Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, leading to various complications and impairments in patients' health-related quality of life (HRQOL). Limited research has been conducted to evaluate the HRQOL of Chinese patients with PNH. Understanding the HRQOL in this specific population is crucial for providing effective healthcare interventions and improving patient' health outcomes. This study aimed to assess HRQOL of Chinese patients with PNH, and identify key determinants. Methods: A cross-sectional study was conducted during 2022 to recruit patients with PNH in China. The study population was recruited from PNH China, one of the largest public welfare PNH patient mutual aid organization in China. Data were collected via an online questionnaire including the EQ-5D-5L (5L), and social-demographic and clinical characteristics. Descriptive statistics were employed to summarize the characteristics of the participants and their HRQOL. Multiple linear and logistic regression analyses were adopted to explore key factors affecting HRQOL. Results: A total of 329 valid questionnaires were collected. The mean (SD) age of the patients was 35.3 (10.0) years, with 52.3% of them being male. The patients reported more problems in Anxiety/Depression (81.5%) and Pain/Discomfort (69.9%) dimensions compared to the other three 5L dimensions. The mean (SD) of 5L health utility score (HUS) and EQ-VAS score were 0.76 (0.21) and 62.61 (19.20), respectively. According to multiple linear regression, initial symptoms (i.e., Anemia [fatigue, tachycardia, shortness of breath, headache] and back pain) and complication of thrombosis were significant influencing factors affecting 5L HUS. Total personal income of the past year, initial symptom of hemoglobinuria and complication of thrombosis were significantly influencing factors of VAS score. Social-demographic and clinical characteristics, such as gender, income, and thrombosis, were also found to be significantly related to certain 5L health problems as well. Conclusion: Our study manifested the HRQOL of PNH patients in China was markedly compromised, especially in two mental-health related dimensions, and revealed several socio-demographic and clinical factors of their HRQOL. These findings could be used as empirical evidence for enhancing the HRQOL of PNH patients in China.
Keywords: Paroxysmal nocturnal hemoglobinuria; Health-related quality of life (HRQOL); EQ-5D-5L; Influencing factors; China
Huaxin Yu, Shengnan Duan and Pei Wang contributed equally to this work and share first authorship.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder, resulting from a somatic mutation in the X-linked gene phosphatidylinositol glycan class A (PIGA) which leads to the expansion of hematopoietic stem cell clones [[
PNH can affect individuals at any age group, showing no significant preferences towards gender, ethnicity, or geographical region. Nevertheless, it manifests most commonly in young adulthood, with the median diagnosis age in the early- to mid-thirties [[
PNH has an extensive adverse impact on various health aspects of patients. According to the International PNH Registry, PNH patients frequently experience symptoms of fatigue, headache, dyspnea, hemoglobinuria, abdominal pain, erectile dysfunction and dysphagia [[
Empirical evidence has suggested that PNH can significantly reduce HRQOL of the patients in western populations [[
This study aimed to assess HRQOL of Chinese patients with PNH, and identify key determinants, supply objective and factual data to policymakers and researchers and call on the whole society to pay attention to PNH and implement favorable policies about rare disease.
In 2022, a cross-sectional survey was conducted in PNH China, a legally recognized public welfare patient mutual aid organization established in April 2012. The organization comprised over 400 members, consisting of patients, their families, volunteers, and dedicated physicians and specialists. The survey assessed the patients' HRQOL measured by 5L, socio-demographic, and clinical characteristics using a self-administered structured questionnaire through a professional online survey platform. The inclusion criteria were: (i) Accessible and willing to join in the study. (ii) Clinical diagnosis of PNH. Prior to the survey, investigators, who were managers of PNH China and well-trained PNH patients, provided a detailed introduction to the patients regarding the survey's purpose, process, rights, and the questionnaire. After providing informed consent, patients could choose to either participate in the survey or directly opt out. If the patients were unable to complete the questionnaire, their guardians were authorized to do so on their behalf.
The study was approved by the Biomedical Ethics Committee of Dalian Medical University.
5L contains a descriptive system including five dimensions: Mobility (MO), Self-Care (SC), Usual Activities (UA), Pain/Discomfort (PD), Anxiety/Depression (AD). Each dimension has five response levels: no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to. The system thus defines a total of 3,125 (5
The questionnaire assessed the following social-demographic characteristics: gender, age, ethnicity, educational status, marital status, fertility situation, school/employment status, total personal income for the past year and health insurance. It also inquired about clinical characteristics, including initial symptoms of PNH, common complications during the past year (i.e., stones, thrombosis, renal failure, pulmonary hypertension, BMF, femoral head necrosis), misdiagnosis, and the latest pathological grade.
