Review question/objective

The research question is: what are the modifiable and non-modifiable factors that influence the utilization of hospital services by adult sickle cell disease patients?

The objective of this systematic review is to determine what modifiable and non-modifiable factors influence utilization of hospital services by adult sickle cell disease patients.

Background

Sickle cell disease (SCD) is the most common genetic disorder of hemoglobin. The illness is caused by a single point substitution of amino acid valine for glutamic acid at the sixth position of beta-chain hemoglibin.1 As a result of this mutation, red blood cells exposed to low oxygen conditions polymerize, develop a sickle shape and become inflexible.1 This process causes hemolysis (rupture of the red blood cells), hyperviscosity (excessive thickening of the blood) and micro-vascular hypoperfusion (decreased distribution of blood to the tissues). Sickle cell disease affects every major organ system and shortens the life expectancy of affected individuals by approximately 30 years.1 Several SCD genotypes exist. The most prevalent genotype, homozygous HgbSS disease, is associated with the most severe clinical manifestations. Between 70,000 and 100,000 individuals in the United States have HgbSS disease.2 Most of those affected are of African ancestry, with a minority being of Hispanic, Middle Eastern, or Asian Indian descent.1 An additional 3.5 million people in the United States are heterozygote carriers of the gene for Hemoglobin S.1

The hallmark of the disease is an acute painful vaso-occlusive crisis. The mechanism by which polymerization of hemoglobin leads to perception of pain in the central nervous system is not well understood.3 Current research suggests highly complex interactions between red blood cells, inflammatory mediators, and the central nervous system.3 Sickle cell disease pain is often unpredictable, poorly controlled and tends to become chronic.4 A current standard of care includes administration of opioids for pain control along with other supportive measures, often in emergency departments (EDs) or inpatient units.1 Vaso-occlusive crises are responsible for the majority of hospital services utilization by SCD patients.5-8

Despite the burden of both chronic and acute pain imposed by SCD, most affected individuals manage the disease at home, and only a minority of crises results in acute care visits.3,9,10 More than two inpatient admissions per year are unusual, and most have no hospital or emergency department (ED) visits in a given year.11 However, people with SCD are overrepresented among high utilizers of EDs and inpatient beds, even when compared to other serious conditions that affect hemoglobin.6,11,12 The evidence suggests that a small proportion of SCD patients account for most health care utilization.6,11,13 Epstein et al. found that 20% of all SCD patients accounted for 54% of total ED visits and 52% of hospital bed days in this population.13 The high utilization of hospital services by a small percentage of adult SCD patients is a legitimate source of concern because of the following reasons.

First, the high number of health care visits leads to questions about the appropriateness of these visits and contribute to negative provider attitudes toward SCD patients in general.4,11,14-18 In the context of chronically crowded EDs and overbooked inpatient units, frequent utilizers of these services are commonly considered as time-consuming illegitimate users of health care resources.4 It is a common perception among providers that these visits can be potentially prevented, and similar and even more appropriate medical care can be delivered at outpatient facilities. Also, SCD patients who are high hospital users for pain management are often viewed in a negative light as "drug-seeking" individuals.4,19-22 As a result, frequent hospitalizations and ED visits lead to tremendous frustration among medical and nursing staff, create mistrust between SCD patients and providers and contribute to negative provider attitudes.11 The evidence suggests that negative provider attitudes toward SCD patients serve as a general barrier to the provision of adequate pain management and are associated with poor adherence to evidence-based guidelines.15,23,24

Second, frequent utilization of hospital services generate a high health care cost.5,6,25-27 A lifetime cost of care per patient with SCD averages $460,151.25 Notably, the majority of the cost (80.5%) is associated with hospitalizations.25 In a recent study analyzing ED charges for SCD, Lanzkron and colleagues found that the overall charges for ED visits for SCD were three times higher when compared to those for asthma, congestive heart failure and human immunodeficiency virus (HIV). The difference was due to a greater frequency of SCD-related visits rather than higher mean charges per hospitalization.26 Also, several studies reported a skewed distribution of hospital utilization by adult SCD patients, such that only 10% to 20% of all SCD patients account for over 50% of the costs of care for this disease.3,8,14

Finally, frequent hospitalizations are risk factors for early mortality in SCD patients.28,29 Houston-Yu et al. analyzed mortality data in patients with SCD who had more than 50 hospitalization days/year or more than six admissions/year.20 During a 24-month follow-up, 15% of these patients died. The mean age of death was 33.5 years. The subset of patients that was included in this study had severe chronic or recurrent pain and other serious complications of SCD. Patients who died had a higher mean number of hospitalization days, suggesting that frequent and prolonged admissions are associated with early mortality in SCD patients.

