.40-0.52), and intermittent or inconstant diplopia/small proptosis (0.52; 95% CI, 0.45-0.58). The highest (best) mean value, 0.60 (95% CI, 0.54-0.67), was observed for the least severe disease state (no diplopia/small proptosis). Conclusions and Relevance: These findings suggest that patients with active, moderate-severe TED may have substantial disutility, with increasing severity of proptosis/diplopia more likely to have detrimental associations with QoL. These health state scores may provide a baseline for determining QoL improvement in these TED health states (utility gains) treated with new therapies.

Healthy food prescription incentive programme for adults with type 2 diabetes who are experiencing food insecurity: protocol for a randomised controlled trial, modelling and implementation studies.

INTRODUCTION: The high cost of many healthy foods poses a challenge to maintaining optimal blood glucose levels for adults with type 2 diabetes mellitus who are experiencing food insecurity, leading to diabetes complications and excess acute care usage and costs. Healthy food prescription programmes may reduce food insecurity and support patients to improve their diet quality, prevent diabetes complications and avoid acute care use. We will use a type 2 hybrid-effectiveness design to examine the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) of a healthy food prescription incentive programme for adults experiencing food insecurity and persistent hyperglycaemia. A randomised controlled trial (RCT) will investigate programme effectiveness via impact on glycosylated haemoglobin (primary outcome), food insecurity, diet quality and other clinical and patient-reported outcomes. A modelling study will estimate longer-term programme effectiveness in reducing diabetes-related complications, resource use and costs. An implementation study will examine all RE-AIM domains to understand determinants of effective implementation and reasons behind programme successes and failures. METHODS AND ANALYSIS: 594 adults who are experiencing food insecurity and persistent hyperglycaemia will be randomised to a healthy food prescription incentive (n=297) or a healthy food prescription comparison group (n=297). Both groups will receive a healthy food prescription. The incentive group will additionally receive a weekly incentive (CDN$10.50/household member) to purchase healthy foods in supermarkets for 6 months. Outcomes will be assessed at baseline and follow-up (6 months) in the RCT and analysed using mixed-effects regression. Longer-term outcomes will be modelled using the UK Prospective Diabetes Study outcomes simulation model-2. Implementation processes and outcomes will be continuously measured via quantitative and qualitative data. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Calgary and the University of Alberta. Findings will be disseminated through reports, lay summaries, policy briefs, academic publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04725630. PROTOCOL VERSION: Version 1.1; February 2022.

Cost analysis and efficacy of recruitment strategies used in a large pragmatic community-based clinical trial targeting low-income seniors: a comparative descriptive analysis.

OBJECTIVE: One of the most challenging parts of running clinical trials is recruiting enough participants. Our objective was to determine which recruitment strategies were effective in reaching specific subgroups. STUDY DESIGN AND SETTING: We assessed the efficacy and costs of the recruitment strategies used in the Assessing Outcomes of Enhanced Chronic Disease Care Through Patient Education and a Value-based Formulary Study (ACCESS) in Alberta, Canada. RESULTS: Twenty percent of the study budget ($354,330 CAD) was spent on recruiting 4013 participants, giving an average cost per enrolled of $88 CAD. Pharmacies recruited the most participants (n = 1217), at a cost of $128/enrolled. "Paid media" had the highest cost ($806/enrolled), whereas "word of mouth" and "unpaid media" had the lowest (~$3/enrolled). Participants enrolled from "seniors outreach" had the lowest baseline quality of life and income, while participants from "word of mouth" had the lowest educational attainment. CONCLUSION: The "health care providers" strategies were especially successful - at a moderate cost per enrolled. The "media" strategies were less effective, short lasting, and more costly. No strategy was singularly effective in recruiting our targeted groups, emphasizing the importance of utilizing a variety of strategies to reach recruitment goals. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579655 . Registered on 19 October 2015.

Neuromyelitis optica spectrum disorder: Patient experience and quality of life.