The gathered data, exported in Excel format, was reviewed to eliminate any illogical patient data entries.
The social-demographic and clinical characteristics, and HRQOL of the patients were summarized using descriptive statistics with mean, standard deviations (SD), medians and interquartile ranges (IQR) for continuous variables; and frequencies, percentages for categorical variables.
Multiple linear regression analysis was utilized to explore the influence of above mentioned socio-demographic and clinical variables on HUS and VAS score (Table 1). To enhance the robustness of the analysis for the categorical variables, each category within a variable must have at least 16 observations according to expert opinion and statistical requirements. Variance inflation factor (VIF) was adopted to assess the multicollinearity among the independent variables, with the VIF value greater than 10 indicating the existence of multicollinearity. Multiple logistic regression was also used to assess the factors of self-reported EQ-5D problems. In the analysis, the responses to each of the five EQ-5D dimensions were classified as with and without problems. Five binary variables were thus generated and adopted as dependent variables in the five separate logistic models. An enter approach was adopted in the regression modelling, with the independent variables being coded as categorical variables and compared with a reference group.
Table 1 Assignment of independent variables
Variables Variable definitions Variable type Male (0), Female (1) Dichotomous variables Respondent's age at the time of interview Continuous quantitative variable Han (0), Other ethnicities (1) Dichotomous variables Junior high school and below (1,0,0) Multi-categorical variable High school, technical secondary school or vocational high school, etc. (0,1,0) Junior college, college degree (0,0,0) Postgraduate or above (0,0,1) Have a partner (0), Single (1) Dichotomous variables No (0), Yes (1) Dichotomous variables No (0), Yes (1) Dichotomous variables <35,128 CNY (0), ≥ 35,128 CNY (1) Dichotomous variables National Basic Medical Insurance [NO (0), Yes (1)], Commercial health insurance [NO (0), Yes (1)] Dichotomous variables Hemoglobinuria [NO (0), Yes (1)] Dichotomous variables Anemia (Fatigue, Tachycardia, Shortness of breath, Headache) [NO (0), Yes (1)] Jaundice [NO (0), Yes (1)] Pancytopenia, bone marrow hematopoietic failure [NO (0), Yes (1)] Abdominal pain [NO (0), Yes (1)] Back pain [NO (0), Yes (1)] Erectile dysfunction [NO (0), Yes (1)] Dysphagia [NO (0), Yes (1)] Cognitive disorder [NO (0), Yes (1)] Stones [NO (0), Yes (1)] Dichotomous variables Thrombosis [NO (0), Yes (1)] Renal failure [NO (0), Yes (1)] Pulmonary hypertension [NO (0), Yes (1)] Bone marrow failure (BMF) [NO (0), Yes (1)] Necrosis of the femoral head [NO (0), Yes (1)] No (0), Yes (1) Dichotomous variables Classic PNH (0,0) Multi-categorical variable PNH in the setting of another specified bone marrow disorder (1,0) Sub-clinical PNH (0,1)
35,128: The 2021 annual average per capita disposable income of Chinese residents CNY: Chinese Yuan
All statistical analyses were performed using SPSS (version 24). The statistical significance of this study was set at 0.05 level.
A total of 332 patients filled the questionnaire. Data from three patients with logical errors were excluded, and the other 329 patients from 26 provinces, autonomous regions and municipalities were included in the subsequent analysis.
