Exploring Factors Associated with Quality of Life in Caregivers of Children and Adolescents with Sickle Cell Disease and HIV: A Comparative Analysis

Introduction Paediatric HIV and sickle cell disease (SCD) are two stigmatising and potentially fatal illnesses that place a significant burden on families. HIV patients benefit from a longstanding free-service national programme in Cameroon, and this could considerably alleviate burden of care on HIV caregivers, possibly leading to better quality of life (QoL) in HIV caregivers compared to SCD caregivers. Our study aimed to compare the QoL between caregivers of children and adolescents with SCD and HIV and explore factors associated with this QoL in Cameroon. Methods and Materials We conducted a hospital-based cross-sectional analytic study at Douala Laquintinie Hospital from February to May 2023. A questionnaire was administered to caregivers of paediatric patients (≤18 years) with SCD and HIV. The Pediatrics Quality of Life-Family Impact Module (PedsQL FIM), the 7-item Generalized Anxiety Disorder (GAD-7), and the 9-item Patient Health Question (PHQ-9) tools were used as measures of quality of life, anxiety, and depression, respectively. Multivariable linear regression was used to determine factors associated with quality of life. A significance level was set at p < 0.05. Results We included 199 caregivers: SCD = 104 and HIV = 95. The mean age of caregivers in our sample was 40.47 ± 10.18 years. Caregivers of paediatric patients with HIV had a better mean quality of life than SCD (93.01 ± 7.35SD versus 64.86 ± 9.20SD, p < 0.001). PHQ-9 score (B = −1.52, 95% CI = [-2.08; −0.96], p=<0.001), GAD-7 score (B = −1.46, 95% CI = [-2.09; −0.83], p=<0.001), spending less than 75 000 FCFA on medications monthly (B = 12.13, 95% CI = [5.73; 18.94], p=<0.001), and being a SCD caregiver (B = −11.62, 95% CI = [-18.46; −4.78], p=0.001) were factors independently associated with quality of life on multivariable analysis. Conclusion Quality of life is lower in caregivers of children and adolescents with SCD than with HIV. Preventing depression and anxiety as well as advocating for the subsidization of medications through a national SCD program may improve quality of life in SCD caregivers.


Introduction
Sickle cell disease (SCD) is one of the most common genetic blood disorders [1].It manifests clinically as painful vasoocclusive crises and chronic haemolytic anemia with episodes of acute worsening and bacterial infections, causing heavy morbidity and mortality in countries with limited resources [2][3][4].According to available evidence, Nigeria is believed to have the highest number of individuals afected by sickle cell disease on a global scale [5].In Cameroon, population carrier frequencies of SCD range from 8% to 34%, with a birth incidence of 1.6% [6].SCD is a chronic illness that impacts physical and social development [7,8].Similar to many other paediatric chronic illnesses, SCD places a signifcant burden on children and their families that may manifest as symptoms of depression and anxiety [1,9,10].Te prevalence of depression in caregivers of patients with SCD has been reported as high as 68.9% [1].Tis impact on families is worse in low-and middle-income countries due to inadequate social welfare and healthcare services [11].Clinical severity of SCD has been reported as a major factor infuencing ability to cope [1,6].
Paediatric human immunodefciency virus (HIV) is a similar stigmatising, debilitating, and potentially fatal illness associated with a high burden of care.According to UNAIDS statistics, 39 million people were living with HIV globally in 2022 and 1.5 million (3.3%) of these people were children aged between 0 and 14 years [12].In Cameroon, as of 2021, there were 510 000 people living with HIV, of which 31 000 (6.1%) were children aged 0-14 years [13].HIV patients beneft from a longstanding free-service national programme which considerably alleviates burden of care [14].Te introduction of free highly active antiretroviral therapy (HAART) has reduced mortality and morbidity among patients living with HIV/AIDS (PLWHA) with a consequent increase in lifespan and quality of life [15,16].
Quality of life is a multidimensional concept infuenced by various factors and varies among individuals and cultures, including objective measures of well-being and subjective perceptions of happiness and fulflment [17].
Research fndings indicate that as a child's illness advances, both the child and their caregivers undergo a decline in quality of life, leading to a notable deterioration in their physical, psychological, social, and economic welfare [18].Caregivers of children with chronic illnesses, such as sickle cell disease and HIV, may experience signifcant impacts on their quality of life due to increased stress, fnancial strain, social isolation, and changes in routines [19,20].
Understanding the quality of life in these caregivers is crucial to identify support areas, intervene efectively, and improve the well-being of both caregivers and the children and adolescents they care for.Tis study specifcally focuses on comparing the quality of life (QoL) of caregivers of children and adolescents with sickle cell disease and HIV and exploring factors associated with this QoL in Cameroon.

