Treatment-related outcome from patient report outcome (PRO) of children with severe and moderate hemophilia A in China: An analysis report of registration data from patient organization "hemophilia home care center".

OBJECTIVES: To assess current treatment-related outcomes for children with severe and moderate haemophilia A (cHA) in China. METHODS: This cross-section Patient Report Outcome (PRO) report collected PRO data of severe and moderate cHAs registered in the 'Hemophilia Home Care Center' database (http://web.bjxueyou.cn) between January 2021 and November 2022. Data included records of bleeding, activities, and concentrates consumption. All patients had a confirmed diagnosis of moderate or severe haemophilia A (FVIII: C ≤ 5%) and were < 18 years old. RESULTS: Among 1038 analysable cases, 9.6% of children with inhibitors had a higher rate of intracranial haemorrhage, dropout school rate, and higher FVIII consumption than children without inhibitors. Among 100 children with inhibitors, 36 patients were treated without immune tolerance induction (ITI), 14 patients with irregular treatment and 50 patients received ITI. Children with ITI had a lower ABR (2.4 (0,6.6) vs. 13.4 (9.5, 26.6), p<.001) and AJBR (0 (0, 3.1) vs. 8.9 (1.6, 19.3), p < .001) compared to those without ITI. Among 938 children without inhibitors, 28.5% received on-demand treatment and 71.5% received prophylaxis. Of 528 children with 1343.8 (1050.4, 2922.9)IU/kg/year median FVIII consumption, 43.0% received low-dose, 43.2% received intermediate-dose, and 13.8% received high-dose regimen; these children with prophylaxis had a lower ABR (3.1 (0, 10.7) vs. 12.8 (2.4, 45.5), p < .001), AJBR (0.5 (0, 3.9) vs. 3.0 (0, 12.0), p < .001) and disability rate (9.0% vs.18.5%, p = .032) compared to children who received on-demand treatment. CONCLUSION: The high rate of drop-out of school and disability still present a huge gap to meet the needs in China. It is necessary to improve the level of medical accessibility and medicine affordability and strengthen the patient/parent's education in China.

Body roundness index is a superior indicator to associate with the cardio-metabolic risk: evidence from a cross-sectional study with 17,000 Eastern-China adults.

BACKGROUND: To investigate the ability of body shape index (ABSI), body roundness index (BRI), waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body adiposity index (BAI) for predicting non-adipose cardio-metabolic risk. METHODS: A total of 17,360 Chinese subjects aged 18-95 years old who escaped cardiovascular disease (CVD) or diabetes were recruited in the cross-sectional study. Anthropometric and biochemical parameters were assessed. Receiver operating characteristic curve (ROC) and multinomial logistic regression were conducted to examine the association of anthropometric indicators with cardio-metabolic risk factors. RESULTS: The mean age of subjects were 53.7(13.1) years, 41.6 % were males. The areas under the curve (AUC) demonstrated that WC, BMI, WHR, WHtR and BRI were able to predict high cardio-metabolic risk (AUC > 0.70). Meanwhile, multinomial logistic regression showed BRI was significantly associated with high cardio-metabolic risk (OR 3.27, 95% CI 3.01-3.55). The optimal cut-off values of BRI for high cardio-metabolic risk were (< 60 y: 3.49 vs. ≥60 y: 3.46) in males and (< 60 y: 3.47 vs. ≥60 y: 3.60) in females. CONCLUSIONS: WC, BMI WHR, and WHtR were potential obesity indicators in discriminating high cardio-metabolic risk, while BAI or ABSI was not. Moreover, BRI revealed superior predictive capacity and significant association with accumulated cardio-metabolic risk factors.

Prevalence and epidemiological determinants of metabolically obese but normal-weight in Chinese population.

