Association between under-dose of enzyme replacement therapy and quality of life in adults with late-onset Pompe disease in China: A retrospective matched cohort study.

BACKGROUND: Due to the high cost of enzyme replacement therapy (ERT), most of adults with late-onset Pompe disease (LOPD) who received ERT used the medication with insufficient dosefs in China. OBJECTIVE: To compare the change in quality of life (QoL) between adults with LOPD receiving under-dose ERT and no ERT, and identify factors associated with the change of QoL. METHODS: A retrospective matched cohort study was conducted among adult patients with LOPD in a nationwide Pompe registry in China. Eligible participants were those who completed two investigations, and didn't expose to ERT at baseline or before. The treated group were those who used ERT during follow-up; the untreated group received general care. The treated and untreated group were matched with a ratio of 1:2. QoL was assessed by the SF-12 and EQ-5D-5L. The dose of ERT was evaluated by the ratio of actual vials patients used divided by the indicated vials patients should use. The treated patients were further classified into mild and severe under-dose users by the median ratio. Multivariate linear regression analyses were performed to estimate the average treatment effect in the treated groups and identify factors associated with the changes of QoL scores. RESULTS: The study sample included 5 mild under-dose users, 6 severe under-dose users, and 22 untreated participants. Compared with the untreated group, mild under-dose ERT had no significant effect on the changes of QoL scores. In contrast, severe under-dose ERT was associated with a decline of physical QoL (ß = -6.19, p = 0.001), but an increase of overall health state (ß = 19.69, p = 0.032). A higher score of physical QoL (ß = -0.74, p = 0.001) and overall health state (ß = -0.69, p<0.001) at baseline was associated with decline in corresponding scores at follow-up. Being female was a contributor to the worsening of the overall health state (ß = -22.79, p = 0.002), while being employed or at school was a predictor of improvement in mental QoL (ß = 5.83, p = 0.002). CONCLUSIONS: A Pompe-disease specific instrument based on patient experiences is warranted to closely monitor changes in QoL on a routine basis. It is desirable for patients with severe under-dose ERT to discuss with physicians whether to adjust treatment strategies.

Clinical characteristics and predisposing factors of lung metastasis in sacral chordoma: a cross-sectional cohort study of 221 cases.

Introduction: Limited studies are available on the topic of lung metastasis in sacral chordoma. The primary objective of this study was to investigate the prevalence, characteristics, associated factors, and prognosis of lung metastasis in sacral chordoma. Methods: A total of 221 cases with primary sacral chordoma, all of whom underwent surgical resection at our center, were included in this study. Comprehensive demographic information, imaging findings, and oncological evaluations were collected and thoroughly analyzed. The diagnosis of lung metastasis in the majority of cases was established through radiographic examinations. Results: The prevalence of lung metastasis in the cohort was 19.5%, with the lung emerging as the predominant site of distant metastasis. Recurrent chordoma cases exhibited a significantly higher lung metastasis rate in comparison to newly diagnosed chordoma cases (33.33% and 12.76%, p=0.0005). Patients with lung metastasis had a larger tumor size, a higher proportion of previous sacral chordoma surgeries and a greater likelihood of postoperative recurrence. Associated factors of lung metastasis were tumor size, postoperative recurrence and radiotherapy. Patients with lung metastasis exhibited decreased median overall survival (91 vs. 144 months for those without lung metastasis, p<0.05) and recurrence-free survival (27 vs. 68 months, p<0.001) times. Discussion: Lung is the most common site of distant metastasis in sacral chordoma with an incidence rate nearly 20%. Larger tumor size and postoperative recurrence are risk factors for lung metastasis while radiotherapy is a protective factor. Occurrence of lung metastasis in sacral chordoma is a negative prognostic factor.

NETosis in tumour microenvironment of liver: From primary to metastatic hepatic carcinoma.