The characteristics of the PNH patients are summarized in Fig. 1. Their mean (SD) age was 35.3 (10.0) years and median age (IQR) was 34.0 (28.0–40.0) years, with 52.3% of the patients being male. The majority of them (70.8%) were between 20 and 39 years, and 58.1% of the patients had attained an education level of junior college or above. A significant majority of patients (64.4%) reported an annual income that fell below the 2021 annual average per capita disposable income of Chinese residents (i.e., 35,128 CNY) [[
Graph: Fig. 1 Indicators of social-demographic and clinical characteristics of all survey patients (N = 329). Age (years old): Mean = 35.3, SD = 10.0, Median = 34.0, IQR = 28.0–40.0, Range = 16.0–74.0. 35,128: the 2021 annual average per capita disposable income of Chinese residents. CNY: Chinese Yuan
Among the patients, 72.6% were diagnosed with classic PNH and 22.2% were diagnosed with PNH in the setting of another specified bone marrow disorder. A significant proportion of patients (63.8%) exhibited hemoglobinuria as an initial symptom. Anemia (fatigue, tachycardia, shortness of breath, headache) constituted the initial symptoms for 61.1% of the patients. Additionally, 15.2% of the patients experienced stone-related complications, and 7.3% presented with thrombosis during the past year. A misdiagnosis was reported by 33.7% of patients. (Fig. 1)
The median duration (IQR) from onset of symptoms to the time of the survey was 89.0 (44.0–155.5) months, and the mean duration (SD) was 104.7 (74.9) months. In the past year, 80.2% of 329 patients surveyed received treatment, whereas 19.8% did not. Among the patients with treatment, 91.3% were administered medication for symptomatic supportive care. Furthermore, 62.1% of these patients underwent red blood cell/platelet transfusion, and 18.2% were treated with novel complement inhibitors, all of which were provided as clinical donations. The proportion of low-dose combined chemotherapy was 1.1%; and hematopoietic stem cell transplant treatment was 0.4%.
The proportion of reporting problems in AD dimension (81.5%) was higher than the prevalence in the other dimensions (PD: 69.9%, UA: 53.5%, MO: 51.4%, SC: 13.4%) (Table 2), and thus only 9.1% of the patients reported full health defined by the 5L (i.e., no problems in all the 5 dimensions). The distribution of the 5L HUS was negatively skewed (Fig. 2), with the mean (SD) and median (IQR) values being 0.76 (0.21) and 0.78 (0.68–0.91). Similarly, the distribution of VAS score was also negatively skewed (Fig. 3), with the mean (SD) and median (IQR) values being 62.61 (19.20) and 62.00 (50.00–79.00), respectively.
Table 2 Sample distribution of EQ-5D-5L [N (%)] of Chinese PNH patients
Dimensions Mobility Self-care Usual Activities Pain/Discomfort Anxiety/Depression 160 (48.6) 285 (86.6) 153 (46.5) 99 (30.1) 61 (18.5) 119 (36.2) 35 (10.6) 133 (40.4) 175 (53.2) 143 (43.5) 38 (11.6) 4 (1.2) 34 (10.3) 41 (12.5) 82 (24.9) 9 (2.7) 5 (1.5) 7 (2.1) 10 (3.0) 36 (10.9) 3 (0.9) 0 (0.0) 2 (0.6) 4 (1.2) 7 (2.1)
Graph: Fig. 2 Frequency distribution of EQ-5D-5L health utility score. (Mean = 0.76, SD = 0.21, Median = 0.78, IQR = 0.68–0.91)
Graph: Fig. 3 Frequency distribution of EQ-5D-5L-VAS score. (Mean = 62.61, SD = 19.20, Median = 62.00, IQR = 50.00–79.00)
Tables 3 and 4 present the 5L HUS and EQ-VAS score across various subgroups. Males had the mean (SD) HUS and VAS score of 0.79 (0.20) and 63.46 (19.47), which are higher than those of females: 0.73 (0.22) for HUS and 61.68 (18.91) for VAS. Compared to the patients older than 20 years, those younger patients reported the highest mean (SD) HUS of 0.80 (0.13) while having the lowest VAS score of 57.75 (20.50). Those with a higher socio-economic status (e.g., better educated, higher income and people who are studying or working) generally exhibited higher HUS and VAS score. The patients who showed initial symptoms and presented with common PNH symptoms had worse HRQOL than those who did not manifest these symptoms. For instance, the patients who exhibited hemoglobinuria as their initial symptom had lower mean (SD) HUS and VAS score of 0.75 (0.22) and 60.42 (19.63), respectively, compared to those who did not show signs of hemoglobinuria with the score being 0.78 (0.19) and 66.48 (17.83). Furthermore, compared to the patients without complications during the past year, those with complication(s) had lower HRQOL. For example, the patients without thrombosis had the mean HUS (SD) of 0.78 (0.20) and VAS score of 63.57 (18.38). In contrast, those with thrombosis reported the mean (SD) HUS of 0.59 (0.32) and VAS score of 50.42 (24.93). Among the patients with different kinds of pathological grades, the patients in the setting of another specified bone marrow disorder exhibited the lowest mean (SD) HUS and VAS score of 0.74 (0.21) and 58.81 (21.31); the patients with the subclinical type had the highest mean (SD) HUS and VAS score of 0.81 (0.23) and 72.59 (21.87).