Methodology
2.1.Study Design and Setting.Tis was a hospital based cross-sectional analytic study.Tis design allowed direct/ simultaneous comparison between the two groups of interest and also permitted efcient data collection and analysis with the limited resources available in our setting.Te study was conducted at the sickle cell center and the HIV management unit, located at Douala Laquintinie Hospital (DLH), a second category health structure in Akwa, Douala, Cameroon.Te sickle cell center is the only center exclusively dedicated to the care of patients with SCD in the city of Douala.Te unit has nine hospitalisation rooms with a capacity of 21 beds.It is managed by a 17-man staf: two pediatricians, two general practitioners, one clinical psychologist, 11 nurses, and one secretary.Te HIV management unit is a day care hospital providing medical consultations, counseling, drug dispensation, and follow-up of PLWHA.

Study Period.
Te study was conducted over four months, from 1st of February to 31st of May 2023.

Sampling and Study Population.
Convenience sampling, a nonprobability technique, was used to select participants based on their availability and accessibility, specifcally targeting caregivers attending routine consultations at Laquintinie for recruitment.We assumed that many caregivers may be unwilling to participate because of the time constraints and fear of stigma.
Te study population was made up of two comparison groups: caregivers of paediatric patients with SCD and HIV.We included caregivers aged 21 years and above, residing with at least one living patient with SCD or HIV aged <18 years and whose disease was confrmed by a laboratory diagnosis.
We excluded caregivers who refused to give informed consent for participation in the study or had a previously diagnosed psychiatric or psychological disease or caregivers of patients with additional chronic diseases like chronic kidney disease, cancer, or congenital heart diseases.Caregivers of patients with a cumulative diagnosis of HIV and SCD were also excluded from the study.

Sample Size Calculation.
Te primary outcome in this study is the QoL score as measured by the Paediatric Quality of Life Family Impact Module (PedsQL FIM) scale.Te main objective of the study was to compare the mean quality of life scores between the two caregivers' subpopulations: HIV and SCD.No study in Africa reporting PedsQL FIM scores in caregivers of patients with HIV was found.Tis is why chronic kidney disease was used as a surrogate reference.
Te total sample size for the study was calculated using the formula [21]: where  [23] and reference from a Nigerian study on cost of care for SCD [24].A cutof value of 75,000 FCFA was chosen to represent expenditures in the sample.However, the study did not measure the level of social and emotional support in a standardised manner.

Paediatric Quality of Life Family Impact Module (PedsQL FIM).
Te Paediatric Quality of Life Family Impact Module (PedsQL FIM) scale was used to assess quality of life.It was created in 2004 to assess the impact on families and parents with medically fragile children [25].Te PedsQL FIM scale assesses the physical, emotional, social, and cognitive functioning, as well as communication and concern, as reported by the parents.Family interactions and everyday activities as described by parents are also measured by the module.Since responses to questions are based on parental perceptions of their children's quality of life (QoL), there are no cutof values established for what is considered to be "bad" QoL for families.
Reponses are on a 5-point Likert scale.Detailed description of the PedsQL FIM scale is available online [26].In the overall sample, in SCD caregivers and HIV caregivers, the total PedsQL FIM scale had a Cronbach alpha coefcient at 0.95, 0.93, and 0.84, respectively.Because evidence suggests that anxiety, depression, and QoL are associated, we sought to measure these concepts with standardised and validated tools [27].We used the GAD-7 and PHQ-9 tools in this study.

