Integrating a problem-solving intervention with routine care to improve psychosocial functioning among mothers of children with sickle cell disease: A randomized controlled trial

Objective To assess the feasibility of a problem-solving skills training intervention in improving psychological outcomes in mothers of infants with sickle cell disease (SCD). Design and methods This parallel randomized controlled trial recruited 64 babies with SCD, 6 to 12 months of age, and their mothers. Baseline measurements assessed mothers’ coping and problem-solving skills, depression, and parental stress before random assignment to intervention or control groups (n = 32 each). Problem-solving skills intervention was delivered through 6 monthly sessions, when babies attended for routine penicillin prophylaxis. All measurements were repeated for both groups at the end of the intervention period. Intention to treat analysis used repeated measures mixed models with the restricted estimation maximum likelihood approach. Results The problem-solving intervention had no significant effect on mothers’ problem-solving skills (adjusted treatment effect: -1.69 points (95% CI:-5.62 to 2.25)), coping behaviours (adjusted treatment effect: 0.65 points (95% CI:- -7.13 to 8.41)) or depressive symptoms (adjusted treatment effect: -0.41 (95% CI: -6.00 to 5.19)). It reduced mothers’ level of difficulty in managing stressful events by 9.5 points (95% CI (-16.86 to -2.16); effect size: 0.21 SD). In the subgroup of mothers at risk of depression (n = 31 at baseline), the intervention reduced depression scores with treatment effect of 10.4 points (95%CI: -18.83 to -1.88; effect size: 0.67 SD). Conclusion This problem-solving skills intervention study suggests feasibility and possible efficacy in improving some maternal outcomes. Further refinement and culturally appropriate adaptations of the intervention could lead to stronger effects.


Introduction
The Child Development Research Group (CDRG) of Tropical Medicine Research Institute (TMRI) has pioneered the use of simple, cost effective interventions in the improvement of development in young at risk children. The Sickle Cell Unit (SCU) has provided care for children with sickle cell disease (SCD) for decades, concurrently pursuing many research projects aimed at improving their lives. This project seeks to combine the strengths of these two groups.
SCD was declared by the United Nations and World Health Organization to be a global public health problem (1), with more than 300,000 affected infants born annually (2). SCD is a public health issue in Jamaica where 1:150 babies are born annually with the condition. Neurocognitive deficits have been demonstrated in pre-school children with SCD (3), even in the absence of cerebrovascular accidents (4-7). Educational delays have also been demonstrated in schoolaged children (8,9). Rehabilitative interventions have been attempted, without much success, in those who already have demonstrated deficits. Reduction in educational attainment impacts on vocational and employment outcomes, and the ability of affected persons to become selfsufficient, productive members of society. In most affected persons, SCD precludes strenuous vocations, so the maximizing of academic potential is critical.
The important risk factors for poor early cognitive development are disease severity, as indicated by anaemia, and increased parental stress (5, 10, 11). Parental stress is also higher in parents/caregivers of children with a chronic illness (12), and can worsen both child and adult outcomes (13). Interventions available in developed countries, such as chronic transfusion and hydroxyurea, which can attenuate anaemia, are not sustainable in the developing world. Integration of an intervention into usual care with little additional cost can have significant impact on maximizing the potential of children given their disease severity.
We have demonstrated benefits to child development in at risk groups of an intervention improving parent-child interactions through play, delivered during home visits by health workers, and more recently in a clinic setting. In addition, problem solving therapy (PST), which is based on cognitive behavioural therapy model, has been shown to be effective in persons with depression, and caregivers of children with chronic illness (14)(15)(16). In children with SCD, enhanced problem solving skills in the parents have shown an association with improvements in the child's quality of life (17). Parental education (17), income and family functioning (13) have been shown have correlations with their problem solving skills and stress levels.
We therefore propose to assess the efficacy of these two interventions, delivered during routine monthly clinic visits, in improving parent psychological outcomes and child development. Our hypothesis is that this parenting intervention will improve maternal and child outcomes.
Our specific hypotheses are: 1. Intervention using parent-child interaction through play improve child developmental scores 2. Intervention using parent-child interaction through PST will improve parental outcomes such as stress, coping, and their problem solving skills

The Study Population
All parents of children aged 6-9 months with severe SCD genotypes (Hb SS disease and Hb Sβ 0 thalassemia) attending the Sickle Cell Unit at Mona Campus, UWI will be informed of the study and given an opportunity to participate. Once the written, informed consent process has been completed, the parent-child dyad will be randomly allocated to intervention or control arms using a random number table. The control dyads will receive usual clinical care.

