The effectiveness of continuous subcutaneous insulin infusion on quality of life of families and glycaemic control among children with type 1 diabetes: A systematic review.

Abstract

Centre conducting the review Hong Kong Centre for Evidence Based Nursing: a Collaborating Centre of the Joanna Briggs Institute The Nethersole School of Nursing The Chinese University of Hong Kong, Hong Kong Commencement date: July 2011 Expected completion date: June 2012 Correspondence Hong Kong Centre for Evidence Based Nursing: a Collaborating Centre of the Joanna Briggs Institute, 8/F, Esther Lee Building, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Email: [email protected] Review objective/question Objectives The main objectives of this systematic review are: To assess the effectiveness of continuous subcutaneous insulin infusion (CSII) compared to multiple daily injections (MDI) on quality of life in families of children with type 1 diabetes. To determine the clinical effectiveness of CSII compared to MDI in terms of glycaemic control expressed in the levels of glycated haemoglobin (HbA1c) in children. A secondary objective is: To examine the health outcomes of CSII compared to MDI in terms of the episodes of severe hypoglycaemia and diabetic ketoacidosis. Review questions The specific review questions to be addressed are: What is the effectiveness of CSII compared to MDI on quality of life in families of children with type 1 diabetes pertaining to physical, psychological, social and spiritual domains of life? What is the effectiveness of CSII compared to MDI on glycaemic control in children with type 1 diabetes? What is the effectiveness of CSII compared to MDI on reducing the episodes of severe hypoglycaemia and diabetic ketoacidosis in children with type 1 diabetes? Background Type 1 diabetes is one of the most common endocrine and metabolic conditions in childhood, and the incidence is increasing in many countries.1 It is estimated that annually 76,000 children aged under 15 years develop type 1 diabetes worldwide.1 Finland has the highest rate of new cases of type 1 diabetes at 57.4 per 100,000 for children under 15 years of age,2 followed by Sweden (41.0),3 Norway (27.9),4 the United Kingdom (24.5),5 the United States of America (23.7)6 and Australia (22.8).1 In Hong Kong, the standardised age-adjusted incidence of type 1 diabetes is 2.4 per 100,000 for children under 15 years of age, and 2.0 per 100,000 for those under 19 years of age.7 Type 1 diabetes involves a process of destruction of the beta cells of the pancreas, leading to absolute insulin deficiency; insulin deficiency can ultimately lead to the development of ketoacidosis, coma and death.8 Type 1 diabetes is a lifelong condition in which both morbidity and treatment affect the patients' quality of life (QoL).9 Childhood diabetes may be a source of stress for all family members and can cause intense parental anxiety.9,10 The care of children with type 1 diabetes can present a variety of particular problems compared to the care of adults with diabetes. Many decisions about aspects of care are made by parents or carers on the child's behalf until the child is mature enough to demonstrate increasing independence in diabetes management.11 Research has consistently documented that parents of very young children with diabetes experience higher levels of family stress than those of older children.12 Children with type 1 diabetes are susceptible to acute and long-term complications of diabetes.13 Insulin treatment may lead to hypoglycaemia, which is the most frequent acute complication of type 1 diabetes.13,14 Severe hypoglycaemic events can lead to behavioural disturbances, unconsciousness, convulsions or death.15 Severe hypoglycaemia is rated by both children and parents as the most anxiety-promoting feature of diabetes, and may lead to loss of self-esteem and social isolation.13 Fear of recurrent hypoglycaemia not only decreases QoL but also hinders adherence to treatment and the achievement of good glycaemic control.9 Moreover, poor glycaemic control, reflected in high blood glucose levels, can in the short-term result in diabetic ketoacidosis, an acute metabolic emergency that can be life-threatening.9,15 Poor control of diabetes may also impair growth, delay puberty and lead to long-term complications.13 The long-term microvascular and macrovascular complications of chronically elevated blood glucose levels include retinopathy, nephropathy, neuropathy, ischaemic heart disease, stroke, and peripheral vascular disease.9,13,16 Achieving optimal glycaemic control is a fundamental goal of treatment in type 1 diabetes.17 The Diabetes Control and Complications Trial, and the Epidemiology of Diabetes Interventions and Complications study have demonstrated that strict glycaemic control reduces the risk of development and progression of late complications in patients with type 1 diabetes.18-20 This reduction can be accomplished with intensive insulin therapy, which is administered by either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with three or more insulin injections per day.18 Recently published meta-analyses of studies comparing CSII and MDI have shown an improvement in glycaemic control with reduction in glycated haemoglobin (HbA1c) of between 0.2% and 0.4% with the use of CSII in patients with type 1 diabetes.21-25 Insulin has been used for the treatment of diabetes since the 1920s.26 The first reported CSII system was developed by Dr. Arnold Kadish in the early 1960s.27 Since its introduction in 1978,27 CSII, often called insulin pump therapy, has become an increasingly popular option for type 1 diabetes management.28 In recent years, technological advancement has made insulin pumps smaller, easier to use, more reliable and flexible.27 The use of CSII for treatment of type 1 diabetes has increased markedly over the past decade.29 CSII administers