Table 3 The EQ-5D-5L health utility score (HUS) and EQ-VAS score of various subgroups (social-demographic characteristics)
Variables N HUS VAS score Mean SD Mean SD Male 172 0.79 0.20 63.46 19.47 Female 157 0.73 0.22 61.68 18.91 < 20 8 0.80 0.13 57.75 20.50 20–39 233 0.77 0.21 62.73 18.89 40–59 80 0.75 0.22 62.63 20.12 ≥ 60 8 0.70 0.34 63.88 20.67 Han 313 0.76 0.22 62.72 19.09 Other ethnicities 16 0.80 0.14 60.50 21.76 Junior high school and below 72 0.70 0.31 56.07 20.44 High school, technical secondary school or vocational high school, etc. 66 0.76 0.19 60.48 19.54 Junior college, college degree 170 0.78 0.17 65.51 17.79 Postgraduate or above 21 0.82 0.14 68.24 19.26 Have a partner 208 0.76 0.21 63.07 19.31 Single 121 0.77 0.22 61.82 19.05 Yes 163 0.76 0.22 62.69 19.48 No 166 0.77 0.21 62.54 18.97 Yes 193 0.80 0.19 65.46 18.63 No 136 0.71 0.24 58.57 19.34 <35,128 CNY 212 0.73 0.24 59.29 19.29 ≥ 35,128 CNY 117 0.82 0.14 68.63 17.56 National Basic Medical Insurance Yes 319 0.76 0.21 62.22 19.17 No 10 0.77 0.25 75.00 16.60 Commercial health insurance Yes 11 0.86 0.12 69.09 27.55 No 318 0.76 0.22 62.39 18.86
HUS: Health utility score VAS: Visual analogue scale SD: Standard deviation 35,128: The 2021 annual average per capita disposable income of Chinese residents CNY: Chinese Yuan
Table 4 The EQ-5D-5L health utility score (HUS) and EQ-VAS score of various subgroups (clinical characteristics)
Variables N HUS VAS score Mean SD Mean SD Yes 210 0.75 0.22 60.42 19.63 No 119 0.78 0.19 66.48 17.83 Yes 201 0.73 0.23 60.30 18.95 No 128 0.82 0.18 66.23 19.09 Yes 154 0.74 0.22 60.95 19.68 No 175 0.78 0.20 64.07 18.69 Yes 123 0.73 0.24 61.38 20.32 No 206 0.78 0.19 63.34 18.50 Yes 58 0.68 0.28 56.72 20.91 No 271 0.78 0.19 63.87 18.61 Yes 47 0.61 0.33 54.36 19.15 No 282 0.79 0.18 63.99 18.89 Yes 37 0.76 0.24 63.92 17.94 No 292 0.76 0.21 62.45 19.37 Yes 27 0.66 0.29 56.37 15.91 No 302 0.77 0.20 63.17 19.39 Yes 5 0.81 0.13 53.40 33.31 No 324 0.76 0.22 62.75 18.95 Yes 50 0.71 0.21 60.02 22.24 No 279 0.77 0.21 63.08 18.61 Yes 24 0.59 0.32 50.42 24.93 No 305 0.78 0.20 63.57 18.38 Yes 9 0.58 0.33 55.11 22.05 No 320 0.77 0.21 62.82 19.11 Yes 8 0.64 0.24 48.88 23.64 No 321 0.77 0.21 62.95 18.99 Yes 7 0.44 0.28 40.14 10.88 No 322 0.77 0.21 63.10 19.05 Yes 4 0.75 0.11 53.75 22.04 No 325 0.76 0.22 62.72 19.17 Yes 111 0.75 0.24 62.68 17.83 No 218 0.77 0.20 62.58 19.90 Classic PNH 239 0.77 0.21 63.06 18.07 PNH in the setting of another specified bone marrow disorder 73 0.74 0.21 58.81 21.31 Sub-clinical PNH 17 0.81 0.23 72.59 21.87 329 0.76 0.21 62.61 19.20
HUS: Health utility score VAS: Visual analogue scale SD: Standard deviation
Negative correlation with HUS was observed with three clinical factors including initial symptoms of anemia (fatigue, tachycardia, shortness of breath, headache) (B=-0.057, 95%CI: [-0.105,-0.010], p = 0.017), back pain (B=-0.146, 95%CI: [-0.214,-0.078], p = 0.000), and complication of thrombosis (B=-0.161, 95%CI: [-0.245,-0.077], p = 0.000) (Table 5).