Objective: To gain insights into NMOSD disease impact, which may negatively affect QoL of patients, their families, and social network. Methods: The current study used validated instruments to assess physical, emotional, and socioeconomic burden of NMOSD on QoL among 193 patients. Results: A majority of patients reported an initial diagnosis of a disease other than NMOSD. Overall, two-thirds of patients reported NMOSD as having a strong negative impact on physical health (Short Form-36 [SF-36] score 27.1 ± 39.1), whereas emotional well-being was relatively unimpaired on average (SF-36 score 54.0 ± 44.9). A subset of patients reported having the highest category of emotional health despite worse physical health or financial burden, suggesting psychological resilience. Pain (r = 0.61) and bowel/bladder dysfunction (r = 0.41) imposed the greatest negative physical impact on overall QoL. In turn, ability to work correlated inversely with worsened health (r = -0.68). Increased pain, reduced sexual function, inability to work, and reduced QoL had greatest negative impacts on emotional well-being. Dissatisfaction with treatment options and economic burden correlated inversely with QoL. Conclusions: Collectively, the current findings advance the understanding of physical, emotional, social, and financial tolls imposed by NMOSD. These insights offer potential ways to enhance QoL by managing pain, enhancing family and social networks, and facilitating active employment.

Amplification-free detection of microRNAs via a rapid microarray-based sandwich assay.

The detection and profiling of microRNAs are of great interest in disease diagnosis and prognosis. In this paper, we present a method for the rapid amplification-free detection of microRNAs from total RNA samples. In a two-step sandwich assay approach, fluorescently labeled reporter probes were first hybridized with their corresponding target microRNAs. The reaction mix was then added to a microarray to enable their specific capture and detection. Reporter probes were Tm equalized, enabling specificity by adjusting the length of the capture probe while maintaining the stabilizing effect brought about by coaxial base stacking. The optimized assay can specifically detect microRNAs in spiked samples at concentrations as low as 1 pM and from as little as 100 ng of total RNA in 2 h. The detection signal was linear between 1 and 100 pM (R2 = 0.99). Our assay data correlated well with results generated by qPCR when we profiled a select number of breast cancer related microRNAs in a total RNA sample.

Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease.

IMPORTANCE: Thyroid-associated ophthalmopathy (TAO) is a common and debilitating manifestation of Graves disease (GD). Presently little is known about factors that may increase the risk of developing TAO among patients with GD. OBJECTIVE: To identify risk factors associated with the development of TAO among individuals with newly diagnosed GD. DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal cohort study, all beneficiaries 18 years of age or older with newly diagnosed GD who were continuously enrolled in a large nationwide US managed care network and who visited an eye care professional 1 or more times from 2001 to 2009 were identified. International Classification of Diseases, Ninth Revision, Clinical Modification billing codes were used to identify those who developed manifestations of TAO. Multivariable Cox regression was used to determine the hazard of developing TAO among persons with newly diagnosed GD, with adjustment for sociodemographic factors, systemic medical conditions, thyrotropin levels, and medical and surgical interventions for management of hyperthyroidism. MAIN OUTCOMES AND MEASURES: Manifestations of TAO measured by hazard ratios (HRs) with 95% CIs. RESULTS: Of 8404 patients with GD who met the inclusion criteria, 740 (8.8%) developed TAO (mean follow-up, 374 days since initial GD diagnosis). After adjustment for potential confounders, surgical thyroidectomy, alone or in combination with medical therapy, was associated with a 74% decreased hazard for TAO (adjusted HR, 0.26 [95% CI, 0.12-0.51]) compared with radioactive iodine therapy alone. Statin use (for ≥60 days in the past year vs <60 days or nonuse) was associated with a 40% decreased hazard (adjusted HR, 0.60 [CI, 0.37-0.93]). No significant association was found for the use of nonstatin cholesterol-lowering medications or cyclooxygenase 2 inhibitors and the development of TAO. CONCLUSIONS AND RELEVANCE: If prospective studies can confirm our finding that a thyroidectomy and statin use are associated with substantially reduced hazards for TAO among patients with GD, preventive measures for this burdensome manifestation of GD may become a reality.

Structural elucidation of olive pomace fed sea bass (Dicentrarchus labrax) polar lipids with cardioprotective activities.