Generalized Anxiety Disorder Scale (GAD-7).
Te sevenitem Generalized Anxiety Disorder scale (GAD-7) was used to diagnose anxiety.It is a frequently used, highly efective, and clinically validated assessment tool for anxiety disorder symptoms [28].GAD-7 ofers a psychometrically sound tool that may be used to identify patients with anxiety disorders in primary care settings as a cost-efective and simply implementable tool.Responses are on a 4-point Likert scale.Te current study defned caregivers whose score was above 4 as having anxiety symptoms (GAD-7 score >4).Detailed description of the GAD-7 scale is available online [29].In the overall sample, in SCD caregivers and HIV caregivers, the GAD-7 scale had a Cronbach alpha coefcient at 0.78, 0.78, and 0.63, respectively.

Patient Health Questionnaire (PHQ-9
). Te 9-item Patient Health Questionnaire (PHQ-9) was used to diagnose depression.It is a commonly used instrument in primary care as it can ofer practitioners a desirable numerical and "objective" diagnosis of depression and permits gauging of its severity [30].PHQ-9 has demonstrated strong validity and reliability as well as greater adaptability even in African settings [31,32].It is a quick, easy, accurate, and reliable measuring method for diagnosing depression and determining its severity.Respondents indicate frequency of depression symptoms in the preceding 2 weeks on a 4-point scale.Te current study defned caregivers whose score was above 4 as having depressive symptoms (PHQ-9 score >4).Detailed description of the PHQ-9 scale is available online [33].In the overall sample, in SCD caregivers and HIV caregivers, the PHQ-9 scale had a Cronbach alpha coefcient at 0.79, 0.78, and 0.58, respectively.
For both GAD-7 and PHQ-9, any participant with a score above 14 received immediate psychological consultation prior to leaving the health facility.Similarly, immediate psychological consultation was ofered to every participant who had a PedQL FIM score below 30 [34].

Data Collection Procedure.
Cases were recruited in a successive and convenient manner on alternate days at the SCD and HIV centers.During the regular health talks at the two centers, a 10-minute time slot was allocated each day to clarify the purpose and objectives of the study.Initially, the researchers communicated orally to express their intentions, and interested participants then approached them individually for a detailed explanation of the study.We entertained any questions and answered them accordingly.We then requested volunteer participation in the study.Caregivers who agreed to participate were registered, and only those who ftted the selection criteria were recruited.Caregivers could decide to be interviewed immediately after consultations or later at their appointed time and day based on their schedule.Tis was carried out after consultations in order not to interfere with their consultation programme.Interviews were conducted using an intervieweradministered questionnaire method to facilitate question clarifcation and improve data quality.Tese interviews were conducted in a quiet, comfortable room without the patient present (except for infants <1 year old) to minimize biased responses.Te average interview duration was 20 minutes.
2.9.Data Management and Analysis.Personally identifable information was removed from the data, which was securely stored in an encrypted online drive with limited access, protected by passwords.
Data analysis was performed using SPSS 23.0 software.Continuous variables were normally distributed and presented as mean ± standard deviation (SD), while categorical variables were presented as numbers (percentage).Te chisquare test was used to analyze diferences between two or Anemia more categorical variables, while Student's t-test was used for diferences between categorical and continuous variables.A Pearson correlation test was used to determine linear association between continuous variables and the total PedsQL FIM score.We used a multivariable linear regression model to identify factors independently associated with quality of life in these two subpopulations.Variables, which were both clinically relevant such as caregiver's age and gender, depression score, anxiety score, patient's age and gender, and estimated cost of care (drugs, hospital fees, transport, and communication) and were found to be statistically signifcant on univariable analysis (p < 0.05), were included in the multivariable analysis.Regression analysis results were presented as unstandardized coefcients (B) with corresponding 95% confdence intervals (CIs).Te reliability of the scales used was assessed using Cronbach's alpha.

