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A Systematic Review of Barriers and Interventions to Improve Appropriate Use of Therapies for Sickle Cell Disease Carlton Haywood Jr, PhD, MA; Mary Catherine Beach, MD, MPH; Sophie Lanzkron, MD; John J. Strouse, MD; Renee Wilson, MSc; Haeseong Park, MD, MPH; Catherine Witkop, MD, MPH; Eric B. Bass MD, MPH; Jodi B. Segal, MD, MPH

Funding/Support: This project was funded under contract 290-02-0018 from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services. Mr Haywood’s effort was supported by a National Research Service Award from the National Heart, Lung, and Blood Institute (5F31HL082037-03). Dr Beach’s effort was supported by K08-HS13903 from AHRQ. Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by AHRQ; the National Heart, Lung, & Blood Institute; or the US Department of Health and Human Services. Clinical experts have expressed concern about underutilization of sickle cell disease (SCD) therapies, including hydroxyurea, prophylactic antibiotics, iron chelation, bone marrow transplantation, pain management during vaso-occlusive crisis, and receipt of routine ambulatory health care. We synthesized studies that identified barriers to and interventions to improve appropriate use of these therapies. Of the 48 studies included in our review, 35 identified therapeutic barriers or facilitators, and 13 evaluated interventions to improve use of therapies. Consistently identified barriers to appropriate pain management were negative provider attitudes and lack of provider knowledge. Four of 9 pain management interventions improved direct measures of pain management quality, while 5 improved indirect measures. One intervention improved receipt of routine ambulatory care. We concluded that interventions to improve pain management in SCD can be effective and should address providers’ negative attitudes and knowledge and that more intervention studies are needed to improve receipt of recommended SCD therapies. Keywords: sickle cell anemia n patient-physician relationship n treatment n health care J Natl Med Assoc. 2009;101:1022-1033 Author Affiliations: Johns Hopkins Berman Institute of Bioethics (Dr Haywood Jr, associate faculty; Dr Beach, core faculty) and Johns Hopkins University School of Medicine (Dr Haywood Jr, assistant professor, Division of Hematology; Dr 1022 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION

Beach, associate professor of medicine and health, behavior, and society; Dr Lanzkron, assistant professor of medicine and director, Adult Sickle Cell Center; Dr Strouse, assistant professor of pediatrics; Dr Bass, professor of medicine; Dr Segal, associate professor of medicine; Ms Wilson, research program coordinator, Evidence-based Practice Center), Baltimore, Maryland; Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, Virginia (Dr Park, MD, housestaff); Dr Witkop, Preventive Medicine and Obstetrics/Gynecology, US Air Force Academy, Colorado. Corresponding Author: Mary Catherine Beach, MD, MPH, Associate Professor of Medicine and Health, Behavior, and Society, Core Faculty, Berman Institute of Bioethics, Johns Hopkins University, 2024 E Monument St, Rm 2-521, Baltimore, MD 21287 ([email protected]).

Introduction

S

ickle cell disease (SCD) is a group of genetic disorders in which hemoglobin polymerizes when deoxygenated, which leads to hemolysis, obstruction of blood vessels by sickled red blood cells, tissue hypoxia, and clinical complications. In 2006 the 59th World Health Assembly adopted a resolution that emphasized the need for greater global attention to SCD.1 It is estimated that more than 200 000 babies are born with the disease each year in Africa alone.2 An additional 60 000 to 100 000 babies are thought to be born with the condition each year outside of Africa.2 Persons with the disease experience a decrease in life expectancy3 as well as significant morbidity.4 Patients with SCD have both chronic and episodic pain and reduced quality of life.5 While painful crisis is the most common reason for emergency department use,6 other life-threatening complications include acute chest syndrome and stroke. Life expectancy for persons with SCD in the United States has steadily improved over the past several decades, largely due to advances such as prophylactic antibiotics for children.7 Because there are effective treatments, meaningful access to these treatments can improve patient outcomes.8 Despite this, studies have suggested that mortality from SCD varies 16 fold between those US states with the lowest and highest rates, and even wider disparities exist at the county level.9 It is concerning if these differences are due to variations in health care quality, provider provision of effective treatments, or access to care.9 In support of VOL. 101, NO. 10, OCTOBER 2009