BACKGROUND: Hepatocellular carcinoma is a common and highly lethal tumour. The tumour microenvironment (TME) plays an important role in the progression and metastasis of hepatocellular carcinoma (HCC). A cell death mechanism, termed NETosis, has been found to play an important role in the TME of HCC. SUMMARY: This review article focuses on the role of NETosis in the TME of HCC, a novel form of cell death in which neutrophils capture and kill microorganisms by releasing a type of DNA meshwork fibres called "NETs". This process is associated with neutrophil activation, local inflammation and cytokines. The study suggests that NETs play a multifaceted role in the development and metastasis of HCC. The article also discusses the role of NETs in tumour proliferation and metastasis, epithelial-mesenchymal transition (EMT), and surgical stress. In addition, the article discusses the interaction of NETosis with other immune cells in the TME and related therapeutic strategies. A deeper understanding of NETosis can help us better understand the complexity of the immune system and provide a new therapeutic basis for the treatment and prevention of HCC. KEY INFORMATION: In conclusion, NETosis is important in the TME of liver. NETs have been shown to contribute to the progression and metastasis of liver cancer. The interaction between NETosis and immune cells in the TME, as well as related therapies, are important areas of research.

Aberrant Immune Features after Recovery from COVID-19 in Patients with Systemic Lupus Erythematosus and Other Autoimmune Diseases.

Considering the large number of individuals who have already been infected and may have reinfection, the post-infection effects of COVID-19 are of great importance for clinical practice and predicting disease trends. However, our understanding of the potential long-term effects, particularly on immunity, after recovering from COVID-19 remains limited. The aim of this study was to investigate the abnormal immunological factors that contribute to the prolonged immunological effects of COVID-19. Two groups of patients were enrolled in the study, including 11 individuals with various autoimmune diseases (AIDs) and 16 patients diagnosed with systemic lupus erythematosus (SLE). Detailed clinical symptoms were closely monitored, and peripheral mononuclear cells were analyzed using flow cytometry. The clinical status was evaluated using the SLE Disease Activity Index (SLEDAI) and the Clinical Global Impressions (CGI) index. The proportions of follicular T helper cells (Tfh) exhibited significant increases in both cohorts (AID: p = 0.03; SLE: p = 0.0008). Conversely, the percentages of Foxp3+ and CD4+ regulatory T cells (Treg) were reduced in patients following COVID-19 infection (AID: p = 0.009, 0.05, resp.; SLE: p = 0.02, 0.0009, resp.). The percentages of Th2 and Th17 cells were significantly increased in SLE patients (p < 0.05). Exacerbated conditions were observed in SLE patients two months after infection (SLEDAI, p < 0.05). Our findings show that COVID-19 infection increases Tfh cells and decreases Treg cells in patients of AIDs, worsening pathogenetic immune status in post-recovery populations.

A luciferase reporter mouse model to optimize in vivo gene editing validated by lipid nanoparticle delivery of adenine base editors.

The rapid development of CRISPR genome editing technology has provided the potential to treat genetic diseases effectively and precisely. However, efficient and safe delivery of genome editors to affected tissues remains a challenge. Here, we developed luminescent ABE (LumA), a luciferase reporter mouse model containing the R387X mutation (c.A1159T) in the luciferase gene located in the Rosa26 locus of the mouse genome. This mutation eliminates luciferase activity but can be restored upon A-to-G correction by SpCas9 adenine base editors (ABEs). The LumA mouse model was validated through intravenous injection of two FDA-approved lipid nanoparticle (LNP) formulations consisting of either MC3 or ALC-0315 ionizable cationic lipids, encapsulated with ABE mRNA and LucR387X-specific guide RNA (gRNA). Whole-body bioluminescence live imaging showed consistent restoration of luminescence lasting up to 4 months in treated mice. Compared with mice carrying the wild-type luciferase gene, the ALC-0315 and MC3 LNP groups showed 83.5% ± 17.5% and 8.4% ± 4.3% restoration of luciferase activity in the liver, respectively, as measured by tissue luciferase assays. These results demonstrated successful development of a luciferase reporter mouse model that can be used to evaluate the efficacy and safety of different genome editors, LNP formulations, and tissue-specific delivery systems for optimizing genome editing therapeutics.

Developing the health state classification system for a condition-specific preference-based measure for patients with myasthenia gravis.