rapid-acting insulin analogue by an external pump that delivers insulin continuously from a refillable storage reservoir via a cannula in the subcutaneous tissues.9 CSII allows programmed insulin delivery with multiple basal infusion rates that simulates the physiological patterns of insulin secretion, and flexible bolus doses of insulin can be activated to cover meals and correct hyperglycaemia.13,30,31 Patients using CSII report that it increases their lifestyle flexibility, and can be adjusted to match their individual needs.13,30 Specific but infrequent complications of CSII include reactions and, occasionally, infections at cannula site, tube blockage and pump malfunction.9 QoL is of particular concern to the families of children with type 1 diabetes, which impacts heavily on the lifestyle of the patients and their families.13 In these families, QoL may be significantly diminished. Many children are unable to cope emotionally with their condition. Type 1 diabetes can cause them embarrassment, result in discrimination and may restrict social relationships.32 School performance and family functioning may be affected as a result. Parents may have to decrease their working hours or quit their job to take care of their child.32 In addition, the focus on achieving optimal glycaemic control may require more skill, time and family involvement in the child's daily diabetes management, including administration of insulin, frequent blood glucose monitoring, calculation of carbohydrate intake, and careful consideration of physical activity.33 There is evidence that managing a complex chronic illness such as type 1 diabetes and intensive treatment regimens can be stressful for some families.34 Diabetes management and complications may have a direct impact on QoL in families.35,36 Several studies have examined the QoL in families relating to insulin regimens in children with type 1 diabetes. Data from studies that have examined CSII have been conflicting. Whereas some studies have shown CSII to be associated with improvements in children's QoL and a decrease in parenting stress,10,37 other studies report no differences.29,33 In the study by Muller-Godeffroy et al.,10 parents reported reduced frequency and difficulty of overall parenting stress and decreased worries about hypoglycaemia, while parents of younger children (4-7 years) reported reduced problems with nutrition management. Sullivan-Bolyai, Knafl, Tamborlane and Grey38 studied parental reflections on managing their young children with CSII and found that parents reported becoming comfortable with CSII between ten days to two or three months after the child started using it, and that CSII provided better glucose control, easier disease management, fewer variables to manipulate and more flexible meal times. Parents also reported that everyone in the family experienced more freedom, flexibility and spontaneity in their daily lives. QoL is increasingly used as an outcome measure for interventions among people with chronic diseases.39-41 Over the last two decades, research on children with type 1 diabetes has shown that diabetes has a profound impact on families and parents, who at the same time have a critical impact on the psychological wellbeing of their child and the metabolic control of their illness.12 CSII has gained increasing popularity among paediatric patients with type 1 diabetes and their families.10,42 CSII provides greater flexibility in lifestyle, which may affect different aspects of family burden and QoL in families.10 Nonetheless, studies investigating the effectiveness of CSII on QoL in families of children with type 1 diabetes have revealed conflicting results. Moreover, the focus of previous reviews has mainly been on QoL in children with type 1 diabetes. It is presumed that CSII provides psychosocial and physical benefits to the families as well. The effectiveness of CSII on QoL in children with type 1 diabetes has been widely reported in the previous reviews and will thus not be the subject of the existing systematic review. Nevertheless, the effectiveness of CSII on QoL in families of children with type 1 diabetes has not been specifically examined and will therefore be the focus of this review. Additionally, the use of CSII has been demonstrated to reduce HbA1c levels without an increased risk of hypoglycaemia in adults when compared to MDI, but results in children have been inconsistent.23,43 This review also aims to assess the effects of CSII on glycaemic control and episodes of severe hypoglycaemia and diabetic ketoacidosis in children with type 1 diabetes in relation to impact on QoL in families. Though there have been a number of reviews in the area of CSII,15,21-25,36,44 this will be the first review that looks specifically at the effectiveness of CSII on QoL in families of children with type 1 diabetes. It is hoped that the findings of this review will help health care providers understand the impact of type 1 diabetes and its treatment on QoL in families of this patient population; and provide health care providers with information to consider when presenting choices of diabetes management to families of children with diabetes.38 Furthermore, the findings will be useful for health care providers to develop education and support programmes or interventions for families that consider CSII for their children. Thus, this review will identify the best available evidence related to the effectiveness of CSII compared to intensive insulin therapy with MDI on QoL of families and glycaemic control among children with type 1 diabetes. Inclusion criteria Types of participants This review will consider all families of patients aged 18 years or below with type 1 diabetes taking insulin treatment. Families of patients who are critically ill or who are pregnant will be excluded. For the purposes of this review, ‘family’ is defined as “the body