Table 5 Factors associated with EQ-5D-5L health utility score of Chinese PNH patients
Independent variable Coefficient (95%CI) P VIF 0.908 (0.781,1.035) 0.000 Female -0.044(-0.091,0.003) 0.067 1.258 -0.002(-0.004,0.001) 0.228 1.604 Other ethnicities -0.001(-0.101,0.100) 0.988 1.079 Junior high school and below -0.031 (-0.091,0.029) 0.315 1.420 High school, technical secondary school or vocational high school, etc. -0.011 (-0.071,0.049) 0.720 1.343 Postgraduate or above 0.010 (-0.080,0.101) 0.823 1.129 Single 0.011 (-0.046,0.067) 0.716 1.727 Yes 0.013 (-0.046,0.073) 0.654 2.005 Yes 0.046 (-0.006,0.099) 0.083 1.534 ≥ 35,128 CNY 0.048 (-0.009,0.104) 0.096 1.657 Yes -0.015 (-0.063,0.033) 0.527 1.219 Yes -0.057 (-0.105,-0.010) 1.208 Yes 0.006 (-0.042,0.055) 0.804 1.346 Yes -0.030 (-0.076,0.016) 0.199 1.133 Yes -0.003 (-0.065,0.060) 0.935 1.301 Yes -0.146 (-0.214,-0.078) 1.317 Yes 0.029 (-0.047,0.105) 0.456 1.331 Yes -0.052 (-0.137,0.032) 0.226 1.236 Yes -0.040 (-0.101,0.021) 0.198 1.102 Yes -0.161 (-0.245,-0.077) 1.101 Yes -0.036 (-0.083,0.010) 0.122 1.097 PNH in the setting of another specified bone marrow disorder -0.028 (-0.082,0.026) 0.307 1.154 Sub-clinical PNH -0.009 (-0.109,0.091) 0.862 1.129 0.193
CI: Confidence interval VIF: Variance inflation factor P: p value 35,128: The 2021 annual average per capita disposable income of Chinese residents CNY: Chinese Yuan
The analysis of VAS score revealed that the patients with the income more than 35,128 CNY in the past year exhibited higher score (B = 5.708, 95%CI: [0.464,10.951], p = 0.033). VAS score was negatively predicted by the initial symptom of hemoglobinuria (B=-5.226, 95%CI: [-9.708,-0.745], p = 0.022) and presence of thrombosis (B=-10.330, 95%CI: [-18.198,-2.463], p = 0.010) (Table 6).
Table 6 Factors associated with EQ-VAS score of Chinese PNH patients
Independent variable Coefficient (95%CI) P VIF 70.136 (58.285,81.987) 0.000 Female -0.153 (-4.532,4.226) 0.945 1.258 0.025 (-0.223,0.273) 0.843 1.604 Other ethnicities -5.460 (-14.875,3.956) 0.255 1.079 Junior high school and below -5.356 (-10.975,0.263) 0.062 1.420 High school, technical secondary school or vocational high school, etc. -4.038 (-9.681,1.605) 0.160 1.343 Postgraduate or above 1.660 (-6.814,10.135) 0.700 1.129 Single 0.354 (-4.960,5.667) 0.896 1.727 Yes -0.190 (-5.712,5.333) 0.946 2.005 Yes 1.961 (-2.944,6.866) 0.432 1.534 ≥ 35,128 CNY 5.708 (0.464,10.951) 1.657 Yes -5.226 (-9.708,-0.745) 1.219 Yes -4.248 (-8.643,0.147) 0.058 1.208 Yes -0.285 (-4.817,4.248) 0.902 1.346 Yes -0.844 (-5.134,3.446) 0.699 1.133 Yes -1.494 (-7.329,4.342) 0.615 1.301 Yes -6.092 (-12.487,0.303) 0.062 1.317 Yes 6.600 (-0.520,13.719) 0.069 1.331 Yes -3.645 (-11.542,4.251) 0.364 1.236 Yes -2.579 (-8.281,3.123) 0.374 1.102 Yes -10.330 (-18.198,-2.463) 1.101 Yes -1.491 (-5.811,2.830) 0.498 1.097 PNH in the setting of another specified bone marrow disorder -4.300 (-9.341,0.740) 0.094 1.154 Sub-clinical PNH 5.157 (-4.201,14.515) 0.279 1.129 0.123
CI: Confidence interval VIF: Variance inflation factor P: p value 35,128: The 2021 annual average per capita disposable income of Chinese residents CNY: Chinese Yuan
Variance inflation factor (VIF) value of all variables in the two linear models was less than 10, indicating the absence of multicollinearity.