Barriers to Care in Sickle Cell Disease

these concerns, one study found that there was inadequate provision of antibiotics to publicly insured children in the United States with SCD.9,10 In addition, although hydroxyurea reduced morbidity in clinical trials and was approved by the Food and Drug Administration in 1998 for the treatment of SCD, another recent study has found that there has been no reduction in morbidity from SCD, which suggests that hydroxyurea is not effectively implemented.11 To clarify the role of hydroxyurea in the treatment of patients with SCD and to improve physician adherence to recommendations regarding its use, the National Institutes of Health Office of Medical Applications of Research commissioned a systematic review to summarize the available data on the efficacy, effectiveness, toxicity, and barriers to the use of hydroxyurea in people with SCD. Because we hypothesized that the evidence regarding barriers to use of hydroxyurea specifically would be sparse, we expanded the focus of our review to include barriers and interventions to improve the use of a range of therapies recommended by the National Heart, Lung, and Blood Institute for the treatment of patients with SCD as found in its 2002 guide, The Management of Sickle Cell Disease. Specifically, we examined: (1) hydroxyurea, which is a pharmacologic agent that induces the production of fetal hemoglobin and is recommended for adults, adolescents, and children with sickle cell anemia or SCD-S ßo thalassemia disease who experience frequent pain episodes (≥3 per year), history of acute chest syndrome, other severe vaso-occlusive events, or severe symptomatic anemia; (2) appropriate pain management, which is recommended in the treatment of any patient who experiences a sickle cell vaso-occlusive pain crisis; (3) prophylactic antibiotics, which are recommended to prevent pneumococcal infection among all children with SCD aged 5 years or younger; (4) Iron chelation, which is used to prevent the complications of iron overload among chronically (or frequently) transfused adults and children with SCD; (5) Bone marrow transplantation, which is currently recommended as a potentially curative treatment for selected SCD patients who have experienced significant sickle-related complications such as stroke, recurrent acute chest syndrome, or pain; and (6) routine, scheduled health care visits, which are a part of an appropriate health maintenance strategy for all individuals with SCD. In this paper, we focus on identified barriers to provider and patient use of recommended therapies for patients with SCD, and on the efficacy and effectiveness of interventions to improve the appropriate use of these therapies.

Methods

The methods we used in our systematic review are completely described in a detailed evidence report.12 Below we provide a concise description of those methods.

Search Strategy and Eligibility Criteria We searched MEDLINE and EMBASE, TOXLine and CINAHL through June 30, 2007, to identify literaJOURNAL OF THE NATIONAL MEDICAL ASSOCIATION

ture on the efficacy, effectiveness, and toxicity of hydroxyurea as well as barriers to the appropriate use of all therapies in people with SCD. We also reviewed reference lists and discussed search results with experts. In order to be eligible for our review, articles had to be written in the English language, describe treatment of humans, and contain original data. We did not exclude any article based on publication date, so any article appearing in the literature through the date of our search was potentially eligible. For evidence of barriers to the use of recommended therapies among patients with SCD, we included 2 types of studies: descriptive studies (both qualitative and quantitative) in which patients, patients’ caregivers, and/or health care providers reported their belief that a particular factor was a barrier; and cross-sectional studies in which a particular factor was identified as a barrier or facilitator through its association with use of an indicated therapy. For evidence of the effectiveness of interventions to improve use of therapies, we included randomized controlled trials, cohort studies with a control population, and pre-post studies. Two reviewers independently reviewed titles and abstracts for eligibility.

Data Extraction We used a sequential review process to abstract data from the eligible articles. A primary reviewer abstracted the data, while a second reviewer checked the primary reviewer’s data abstraction for completeness and accuracy by reading the article and reviewing the primary reviewer’s data abstraction form. Reviewer pairs were formed to include personnel with both clinical and methodological expertise. Differences of opinion were resolved by discussion between the reviewers or, if necessary, through consensus adjudication by the entire research team. Reviewers were not masked to the articles’ authors, institutions, or journals.13 For all articles, reviewers extracted information on general study characteristics, participant characteristics, and types of barriers identified. For the qualitative studies, the reviewer categorized complex data; for example, if the study reported “Many patients felt that doctors did not have sufficient knowledge of SCD to make valid treatment decisions,” this was abstracted as “poor provider knowledge.” Participant statements such as “The nurses’ perceptions of their sickle cell patients were overwhelmingly negative” and “Patients report negative experiences of hospital care, characterized by stigmatization (being treated differently from other inpatients and as though they were drug addicts)” were recorded as “poor provider attitudes.” Differences of opinion were resolved through discussion. For each intervention study, we categorized the main intervention components as clinical protocol/pathway, provider sensitivity training, establishment of day hospital (ie, the establishment of a dedicated sickle cell facility with staff knowledgeable about sickle cell providing principle-based individualized care), audit and feedback (ie, VOL. 101, NO. 10, OCTOBER 2009 1023


