Beta (β) thalassemia is an autosomal recessive hematological disorder characterized by the inadequate production of functional hemoglobin due to an abnormality in the genes that produce β chains of hemoglobin.1 Based on the number of chains involved, β-thalassemia can be classified into three forms: minor, intermedia, and major, all varying in clinical presentation and symptoms.2 Among these, β-thalassemia major (β-TM) is the most serious and life-threatening, requiring regular lifelong blood transfusions to avoid chronic anemia.3 However, numerous transfusions can lead to the development of iron overload, in which high levels of iron are deposited in various organs, potentially resulting in cardiac failure, diabetes mellitus, endocrine abnormalities, and renal and skeletal system complications.2,4

In comparison, thalassemia minor is a carrier state, and thalassemia intermedia is mild to moderate in severity, with the majority of patients not requiring blood transfusion. Therefore, they are not as severe as TM, who are blood transfusion-dependent, and thus are not included in this study.

Routine blood transfusion therapy and advancements in iron-chelating medications have improved the life expectancy and survival of patients with β-TM worldwide.5 However, individuals with β-TM suffer significant impairment to their health-related quality of life (HRQoL) compared to the general population and patients with other chronic noncommunicable diseases.6–9 Affected individuals suffer from physical, mental, and social consequences due to the need for regular hospital visits for blood transfusions as well as a result of iron overload complications, including organ damage, liver and spleen enlargement, and changes to their physical appearance due to delayed growth and bone deformities of the face and skull.10–12 Other challenges reported include low self-esteem, stress, fatigue, reduced mental well-being, and difficulties fulfilling their personal and familial responsibilities and managing their illness.13,14

According to data from the Gulf Family Health Survey, the average prevalence of β-thalassemia trait in Oman is ~2%, although this varies between governorates. The highest prevalence rates have been identified in the North Al Batinah (3.9%) and Muscat (2.8%) governorates.15 The hematology departments in hospitals located in Muscat, including Sultan Qaboos University Hospital (SQUH), get patients referred to them from various governorates in Oman with few hospitals providing care to patients in more distant areas. Although several previous studies from Oman have examined the QoL of pediatric patients with β-TM, very few have targeted the affected adults.16,17 There is a need to evaluate factors that may affect the HRQoL of adult patients, especially the physical, psychological, and social consequences of the disease, to help healthcare providers improve treatment outcomes and tailor counseling to these patients’ specific needs. This study aimed to evaluate the HRQoL of adult patients with β-TM in Oman, considering various sociodemographic, social, and clinical characteristics impacts on HRQoL outcomes.

Methods

This prospective cross-sectional study was conducted at SQUH, a tertiary care institution located in Muscat, Oman, with patients referred from all over the country. The target population included all adult patients with β-TM who were followed-up at SQUH between September and November 2022. The inclusion criteria consisted of Omani patients aged ≥ 18 years with β-TM who were either attending appointments at the SQUH outpatient department or visiting the day-care unit to receive blood transfusions during the study period. Non-Omani patients, aged < 18 years of age, patients diagnosed with β-thalassemia minor or intermedia, patients admitted to the hospital inpatient wards, and those who were in an unstable condition were excluded from the study.

The sample size was determined based on the total number of Omani adult patients with β-TM at SQUH in 2022 (N = 100). Based on a previous study,18 a SD of 23.1 and a permissible error of 5% calculated from the mean score of 54.7, a sample size of 74 patients was required.

n = [N × Z2 × (SD)2] / [d2 × (N-1) + Z2 × (SD)2]

Data on HRQoL were collected using the Arabic version of the 36-item shortform health survey (SF-36).18,19 It is a rigorously tested questionnaire designed to evaluate eight domains of HRQoL, which includes the respondent’s evaluations of their overall health, physical capabilities in work and daily life, vitality (indicating their levels of energy or fatigue), physical discomfort, emotional well-being, which includes feelings of contentment and anxiety, limitations in roles due to physical or emotional issues, social interactions, and personal perceptions of any health changes.19

There are two distinct concepts measured by the SF-36: a physical dimension and a mental dimension through the eight domains. All scales contribute in different proportions to the scoring of both physical and mental measures. The SF-36 is widely used for assessment of HRQoL in diverse settings and it has been found to be reliable and valid for measuring QoL of individuals with several chronic health conditions and in several countries.19