Significant factors influencing the 5L problems were shown in Table 7. Patients with initial symptoms of anemia (fatigue, tachycardia, shortness of breath, headache) experienced an increased risk of reporting problems in MO (OR [95%CI]: 2.37[1.40,4.02], p = 0.001), SC (OR [95%CI]: 3.69[1.46,9.38], p = 0.006), and UA (OR [95%CI]: 3.06[1.78,5.26], p = 0.000) dimensions. Compared to the patients with an income below 35,128 CNY, those who earned higher had experienced fewer SC problems (OR [95%CI]: 0.32[0.11,0.94], p = 0.038). Compared to male, female faced a higher risk of UA problems (OR [95%CI]: 1.79[1.04,3.08], p = 0.036). Moreover, compared with the patients who were neither studying nor employed, the patients who were studying or employed experienced less UA problems (OR [95%CI]: 0.51[0.28,0.94], p = 0.032). Compared with the patients without complications of thrombosis and stones during the past year, the patients with complications of stones (OR [95%CI]: 2.78[1.15,6.71], p = 0.023) and thrombosis (OR [95%CI]: 5.30[1.15,24.55], p = 0.033) experienced an increased risk of PD problems. The patients with sub-clinical PNH tended to report fewer AD problems than the patients with classic PNH (OR [95%CI]: 0.23[0.07,0.73], p = 0.013).
Table 7 Multivariate analyses evaluating associations of factors with each of the five health dimensions
Dimensions Mobility Self-Care Usual Activities Pain/Discomfort Anxiety/Depression OR (95%CI) P OR (95%CI) P OR (95%CI) P OR (95%CI) P OR (95%CI) P Female 1.67(0.99,2.82) 0.055 0.96(0.44,2.10) 0.915 1.79(1.04,3.08) 1.13(0.64,2.01) 0.666 1.67(0.85,3.27) 0.136 1.03(0.99,1.06) 0.118 1.03(0.98,1.07) 0.230 1.02(0.99,1.05) 0.236 1.02(0.98,1.05) 0.395 1.01(0.97,1.04) 0.806 Other ethnicities 1.41(0.46,4.32) 0.544 0.52(0.06,4.72) 0.565 1.96(0.59,6.54) 0.274 1.44(0.41,5.01) 0.567 0.96(0.24,3.90) 0.959 Junior high school and below 0.63(0.32,1.23) 0.172 1.19(0.49,2.93) 0.700 0.54(0.27,1.08) 0.081 0.80(0.38,1.68) 0.559 0.48(0.20,1.17) 0.107 High school, technical secondary school or vocational high school, etc. 1.37(0.69,2.70) 0.368 0.80(0.29,2.19) 0.662 1.55(0.76,3.16) 0.232 1.63(0.77,3.45) 0.206 0.44(0.19,1.01) 0.053 Postgraduate or above 0.91(0.34,2.46) 0.847 1.62(0.30,8.64) 0.574 1.66(0.59,4.64) 0.335 0.65(0.23,1.82) 0.410 2.30(0.48,11.03) 0.297 Single 0.63(0.33,1.19) 0.156 0.93(0.36,2.41) 0.887 0.58(0.30,1.13) 0.107 0.62(0.32,1.23) 0.173 2.07(0.89,4.82) 0.090 Yes 0.96(0.49,1.86) 0.895 1.33(0.49,3.63) 0.582 0.82(0.41,1.63) 0.570 0.82(0.40,1.70) 0.602 1.23(0.54,2.80) 0.621 Yes 0.58(0.32,1.05) 0.071 0.58(0.25,1.34) 0.202 0.51(0.28,0.94) 0.68(0.36,1.29) 0.239 0.61(0.28,1.31) 0.200 ≥ 35,128 CNY 0.74(0.39,1.38) 0.339 0.32(0.11,0.94) 0.85(0.44,1.64) 0.630 1.07(0.55,2.08) 0.846 0.77(0.35,1.68) 0.508 Yes 