The purpose of this study was to structurally characterise the polar lipids of sea bass (Dicentrarchus labrax), fed with an experimental diet containing olive pomace (OP), that exhibit cardioprotective activities. OP has been added to conventional fish oil (FO) feed at 4% and this was the OP diet, having been supplemented as finishing diet to fish. Sea bass was aquacultured using either FO or OP diet. At the end of the dietary experiment, lipids in both samples of fish muscle were quantified and HPLC fractionated. The in vitro cardioprotective properties of the polar lipid fractions, using washed rabbit's platelets, have been assessed and the two most biologically active fractions were further analysed by mass spectrometry. The gas-chromatrograpy-mass spectrometric data shows that these two fractions contain low levels of myristic (14:0), oleic (18:1 cis ω-9) and linoleic acids (18:2 ω-6), but high levels of palmitic (16:0) and stearic acids (18:0) as well as eicosadienoic acid (20:2 ω-6). The first fraction (MS1) also contained significant levels of arachidonic acid (20:4 ω-6) and the omega-3 fatty acids: eicosapentaenoic acid (22:5) and docosahexaenoic acid (22:6). Electrospray-mass spectrometry elucidated that the lipid composition of the two fractions contained various diacyl-glycerophospholipids species, where the majority of them have either 18:0 or 18:1 fatty acids in the sn-1 position and either 22:6 or 20:2 fatty acids in the sn-2 position for MS1 and MS2, respectively. Our research focuses on the structure/function relationship of fish muscle polar lipids and cardiovascular diseases and structural data are given for polar lipid HPLC fractions with strong cardioprotective properties.

Effects of an enhanced secondary prevention program for patients with heart disease: a prospective randomized trial.

BACKGROUND: Secondary prevention medications in cardiac patients improve outcomes. However, prescription rates for these drugs and long-term adherence are suboptimal. OBJECTIVE: To determine whether an enhanced secondary prevention program improves outcomes. METHODS: Hospitalized patients with indications for secondary prevention medications were randomly assigned to either usual care or an intervention arm, in which an intensive program was used to optimize prescription rates and long-term adherence. Follow-up was 19 months. RESULTS: A total of 2643 patients were randomly assigned in the study; 1342 patients were assigned to usual care and 1301 patients were assigned to the intervention arm. Prescription rates were near optimal except for lipid-lowering medications. Rehospitalization rates per 100 patients were 136.2 and 132.6 over 19 months in the usual care and intervention groups, respectively (P=0.59). Total days in hospital per patient were similar (10.9 days in the usual care group versus 10.2 days in the intervention group; P not significant). Crude mortality was 6.2% and 5.5% in the usual care and intervention groups, respectively, with no significant difference (P=0.15) in overall survival. Post hoc analysis suggested that after the study team became experienced, days in hospital per patient were reduced by the program (11.1+/-0.91 and 8.9+/-0.61 in the usual care and intervention groups, respectively; P<0.05). CONCLUSIONS: The intervention program failed to improve outcomes in the present study. One explanation for these results is the near optimal physician compliance with guidelines in both groups. It is also possible that a substantial learning curve for the staff was involved, as suggested by the reduction in total days in hospital in the intervention patients during the second part of the study.

Acción Mutua (Shared Action): a multipronged approach to delivering capacity-building assistance to agencies serving Latino communities in the United States.

Culturally appropriate, theory-based capacity-building assistance can serve a vital role in helping HIV prevention providers remain up-to-date, effective, and responsive to those they serve. Funded by the Centers for Disease Control and Prevention (CDC), AIDS Project Los Angeles, in collaboration with San Francisco State University's César E. Chávez Institute, conducted full-day site visits and qualitative interviews in 2005 with mid-level management staff of CDC-funded community-based organizations delivering HIV prevention services to Latino communities in the western region of the United States. We found that agencies we visited (1) had not yet adapted the evidence-based interventions they were using at the time of our visit and (2) requested technical assistance and training in the areas of program development, evaluation, group facilitation techniques, consumer recruitment, client retention, intervention adaptation, and materials development. Findings from this needs assessment were used to inform our seven-pronged approach to delivering capacity-building assistance entitled "Acción Mutua" (Shared Action). The approach emphasizes strategic partnerships, stakeholder involvement, organizational self-assessment, culturally appropriate materials development, interactive training, tailored onsite technical assistance, and professional networking opportunities. This article describes our approach in detail, the assessment process we used to develop it, and its implications for capacity-building practice.

Gene prediction using the Self-Organizing Map: automatic generation of multiple gene models.

BACKGROUND: Many current gene prediction methods use only one model to represent protein-coding regions in a genome, and so are less likely to predict the location of genes that have an atypical sequence composition. It is likely that future improvements in gene finding will involve the development of methods that can adequately deal with intra-genomic compositional variation. RESULTS: This work explores a new approach to gene-prediction, based on the Self-Organizing Map, which has the ability to automatically identify multiple gene models within a genome. The current implementation, named RescueNet, uses relative synonymous codon usage as the indicator of protein-coding potential. CONCLUSIONS: While its raw accuracy rate can be less than other methods, RescueNet consistently identifies some genes that other methods do not, and should therefore be of interest to gene-prediction software developers and genome annotation teams alike. RescueNet is recommended for use in conjunction with, or as a complement to, other gene prediction methods.