retrospective audit of sickle cell care as indicated in medical records, followed by the provision of feedback to clinicians about positive or negative data or trends noted in the audit), or establishment of fast-track admission procedures. We also determined the extent to which the measured study outcomes were direct measures of our outcomes of interest (eg, provision of appropriate pain management or receipt of routine, scheduled care). For example, in the pain management interventions, we considered utilization outcomes (eg, duration of hospitalization, costs, or emergency department “treat and release rates”) and descriptive comments from patients (without an explicit analysis of those comments) to be a form of indirect evidence, and most chart abstracted measures of pain management quality (eg, rates of patient-controlled analgesia or use of pain consults) and patient ratings of their experience to be a form of direct evidence. For each intervention study, we also determined by discussion if there was improvement, potential improve-

ment, no improvement, or a detrimental effect. We categorized intervention studies as “improvement” if any measure of direct evidence showed statistically significant improvement and no outcomes (direct or indirect) worsened. We categorized intervention studies as “potential improvement” if (1) at least 1 outcome measure (direct or indirect) improved and 1 outcome measure worsened; (2) the authors stated that there were improvements in direct outcomes but did not show any statistical evidence to support this conclusion; (3) only indirect outcomes measures showed improvement; or (4) the design of the study was such that the risk of bias was not minimized as with through multivariate statistical techniques or standard epidemiological, health services, or qualitative designbased techniques. We categorized intervention studies as “no improvement” if there was no improvement in any outcome and no outcomes worsened. We categorized intervention studies as “detrimental” if any measured outcomes worsened and no outcomes improved.

Table 1. Detailed Description of Studies on Barriers to Receipt of Appropriate Pain Management During Study

Study Design

Study Population/ Location

N

Summary of Reported Barriers

Booker, M.J., 200641

Qualitative: Focus groups

Patients (adults)/UK

10

NA, PPK

Rouse, C.M., 200442

Qualitative: Observations made Nurses, doctors, while performing anthropological patients/California research on two children’s and Pennsylvania hospitals

Not reported

NA

200

NA, PPK, T, IAT

NA

Pack-Mabien, Quantitative: Written 31-item A., 200136 multiple choice survey to obtain information on nurses’ attitudes and perceived barriers to pain management

Nurses/USA

Maxwell, K., 199943

Qualitative: 18 semistructured Patients (adults)/ interviews with 15 individuals and 8London focus groups

57

Waters, J., 199550

Mixed: Questionnaires with qualitative analysis of openended responses.

Nurses (inpatient), patients (adults)/UK

26 (9 patients and NA, PPK, T, IAT 17 nurses)

Tucker, C., 199544

Qualitative: Focus groups

Patients (adults)/ California

Not reported

1024 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION

NA, PPK

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Quality Assessment

Grading of Evidence

We assessed the quality of randomized studies using the scoring system developed by Jadad et al.14 To assess the quality of other study designs (eg, pre-post studies, studies employing surveys, and qualitative studies), we developed a separate form for each study type to identify key elements that should be reported, as advocated by leaders in the field.15-18 The quality assessments were done independently by paired reviewers. The results of the 2 reviewers were averaged.

We graded the quantity, quality, and consistency of the evidence by adapting an evidence grading scheme recommended by the GRADE Working Group19 and modified in the Evidence-Based Practice Center manual.20 We assessed the quality and consistency of the evidence by evaluating the risk of bias in the studies (as indicated by the study-quality scores), the directness with which the data addressed the study question, and the precision and strength of the findings within individual studies. For each therapy of interest, 2 investigators graded the strength of the evidence and then all investigators reached consensus. The body of literature addressing interventions to improve use of therapies closely followed these guidelines. We separately considered evidence about the existence of barriers, adapting the evidence grading scheme substantially. For this body of literature, we first judged the quantity of the evidence on the basis of the number of studies that identified a particular factor as a barrier, facilitator, or

Data Synthesis We created detailed evidence and summary tables with information extracted from eligible studies. We did not attempt to quantitatively pool the data for any of the outcomes using the methods of a formal statistical metaanalysis because of the substantial heterogeneity among the studies in terms of their target populations of interest, study designs, and outcome measures. Vaso-occlusive Crisis Detailed Description of Reported Barriers