Ethical Considerations.
Te study obtained ethical clearance from the Institutional Review Board (IRB/UD) with the reference number 3538/IEC-UD/03/2023/T.All participants provided informed consent after receiving a detailed explanation of their rights and associated risks.Te tools used in the research are freely available online for academic purposes.Data collection maintained anonymity, and interviews were conducted in a private room to ensure confdentiality.Measures were taken to address potential psychological harm, with immediate psychological care provided to caregivers in distress.Equal access to participation was ensured for all potential eligible participants, regardless of socioeconomic, racial, or demographic diferences.

Operational Defnitions
(1) Caregiver: An adult aged 21 years and above who lives and is the principal care provider to at least one child with SCD or HIV, during steady state, illness, or disability.(2) Anxiety: Anxiety refers to the manifestation of worry, nervousness, or discomfort arising from the anticipation of potential harm or threat [35].For this study, participants with a score of 5 or above on the GAD-7 scale were considered to exhibit signifcant levels of anxiety.(3) Depression: Depression is a mood disorder characterized by enduring feelings of sadness and a diminished interest in activities [36].In this study, caregivers who scored 5 or higher on the PHQ-9 questionnaire were identifed as experiencing signifcant levels of depression.(4) Quality of life: Quality of life (QoL) relates to the overall well-being and satisfaction, encompassing both positive and negative aspects, of a population or an individual at a particular moment [17].In this study, the quality of life was measured using the score obtained from the PedsQL FIM scale.

Participant Recruitment.
We approached 220 participants and retained 199 participants gaining a response rate of 90.5%.Te participants were composed of 104 (52.3%) caregivers of patients with SCD, and 95 (47.7%) were caregivers of participants with HIV as shown in Figure 1.
Tere were no missing data in our sample.

Discussion
In our context, when available, psychological care services are mainly ofered to patients and not caregivers.Caregivers are generally excluded despite the fact that they play a central role in providing medical and psychological care to patients and also bear all care-related expenditures [11,37].Te purpose of our study was to characterise the quality of life (QoL) in caregivers of paediatric patients with SCD (SCDc) and compare it to caregivers of paediatric patients with HIV (HIVc) using the PedsQL FIM scale.We measured factors that could possibly infuence the QoL in our population based on available literature, tested their infuence on QoL, and fnally compared these factors between the two subpopulations of interest.Caregivers were predominantly females similarly reported by other studies [1,38,39].Numerous studies have reported that female caregivers are able to sacrifce their social lives, are more emotionally invested in the sick compared to male caregivers, and even when accessible, ask for less assistance from others, and therefore tend to experience depression more frequently than males [40,41].