PURPOSE: This study aimed to generate the health state classification system (HCS) of a condition-specific preference-based measure to capture the health-related quality of life (HRQoL) of patients with myasthenia gravis (MG) from the 15-item Myasthenia Gravis Quality of Life Scale (MG-QoL15r). MATERIALS AND METHODS: An HCS was derived from the MG-QoL15r in a large sample of 1739 patients with MG based on psychometric analysis, including factor analysis, item response theory analysis, and discussions with experts. Reliability, construct and convergent validity, and item fit of the HCS were further assessed using another sample. RESULTS: The HCS has six dimensions: social activity, hobbies and fun activities, meeting family needs, work performance, mobility, and emotion, and it demonstrates good internal consistency reliability. The unidimensionality of the HCS was confirmed using confirmatory factor analysis. Satisfied convergent validity was supported by a significant association with the 12-item Short Form Survey (SF-12). CONCLUSIONS: Based on a solid process of development and consultations with clinical professionals and patients, a valid MG-specific preference-based measure, MGQoL-6D, was developed. Further research will estimate the local preference weight to support the MG-related cost-utility analysis.IMPLICATION FOR REHABILITATIONA new condition-specific health state classification system (HCS) named Myasthenia gravis Quality of Life Scale (MGQoL-6D) is proposed.MGQoL-6D classifies MG health states as a combination of six dimensions with three response levels.The dimensions of the HCS are social activity, hobbies and fun activity, family needs, work performance, mobility, and emotion.The HCS and the upcoming value set of the MGQoL-6D could support the cost-effectiveness analysis of MG-related clinical and rehabilitated interventions.

Predictors and prognostic stratification for lupus low disease activity state: results from a prospective clinical trial.

OBJECTIVE: To identify predictors for lupus low disease activity state (LLDAS), early-achieved LLDAS and long-term disease activity, and to refine a prognostic stratification tool for use in active SLE patients. METHOD: A total of 245 active SLE patients were enrolled, followed up quarterly from 2014 to 2016. LLDAS-50 was defined as the maintenance of LLDAS for ≥50% of the observed time. LLDAS at 3 months after cohort entry (LLDAS-3mo) was considered an early-achieved LLDAS. Multivariate analysis was performed to identify predictors for LLDAS, early-achieved LLDAS and long-term disease activity. Based on the factors associated with LLDAS, a prognostic stratification tool for LLDAS was established. RESULTS: The 2-year probability of achieving LLDAS was 62.9% (154/245). Multivariate analysis-determined renal involvement, haematological involvement and hypocomplementaemia were negative predictors for achieving LLDAS and LLDAS-50. In multivariate logistic analysis, antiphospholipid antibodies positivity, hypocomplementaemia, renal involvement and haematological involvement were identified as negative predictors for achieving LLDAS-3mo. LLDAS-3mo (P < 0.0001; risk ratio: 47.694; 95% CI: 13.776, 165.127) was a strong predictor for LLDAS-50. The probability of achieving LLDAS, LLDAS-50 and LLDAS-3mo were 88.9% (32/36), 69.4% (25/36) and 41.7% (15/36) in the low-risk group, 65% (65/100), 51.0% (51/100) and 32.0% (32/100) in intermediate-risk group, and 52.8% (57/108), 27.8% (30/108) and 13.0% (14/108) in high-risk group respectively. Significant differences (P < 0.0001) were observed in the LLDAS Kaplan-Meier estimates for the three risk groups based on the identified risk factors. CONCLUSION: Renal involvement, haematological involvement and hypocomplementaemia were negative predictors of LLDAS achievement and maintenance. LLDAS-3mo was a positive predictor for the long-term sustainment of LLDAS.

Effectiveness of an adapted physical activity intervention on health-related physical fitness in adolescents with intellectual disability: a randomized controlled trial.