Each item in the questionnaire is represented as a single variable and scaled from 0 to 100, wherein a higher score is indicative of a more favorable QoL. The original English-language version of the SF-36 has been proven to act as a reliable measure of HRQoL, with Cronbach’s alpha values ranging from 0.78 to 0.93.20 The Arabic version was tested for internal consistency and reliability in a sample of adult Saudi Arabian citizens with sickle cell disease and showed good reliability across all eight domains (Cronbach’s alpha value range from 0.6–0.86).18

An additional questionnaire was developed, consisting of two sections. The first section sought to determine the sociodemographic background of the participants, including their gender, age, place of residence, education level, and employment and marital status. The second section collected information related to the clinical and perceived social impact of the disease. This included information regarding the frequency of blood transfusions per month, average ferritin level within the last three months before the survey being administered, degree of compliance with iron-chelating medications, physical activity level, presence of other comorbid chronic diseases, and several disease-related complications like hepatosplenomegaly, skin ulceration, growth retardation, and heart complications. The final version of the questionnaire was piloted among six patients before the study commencement to check for length, clarity, and appropriateness to be self-administered. The pilot study resulted in minor amendments in the sociodemographic and clinical information sections to enhance the questions, clarity and flow and to further ease data analysis.

Data were collected using a link to the online questionnaire distributed electronically by the researchers to the mobile devices of selected participants attending the hospital clinics. In addition, a quick response code to the online survey was generated and displayed in the outpatient department and day-care units to be scanned by visiting patients. All participants received a study information sheet and were required to fill out an informed consent form.

All collected data were entered into and analyzed using the SPSS software (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.). The participants’ demographic and clinical characteristics were presented as frequencies and percentages for categorical variables and as means and SDs or medians for continuous variables, depending on the normality of the data distribution. SF-36 scores were calculated and presented for each of the eight HRQoL domains as a mean or median score, according to the normality of data distribution determined using a simple Kolmogorov-Smirnov test. The scores of the domains of vitality and general health did not follow a normal distribution, while the scores of all the other six domains did follow a normal distribution. After checking the distribution pattern of the SF-36 scores, associations between various HRQoL domain scores and selected sociodemographic, clinical, and social impact characteristics were examined using appropriate tests of significance, including the independent student’s t-test or Mann-Whitney U test for two independent samples for scores following normal and non-normal distribution respectively tested using the simple Kolmogorov-Smirnov test. For three or more independent samples, analysis of variance or Kruskal-Wallis tests were administered for scores following normal and non-normal distribution respectively tested using the simple Kolmogorov-Smirnov test. A p-value of ≤ 0.05 was considered statistically significant.

Ethical approval was obtained from the Medical Research and Ethics Committee of the College of Medicine and Health Sciences, SQU (MREC #2782). Informed written consent was obtained from all participants before taking part in the study.

Results

A total of 78 Omani adult patients with β-TM met the inclusion criteria and completed the distributed questionnaires. The mean age of the respondents was 26.0±0.8 years, with only three (3.8%) patients aged > 45 years. Just over half (n = 42; 53.8%) of the patients were male. Most patients originated from the Al Batinah North (n = 21; 26.9%) and Muscat (n = 20; 25.6%) governorates. In addition, the majority were unmarried (n = 44; 56.4%), did not have university-level educational qualifications (n = 45; 57.7%), and were unemployed (n = 44; 56.4%) [Table 1]. A considerable proportion of patients (n = 32; 41.0%) reported never exercising during the week.

The majority of patients required an average of three blood transfusions per month (n = 47; 60.3%) and were compliant with iron therapy (n = 70; 89.7%), the most frequent form of which was oral iron chelators (n = 65; 83.3%), followed by both oral and pump infusions of iron chelators (n = 10; 12.8%). In total, 35 (44.9%) patients reported iron overload and 14 (17.9%) reported having other chronic diseases besides thalassemia. In addition, 38 (48.7%) patients reported that their β-TM had caused mental issues, including symptoms of anxiety (n = 20; 25.6%), depression (n = 11; 14.1%), and sleep disturbances (n = 7; 9.0%).