BACKGROUND: There is metabolic heterogeneity in normal-weight individuals, however, there has been limited research in the Chinese population. This study aimed to investigate the prevalence, distribution and epidemiological determinants of metabolically obese but normal-weight (MONW) in a Chinese population. METHODS: A total of 17,876 normal-weight individuals were recruited from 37,815 individuals in Zhejiang province in southeastern China. Normal-weight was defined as a body mass index (BMI) of 18.5-23.9 kg/m2. Metabolically abnormal traits were assessed by metabolic syndrome criteria from the International Diabetes Federation (IDF) in 2015. MONW was defined as individuals who had at least two metabolically abnormal trait but normal weight. Multiple logistic regression was used to investigate MONW risk factors, adjusting for potential confounders. RESULTS: The prevalence of metabolic abnormality was 34.1% in normal-weight individuals, and the overall prevalence of MONW was 16.1% in the general population. Different MONW distributions were found between men and women depending on age. Compared with women, men had a significantly higher MONW prevalence among those aged < 45 years old, and there was a lower prevalence for those aged ≥50 years old. Higher BMI or waist circumference (WC), central obesity, menopause, and family histories of hypertension, diabetes, and cardiovascular diseases, increased MONW risk. Higher education levels, regular alcohol drinking, and balanced or vegetarian food preferences reduced MONW risk. CONCLUSIONS: Normal-weight individuals have metabolic heterogeneity in China. The MONW distribution between men and women depends on age. BMI, WC, dietary factors, and family history of chronic diseases, are associated with metabolic status.

Cost-effectiveness Analysis of Prophylaxis Versus On-demand Treatment for Children With Moderate or Severe Hemophilia A in China.

BACKGROUND: It is still being determined if prophylaxis (PR) has superior cost effectiveness compared with on-demand (OD) treatment for moderate or severe hemophilia A (HA) children in China. OBJECTIVE/PURPOSE: To evaluate the cost-effectiveness of PR and OD treatment for children with moderate or severe HA without inhibitors in China. METHODS: A retrospective cost-effectiveness study was conducted on 640 HA children (373 and 267 children were on the PR and OD treatment, respectively) from January 2021 to November 2022. The Markov model was used to estimate the economic and clinical outcomes and would run for 17 yearly cycles with the initial age at 2 years. The transfer probabilities were extracted from the data of "Hemophilia Home Care Center" and the literature published. All patients' drug costs were collected from the data of "Hemophilia Home Care Center". One-way and probabilistic sensitivity analyses were conducted on the data to evaluate the robustness of the results. RESULTS/FINDINGS: PR was consistently associated with higher overall quality-adjusted life years (QALYs) compared with OD treatment (9.59 QALYs vs. 6.85 QALYs). The incremental cost-effectiveness ratio (ICER) of PR compared with the OD treatment was calculated to be approximately US$12,151.35 (RMB¥81,778.55) per QALY gained. This amount was lower than the willingness-to-pay (WTP) threshold of US$38,212.74 (RMB¥257,171.71). One-way sensitivity analysis found that the results were sensitive to the cost of OD and PR treatments. CONCLUSIONS/IMPLICATIONS: This study indicated that PR is cost-effective compared with OD treatment for children with moderate or severe HA without inhibitors in China.

Low-dose immune tolerance induction for severe hemophilia A inhibitor patients: Immunosuppressants are generally not necessary for inhibitor-titer below 200 BU/mL.

Importance: It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor-titer ≥200 Bethesda Units (BU)/mL (LD-ITI-IS200 regimen) and LD-ITI combining with IS when SHA patients had inhibitor-titer ≥40 BU/mL (LD-ITI-IS40 regimen). Objective: To compare the efficacy of the LD-ITI-IS200 regimen with that of the LD-ITI-IS40 regimen for SHA patients with high-titer inhibitors. Methods: A prospective cohort study on patients receiving LD-ITI-IS200 compared to those receiving LD-ITI-IS40 from January 2021 to December 2023. Both received LD-ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD-ITI-IS200 regimen and ≥40 BU/mL in the LD-ITI-IS40 regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected. Results: We enrolled 30 patients on LD-ITI-IS200 and 64 patients on LD-ITI-IS40, with similar baseline clinical characteristics. A lower IS-use rate was discovered in the LD-ITI-IS200 regimen compared to the LD-ITI-IS40 regimen (30.0% vs. 62.5%). The two regimens (LD-ITI-IS200 vs. LD-ITI-IS40) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD-ITI-IS200 than for LD-ITI-IS40 (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor-titer 40-199 BU/mL, 10 non-IS-using (on LD-ITI-IS200 regimen) and 28 IS-using (on LD-ITI-IS40 regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months). Interpretation: In LD-ITI, IS are not necessary for inhibitor titer <200 BU/mL.