Participants likened dealing with health care professionals to a battle, whereby they felt that they had to work hard to convince the doctors that they were in genuine pain and need of help. Some patients felt so disbelieved that they actively avoid consulting when in crisis, for fear of being perceived as opioid dependent. Many patients felt that doctors did not have sufficient knowledge of sickle cell disease to make valid treatment decisions. Residents and nurses dismissed patients’ demands for pain relief as drug-addiction, malingering, or manipulation. Furthermore, several staff members stated that “patients were being denied proper medical care, unfairly accused of drug use or criminal behavior, and generally being treated with less respect.” With few exceptions the nurses’ perceptions of their sickle cell patients were overwhelmingly negative. While nurses believe cancer patients’ self-reporting of pain, they generally believed that their sickle cell patients inflate their level of pain. 63% of nurses believed that drug addiction frequently develops in sickle cell patients and 49% reported that they did not have broad knowledge of sickle cell disease. 59% reported inadequate pain assessment tool was the greatest barrier in the management of pain episodes. Other barriers reported were lack of time for psychological support of patients (58%), nurse reluctance to provide opioids (37%), narrow range of available analgesics (37%), physicians’ reluctance to prescribe opioids (33%), and the belief that most sickle cell patients are drug addicts (32%). In focus groups, patients report negative experiences of hospital care, characterized by mistrust (being suspected by health professionals of exaggerating pain), stigmatization (treated differently from other inpatients--”drug addicts”), lack of control (health professionals exerted control and failed to involve patients in decision-making), neglect (of personal care, monitoring of vital signs, psychosocial support). Factors reported by the subset of 13 nurses who felt they could better relieve sickle cell pain were time, lack of knowledge of narcotic analgesia, fears of overdosing and addiction, and lack of experience with sickle cell patients. The majority of patients considered nurses’ knowledge of sickle cell crisis and sympathy towards them as a patient group to be poor. Evidence of unsatisfactory pain management evidenced by comment from patient: “. . . you can just tell sometimes that they don’t agree with having to give you the injection” In 12 support group sessions of 2-8 patients each, patients all agreed on two major problem areas: (1) obtaining appropriate medical care in the ER (long time to admission, feeling “forgotten”, would delay hospital visits out of “dread”) and (2) difficulty relating to members of the health care team (poor communication, “providers did not believe them”, pain medication “not strong enough”, discharged “too soon”, being told “the pain is all in your head”). Also, patients noted lack of knowledge by providers and feel they are encouraged to ‘act out’ the pain in order to be taken seriously and medicated appropriately. Several group members said that “they would do everything possible” to keep from coming to the hospital because they dreaded it.

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neither: high (>10), moderate (6-10), low (3-5), or insufficient (0-2). The initial quantity grade for the evidence was then lowered by 1 level if the studies failed to protect against the risk of bias through controlling for potential confounders (for the cross-sectional studies) or if the studies did not report on the views of both providers and patients (for the qualitative studies). The resulting score was then revised further based on the consistency of findings across studies. The score was lowered by 1 level if less than 75% and by 2 levels if less than 50% of the studies examining a particular factor found it to be a barrier, facilitator, or have no association with the therapy of interest. The score was raised by 1 level if 100% of the studies examining any particular independent variable found it to be a barrier, facilitator, or have no association with the therapy of interest.

Role of the Funding Source This topic was nominated by the National Institutes of Health Office of Medical Applications of Research

and selected by the Agency for Healthcare Research and Quality (AHRQ) for systematic review by an evidencebased practice center. A representative from AHRQ served as a task order officer and provided technical assistance during the conduct of the full evidence report and provided comments on draft versions of the full evidence report. AHRQ did not directly participate in the literature search; determination of study eligibility criteria; data analysis or interpretation; or preparation, review, or approval of the manuscript for publication.