This study aimed to examine the effects of an adapted physical activity (APA) intervention on health-related physical fitness (HRPF) in adolescents with intellectual disability (ID). With a randomized controlled trial design, adolescents aged 12-18 years, with mild and moderate ID, and being overweight and obese were recruited and randomly assigned to either an intervention or a control group. The APA intervention consisted of overall moderate intensity aerobic and resistance exercise, with a duration of 45 min/session, a frequency of 2 sessions/week, and lasting for 9 months. A negative control was involved, in which participants received no treatment. Changes in four fitness tests, including the 9-min run/walk, handgrip strength, 30-s sit-ups, and sit-and-reach tests, were assessed between the groups using general linear models. A total of 57 participants (39 in the intervention group and 18 in the control group) completed the study. Significant mean differences in changes in the 9-min run/walk test (413.6 m [95% CI 146.72 m, 680.41 m], p = 0.003) and the right-side sit-and-reach test (2.2 cm [95% CI 0.37 cm, 4.09 cm], p = 0.020) respectively were observed in the intervention group, compared to the control group. No significant between-group improvement was observed for the handgrip strength and the 30-s sit-ups tests. The APA intervention induced beneficial effects on cardiorespiratory fitness and potential beneficial effects on flexibility for adolescents with ID. However, no significant effects of this intervention on muscular strength and endurance were observed in this study. Future studies should consider involving effective exercises in interventions to improve muscular strength and endurance.

The Relationships between Parenting Practices and Child Health-Related Behaviors in Children with Intellectual Disability: The Moderating Role of Child Body Weight Status.

This study aimed to examine the associations between parenting practices and child health-related behaviors, and the moderating role of child body weight status in children with intellectual disability (ID). A cross-sectional study was conducted among a sample of children with ID in Hong Kong; 440 participants were included in this study. All the variables investigated were collected from questionnaires, except body weight status, which was objectively measured. Logistic regression analysis was used to examine the associations between parenting practices and children's unhealthy behaviors. Interaction items were added to investigate the moderation effect of child body weight status, adjusting for significant background characteristics. Results showed that the parenting practices of "restricting access to unhealthy food and sedentary behaviors (RA)" (OR range: 0.63-0.64) and "using food or sedentary behaviors as rewards (UR)" (OR range: 1.28-1.60) were significantly associated with some eating behaviors, but not with sedentary behaviors. Body weight status significantly moderated these associations. Only RA showed favorable effects on some eating behaviors in children with overweight and obesity (OR range: 0.17-0.28), whereas the effects of UR differed by body weight status. Future research should focus on developing educational interventions which encourage parents to use practices that are tailored towards children's individual characteristics.

Promoting Physical Activity among Workers: A Review of Literature and Future Directions on Developing Theory-Based Interventions.

Insufficient physical activity (PA) has been identified as a leading risk factor for premature and all-cause death, as well as non-communicable diseases. Employees, especially those with low occupational PA, are more vulnerable to physical inactivity, and studies in this population are scarce. However, employees may receive benefits for both health and work productivity from PA. Therefore, well-designed behavior change studies to promote PA in employees are urgently needed, especially during the COVID-19 pandemic. Literature was searched before 30 July 2022, and updated evidence was summarized. This review elaborates on the evidence related to insufficient PA and further provides an overview of theory-based interventions for promoting PA. Evidence indicates that intervention mapping (IM) was a useful tool to develop, implement, and evaluate behavior change interventions. Based on the IM framework, reviewing the theory- and evidence-based change methods and delivery modes, and further identifying the research gaps and limitations of existing interventions could provide promising suggestions and directions for development of well-founded interventions promoting PA among employees. The updated knowledge base for developing future interventions may boost efficacy and provide firm conclusions for researchers in this area.

Effects of a School-Based Physical Activity Intervention for Obesity, Health-Related Physical Fitness, and Blood Pressure in Children with Intellectual Disability: A Randomized Controlled Trial.

Children with intellectual disability (ID) are more vulnerable to health conditions than their typically developing peers. Evidence of effective interventions is scarce. A randomized controlled trial was conducted in 30 overweight and obese children with intellectual disability (ID) in China to evaluate a 12-week school-based physical activity intervention for obesity, health-related physical fitness (HRPF), and blood pressure. The intervention consisted of 24 physical activity (PA) sessions (2 sessions/week, 60 min/session), with exercise intensity progressively increasing from a moderate level to a vigorous level. All participants were followed up for 12 weeks after the intervention period to evaluate sustained effects. Outcomes were repeatedly measured at baseline, after the intervention, and after follow-up. The intervention was effective in reducing some obesity-related outcomes (including weight and body mass index) and improving some HRPF-related outcomes (including the 6 min walk test and the 30 s sit-to-stand test), with the significant effects being sustained after the 12-week follow-up. No effect was observed on blood pressure. The findings of this study contribute to the development and implementation of PA interventions to reduce obesity and improve HRPF in children with ID.