Metabolically Abnormal But Normal-Weight Individuals Had a Higher Risk of Type 2 Diabetes Mellitus in a Cohort Study of a Chinese Population.

Aims: Obesity is a heterogeneous disease in terms of body mass index (BMI) and metabolic status. The purpose of this study was to investigate the risk of type 2 diabetes mellitus (T2DM) in subjects with metabolically abnormal but normal weight (MANW) in China. Materials and Methods: A prospective cohort with a total of 17,238 participants of the Zhejiang metabolic syndrome cohort was recruited. According to the standard of the Working Group on Obesity in China, general obesity is defined. Metabolic abnormality was defined as two or more abnormal components (elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), elevated systolic blood pressure (SBP) or diastolic blood pressure (DBP) or use of antihypertensive therapy, and elevated fasting plasma glucose or antidiabetic treatment). The hazard ratio (HR) and its 95% CI were calculated using a multiple regression model, adjusted for the potential confounding factors. Results: Compared with metabolically normal and normal weight (MNNW) subjects, the metabolically abnormal and obesity/overweight (MAO) subjects had the highest risk of T2DM disease, with an HR of 4.67 (95% CI: 3.23-6.76), followed by MANW subjects (HR = 2.61, 95% CI: 1.74-3.92) and metabolically normal but obesity/overweight (MNO) subjects (HR = 2.09, 95% CI: 1.29-3.38) after adjusting for age, sex, smoking, drinking, physical activity, and family history of diabetes. Compared with that in the MNNW subjects, the HR in MANW subjects was significantly higher than that in MNO subjects. In normal-weight subjects, the HR of T2DM was significantly positively correlated with the number of components with metabolic abnormalities. Conclusions: MANW subjects had a higher risk of T2DM. MANW subjects should be given more attention in the prevention and control of common chronic diseases.

Dynamic Changes of Metabolic Syndrome Alter the Risks of Cardiovascular Diseases and All-Cause Mortality: Evidence From a Prospective Cohort Study.

Background: Metabolic syndrome (MetS) at baseline increases the risks of cardiovascular diseases (CVD) and all-cause mortality. However, MetS status is changeable during follow-up. The associations of dynamic changes of MetS with CVD and all-cause mortality remain unclear. Methods: Thirty-one thousand four hundred eighty-one eligible subjects were included from the Kailuan cohort. Dynamic changes of MetS were divided into four patterns as MetS-free, MetS-developed, MetS-recovery and MetS-stable. The outcomes were CVD, all-cause mortality, and the subtypes of CVD as myocardial infarction (MI), stroke and heart failure. Multiple Cox regression models were used to calculate the adjusted hazard ratios (HRs) and confidence intervals (95% CIs). Results: Altered risks of CVD, the subtypes of CVD, and all-cause mortality were observed among different dynamic patterns of MetS. Compared with the MetS-free group, MetS-developed group increased the risks of CVD (HR = 1.78, 95% CI = 1.51-2.11), MI (HR = 1.54, 95% CI = 1.01-2.34), stroke (HR = 1.78, 95% CI = 1.45-2.18), and heart failure (HR = 1.63, 95% CI = 1.11-2.39). MetS-recovery group decreased these risks with the HRs of 0.59 (95% CI = 0.48-0.72) for CVD, 0.62 (95% CI = 0.41-0.96) for MI, 0.59 (95% CI = 0.46-0.75) for stroke, and 0.56 (95% CI = 0.34-0.91) for heart failure compared with the MetS-stable group. However, the increased risk in the MetS-developed group and the decreased risk in the MetS-recovery group were not significant for all-cause mortality. When stratified by the onset age of MetS status change, early development of MetS (<50 years) had higher risks of CVD (HR = 2.20, 95% CI = 1.58-3.05), MI (HR = 2.35, 95% CI = 1.00-5.50), stroke (HR = 2.05, 95% CI = 1.38-3.05), heart failure (HR = 2.63, 95% CI = 1.15-6.04), and all-cause mortality (HR = 1.61, 95% CI = 1.13-2.30) than late development (≥50 years). Early recovery of MetS had lower risks with the HRs of 0.38 (95% CI = 0.24-0.59) for CVD, 0.43 (95% CI = 0.18-1.06) for MI, 0.37 (95% CI = 0.21-0.64) for stroke, 0.30 (95% CI = 0.09-1.04) for heart failure, and 0.68 (95% CI = 0.43-1.06) for all-cause mortality than late recovery. Conclusion: Dynamic changes of MetS altered the risks of CVD and all-cause mortality, especially in individuals with an early onset age. These findings highlight the importance of dynamic changes of MetS and onset age on the prevention and control for CVD.