Results Data Synthesis Our search identified 48 studies that met our eligibility criteria for the questions about barriers to use of therapies for SCD. Of these, 35 were descriptive or cross-sectional studies identifying barriers or facilitators to therapy10,21-53 and 13 studies evaluated interventions to improve use of therapies.54-66

Table 1. Detailed Description of Studies on Barriers to Receipt of Appropriate Pain Management During Study Population/ Location

N

Qualitative: In-depth semistructured individual and group interviews

Nurses (inpatient), patients (adults)/UK

20 (10 nurses and NA, R 10 patients)

Qualitative: Phone interviews

Patients (adults, SCD self-help group leaders)/USA

11

Study

Study Design

Alleyne, J., 199445

Shelley, B., 199446

Summary of Reported Barriers

NA, PPK

Strickland, O. Qualitative: Focus groups L., 200147

Patients (adults), family 21 (10 patients and NA members/USA 11 family members)

Murray, N., 198837

Quantitative: Questionnaires

Patients (adults)/UK

Harris, A, 199848

102

NA

Qualitative: Standardized, Patients (adults)/UK structured open-ended interviews

27

NA

Labbe, E., 200551

Quantitative: Questionnaires

Doctors/Alabama

109

NA, IAT

Butler, D. J., 199349

Qualitative: Authors’ reports of themes that arose a in SCD support group that included medical residents

Patients (adults), Doctors/USA

24

NA

Abbreviations: IAT, inadequate assessment tools; NA, negative attitudes; PPK, poor provider knowledge; R, patient race; SCD, sickle cell




Barriers to Use of Recommended Therapies Among Patients With Sickle Cell Disease The only types of SCD therapies for which barriers and facilitators have been sufficiently studied are provider provision of pain management during vaso-occlusive crisis (VOC) and patient adherence to prophylactic antibiotics. A comprehensive listing of all factors (barriers and facilitators) reported in the literature about these 2 therapies is included in Appendix A. In terms of appropriate pain management (Table 1), 8 studies identified patient-reported barriers, 2 provider-reported barriers, and 3 both. The 2 most common barriers identified by patients and providers were negative provider attitudes (13 studies) and lack of provider knowledge (5 studies). These negative provider attitudes included providers not believing that patients were genuinely in pain,37,41-45,48,49,51 providers being suspicious of drug abuse or addiction,36,41-43,46,47,50,51 provider stigmatization of patients with SCD,43,45 provider insensitivity

or lack of sympathy50 and unspecified negative perceptions or attitudes.42,46,48 We concluded that the evidence was high and moderate that negative provider attitudes and poor provider knowledge, respectively, are barriers to use of appropriate pain medications during VOC (Table 2). The only consistent association with the use of prophylactic antibiotics was that patient sex was not associated with the use of antibiotics in any of the 3 studies in which it was examined. We concluded there was moderate evidence that patient sex was not related to use of prophylactic antibiotics (Table 2). Patient age, frequent hospital visits, and patient/caregiver knowledge were all studied in 2 or more studies, but the association of these factors to use of antibiotics was not consistent and all were given an evidence grade of low (Table 2). No factors were sufficiently and consistently studied or identified as barriers or facilitators to any of the other recommended therapies for SCD that we studied.

Vaso-occlusive Crisis (contd) Detailed Description of Reported Barriers All patients expressed dissatisfaction with pain management. All or most patients reported they had to demand painkillers, that nurses doubt the genuine nature of the pain, lack of involvement in pain control, and that nurses were not sympathetic to pain, telling them, “You’ll have to wait.” One patient said, “I’ve got the feeling that some of them purposely prolong it.” One nurse suggested that there might be a link between young black people and drug-taking which caused nursing staff to be suspicious of the patients. Some nurses reported that patients could not be “trusted to be responsible” with patient-controlled analgesia. Perceived problems in health care include inadequate staff training and high turnover, health providers’ fears of drug addiction, negative attitudes of physicians to patients, unfamiliarity of staff with SCD, routine accusations of drug-seeking, insensitivity to patients’ pain, and negative reactions to patient attempts to be involved in the course of their own care. Almost half of group leaders reported negative reactions on the part of some physicians to patients, including ignoring patients and making blunt remarks about the doctor’s knowledge vs. the ‘lay’ patient. Group leaders reported that these sorts of incidents keep some SCD patients from the ED, even when they are in pain. In focus group sessions, adults with SCD stated the belief that nurses would not give them pain medications when needed because the nurses believed that persons with SCD are addicts. Adults with SCD also stated the belief that some medical providers are intimidated when patients demonstrate knowledge about their disease or their pain control. Of the 88 patients who went to the hospital for care, 57/88 patients thought staff did not appreciate amount of pain they were having. 44% made a complaint about staff’s negative attitude to people with SCD, 26% felt staff generally lacked knowledge and understanding of SCD and pain crises, 22% said staff did not believe or appreciate that they were in pain “they treat us like liars” and 19% said nurses were slow to give analgesia and attended to other “less urgent” tasks (“pillows”). Physicians hold a number of beliefs and attitudes which may affect the quality of pain management. Most (86%) physicians disagreed that the most reliable indicator of pain is the patient’s self-report. Physiological and behavioral measures were also commonly cited tools used to assess pain. The top 5 barriers to optimal pain management as reported by these physicians were lack of psychological support, fear that the patient is a drug abuser, reluctance to prescribe opioids, disbelief in patient’s report of pain severity, and inadequate pain assessment tools. During their lives, each member of the group had experienced many negative interactions with health care providers, including routinely being treated with suspicion and distrust. Patients expressed extreme frustration in attempting to convince health professionals of their distress. disease; T, lack of time.