Anemia
However, in our study, though females predominated, caregiver's gender did not infuence quality of life.
Using the PHQ-9 score, one in two (50%) SCDc had depression in our sample.In the USA, using the Center for Epidemiological study-Depression Scale Revised (CESD-R-10), prevalence of depression was reported at 40% [42].However, a context-similar study conducted in Kenya has reported an even higher prevalence of depression at 69.53% [1].Tough cycles of negative cognitions, emotions, and actions may impact coping strategies in caregivers generally, fnancial hardship may be a major factor contributing to the high prevalence of depression in African settings [43][44][45][46].In our study, the prevalence of anxiety among SCD caregivers was 46.2%.It has been reported as low as 16% in the USA [42] and as high as 92.6% in Nigeria [47].Recurring lengthy clinic appointments and increased psychological stress due to the unpredictability of sickle cell crises's outcome are factors promoting anxiety in caregivers of patients with SCD [48].No HIV caregiver had depression, and only 1.05% had anxiety.Tis fnding was contrary to the median PHQ-9 at 6.0 (denoting mild depression) obtained by Mwangala et al. in Kenya [49].Te poor reliability of the PHQ-9 questionnaire in HIV caregivers in our study (Cronbach alpha coefcient at 0.58) may explain why these values difer.Other tools like the Beck Depression Inventory-II (BDI-II) and the Center for Epidemiology Studies Depression Scale (CES-D) may provide suitable alternatives [50], but these tools also need to be validated in large-scale studies in Cameroon.
To evaluate the quality of life of caregivers, the PedsQL FIM score was used.Te mean PedsQL FIM score in SCDc was 64.86 ± 9.20.Tis was lower than that reported in the USA (75.7) but much higher than that reported in Kenya (43.76) [1,42].In our study, depression score, anxiety score, spending more than 75,000 FCFA on medications monthly, and being a SCDc had a negative impact on the quality of life of caregivers.Depression is a recognized factor infuencing QoL [9,49].Untreated anxiety and depression could result in impaired economic productivity, reduced ability to perform work and social roles, loss of relationships, physical decline, and problem-solving defcits for the caregivers, hence negatively impacting their QoL [49].Mwangala et al. [49] also reported that caregiver's age and secondary level of education negatively infuence the QoL of caregivers, while Van den tweel [9] additionally reported that limitation in daily activities and vitality negatively infuenced QoL.SCD is a chronic disease, which may lead to debilitating complications like stroke [3,51,52] and femoral osteonecrosis [53,54] which could signifcantly impair patient's mobility and autonomy making them fully dependent on caregivers.In addition, the intensity of pain crises may cause insomnia and psychological distress in caregivers, which may afect their quality of life [55].We reported a positive correlation between caregiver's age and quality of life; however, this was not a signifcant independent factor.Increasing the caregiver's age has been reported to be associated with less anxiety and depression and therefore better quality of life.Tis is believed to be due to better stress coping strategies with advanced age [56].Contrary to some reports [49,56,57], educational status did not afect quality of life in our study.It is assumed that education infuences not just a person's income but also their ability to make wiser choices about their health and family.People with higher levels of education also have much lower unemployment rates [58].
Financial barrier, which may impair easy access to healthcare services in African context, is likely to have a big infuence on quality of life [59].In our study, spending less on medications improved QoL.Cameroon has a national programme for HIV, which gives room for better organisation of patient care and free access to most, if not, all HIVrelated health services.Free services promote healthcare access and enables caregivers to redirect already limited resources to other sectors of life, thereby reducing fnancial stress and consequently improving quality of life.Higher expenditures per hospitalisation, higher number of hospitalisations yearly [24], and the unpredictability of crises generate a more signifcant fnancial burden for SCD caregivers compared to HIV caregivers.With all these, it is therefore not surprising that HIV caregivers have a better quality of life than SCD caregivers.
Te monocentric nature of the study, the use of the convenience sampling technique, the use of scales with limited reliability, and the nonevaluation of disease severity constitute methodological limitations and therefore limit the interpretation of our results.Nonetheless, this study is novel as it addresses a signifcant issue in the care of patients with SCD and generates baseline data for further studies.It is the frst Cameroonian study that used a standardised scale to evaluate and determine factors infuencing quality of life in caregivers of HIV and SCD.

Conclusion
Quality of life is lower in caregivers of patients with SCD compared to HIV.In order to improve care in children and adolescents with SCD and quality of life of their caregivers, psychological care should be geared towards preventing, diagnosing, and treating depression and anxiety in SCD caregivers.Subsidization of medication expenditures may be benefcial in improving quality of life in caregivers with SCD.

Figure 2 :
Figure 2: Diference in individual domain scores of the PedQL FIM scale between caregivers of HIV and SCD at Laquintinie between February and May 2023.

Table 1 :
Figure 1: Recruitment fowchart of caregivers of SCD HIV at Laquintinie between February and May 2023.SCD � sickle cell disease; HIV � human immunodefciency virus.Comparing selected variables between caregivers of SCD and HIV at Laquintinie between February and May 2023.Paediatric Quality of Life Family Impact Module.GAD-7 � 7-item Generalised Anxiety Disorder Scale.PHQ-9: 9-item Patient Health Questionnaire Scale.Bold values represent statistical signifcance at p < 0.05.

Table 2 :
Categorical variables associated with quality of life in caregivers of SCD and HIV at Laquintinie between February and May 2023.REF � reference category.SD � standard deviation.PedsQL FIM � Paediatric Quality of Life Family Impact Module.NaN � not applicable since single patient.p values * represent comparative analysis of the REF category and the exposure category in the overall sample.

Table 3 :
Univariate and multivariable analysis of factors associated with quality of life in caregivers of SCD and HIV consulted at Laquintinie between February and May 2023.