The Associations of Two Novel Inflammation Indexes, SII and SIRI with the Risks for Cardiovascular Diseases and All-Cause Mortality: A Ten-Year Follow-Up Study in 85,154 Individuals.

BACKGROUND: SII and SIRI are two novel systemic inflammation indexes that were suggested in predicting poor outcomes in cancers. However, no studies have examined their effect on cardiovascular diseases (CVDs) and all-cause mortality. Thus, this study aims to investigate associations between SII, SIRI, and the risks for CVDs and all-cause mortality. METHODS: A total of 85,154 participants from the Kailuan cohort were included and followed up for incidents of CVDs (including MI, stroke) and all-cause death for 10 years. Multiple Cox regression was used to calculate the adjusted hazard ratios (HRs). RESULTS: During the follow-up period, 4262 stroke events, 1233 MI events, and 7225 all-cause deaths were identified, respectively. Compared with the lowest quantile (Q1) of SII or SIRI, after adjusted for most cardiovascular risk factors, both indexes showed positive associations with the risk for stroke (adjusted HRs in Q4 were 1.264 (95% CI: 1.157,1.382) for SII, 1.194 (95% CI: 1.087,1.313) for SIRI), and all-cause death (adjusted HRs in Q4 were 1.246 (95% CI: 1.165,1.331) for SII, 1.393 (95% CI: 1.296,1.498) for SIRI). Additionally, higher SII and SIRI are also associated with increased risk of hemorrhagic stroke and ischemic stroke. Higher SIRI but not SII exhibited a higher MI risk, the adjusted HR in Q4 was 1.204 (1.013,1.431). The significant association remained after additional adjustment for CRP. Subgroup analysis and sensitivity analysis displayed consistent results except for SIRI with MI, where the association did not arrive at significance in subjects aged ≥60. CONCLUSION: Elevated SII and SIRI increased the risk of stroke, two stroke subtypes, and all-cause death. Higher SIRI, but not SII associated with increased MI incidence, and the association of SIRI was only significant in subjects aged <60.

Increased Stroke Risk in Metabolically Abnormal Normal Weight: a 10-Year Follow-up of 102,037 Participants in China.

The purpose of this study was to investigate the risks of stroke in subjects with metabolically abnormal normal weight (MANW) in China. We recruited 102,037 participants from the Zhejiang Metabolic Syndrome Cohort and the Kailuan cohort. The mean years of follow-up were 9.9 years. General obesity was defined by body mass index (BMI) ≥ 28, overweight by BMI < 28 and ≥ 24, and normal weight by BMI < 24 and ≥ 18.5. Metabolic abnormality was defined as two or more abnormal components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated systolic blood pressure or diastolic blood pressure, or use of antihypertensive drug therapy, elevated fasting plasma glucose, or antidiabetic treatment). A multiple Cox regression model was used to calculate hazard ratio (HR) and its 95% confidence interval (CI), adjusted by potential confounding factors. Overall HR of the risks in two cohorts was calculated by a meta-analysis. Compared with the subjects who were metabolically normal with normal weight (MNNW), the pooled HR for stroke in MANW subjects was 1.82 (95% CI, 1.59-2.07). The risks of stroke in MANW subjects were significantly lower than that in subjects with metabolically abnormal obesity (MAO), but higher than that in those with metabolically normal obesity (MNO) (P < 0.05). These associations remained in the subtypes of cerebral infarction and cerebral hemorrhage. In normal-weight subjects, the HR for stroke was significantly positively correlated with the number of abnormal metabolic components (Ptrend < 0.001). In brief, metabolic abnormality increased the risk of stroke irrespective of obesity status. MANW individuals showed a greater risk of stroke, and this risk was positively correlated with the number of abnormal metabolic components.