Only 12 (15.4%) patients suffered from three or more β-TM-related complications. Overall, the most common complication was osteoporosis (n = 28; 35.9%) followed by delayed growth/development (n = 27; 34.6%), gum and dental problems (n = 20; 25.6%), splenomegaly (n = 18; 23.1%), craniofacial bone deformities (n = 14; 17.9%), and hepatomegaly (n = 10; 12.8%). A total of 30 (38.5%) patients had a history of splenectomy. Among the 15 female patients who were married, seven (46.7%) reported experiencing pregnancy difficulties due to β-TM.

Patients were asked a series of questions to determine the perceived social impact of the disease. A total of 12 (15.4%) patients reported having been bullied at school because of their illness, while 34 (43.6%) indicated that β-TM had negatively affected their academic performance. Twenty-four (30.8%) patients reported social limitations due to the disease. In addition, 25 (32.1%) patients claimed that their illness was a reason for delaying marriage, although only three patients (3.8%) reported that β-TM had caused marital issues and affected their relationships with their children. A total of 31 (39.7%) patients stated that they had experienced issues in the workplace due to their diagnosis. However, the vast majority (n = 72; 92.3%) reported receiving family support regarding their medical condition [Table 2].

Of the eight HRQoL domains included in the SF-36 tool, role limitations due to emotional problems had the highest score (median score = 100), followed by physical functioning (median score = 85), indicating that the patients reported generally high QoL in these domains. On the other hand, the domains of general health and vitality scored the lowest, with mean scores of 60.2±15.9 and 59.1±20.5, respectively, indicating poorer HRQoL in these domains [Table 3].

A bivariate analysis was conducted to determine associations between selected characteristics and scores for each of the eight individual HRQoL domains. In terms of sociodemographic characteristics, being employed was associated with higher scores in the domains of role limitations due to physical function (p = 0.001) and role limitations due to emotional problems (p < 0.001). Higher levels of education were also significantly associated with better scores in the domains of role limitations due to physical function (p = 0.045) and general health (p = 0.039). Married patients reported significantly better QoL in the domains of social functioning (p = 0.049) and role limitations due to emotional problems (p = 0.013). Although female patients reported worse scores for physical functioning compared to male patients, this association did not cross the threshold for statistical significance (p = 0.053) [Table 4].

Various associations were observed between clinical and social impact characteristics and scores in certain HRQoL domains. Perceptions that the disease had contributed to delayed marriage weresignificantly associated with worse HRQoL in the domains of role limitations due to physical function (p = 0.022), role limitations due to emotional problems (p = 0.040), and social functioning (p < 0.001). In turn, the belief that β-TM had negatively affected patients’ academic achievements were significantly associated with worse scores in the role limitations due to physical function (p = 0.009), role limitations due to emotional problems (p = 0.039), social functioning (p = 0.012), and general health
(p = 0.016) domains. Perceived workplace difficulties were associated with poorer scores in the domains of role limitations due to physical function (p = 0.038) and social functioning (p = 0.040).

Patients who exercised three times or more per week reported significantly better QoL in the physical function domain compared to those who exercised less frequently (p = 0.046). Patients who received family support scored better in the vitality (p = 0.019), emotional well-being (p = 0.004), and general health (p = 0.020) domains. In addition, significantly poorer scores for the general health domain were observed among patients who had iron overload (p = 0.031) and three or more complication due to their illness (p = 0.038). Moreover, a history of mental issues was associated with poorer scores in six out of eight HRQoL domains, including role limitations due to physical function (p = 0.006), role limitations due to emotional problems (p = 0.026), vitality (p = 0.022), emotional well-being (p = 0.003), social functioning (p < 0.001), and general health (p < 0.001) [Table 5].

Discussion

Patients with β-TM often undergo regular blood transfusions and may require other medical interventions. Since patients with β-TM depend on regular blood transfusions for their survival, they tend to develop complications related to iron overload.3 A better understanding of the HRQoL of affected individuals helps healthcare providers to evaluate the impact of these treatments on their daily lives, including potential side-effects and complications.2,4 Moreover, chronic diseases like β-TM can have severe psychosocial and emotional implications.13,14 As such, HRQoL-related research allows for a more nuanced understanding of how patients dealing with chronic, lifelong conditions like β-TM cope with the long-term impact of the disease and its treatment on various aspects of their lives. In addition, HRQoL is an important metric by which healthcare providers can identify areas for quality improvement and resource allocation purposes. It can inform strategies to enhance patient support, symptom management, and psychosocial care, leading to improved overall well-being, and can also aid in promoting a focus on comprehensive patient-centered outcomes as part of a holistic approach to medical care. The aim of this study was to assess the HRQoL of adult patients with β-TM in Muscat, Oman. To the best of our knowledge, there is a scarcity of research originating from Oman focusing on this topic, particularly among adults.