Hypertension and Associated Risk Factors among Children with Intellectual Disability: A Cross-Sectional Study.

To investigate the prevalence of hypertension and associated risk factors in Chinese children with intellectual disability, a cross-sectional study was conducted in a sample of 558 children with intellectual disability aged 6-18 years in Hong Kong, and 452 (81.0%) with valid data were included in the data analysis. Blood pressure was measured according to a standard protocol. Hypertension was defined using the age-, gender-, and height-specific classification criteria recommended by the 2018 Chinese Guidelines for Children. Multivariate and hierarchical logistic regression was fitted to examine the associations of hypertension with potential risk factors. Overall, 31.4% of the participants were classified as having hypertension. Obese children were more likely to develop hypertension than non-obese children (adjusted OR = 2.77, 95% CI: 1.28, 5.99, p = 0.010). A paternal education of college or above and a paternal occupation of clerks, sales representatives, and workers were also associated with an increased risk of hypertension. The prevalence of hypertension is high among Chinese children with intellectual disability. Obesity was the strongest risk factor. Further longitudinal studies are warranted to confirm our findings. Nevertheless, preventions against obesity are promising to receive doubled benefits in reducing both obesity and hypertension, given its strong relationship with hypertension in this special population.

Lipid-Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Components.

Gene editing mediated by CRISPR/Cas9 systems is due to become a beneficial therapeutic option for treating genetic diseases and some cancers. However, there are challenges in delivering CRISPR components which necessitate sophisticated delivery systems for safe and effective genome editing. Lipid nanoparticles (LNPs) have become an attractive nonviral delivery platform for CRISPR-mediated genome editing due to their low immunogenicity and application flexibility. In this review, we provide a background of CRISPR-mediated gene therapy, as well as LNPs and their applicable characteristics for delivering CRISPR components. We then highlight the challenges of CRISPR delivery, which have driven the significant development of new, safe, and optimized LNP formulations in the past decade. Finally, we discuss considerations for using LNPs to deliver CRISPR and future perspectives on clinical translation of LNP-CRISPR gene editing.

Interventions for health-related physical fitness and overweight and obesity in children with intellectual disability: Systematic review and meta-analysis.

BACKGROUND: Poor health-related physical fitness (HRPF) and overweight and obesity are common health problems for children with intellectual disability. This study aimed to review existing lifestyle intervention studies, and identify effective strategies for this population. METHODS: A systematic search was undertaken in three databases. The random-effects model was used to pool the weighted results by inverse variance methods, and the I2 statistic was applied to assess heterogeneity among the included studies. RESULTS: Most of the identified interventions (27/29) adopted physical activity (PA). For obesity-related outcomes, the results showed no significant effect of PA studies on reducing obesity. For HRPF outcomes, significant effects were found on 6-min walk distance (51.86 m, 95% CI [16.49, 87.22], p < .05). CONCLUSIONS: PA is the predominant intervention component adopted and may contribute to improving cardiopulmonary fitness; but the lack of research limits our ability to draw any confirmed conclusion on obesity-related outcomes and other HRPF outcomes.

Increasing the Targeting Scope of CRISPR Base Editing System Beyond NGG.

Genome editing provides a new therapeutic strategy to cure genetic diseases. The recently developed CRISPR-Cas9 base editing technology has shown great potential to repair the majority of pathogenic point mutations in the patient's DNA precisely. Base editor is the fusion of a Cas9 nickase with a base-modifying enzyme that can change a nucleotide on a single strand of DNA without generating double-stranded DNA breaks. However, a major limitation in applying such a system is the prerequisite of a protospacer adjacent motif sequence at the desired position relative to the target site. Progress has been made to increase the targeting scope of base editors by engineering SpCas9 protein variants, establishing systems with broadened editing windows, characterizing new SpCas9 orthologs, and developing prime editing technology. In this review, we discuss recent progress in the development of CRISPR base editing, focusing on its targeting scope, and we provide a workflow for selecting a suitable base editor based on the target nucleotide sequences.