of persons who live in one house or under one head”, as per the definition given by the Oxford English Dictionary.45,46 Type I diabetes is defined as a metabolic disorder of multiple aetiology characterised by hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from destruction of the beta cells of the pancreas and insulin deficiency.8 Given the changes in classification and diagnostic criteria for type 1 diabetes over the years, this review will consider studies which based diagnosis on the valid diagnostic criteria for the illness at the time of the study.23 Types of interventions Interventions of interest will be CSII compared with MDI. In this review, CSII is defined as continuous insulin infusion by an external pump that can be programmed to deliver basal rates and flexible bolus doses of insulin to cover meals and correct hyperglycemia via a cannula in the subcutaneous tissues.9,31 MDI is defined as three or more insulin injections per day. MDI can be given by syringe or insulin pen or a combination thereof. All insulin preparations and doses will be considered. Type of comparator The comparator of interest is: Comparison between patients using CSII by insulin pump versus MDI with three or more insulin injections per day. Types of outcome measures The primary outcomes of interest are: Quality of life in families of patients aged 18 years or below with type 1 diabetes.Quality of life is defined as a multi-dimensional evaluation of an individual's current life circumstances, encompassing physical, psychological, social, and spiritual dimensions.47 Primary outcome measures include self-reported measures of quality of life by family members, such as Paediatric Inventory for Parents, Parenting Stress Index, Brief Symptom Inventory, and Beck Depression Inventory.Glycaemic control as measured by percentage of glycated haemoglobin (HbA1c). The secondary outcomes of interest are: Number of severe hypoglycaemic episodes.Severe hypoglycaemia is defined as hypoglycaemia requiring third party assistance, including unconsciousness, seizure, glucagon administration and emergency attendance or admission to hospital.44Number of diabetic ketoacidosis.Diabetic ketoacidosis is defined as heavy glycosuria and ketonuria; hyperglycaemia (blood glucose level > 11 mmol/L); venous pH < 7.3; and bicarbonate < 15 mmol/L.7 Types of studies This review will consider all studies that used a randomised controlled trial (RCT) design to compare CSII with MDI with respect to QoL of families and glycaemic control among patients aged 18 years or below with type 1 diabetes. In the absence of RCTs, other research designs such as quasi-randomised controlled trials and observational studies will be included in the review. Studies will only be eligible for inclusion if they report the primary outcomes of interest in this review. Studies which report the secondary outcomes of interest only will not be eligible for inclusion. Additionally, studies which include a mixed group of patients with diabetes (type 1 and type 2, as well as children and adults) will be excluded from the review unless the respective results have been presented separately for each type of patient. Exclusion criteria Studies will be excluded from the review if they: were not written in either English or Chinese languages; were literature reviews, systematic reviews, protocols, clinical guidelines, case reports, editorials, commentaries, or reports of expert opinions. Search strategy The search strategy aims to find both published and unpublished studies in English and Chinese using a three-step search strategy. Firstly, an initial limited search of MEDLINE and CINAHL will be conducted with identification of keywords followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe relevant articles.48 Secondly, a more extensive search of a range of databases using all identified keywords and index terms will be performed to identify potential articles for inclusion in the review. As index terms vary across databases, individual search strategies will be developed for each database (e.g., Appendix I shows the search strategy to be used in MEDLINE). Thirdly, hand searching of relevant postgraduate and doctoral dissertations, conference proceedings and journals such as Pediatric Diabetes and Diabetes Care will be undertaken to identify additional literature. An online search of databases and websites such as Google Scholar will also be carried out to identify studies relevant to the field of interest. In addition, the reference lists and bibliographies of all identified articles will be searched for additional studies. Furthermore, related researchers, organisations and manufacturing companies will be contacted to identify additional published, unpublished and ongoing trials. The search will be conducted for the period 1978 to 2011 as CSII was introduced in 1978. The databases to be searched for studies in English will include: MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, All EBM Reviews, Bandolier - Evidence Based Health Care, BioMed Central, Centre for Reviews and Dissemination, ISI Web of Science, PsycINFO, PsycArticles, PubMed, Scirus, Scopus, Turning Research into Practice, British Nursing Index, Health Sciences, ProQuest Health and Medical Complete. The databases to be searched for studies in Chinese will include: Hong Kong Index to Chinese Periodical, China Journal Net, Chinese Medical Current Contents, Chinese Biomedical Literature Database, China Academic Journals Full-Test Database - Medicine/Hygiene Series, Taiwan Electronic Periodical Services, HyRead, WanFang Data, SymbolSymbol.Figure: No Caption available.Figure: No Caption available.The search for unpublished studies or grey literature will include: Agency for Healthcare Research and Quality, Academic Archive Online, Dissertation Abstracts International, Grey Literature Report (via New York Academy of