In the current study, adult patients with β-TM reported the lowest scores for general health (mean SF-36 score = 60.2±15.9) and vitality (mean SF-36 score = 59.1±20.5), indicating that patients perceived themselves to have comparatively poorer QoL in these HRQoL domains. In contrast, the highest scores were seen for role limitations due to emotional problems (median SF-36 score = 100) and physical functioning (median SF-36 score = 85). Nonetheless, it is important to note that the sample scored relatively highly in all eight domains when using a threshold score of 50 as to differentiate between lower and higher HRQoL.19,21 A previous study from Bangladesh also noted that patients with β-TM reported relatively high physical functioning (mean SF-36 score = 72.47±27.01); however, the next highest score was observed for bodily pain (mean SF-36 score = 71.52±27.56), with the lowest scores seen for social functioning and general health.6 Mean scores for the latter two domains (44.24±23.33 and 48.19±16.94, respectively) fell below the threshold, indicating that Bangladeshi patients experienced poorer HRQoL in these aspects.6 Similarly, in a longitudinal cohort study of North American and UK patients, below-threshold scores were reported for all eight domains, of which the poorest were general health (41.5), role limitations due to emotional problems (46.78), and social functioning (46.79), while the best were bodily pain (49.41) and emotional well-being (49.04).22 These findings indicate that patients with β-TM tend to report low scores for general health, with varying findings for other domains of HRQoL, perhaps due to varying population characteristics.

Indeed, we observed certain sociodemographic factors were associated with higher scores in various HRQoL domains, including employment status, education level, and marital status. However, while female patients reported worse scores compared to males in the physical functioning domain, this association was not statistically significant
(p = 0.053). In contrast, other researchers have reported that female patients with β-TM tend to have lower HRQoL in general, particularly in the domains of physical functioning, bodily pain, and role limitations due to emotional problems.6,22 Given that the female gender has been associated with lower HRQoL in the general population, and that the correlation reported above was on the borderline of statistical significance, it is possible that the lack of association seen in the present study was due to the sample size or heterogeneity.22,23 Further research is therefore needed to confirm whether gender has a significant impact on HRQoL among patients with β-TM in Oman.

Most of our patients had not attained higher educational qualifications (57.7%) and faced difficulties in securing a job (56.4%), likely because of their medical condition. In a previous study, Daar et al,17 reported that adults with β-TM in Oman demonstrated significant impairments to their short-term working memory, executive functioning (i.e., verbal fluency), and verbal and auditory processing, all of which could impact their ability to secure employment as well as their academic and job performance. Indeed, over one-third of patients in the present study believed that their condition had impacted their academic achievements and caused them problems or difficulties in the workplace (43.6% and 39.7%, respectively). Li et al,24 reported that a similar proportion (40%) of adults with β-TM responding to a global survey believed their condition often or always limited their career opportunities. Moreover, 41.7%, 34.4%, and 19.5% of employed respondents admitted that their β-TM had resulted in productivity loss, impaired job performance, and absenteeism, respectively.

Pakbaz et al,25 reported that fewer adults with β-TM in North America were able to secure full-time employment compared to the general population, despite there being no association between employment or educational achievement and transfusion or chelation requirements.

Nonetheless, despite the difficulties caused by their condition, patients who were employed in the current study showed significantly higher scores in the domains of role limitations due to physical function (p = 0.001) and role limitations due to emotional problems (p < 0.001), while patients with a university degree reported significantly better scores in the domains of role limitations due to physical function (p = 0.045) and general health (p = 0.039). Both employment status and education level have been reported as significant contributors to HRQoL in other β-TM-related research.7,26,27 However, the belief that β-TM had negatively affected academic achievements was significantly associated with poorer scores in various domains of HRQoL in the current study, including general health, role limitations due to physical function and emotional problems, and social functioning (p < 0.05 each). Moreover, perceived workplace difficulties were associated with poorer scores in the domains of role limitations due to physical function (p = 0.038) and social functioning (p = 0.040).