Effectiveness of an adapted physical activity intervention for weight management in adolescents with intellectual disability: A randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a 9-month school-based adapted physical activity (APA) program for reducing weight among adolescents with intellectual disability (ID). METHODS: In this randomized controlled trial, adolescents with ID, aged 12-18 years, who were overweight/or with obesity were randomly assigned into intervention and control groups. The APA intervention consisted of aerobic and resistance exercises with an overall moderate intensity and was delivered at a frequency of two sessions per week for 9 months. Changes in body mass index (BMI, primary outcome) and changes in BMIz, weight, percent body fat, waist circumference and waist-to-height ratio (secondary outcomes) were examined using general linear models. RESULTS: In total 61 subjects (39 in the intervention and 22 in the control) completed the study and were included in the analyses. At 9 months, the intervention group exhibited a reduced BMI of -0.66 kg/m2 (95% CI -1.06 to -0.25 kg/m2 , p = 0.002), while a significant increase in BMI was observed in the control group. A significant post-intervention between-group difference in change in BMI (-1.31 kg/m2 [95% CI -1.99 to -0.63], p < 0.01) was found in favour of the intervention group. Similar results were also observed for all secondary outcomes. CONCLUSIONS: This study provides evidence that a 9-month APA intervention induced clinically meaningful effects on weight loss in adolescents with ID.

Psychometric evaluation of the Fear of Cancer Recurrence Inventory (FCRI) and development of a short version in patients with follicular lymphoma.

PURPOSE: To evaluate the psychometric properties of the Chinese Fear of Cancer Recurrence Inventory (FCRI-C) in follicular lymphoma (FL) survivors. MATERIALS AND METHODS: A nationwide cross-sectional study was conducted online between July and September 2020. The following psychometric properties of the FCRI-C were evaluated: construct, convergent, and discriminant validity, and reliability. Item variance was assessed using differential item functioning (DIF). A short version of the FCRI-C was developed using a two-parameter item response theory (IRT) model. The patterns of response scale, item fit, and item information were assessed. The receiver operating characteristic (ROC) curve was used to determine the clinical cut-off point for the FCRI-C. RESULTS: A total of 326 FL survivors completed the questionnaire. The confirmatory factor analysis supported the bi-factor structure of the FCRI-C. The IRT analysis confirmed a 10-item short version of the FCRI-C. Satisfactory convergent and discriminant validity were underpinned by a priori hypotheses. Cronbach's alpha of 0.95 and intraclass correlation coefficient of 0.82 indicated good internal consistency and test-retest reliability. The ROC curve determined a cut-off point of 83 and 20 for the full and short versions, respectively. CONCLUSIONS: The FCRI-C used to measure and screen the levels of FCR in Chinese FL survivors was found to be valid and reliable.Implications for RehabilitationThe Chinese Fear of Cancer Recurrence Inventory (FCRI-C) is a reliable and valid measure to evaluate the fear of cancer recurrence (FCR) in follicular lymphoma survivors.The short version of the FCRI-C provides a rapid screening tool for the clinical detection of FCR in patients.The cut-off point of the FCRI-C could differentiate patients between "high" and "low" levels of FCR in clinical practice.

Patient-Identified Problems and Influences Associated With Diagnostic Delay of Acromegaly: A Nationwide Cross-Sectional Study.