Procedures
A study coordinator, who is not involved in anyway directly with clinical care of persons with SCD, will approach the parent/caregiver either at the SCU while they are waiting to be seen by their physician/ or via telephone contact. The purpose and the procedures for the study will be thoroughly explained to them and all queries will be addressed. The concept of randomization to intervention or control will be explained by the study coordinator during the informed consent process.
Each dyad will have 8 study visits: As the two genotypes (SS and Sβ 0 thalassemia) may be indistinguishable clinically as well as haematologically at initial screening of baby at entry to care at SCU, the genotypes are usually confirmed at 9-12 months of age when their HbA2 and HbF levels stabilize and hence assist to confirm the diagnosis. This is done free of cost to the patient. These data will be used to assess anemia in the study. No additional blood tests will be required.

Assessment
Assessments will be done at baseline (T0) and six months later, after completion of the intervention (T1), and will include: • Assessment of development status of the child, • Assessment of parent problem solving skills and , stress, and coping.
All assessments will be conducted by trained testers (who are blinded to the randomization arm of the participant) and all questionnaires will be interviewer administered in private surroundings. All questionnaires will be pilot tested prior to commencement of the study with parent/child dyads not included in the study. It is anticipated that the time for completion of assessments and questionnaires will be 60-90 minutes.

Instruments
Social Problem-Solving Inventory-Revised (SPSI-R): This is a 25-item instrument for use in persons over 13 years of age. It provides a total (SPSI-R-Total), as well as the following 5 major scale scores: • Positive Problem Orientation (PPO) • Negative Problem Orientation (NPO) • Rational Problem Solving (RPS) • Impulsive/Careless Style (ICS) • Avoidance Style (AS) It has been used in studies across a variety of clinical conditions including Cancer, Diabetes, caregivers of persons and children with chronic diseases, etc. Email has been sent to distributors of this instrument seeking permission and/or applying for license to use.

Intervention
Interventions will be undertaken in a private room, away from the general clinic. This will avoid leakage of the intervention to the control group. Both interventions, i.e. Problem-Solving Therapy (PST) and Play Therapy, will be conducted by clinic nurses who will undergo an initial period of training in each intervention with the study investigators. These interventions will be done during monthly clinic visits when the babies must attend for receiving penadur injections for infection prophylaxis. The interventions will be done with small groups of parents and will take no longer than an hour.

Play Therapy
Short films that have been developed to deliver a series of child development messages will be shown at the monthly visits. Nine modules of approximate length 3 minutes each have been developed and cover the topics: Love, Comforting baby, Talking to babies and children, Praise, Using bath time to play and learn, Looking at books, Simple toys parents can make, Drawing and games, and Puzzles. Three topics will be shown together at each visit, allowing each topic to be shown on more than one occasion. Nurses at the SCU will be trained to discuss the video messages with the parents/caregivers, demonstrate activities they can do with their children and how to make simple toys from household materials. Opportunities will be given for parents/caregivers to try some of the activities and they will be encouraged to make them part of their daily routine.

PST
Problem solving therapy aims to empower patients or caregivers in attending to daily social and other challenges that might arise especially with the presence of a chronic illness. The approach is based on cognitive behavioural therapy and has been shown to be of use in primary care settings (15,16,18,19). It encourages persons to use existing resources and skills to function better and find solutions to problems (20). It will be delivered in 6 sessions over the 6-week period and will last for about 30 minutes per session. The stages of PST are: identification of the problems; generating possible solutions; evaluating and implementing preferred solution; and evaluating to see if the solutions were successful (14,18). PST has been used effectively in various stress related conditions, anxiety, and stress.
The parent/caregiver will be taught a process of problem solving with reference to general everyday problems as well as specific problems which may arise while parenting a child with SCD.

Sample size and statistical considerations
A Jamaican trial of home visiting parent intervention integrated into primary care demonstrated an effect size of 0.8 SD (21). Due to the smaller number of contacts with parents in the new intervention, we hypothesized an effect size of 0.67 SD. A sample comprising 35 children per group achieves 80% power to detect the hypothesized effect. All analyses will be performed using the statistical software STATA 12.0, based on intention-totreat principles. Descriptive statistics (means ± SD, or median and interquartile ranges, as appropriate) will be used to describe the study sample with regards to baseline characteristics. Comparisons of primary and secondary outcomes at both T0 and T1 between the intervention and control groups will be analyzed. When relevant the change in outcomes from baseline to follow-up will be assessed. Statistical significance is being set at P < 0.05.

Confidentiality Procedures
Confidentiality of all participants will be protected within legal limits. Each parent-child dyad will be assigned a study number and all relevant clinical and experimental data will be stored in notebooks and computers at the SCU under the assigned number. Access to data will be limited to those personnel directly involved in the study.