Goulas et al,28 suggested that patients who receive iron chelation regularly have fewer limitations in their ability to work and thus have higher HRQoL. Just under half (44.9%) of the patients in this study reported suffering from uncontrolled levels of iron overload (i.e., above 3000 units); moreover, this factor was significantly associated with poorer scores in the general health domain in comparison to patients who had lower levels of iron overload (p = 0.031). However, compliance with iron-chelating medications was not found to significantly affect scores for any of the HRQoL domains. The most common disease-related complications reported by patients was osteoporosis (35.9%), followed by developmental delay (34.6%), which can be explained by multiple factors including bone marrow expansion, imbalanced cytokine profiles, and the deposition of iron in the pituitary, thyroid, gonads, and other glands, resulting in hormone secretion deficiency and decreased peak bone mass.29,30 In addition, patients who had three or more complications reported significantly lower scores in the general health domain of HRQoL (p = 0.038). In line with these findings, Sobota et al,22 reported that a greater number of disease complications was associated with significantly lower HRQoL scores among patients from North America and the UK. A study from Iran reported that the presence of disease complications was linked with poorer QoL among patients with β-TM.31

In the current sample, 48.7% of all patients reported a history of mental health problems, including symptoms of anxiety (25.6%), depression (14.1%), and sleep disturbances (9.0%). Studies from Iran and Lebanon have similarly reported high rates of anxiety, depression, and other mental health issues among patients with β-TM.32,33 As is to be expected, a history of disturbed mental well-being, as perceived and reported by the patients, was negatively related to HRQoL in six out of eight domains, including emotional well-being, social functioning, general health, vitality, and role limitations due to physical health and emotional problems (p < 0.05 each). Moreover, patients who believed that their condition had contributed to a delay in their getting married scored significantly lower scores in the domains of social functioning and role limitations due to physical health and emotional problems. In contrast, married patients reported better scores in the domains of social functioning (p = 0.049) and role limitations due to emotional problems (p = 0.013). This may be because marital status has been hypothesized to play a protective role in QoL, especially against the development of depressive symptoms and mental illnesses in late adulthood, factors strongly correlated to lower HRQoL.34 In turn, patients who reported exercising three times or more per week scored significantly higher in the physical functioning domain compared to those who did not. Several studies have shown the benefits of regular exercise in improving β-TM-related laboratory variables as well as QoL.35,36

The HRQoL of Omani adult patients with β-TM is not yet known. This study adds to the existing literature information on the QoL of this group of patients from Oman using a standardized and valid HRQoL tool. It has extensively evaluated information on various sociodemographic, clinical, and social characteristics of patients with β-TM to their HRQoL scores across the different domains of the SF-36 to better understand the factors that influence their perceived QoL, and thus help better counseling of patients by their healthcare providers. This study was subjected to several limitations. While prospective cross-sectional studies can identify associations between variables, they do not establish causation. Moreover, the sample included patients seen at a single institution, thereby limiting the generalizability of the findings. Future research should consider conducting a multi-centric study to help overcome issues of data representativeness when assessing patients with β-TM in Oman. In addition, using standardized and validated tools to measure patients’ mental status would provide a more accurate assessment of each patient’s mental well-being compared to the subjective reports used in this study, which could have subjected the findings to bias.

Conclusion

Adult patients with β-TM in Oman reported generally high HRQoL, although the domains of general health and vitality were among the lowest-scored domains, indicating poorer QoL compared to other domains. Uncontrolled iron overload leading to disease complications was found to be linked with poor QoL across many domains, affecting the patients’ academic, social, and mental health status. Healthcare providers should emphasize the importance of patient compliance with iron chelation medications to help avert the more serious disease-related complications that could compromise the patient’s QoL. Moreover, given the study findings, healthcare providers are encouraged to regularly screen patients for mental health issues and advise them as to the benefits of regular physical activity.

Disclosure

The authors declared no conflicts of interest. No funding was received for this study.

