Health-Related Quality of Life Among Patients With Sickle Cell Disease in an Adult Hematology Clinic in a Tertiary Hospital in Lagos, Nigeria

Background Sickle cell disease (SCD) is a genetic disease of public health concern. Improved quality healthcare has increased the life expectancy of these patients; however, they also face an increased frequency of vaso-occlusive crises and other SCD complications. These complications affect their quality of life, an area of care, which healthcare providers often overlook. We sought to determine the health-related quality of life among patients living with sickle cell disease in Lagos, Nigeria. Materials and methods We conducted a cross-sectional study of 198 patients with sickle cell disease who attended the adult sickle cell clinic at a tertiary hospital in Lagos, Nigeria, during the period from October 1, 2018, to February 28, 2019. A self-administered questionnaire was used to obtain the clinical and socio-demographic characteristics of the patients and the 35-item Short-Form Health Survey (SF-36) questionnaire was used to determine their health-related quality of life (HRQoL). Determinants of HRQoL were established using bivariate and multivariate regression analysis. Results The mean age of the 198 patients who participated in the study was 28.4±9.1 years, mean steady-state hemoglobin was 8.2 ± 1.3 g/dl, and 85 (42.9%) patients had a monthly income of 150 USD or less. In the previous year, 65 (32.1 %) and 33 (16.6%) patients, respectively, suffered one to two episodes (s) of acute bone pain crises and acute chest syndrome, and 43 (24.7%) had blood transfusion. Using the scoring system for SF-36 provided by RAND Health, role limitation due to physical health had the lowest median score of 50 (interquartile range {IQR}: 0-100). On bivariate analysis, bone pain crisis was associated with statistically significant low scores across all the 8 HRQoL domains of the SF36 questionnaire. Other variables, including having received blood transfusion, recent hospitalization, acute chest syndrome, lower level of income, and younger age, were also associated with significantly low scores. On regression analysis, bone pain crisis, level of income, and acute chest syndrome were found to be independent determinants of quality of life in the patients. Conclusion Sickle cell disease has a negative impact on the health-related quality of life of those affected. The presence of bone pain crisis is an important predictor of health-related quality of life in sickle cell disease patients. To improve patient outcomes, healthcare providers should take a holistic approach in evaluating and managing this disease, taking into cognizance how the complications and the financial burden of this disease impact the quality of life of affected patients.


Introduction
Sickle cell disease (SCD) refers to a group of heterogenous hemoglobinopathies caused by a mutation of the hemoglobin gene, leading to the production of abnormal hemoglobin -hemoglobin S (Hb S). Clinical manifestations of the disease arise largely from red blood cell sickling, which leads to tissue ischemia and an increased rate of hemolysis [1,2].
Sickle cell disease is of public health concern [3]. About 300,000 babies are born with SCD each year and 1 2, 3 4 4 2 4 2 2 4 2, 3 two-thirds of this population are found in sub-Saharan Africa (SSA) [4]. Nigeria, India, and the Democratic Republic of Congo carry half of the disease burden [4]. A retrospective study in Benin City, Nigeria, found the prevalence of SCD as 2.39% in 2012 [5]. Recently, with growing awareness of the disease and improved systems of healthcare, there has been some improvement in the survival of SCD patients well into adulthood [6,7]. While this reduces the mortality rate of SCD, these patients are nonetheless faced with debilitating SCD co-morbidities. They experience frequent vaso-occlusive crises (VOCs), resulting in frequent bone pain crises, end-organ damage to the liver, lung, spleen, kidneys, and brain, among others. These lead to frequent emergency room visits, and lengthy hospital stays in those with complications. Patients with SCD live with this burden all through their lives and it almost always influences their quality of life.
Health-related quality of life (HRQoL) is an important concept in chronic diseases, and this is defined by WHO as an assessment of a multi-dimensional concept incorporating the individual's perception of health status, psychosocial status, and other aspects of life [8]. Psychosocial and socio-economic problems resulting from the clinical burden of SCD affect QoL among individuals living with sickle cell disease [9]. This important area in the care of patients living with SCD is often ignored by healthcare providers, who focus exclusively on the clinical aspects of the disease. These patients are at a high risk of depression, suicide, drug addiction, financial troubles, and impairment in family and community social activities.
The health-related quality of life of several chronic medical conditions, including sickle cell disease, has been studied extensively [10][11][12][13]. However, only a few studies are available in the literature regarding HRQoL of adult patients living with SCD in Nigeria, the country with the highest number of adults living with the disease [10,14]. We aimed to determine the health-related quality of life (HRQoL) of adult sickle cell patients in Lagos, Nigeria