Parasomnias and sleep disordered breathing in Caucasian and Hispanic children - the Tucson children's assessment of sleep apnea study.

BACKGROUND: Recent studies in children have demonstrated that frequent occurrence of parasomnias is related to increased sleep disruption, mental disorders, physical harm, sleep disordered breathing, and parental duress. Although there have been several cross-sectional and clinical studies of parasomnias in children, there have been no large, population-based studies using full polysomnography to examine the association between parasomnias and sleep disordered breathing. The Tucson Children's Assessment of Sleep Apnea study is a community-based cohort study designed to investigate the prevalence and correlates of objectively measured sleep disordered breathing (SDB) in pre-adolescent children six to 11 years of age. This paper characterizes the relationships between parasomnias and SDB with its associated symptoms in these children. METHODS: Parents completed questionnaires pertaining to their child's sleep habits. Children had various physiological measurements completed and then were connected to the Compumedics PS-2 sleep recording system for full, unattended polysomnography in the home. A total of 480 unattended home polysomnograms were completed on a sample that was 50% female, 42.3% Hispanic, and 52.9% between the ages of six and eight years. RESULTS: Children with a Respiratory Disturbance Index of one or greater were more likely to have sleep walking (7.0% versus 2.5%, p < 0.02), sleep talking (18.3% versus 9.0%, p < 0.006), and enuresis (11.3% versus 6.3%, p < 0.08) than children with an Respiratory Disturbance Index of less than one. A higher prevalence of other sleep disturbances as well as learning problems was observed in children with parasomnia. Those with parasomnias associated with arousal were observed to have increased number of stage shifts. Small alterations in sleep architecture were found in those with enuresis. CONCLUSIONS: In this population-based cohort study, pre-adolescent school-aged children with SDB experienced more parasomnias than those without SDB. Parasomnias were associated with a higher prevalence of other sleep disturbances and learning problems. Clinical evaluation of children with parasomnias should include consideration of SDB.

Change in tumor cellularity of breast carcinoma after neoadjuvant chemotherapy as a variable in the pathologic assessment of response.

BACKGROUND: Complete pathologic response of breast carcinoma to neoadjuvant chemotherapy is a well defined outcome that correlates with prolonged survival. Categorization of incomplete response depends on accurate measurement of residual tumor size but is complicated by the variable histopathologic changes that occur within the tumor bed. In the current study, the authors investigated the contribution of assessing tumor cellularity in the pathologic evaluation of response to chemotherapy. METHODS: The slides from diagnostic core needle biopsy and the subsequent matched resection specimens were examined in 240 patients with breast carcinoma: 120 "treated" patients who received neoadjuvant chemotherapy and 120 "control" patients who received primary surgical management within a few weeks of diagnosis. Clinical response and residual tumor size were evaluated in 108 treated patients who completed a clinical trial with paclitaxel and then received combined 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Tumor cellularity was assessed from hematoxylin and eosin-stained tissue sections as the percentage of tumor area that contained invasive carcinoma. RESULTS: After neoadjuvant chemotherapy, tumor cellularity decreased from a median of 40% in core needle biopsy to 10% in resection specimens (P<0.01; Wilcoxon signed rank test). The cellularity of core needle biopsy (median, 30%) tended to underestimate the cellularity of resection specimens (median, 40%) in the control group (P<0.01). Changes in cellularity varied within each clinical response category, particularly partial response and minor response. The greatest reduction was observed in the cellularity of residual primary tumors that measured < or =1 cm (pathologic T1a [pT1a] and pT1b tumors), but changes in cellularity varied in the pT1, pT2, and pT3 residual tumor categories. The shape of the distribution of tumor size, expressed as the greatest dimension in cm, was similar in the control group and the treatment group (excluding complete pathologic response); however, when residual tumor size and cellularity were combined, the distribution of pathologic response shifted left (toward complete response) with a steep decline, suggesting that many tumors had a large reduction in cellularity but little change in the tumor size. CONCLUSIONS: Cellularity of the tumor mass was reduced significantly by neoadjuvant chemotherapy, and the change varied widely in different categories of clinical response. Although residual tumors measuring < or =1 cm in greatest dimension had the most reduction in tumor cellularity, there was broad variability for all residual tumor groups (pT1-pT3). The frequency distribution of residual tumor size was altered markedly by the inclusion of tumor cellularity, indicating that the product of pathologic size and tumor cellularity may provide more accurate pathologic response information than tumor size alone.