Acknowledgments

The author would like to thank all the patients who took part in this study as well as the medical team of the Hematology Department at SQUH for facilitating the data collection process for this study.

references

1. 1. Nienhuis AW, Nathan DG. Pathophysiology and clinical manifestations of the β-thalassemias. Cold Spring Harb Perspect Med 2012 Dec;2(12):a011726.
2. 2. Origa R. β-Thalassemia. Genet Med 2017 Jun;19(6):609-619.
3. 3. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis 2010 May;5:11.
4. 4. Angastiniotis M, Lobitz S. Thalassemias: an overview. Int J Neonatal Screen 2019 Mar;5(1):16.
5. 5. Farmakis D, Giakoumis A, Angastiniotis M, Eleftheriou A. The changing epidemiology of the ageing thalassaemia populations: a position statement of the thalassaemia international federation. Eur J Haematol 2020 Jul;105(1):16-23.
6. 6. Hossain MJ, Islam MW, Munni UR, Gulshan R, Mukta SA, Miah MS, et al. Health-related quality of life among thalassemia patients in Bangladesh using the SF-36 questionnaire. Sci Rep 2023 May;13(1):7734.
7. 7. Ansari Sh, Baghersalimi A, Azarkeivan A, Nojomi M, Hassanzadeh Rad A. Quality of life in patients with thalassemia major. Iran J Ped Hematol Oncol 2014;4(2):57-63.
8. 8. Pakbaz Z, Treadwell M, Yamashita R, Quirolo K, Foote D, Quill L, et al. Quality of life in patients with thalassemia intermedia compared to thalassemia major. Ann N Y Acad Sci 2005;1054:457-461.
9. 9. Alzahrani RA, Almutairi OM, Alghoraibi MS, Alabdulwahed MS, Abaalkhail MK, Alhawish MK, et al. Quality of life in transfusion-dependent thalassemia patients. J Taibah Univ Med Sci 2017 Jun;12(5):465-470.
10. 10. Abetz L, Baladi JF, Jones P, Rofail D. The impact of iron overload and its treatment on quality of life: results from a literature review. Health Qual Life Outcomes 2006 Sep;4:73.
11. 11. Arab-Zozani M, Kheyrandish S, Rastgar A, Miri-Moghaddam E. A systematic review and meta-analysis of stature growth complications in β-thalassemia major patients. Ann Glob Health 2021 Jun;87(1):48.
12. 12. Karakas S, Tellioglu AM, Bilgin M, Omurlu IK, Caliskan S, Coskun S. Craniofacial characteristics of thalassemia major patients. Eurasian J Med 2016 Oct;48(3):204-208.
13. 13. Yengil E, Acipayam C, Kokacya MH, Kurhan F, Oktay G, Ozer C. Anxiety, depression and quality of life in patients with beta thalassemia major and their caregivers. Int J Clin Exp Med 2014 Aug;7(8):2165-2172.
14. 14. Tarım HŞ, Öz F. Thalassemia major and associated psychosocial problems: a narrative review. Iran J Public Health 2022 Jan;51(1):12-18.
15. 15. Al-Riyami A, Ebrahim GJ. Genetic blood disorders survey in the Sultanate of Oman. J Trop Pediatr 2003 Jul;49(S1)(Suppl 1):i1-i20.
16. 16. Mevada ST, Al Saadoon M, Zachariah M, Al Rawas AH, Wali Y. Impact of burden of thalassemia major on health-related quality of life in Omani children. J Pediatr Hematol Oncol 2016 Jul;38(5):384-388.
17. 17. Daar S, Al Saadoon M, Wali Y, Al Mujaini R, Al Rahbi S, Chan MF, et al. Cognitive function in adults with beta-thalassemia major in Oman: a pilot study. Oman Med J 2021 Nov;36(6):e322.
18. 18. Ahmed AE, Alaskar AS, Al-Suliman AM, Jazieh AR, McClish DK, Al Salamah M, et al. Health-related quality of life in patients with sickle cell disease in Saudi Arabia. Health Qual Life Outcomes 2015 Nov;13(1):183.
19. 19. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992 Jun;30(6):473-483.
20. 20. McHorney CA, Ware JE Jr, Raczek AE. The MOS 36-item short-form health survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 1993 Mar;31(3):247-263.