Materials And Methods
We carried out an analytical cross-sectional study designed to measure the health-related quality of life (HRQoL) of patients with sickle cell disease, who attended the adult sickle cell clinic of the Department of Internal Medicine, Lagos University Teaching Hospital Lagos, Nigeria, during the period from October 1, 2018, to February 28, 2019. Lagos is a cosmopolitan city and the commercial nerve center of Nigeria, with an estimated population of over 13 million people, of diverse ethnic and religious backgrounds [15]. Patients living with SCD who had been attending the clinic for a minimum of five years and who consented to participate in the study were consecutively recruited.
A self-administered structured questionnaire was used to collect data on the clinical and socio-demographic characteristics of the patients. This included age, gender, marital status, level of education, estimated monthly income, frequency of occurrence of vaso-occlusive crises, the presence of chronic complications of sickle cell disease, and presence of co-morbidities.
The HRQoL of the patients was determined using the Medical Outcome Study (MOS) 35-item Short-Form Health Survey (SF-36) questionnaire, developed by RAND Health, a universally accepted evaluation tool for assessing HRQoL of many chronic diseases (Appendices) [16][17][18][19]. It has 35 items to assess eight aspects of health: physical function (10 items), physical role health (four items), emotional role functions (three items), energy/fatigue (four items), emotional wellbeing (five items), social function (two items), bodily pain (two items), and general health perceptions (five items) [19]. Data collected were scored using the scoring system for SF-36, with the score of each variable ranging from 0 to 100. Higher scores indicate better quality of life and lower scores poor quality of life.

Statistical analysis
Data analysis was done using the Statistical Package for Social Sciences (SPSS) version 21 (Cary, NC: SPSS Inc.). Descriptive statistics were represented as frequencies and percentages, while normally distributed continuous variables were represented as mean and standard deviation (±SD). The median and interquartile range represented ordinal and skewed variables. We used bivariate analysis to determine the associations between socio-demographic, clinical characteristics, and the different HRQoL domains. Independent determinants of HRQoL were established using multivariate regression models. A statistically significant difference was set at a p-value <0.05.
Ethical approval for the study was obtained from the Lagos University Teaching Hospital Health Research Ethics Committee (certificate number: ADM/DCST/HREC/2534).

Socio-demographic and clinical characteristics of study participants
A total of 198 adults with sickle cell disease participated in this study.

Sickle cell-related events/complications in the previous year
Moderate-to-severe bone pain crisis was the most frequent sickle cell disease-related presentation, with about 60.1% of the patients having had at least one to two episodes in the previous year. One hundred and forty-four (72.7% ) patients were hospitalized at least once and 35.8% of them had been transfused at least once in the previous year. Chronic leg ulcer was the most common sickle cell-related chronic complication, affecting about 12.6% of the population ( Table 2, Figure 1).

Relationship between HRQoL domains and socio-demographic and clinical characteristics among study participants
The relationship between HRQoL domains, socio-demographic and clinical characteristics of the participants are shown in Table 4 and Table 5, respectively. Age and level of income had significant associations with pain, emotional well being, physical functioning, and role-limitation due to physical health ( Table 4). 2022