Medicine), Index to Theses, Lancashire Care Library and Information Service, MedNar, National Library of Medicine Gateway, Netting the Evidence, the Networked Digital Library of Theses and Dissertations, Digital Dissertation Consortium, ProQuest Dissertations and Theses, and PsycEXTRA. The initial search terms will include: English search terms Diabetes mellitus or diabet* or type 1 diabet* or insulin depend* diabet* or IDDM or juvenil* diabet* or child* diabet* or keto* diabet* or britt* diabet* Insulin* or insulin inject* or multiple daily inject* Continuous subcutaneous insulin infusion or infusion pump* or insulin infusion system* or CSII Child* or newborn* or infant* or toddler* or teen* or adolescen* or youth* or p?ediatric* Famil* or family member* or parent* or father* or mother* or sibling* Quality of life or life satisfaction or psychosocial health or well?being Chinese search terms Symbol Symbol Symbol Symbol Symbol Symbol Figure: No Caption available.Figure: No Caption available.Figure: No Caption available.Figure: No Caption available.Figure: No Caption available.Figure: No Caption available.Assessment of eligibility All identified studies from the search will be assessed independently by two reviewers for relevance to the review based on the title and abstract. The assessment will be implemented using the inclusion and exclusion criteria with regard to the types of studies, participants, interventions and outcome measures of the studies. If the study meets the inclusion criteria or the abstract of a study is inconclusive, the full text will be retrieved for further scrutiny. Decisions to include studies in the review will be made by two independent reviewers after evaluation of the full text of all retrieved studies. A study eligibility verification form (Appendix II) will be used to verify the eligibility of the study. In all instances, differences of opinion between reviewers will be resolved by discussion or consultation with a third reviewer. The details of all identified studies will be managed using the bibliographic software (RefWorks). In case of duplicate publications, all available data will be evaluated by comparing the author names, settings, participants, interventions, outcomes, date and duration of the studies. Duplicate studies will be removed. Assessment of methodological quality The methodological quality of each eligible study will be assessed by two independent reviewers prior to inclusion in the review using Joanna Briggs Institute (JBI) critical appraisal instruments appropriate to the study design. Critical appraisal checklists for either experimental studies (Appendix III) or comparable cohort/case control studies (Appendix IV) will be utilised. The critical appraisal process aims to assess the quality of a study and determine the extent to which the study has excluded the possibility of bias in its design, conduct and analysis.48 Disagreements between the reviewers will be resolved through discussion, or with a third reviewer. Data extraction Data of the included studies will be extracted independently by two reviewers using a modified version of the JBI Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) data extraction form, which has been specifically developed for the questions in this systematic review (Appendix V). Discordances between the reviewers will be resolved through discussion. The data extraction form will be pilot-tested on ten randomly-selected included studies by two independent reviewers and refined accordingly prior to commencement of the review.49 The data extracted will include specific details about the study methods, settings, populations and participant demographics, patient inclusion and exclusion criteria, descriptions of interventions, outcome measures, results, and the number and reasons for withdrawals and dropouts. Where feasible, attempts will be made to contact the primary authors of the relevant studies for missing information or clarification of study details. Data synthesis Where possible, quantitative results of comparable studies will be pooled in statistical meta-analysis using the JBI-MAStARI. All results will be subject to double data entry to reduce the risk of errors. For the summary effect measure for dichotomous data, relative risk, odds ratio and 95% confidence interval will be calculated for the included studies. For continuous data, mean difference and 95% confidence interval will be calculated when outcome measurements in all studies are made on the same scale. However, standardised mean difference and 95% confidence interval will be calculated when the studies collect continuous outcome data using different scales. Clinical heterogeneity of the studies will be assessed by considering the settings, populations, interventions and outcome measures. The extent of statistical heterogeneity between studies will be investigated using the chi-square test and I2. I2 depicts the percentage of total variation in estimated effects that is attributable to heterogeneity rather than chance. A fixed effects model will be used if there is no clinical or statistical heterogeneity between studies. A random effects model will be employed if there is no clinical heterogeneity but statistical heterogeneity is present.50 Potential publication bias will be assessed using funnel plot and Egger's test. Subgroup analysis is planned to evaluate the following comparisons: parent gender (mother and father), child age group (children and adolescents), type of insulin used in MDI groups, and duration of study. If statistical pooling of results of the included studies is not appropriate or possible, the findings will be presented in a narrative summary. Conflict of interest No conflict of interest. Acknowledgements We would like to thank Professor Ann SHIU and Professor Janita CHAU for their valuable advice and comments on the development of this protocol.