Background: Insidious-onset acromegaly may easily be overlooked by non-specialists of acromegaly and cause diagnostic delay. This study aims to examine the association between diagnostic delay and advice from doctors before any confirmed diagnosis and subsequent comorbidities, and elicit patient-perceived reasons for misdiagnoses. Methods: An online nationwide cross-sectional study was conducted through China Acromegaly Patient Association. Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) levels at diagnosis and cancerous, endocrine-metabolic, musculoskeletal, cardiovascular, respiratory, and psychiatric comorbidities were reported by patients. The association between diagnostic delay and pre-diagnostic advice from doctors as well as subsequent comorbidities after diagnosis were examined. Results: In total, 447 valid responses were collected. Overall, 58.8% patients experienced misdiagnoses, and 22.6% had diagnostic delay. Before arriving at any diagnosis, patients without treatment (adjusted odds ratio [AOR]: 3.66, 95% confidence interval [CI]: 1.30-10.33) or receiving treatment to symptoms only (AOR: 7.05, 95%CI: 4.09-12.17) had greater chance of being misdiagnosed, and hence had diagnostic delay. Patients believed insufficient specialists, limited awareness of acromegaly of non-specialists and poor doctor-patient communications were major reasons of misdiagnosis. Diagnostic delay were associated with higher GH level at diagnosis and endocrine-metabolic, musculoskeletal and cardiovascular comorbidities (all P<0.05). Conclusions: Suboptimal pre-diagnostic advice for patients, reflecting limited awareness of acromegaly among non-specialists, may delay the diagnosis and increase comorbidities. Feedbacks on the patients' final diagnosis from specialists to non-specialists should be considered, and doctor-patient communication and clinical decision-making process should be improved. Comorbidities should be screened and monitored particularly for patients with diagnostic delay.

Mapping of the acromegaly quality of life questionnaire to ED-5D-5L index score among patients with acromegaly.

OBJECTIVE: This study aimed to develop a mapping function that links the acromegaly quality of life (AcroQoL) questionnaire to EQ-5D-5L to obtain a preference-based utility value to inform economic evaluation. METHODS: A nationwide cross-sectional questionnaire survey among patients with acromegaly was conducted online in China during 17 December 2019 to 6 January 2020. The study sample was randomly divided into a training set and a validation set. Ordinary least squares (OLS), Tobit, beta-based mixture, and adjusted limited dependent variable mixture models were tested for development of the function in the training set. Total and subscale scores and individual items of AcroQoL were included as predictors in the models along with their squared terms and demographic and clinical characteristics, and selected by backward stepwise selection. The root mean square error, mean absolute error, Akaike's information criterion, Bayesian information criterion and adjusted R-square were used to assess goodness of fit and predictive ability of the models. RESULTS: There were 424 adult patients with acromegaly eligible for this analysis. Average EQ-5D-5L index score and AcroQoL score for them was 0.82 (SD = 0.15) and 44.3 (SD = 22.9), respectively. A total of 60 candidate models were tested. Considering model simplicity and predictive ability in both training and validation set, the best model was the OLS model using scores of physical dimension and its square term as predictors. CONCLUSION: A validated mapping function was developed in this study for estimating EQ-5D scores using AcroQoL outcomes. Its external validity can be further tested in other population with Acromegaly.

Evaluating the psychometric properties of the EQ-5D-5L and SF-6D among patients with haemophilia.

OBJECTIVE: The aim of this study was to evaluate the psychometric properties of the EQ-5D-5L and SF-6D, and to compare their performance among patients living with haemophilia in China. METHODS: A total of 875 Chinese patients completed the EQ-5D-5L, SF-6D, and Haem-A-QoL questionnaires. Construct validity of the EQ-5D-5L and SF-6D dimensions and indices was assessed by testing hypotheses relating these measures to Haem-A-QoL and clinical measures. The Spearman correlation coefficient was used to assess convergent validity, and one-way analysis of variance (F statistic) was used to assess the known-groups validity (discriminatory power). The agreement between EQ-5D-5L and SF-6D indices was assessed using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. RESULTS: Both the EQ-5D-5L and SF-6D indices showed acceptable ceiling and floor effects. As hypothesised, both EQ-5D-5L and SF-6D were significantly correlated with Haem-A-QoL (both dimensions and overall score). EQ-5D-5L and SF-6D indices as well as EQ-VAS differentiated patients are known to differ in severity of haemophilia, bleeding status, disabling levels, and comorbidity. The F statistics in the known-groups comparisons suggested that the EQ-5D-5L was slightly more discriminative than the SF-6D. ICC (0.41) and Bland-Altman plot confirmed that the agreement between the EQ-5D-5L and SF-6D indices was poor. CONCLUSION: Both EQ-5D-5L and SF-6D showed satisfactory construct validity in the measurement of the HRQoL among patients with haemophilia. However, the two instruments may not be used interchangeably in this patient population due to their poor agreement and differing discriminatory power.