1.04(0.61,1.77) 0.886 0.93(0.42,2.05) 0.858 0.89(0.51,1.54) 0.671 0.77(0.43,1.39) 0.387 0.82(0.41,1.66) 0.587 Yes 2.37(1.40,4.02) 3.69(1.46,9.38) 3.06(1.78,5.26) 1.68(0.97,2.92) 0.065 1.22(0.64,2.34) 0.546 Yes 0.98(0.57,1.68) 0.932 0.62(0.27,1.46) 0.275 1.68(0.96,2.93) 0.069 1.15(0.64,2.05) 0.646 1.24(0.63,2.48) 0.534 Yes 1.45(0.87,2.42) 0.156 1.35(0.65,2.81) 0.422 1.23(0.72,2.08) 0.455 1.16(0.65,2.05) 0.620 0.80(0.41,1.56) 0.518 Yes 0.59(0.30,1.18) 0.134 0.45(0.15,1.33) 0.150 0.58(0.29,1.20) 0.143 0.93(0.41,2.08) 0.853 1.44(0.51,4.05) 0.494 Yes 1.41(0.66,3.03) 0.375 2.57(0.94,7.03) 0.066 2.15(0.95,4.84) 0.066 2.02(0.77,5.31) 0.153 2.06(0.62,6.83) 0.236 Yes 0.93(0.41,2.13) 0.870 0.92(0.28,3.02) 0.884 0.60(0.26,1.40) 0.234 0.78(0.30,1.99) 0.601 1.13(0.39,3.30) 0.824 Yes 1.73(0.67,4.44) 0.257 2.02(0.56,7.19) 0.281 1.01(0.38,2.66) 0.982 3.43(0.90,13.03) 0.070 1.08(0.29,4.02) 0.914 Yes 1.40(0.70,2.81) 0.344 0.92(0.35,2.46) 0.872 2.03(0.98,4.22) 0.058 2.78(1.15,6.71) 1.75(0.64,4.75) 0.273 Yes 2.08(0.80,5.40) 0.133 2.22(0.66,7.55) 0.200 1.56(0.60,4.08) 0.363 5.30(1.15,24.55) 4.03(0.51,31.98) 0.187 Yes 1.33(0.79,2.23) 0.286 1.89(0.90,3.97) 0.093 1.05(0.62,1.79) 0.851 1.21(0.68,2.14) 0.516 1.14(0.58,2.24) 0.697 PNH in the setting of another specified bone marrow disorder 1.33(0.73,2.43) 0.357 1.20(0.50,2.84) 0.683 1.86(0.99,3.50) 0.055 1.57(0.80,3.06) 0.190 0.92(0.43,1.94) 0.822 Sub-clinical PNH 1.41(0.47,4.26) 0.540 2.77(0.62,12.32) 0.182 0.63(0.19,2.10) 0.456 0.33(0.10,1.07) 0.066 0.23(0.07,0.73)
CI: Confidence interval OR: Odds Ratio P: p value 35,128: The 2021 annual average per capita disposable income of Chinese residents CNY: Chinese Yuan
The study expounded the socio-demographic and clinical characteristics of Chinese PNH patients and assessed their HRQOL based on a sample with better representativeness. Furthermore, we explored the determinants influencing HRQOL of the patients within the Chinese context. Hence, the study has deepened the understanding of the profile and HRQOL of PNH patients in China.
Consistent with previous findings [[
Of significant note, our study revealed that 63.8% of the patients initially presented with hemoglobinuria, a clinical hallmark of PNH [[
Consistent with previous evidence [[
Compared to HRQOL of the general Chinese population measured by 5L [[
The regression results showed that demographic characteristics, gender, school/employment status, total personal income, and clinical characteristics such as initial symptoms of hemoglobinuria, anemia (fatigue, tachycardia, shortness of breath, headache), and back pain, complications of stones, thrombosis, and pathological grade were significant factors exerting differential effects on HUS, VAS score, or certain EQ-5D dimensions in Chinese PNH patients.