Discussion
We determined the health-related quality of life (HRQoL) of patients with SCD, an area of care, which healthcare givers often neglect. Those who experienced bone pain crisis had lower scores across all domains of the SF-36 scale compared to those who did not. In addition, we found the level of income, the presence of major bone pain crises, and acute chest syndrome as independent predictors of quality of life in these patients.
Sickle cell disease limited physical activity, increased fatigue, and bodily pain in our patients. Several studies on HRQoL among patients living with SCD had similar findings. A study by Dampier et al. found that pain, either acute or chronic, impairs health status and quality of life more than any other SCD-related complication [20]. Similarly, in our study, bone pain crisis was a major determinant of reduced quality of life in our patients. The score for bone pain crisis was significantly low across all eight domains. Pain is the hallmark of SCD, and it accounts for most of the emergency room visits in patients living with the disease [21]. Those living with SCD describe their pain as unimaginable, agonizing, and sometimes impossible to describe [22]. Pain in SCD, acute or chronic, reduces the quality of life in several ways and is not limited to altered mood, irritability, depression, anxiety, and sleep disturbance [23]. Work and school performance may be affected when the pain becomes significant. Unemployment and underemployment are also potential problems. This may lead to the inability to access and afford quality health care particularly in a country like Nigeria where most of her citizens pay out of pocket for healthcare. Many studies have shown that access to good healthcare services improves the quality of life of sickle cell patients by reducing the frequency of bone pain crises and its associated issues like prolonged hospitalization and frequent emergency room visits. Dampier et al. also found pain diminished SF-36 scale scores. They suggested that more effective management of persistent pain could substantially improve the quality of life for many adults with SCD.
The level of income was an independent determinant of quality of life in our study. In Lagos, a study by Okany et al. on the influence of socio-economic status on quality of life in patients living with SCD found that the frequency of bone pain crisis was significantly higher in social class III patients than in social class I and social class II (p < 0.01) [24]. In Nigeria, over 70% of its citizens have a monthly income of 150 USD or less, and over 97% do not have health insurance and have to pay out-of-pocket for healthcare. Ultimately, given the chronic nature of SCD, it becomes challenging for these patients to maintain access to and afford proper health care services [25]. Many studies have demonstrated that access to good healthcare in patients living with SCD reduces bone pain crises, which our study found to be an independent determinant of HRQoL.
Acute chest syndrome, a frequent and life-threatening complication of SCD, was an independent determinant of HRQoL in our study. The majority of patients who present at government-owned hospitals in low-and middle-income countries, such as ours come from a low socio-economic background. They prefer treating their symptoms with traditional alternatives and over-the-counter medications to presenting at the hospital because of the high cost of health care. This usually results in late disease presentation and a higher frequency of SCD complications. Acute chest syndrome is a significant cause of morbidity and mortality in patients living with SCD. Interstitial lung disease and pulmonary hypertension, which are long-term complications of ACS, may limit exercise tolerance, reduce physical functioning, and could reduce the quality of life [26].
We found that SCD did not have a significant negative effect on the emotional and social well-being of the patients. We expected contrary results because of the stigma attached to the disease. Some studies had similar findings [14,27]. The PISCES project, a study on HRQoL in patients living with sickle cell disease in the United States, found SCD patients had similar mental health and emotional well-being levels compared to the general population [27]. A local study by Adeyemo et al. on HRQoL of SCD among adolescents in Lagos, Nigeria, reported similar findings [14]. These studies were carried out in urban areas, where increased disease awareness in the general population through the media, health education programs, social support groups increase the knowledge and awareness of the disease, reduce fear and make them emotionally stable. Also, studies have found that patients with chronic diseases like SCD, over time, develop coping strategies towards managing it. A study by Riis et al. explained that patients with chronic diseases adapt to their disease and develop a coping mechanism, where there is a tendency to focus more on the positive experience of the disease [28]. Religion is a solid coping means and offers hope for those suffering from chronic and debilitating diseases like sickle cell disease. A study done by Anie et al. found that Nigerians with SCD had better coping strategies than those in the UK due to their socio-cultural and religious beliefs of Nigerians [29]. In Nigeria, over 95% of the populace are religious, and this may perhaps explain our findings [30].
This study is not without limitations. We conducted this research in a tertiary hospital in Lagos, a cosmopolitan city, where there is increased disease awareness among the people, with more access to education and health resources than other parts of the country. Therefore, these findings may not be representative of the country's general population. Another limitation is that we used the SF-36 questionnaire, a generic questionnaire applicable to most chronic diseases rather than a tailored, diseasespecific questionnaire, in this case, SCD. Therefore, there is a need to create a validated disease-specific questionnaire to include questions unique to SCD. Lastly, given the cross-sectional study design, we could not make causal inferences from the results obtained, even those obtained from the regression analysis.

Conclusions
This study has shown bone pain is a significant predictor of HRQoL. Therefore, developing strategies to reduce the frequency of bone pain crises will improve the HRQoL of patients living with SCD. A multipronged approach is therefore needed, where the patient, healthcare provider, caregiver, and the government are stakeholders in finding ways of improving the quality of life of sickle cell disease patients.

Appendices Medical Outcomes Study Short Form 36 Health Survey questionnaire
This survey asks for your views about your health. This information will help keep track of how you feel and how well you are able to do your usual activities. Thank you for completing this survey! For each of the following questions, please circle the number that best describes your answer (circle one number on each line). Much better now than one year ago 1 Somewhat better now than one year ago 2 About the same 3 Somewhat worse now than one year ago 4 Much worse now than one year ago 5      These questions are about how you feel and how things have been with you during the past four weeks. For each question, please give the one answer that comes closest to the way you have been feeling (circle one number on each line).

How much of the time during the past 4 weeks …
All of the     Additional Information Disclosures Human subjects: Consent was obtained or waived by all participants in this study. Lagos University Teaching Hospital Health Research Ethics Committee issued approval #ADM/DSCT/HREC/APP/2534. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.