Benefits &Risks to the participants
There is no payment for participation. However, we will transport the dyads to clinic for the initial and final assessments. This is necessary because the Child Development Research Groups has found that children who travel on Jamaican public transportation do not perform optimally in developmental tests. We also will pay bus fare, a maximum of J$2,500 but based on where the dyad lives, for the six visits during the intervention.
If the intervention is useful, parents may benefit from improved mental health and infants improve in development. Furthermore, these parents will be able to apply the skills they have learned to their relationships with other children. After the second assessment, all parents will be given the results of their children's developmental assessments and appropriate referrals made if deficits are identified. At the end of the study, all control dyads will also be given the toys used in the intervention. If the intervention demonstrates benefit, the control dyads will have it delivered as a group. This is a proof of concept/pilot study. Were it to show benefit, the intervention could be developed further with the SCD Working Group lead by the Ministry of Health to determine whether it is feasible to scale up in the future.
The study will present minimal risks to the participants beyond those associated with blood sampling, which will be conducted by trained medical technologists. If any of the questions cause any emotional discomfort to the participants, they will be referred for appropriate counselling by the social worker at SCU.

TITLE OF PROTOCOL:
Integrating a parenting intervention with routine care to decrease parental stress and improve early developmental outcomes in children with sickle cell disease

PURPOSE OF THE STUDY
Children with sickle cell disease (SCD) are at risk of various complications, many of which arise suddenly and which may require the parent to make quick and correct decisions. They are also at risk of delays in their development. There are many techniques that have helped other children's development and parents' coping skills. We wish to see if some of these methods will assist both the child with SCD and their families.
This study is being undertaken to determine how having a baby with SCD might affect you the parent emotionally, how well you are coping with and managing any challenges. We also wish to understand the baby's development and see whether some new activities at the clinic might help parents levels of stress and coping capabilities as well as the baby' development .

PROCEDURES
You are being asked to participate in this study because you have just had a new baby who has been diagnosed with SCD. If you decide to participate, you will be asked to complete a questionnaire, which asks various questions about how you are feeling emotionally, how well you are coping, and how well you are able to face challenges. We will also be doing a test, using toys, on your baby to see how s/he is developing. The questionnaire and testing will take about 60-90 minutes of your time for completion. Even though your I.D. number will be seen on the questionnaire, your baby's or your identity will never be disclosed and strict confidence will be maintained.
Some of the parents who take part in the study will be asked to join us for some new sessions once per month for the next six months during the regular monthly visits to the clinic for the baby's penadur injections. Other parents will come to the clinic for the regular monthly visits as usual without these new sessions. The group in which you will be in is determined randomly and at the end of the interview period. If you are in the group with sessions, we will have discussions and demonstrations of ways to help young babies develop well. It will include showing you short videos on ways to interact with your child. We will also discuss ways to tackle any problems or challenges you might encounter and your own experiences. Each session is expected last about 1 hour.
After the 6 months you will be asked to attend the clinic to complete the same questionnaire again and the baby's development will also be reassessed.
After the second assessment, all parents will be given the results of their children's developmental assessments and appropriate referrals made if deficits are identified. If you are in the group who did not have sessions, you will be given the toys used in the intervention at the end of the study. Also, if the intervention demonstrates benefit, you will have the opportunity to attend group sessions where we will show the videos and discuss problem solving.
The results of the blood test which are routinely done by the SCU at no cost to you to confirm the type of sickle cell disease your child has will be used by us to check whether anemia affects development. This is done when your baby is 9-12 months of age.

BENEFITS AND RISKS
There will be no financial benefits to you if you agree to participate in this study. We will transport you and your infant to clinic for the initial and final assessments. This is necessary so that your infant will not be tired when doing the developmental tests. We also will reimburse bus fare, based on where you live, for the six visits during the intervention. The results of this study will assist in determining if there are benefit of these techniques and whether they should be offered to other children and families. There are no physicals risks to you as a result of this study. However if any of the questions cause any emotional discomfort, you can be referred for appropriate counselling by the social worker at SCU at no cost to you.

ALTERNATIVES
You do not have to participate in this study if you do not want to do so. Also, you can decide at any time during the study that you wish to withdraw. If you do not participate, or withdraw during the study, there will be no change in your present or future care at the Sickle Cell Unit or the University Hospital of the West Indies.
If there are any questions, the study staff will try their best to answer them to your satisfaction.

STATEMENT OF DECLARATION
I have read the information provided above and/or it has been read and explained to me. All my questions have been answered to my satisfaction. My signature below indicates that I give my consent to participate in the study. In so doing, I understand that I can withdraw my consent at any time as I so desire. I also understand that any questions that I may have in the future will be answered willingly and promptly.

Integrating a parenting intervention with routine care to improve parental psychosocial functioning and early developmental outcomes in children with sickle cell disease
This study seeks to determine how parents of a new baby with sickle cell disease cope, how confident they feel in facing challenges of parenting and their emotional feelings; as well as the baby's development. The study will further determine if certain methods can be employed during routine visits to the sickle cell clinic that could improve both the child's development as well as parent's stress and coping capacities.
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