21. 21. Wagner AK, Gandek B, Aaronson NK, Acquadro C, Alonso J, Apolone G, et al. Cross-cultural comparisons of the content of SF-36 translations across 10 countries: results from the IQOLA project. International quality of life assessment. J Clin Epidemiol 1998 Nov;51(11):925-932.
22. 22. Sobota A, Yamashita R, Xu Y, Trachtenberg F, Kohlbry P, Kleinert DA, et al; Thalassemia Clinical Research Network. Quality of life in thalassemia: a comparison of SF-36 results from the thalassemia longitudinal cohort to reported literature and the US norms. Am J Hematol 2011 Jan;86(1):92-95.
23. 23. Cherepanov D, Palta M, Fryback DG, Robert SA. Gender differences in health-related quality-of-life are partly explained by sociodemographic and socioeconomic variation between adult men and women in the US: evidence from four US nationally representative data sets. Qual Life Res 2010 Oct;19(8):1115-1124.
24. 24. Li N, Drahos J, Boateng-Kuffour A, Calvert M, Levine L, Dongha N, et al. Health-related quality of life and disease impacts in adults with transfusion-dependent β-thalassemia: preliminary results from the global longitudinal survey. Blood 2022;140(Suppl 1):10869-10870.
25. 25. Pakbaz Z, Treadwell M, Kim HY, Trachtenberg F, Parmar N, Kwiatkowski JL, et al. Education and employment status of children and adults with thalassemia in North America. Pediatr Blood Cancer 2010 Oct;55(4):678-683.
26. 26. Adam S. Quality of life outcomes in thalassaemia patients in Saudi Arabia: a cross-sectional study. East Mediterr Health J 2019 Dec;25(12):887-895.
27. 27. Bou-Fakhredin R, Ghanem NN, Kreidieh F, Tabbikha R, Daadaa H, Ajouz J, et al. A report on the education, employment and marital status of thalassemia patients from a tertiary care center in the Middle East. Hemoglobin 2020 Jul;44(4):278-283.
28. 28. Goulas V, Kourakli-Symeonidis A, Camoutsis C. Comparative effects of three iron chelation therapies on the quality of life of greek patients with homozygous transfusion-dependent Beta-thalassemia. ISRN Hematol 2012;2012:139862.
29. 29. Gaudio A, Morabito N, Catalano A, Rapisarda R, Xourafa A, Lasco A. Pathogenesis of thalassemia major-associated osteoporosis: a review with insights from clinical experience. J Clin Res Pediatr Endocrinol 2019 May;11(2):110-117.
30. 30. De Sanctis V. Growth and puberty and its management in thalassaemia. Horm Res 2002;58(Suppl 1):72-79.
31. 31. Haghpanah S, Nasirabadi S, Ghaffarpasand F, Karami R, Mahmoodi M, Parand S, et al. Quality of life among Iranian patients with beta-thalassemia major using the SF-36 questionnaire. Sao Paulo Med J 2013;131(3):166-172.
32. 32. Naderi M, Hormozi MR, Ashrafi M, Emamdadi A. Evaluation of mental health and related factors among patients with beta-thalassemia major in south east of Iran. Iran J Psychiatry 2012;7(1):47-51.
33. 33. Khoury B, Musallam KM, Abi-Habib R, Bazzi L, Ward ZA, Succar J, et al. Prevalence of depression and anxiety in adult patients with β-thalassemia major and intermedia. Int J Psychiatry Med 2012;44(4):291-303.
34. 34. Gutiérrez-Vega M, Esparza-Del Villar OA, Carrillo-Saucedo IC, Montañez-Alvarado P. The possible protective effect of marital status in quality of life among elders in a U.S.-Mexico border city. Community Ment Health J 2018 May;54(4):480-484.
35. 35. Arian M, Memarian R, Vakilian F, Badiee Z. Impact of an 8-week walking program on quality of life in patients with thalassemia major. KAUMS Journal (FEYZ) 2013;17(5):463-470.
36. 36. Hasanpour Dehkordi A, Hasani T, Fekri K, Deris F, Etemadifar S. Effects of aquatic exercise on dimensions of quality of life and blood indicators in patients with beta-thalassemia major. Int J Prev Med 2020 Aug;11:128.