Utilization of hospital services by adult SCD patients is correlated with high health care costs and adverse clinical outcomes. In this context, understanding the factors that influence utilization of hospital services by adult SCD patients is a first step in improving their medical care while reducing health care expenditures. Several studies have addressed the effect of non-modifiable (age, gender, ethnicity) and modifiable factors (insurance status, disease-related complications and comorbidities, availability of outpatient care) on the pattern of hospitalizations and acute ED visits in this population.4,13,14,30,31 Several variables have been found to be associated with higher hospital utilization: more severe disease and disease-related complications, worse pain, higher white blood cell counts, lower hemoglobin levels, asthma, being publically insured, being 18 to 30 years old, and an inability to obtain follow-up appointments with hematology.4,11,13,14,30,32 The evidence from a number of studies has shown that a substantial minority of SCD patients are high hospital utilizers. However, high utilizers with SCD are more severely ill, as measured by laboratory variables, have more pain, more distress, and a lower quality of life.3,4

Despite the growing interest in the factors associated with the use of hospital services among SCD patients, to date no comprehensive appraisal of the evidence has been attempted. A systematic review of the available studies will add to the body of knowledge and will inform hospital administrators, policy makers and clinicians caring for this patient population of the factors that influence hospital utilization by individuals affected by SCD in order to develop tailored interventions to address these factors.

Inclusion criteria

Types of participants

The review will consider studies that include adult SCD patients of both sexes who have utilized hospital services. The review will include adult SCD patients who have visited EDs, been admitted to the hospital from the EDs or been admitted directly to the hospital from the community. This review will include adult SCD patients who have utilized hospital services for acute or emergent care. The review will exclude participants who have utilized hospital services for elective treatments in order to determine factors that may be exclusive to the use of hospital services for acute care.

Types of intervention(s)/phenomena of interest

This review will consider studies that explore factors that influence utilization of hospital services (such as the frequency of ED visits and inpatient admissions among adult SCD patients, and the risk of high utilization of hospital services). The factors will include non-modifiable (age, sex, ethnicity, SCD genotype) and modifiable factors, such as socioeconomic (education, income, insurance status, availability of outpatient care), psychological (anxiety, depression, perceived optimism, perceived discrimination) and disease-related factors (Hgb level, presence of complications, presence of comorbidities, severity of pain, opioid dependence).

Types of outcomes

The primary outcome of interest is the utilization of hospital services which may be measured as: the frequency of ED visits and inpatient admissions among adult SCD patients, and the risk of high utilization of hospital services. Studies that do not report on the outcome of interest, as a primary or secondary outcome, will be excluded.

Types of studies

The review will consider epidemiological study designs including before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies.

Search strategy

The search strategy will aim to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms will be then undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Only studies published in the English language will be considered for inclusion for this review. A search range based on the year of publication will not be set to allow greater sensitivity.

The databases to be searched include: MEDLINE, CINAHL, ScienceDirect, PsycINFO, ProQuest, Academic Search Premier and HNS Research Register.

The search for gray literature will include:

ProQuest Dissertation and Theses Database, the directory of gray literature via the New York Academy of Medicine website and Google Scholar/MedNar.

Initial keywords to be used will be:

Sickle cell disease OR

Sickle cell anemia

AND

Adult

AND

Emergency department OR

Emergency room OR

Emergency ward

AND

Hospital OR

Hospital services OR

Hospitalization OR

Inpatient

AND

Utilization OR

Use OR

Admission OR

Visit.

Assessment of methodological quality

Papers selected for retrieval will be assessed by two independent reviewers (IB and YTJ) for methodological validity prior to inclusion in the review using standardized critical appraisal instrument from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). The decision as whether to include or exclude a study can be made based on the meeting five out of nine criteria of JBI-MAStARI critical appraisal instrument. Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer (ME). Reviewers will try to contact authors of primary studies for missing information or to clarify unclear data.

Data extraction

Data will be extracted from papers included in the review using standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the modifiable and non-modifiable factors of interest, populations, study methods and outcomes of significance to the review question and specific objectives.

Data synthesis

Quantitative data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odd ratio (for categorical data), weighted mean differences and correlation coefficients (for continuous data) and their 95% confidence intervals will be calculated for analysis. For studies that report only the results of regression analyses, we will aim to extract the unadjusted effect sizes for the predictors of interest to facilitate greater comparability of the effect size data across studies. Where effect sizes are expressed as odd ratios or weighted mean differences, JBI-MAStARI will be used for statistical pooling. Where effect sizes are expressed as correlation coefficients, Comprehensive Meta-Analysis software will be utilized. Heterogeneity will be assessed statistically using the standard Chi-square and also be explored using subgroup analysis based on the different study designs included in this review. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.

Conflicts of interest

The authors declare that there are no conflicts of interests.

Acknowledgements

This systematic review is undertaken in partial fulfillment of the requirements of the Doctor of Nursing Practice degree (IB).

References