Gender was the key factor associated with UA problems (OR = 1.79), which may be attributed to multiple factors including cultural and social expectations. Meanwhile, the patients with PNH at school or in the work environment were at lower risk of UA problems relative to patients who were not at school or employed (OR = 0.51). This may be because these settings provide better support and adaptation, as well as opportunities to promote patients' participation in daily activities and to maintain function [[
Our findings confirm that the initial symptoms of PNH (i.e., hemoglobinuria, anemia [fatigue, tachycardia, shortness of breath, headache] and back pain) have a significantly negative impact on HRQOL of the patients. The symptoms not only lead to physical discomfort, but also aggravate psychological burden, thus affecting the patient's overall HRQOL [[
Thrombosis was a key factor affecting HRQOL, specifically on the PD dimension in our study. The finding is consistent with relevant findings from the international PNH registry [[
Our research has identified key factors that influence specific dimensions of HRQOL in Chinese patients with PNH, such as physical functioning and mental health. Addressing these specific areas requires targeted and comprehensive measures. Firstly, existing health policies need to place greater emphasis on the recognition and management of early symptoms to mitigate the long-term impact of PNH. This can be achieved by integrating advanced screening technologies in primary care, increasing public health education, and developing more precise diagnostic and treatment guidelines. Secondly, the health system needs to integrate more effective disease management strategies, including patient education, psychological support, and the optimal allocation of medical resources. Furthermore, enhancing healthcare providers' ability to recognize early symptoms of PNH is crucial. We recommend regular professional training and workshops to improve medical personnel's sensitivity to PNH diagnoses. Collaboration with hematologists is also suggested to promote shared learning experiences and ensure a multidisciplinary approach to PNH management. Strengthening public awareness of PNH is also necessary. Media campaigns, community educational activities, and cooperation with patient support groups can effectively increase societal attention to this disease. Through these measures, we hope to improve the HRQOL for patients with PNH.
Our study has several limitations. First, the PNH patients recruited were all from a single institution, though it is the largest one for the patients in China. Second, we can not infer clear causality between HRQOL and the factors assessed due to the cross-sectional design. Although the associations provide useful initial insights into HRQOL in Chinese patients with PNH, an in-depth exploration of its longitudinal impact is still warranted. Third, the current sample size may have limited the detailed analysis of all variables.
In summary, the study described the profile and HRQOL of PNH patients in China, and elucidated the significant socio-demographic and clinical characteristics affecting their HRQOL. The findings could be adopted as the evidence for enhancing health status of PNH patients in China.
The authors would like to thank all the study participants for their time and insight.
HY, SD, RF, ZL, NY and SC designed the studies. YY, PM, JS, NZ, HH, SC assisted with data collection and participated in survey. HY, SD, PW analyzed and interpreted data and wrote the manuscript. PW, NY, SC revised the manuscript. All authors read and approved the final manuscript. The authors declare that there are no conflicts of interest in the present work.
"A Real World Study on the Situation of Children's Medical Security in Liaoning Province Based on Interrupted Time Series Analysis, LJKMR20221296" and "Dalian Medical University Maternal Diseases on Newborns Interdisciplinary Research Cooperation Project Team Funding, JCHZ2023016".
The funder did not influence on the conceptualization, study design or protocol, data analysis, the interpretation and collection of data, the conclusions drawn, preparation of the manuscript, or the decision to publish.
The data that support the findings of this study are available from PNH China, but restrictions apply to the availability of these data, which were used under licence for the current study and so are not publicly available. The data are, however, available from the authors upon reasonable request and with the permission of PNH China.
The study was approved by the Biomedical Ethics Committee of Dalian Medical University. Informed consent has been obtained of all patients.
Not applicable.
The authors declare that they have no competing interests.
- Paroxysmal nocturnal hemoglobinuria
- Phosphatidylinositol glycan class A
- Thrombotic events
- Bone marrow failure
- Health-related quality of life
- EQ-5D-5L
- Chinese Yuan
- Mobility
- Self-Care
- Usual Activities
- Pain/Discomfort
- Anxiety/Depression
- Health utility score
- Visual analogue scale
- Standard deviations
- Interquartile ranges
- Variance inflation factor
- Confidence interval
• p value
- Odds Ratio
Below is the link to the electronic supplementary material.
Graph: Supplementary material 1: Fig. 1
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By Huaxin Yu; Shengnan Duan; Pei Wang; Rong Fu; Zixuan Lv; Yuchi Yu; Pu Miao; Junwei Shi; Niekun Zhuang; Huiying Hu; Ni Yuan and Sijia Che
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