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Interventions to Improve Use of Recommended Therapies Among Patients with Sickle Cell Disease Nine intervention studies targeted providers to improve provision of pain medications to patients with VOC (Table 3). Of these 9 studies, all used a pre-post design and 3 studies also had a concurrent control group. Three of the 9 studies included only children with SCD; 1, only adults; and the remainder did not specify. Seven of the 9 studies were conducted in the United States and 2 in the United Kingdom. The natures of the provider-targeted interventions were as follows: 6 of the interventions utilized a new clinical protocol to affect provider practice patterns, 1 involved conducting a retrospective audit of the quality of prior sickle cell care and providing feedback to providers on the results, and 2 involved changing the structure and organization of sickle cell care through use of a day hospital or a fast-track admission process. Only 1 study also addressed provider attitudes through sensitivity training. Five of the 9 studies measured a direct outcome (eg, pain management quality or patient ratings) while the remainder measured indirect outcomes (eg, utilization or costs). Four studies demonstrated improvement and 5 showed potential improvement. We concluded that there was moderate evidence that providertargeted interventions can improve appropriate provision of pain medications to SCD patients with VOC. Four studies evaluated the impact of patient interventions (Table 4): 3 of these attempted to improve selfmanagement, such as adherence to prophylactic antibiotics (n = 1), desferoxamine (n = 1), and health-promoting activities (n = 1), and 1 study evaluated the effect of telephone outreach on utilization of routine ambulatory

appointments. All 4 patient interventions were focused on children with SCD. None of the 3 studies to improve self-management had any effect, and we concluded that there was low evidence that patient adherence interventions do not improve use of therapies. The 1 study that used structured telephone outreach showed a significant and strongly positive effect on receipt of routine ambulatory care, and we concluded that there was moderate evidence that patient-targeted interventions can improve receipt of routine ambulatory care for SCD.

Recommendations and Conclusions Our review found that patients and providers consistently report that negative provider attitudes and poor provider knowledge of SCD are barriers to the receipt of appropriate pain management during VOC. These findings are very concerning, and further investigation to overcome these barriers is essential. Fortunately, our review also suggests that interventions to improve the quality of pain management provided to patients with VOC can be effective. Finally, our review uncovered 1 high-quality, promising study which was successful in increasing the use of routine ambulatory care by children with SCD. In our reviewed studies, poor provider attitudes toward and knowledge of SCD were both acknowledged by providers and experienced by patients. This suggests that future efforts to measure and improve upon these attitudes and knowledge may involve a combination of provider selfreport and patient ratings of their experiences. To our knowledge, there are no validated instruments that allow providers to self-assess these attitudes and knowledge, and therefore validated instruments should be developed. While

Table 2. Barriers and Facilitators to Use of Appropriate Therapy Among Patients with Sickle Cell Disease Examined in More Than 2 Studies Found to Be… Barrier Facilitator (n) (n) 13 0

Neither Evidence Grade (n) 0 High that negative provider attitudes are a barrier to provider provision of pain medication

Type of Therapy Pain management during vasoocclusive crisis

Factor Negative provider attitudes Poor provider knowledge

5

0

0

Moderate that poor provider knowledge is a barrier to provider provision of pain medication

Prophylactic antibiotics

Patient/caregiver knowledge

0

2

1

Low that patient/caregiver knowledge is related to patient use of antibiotics

Frequent hospital visits

0

1

2

Low that hospital visits are related to patient use of antibiotics

Patient sex

0

0

3

Moderate that patient sex is not related to patient use of antibiotics

Younger patient age

0

1

3

Low that younger patient age is related to patient use of antibiotics




generic instruments to evaluate patient experiences exist and should be implemented, it may also be necessary to develop instruments specifically for patients with pain secondary to VOC. Using generic or sickle cell–specific instruments, then, we recommend the systematic and routine evaluation of sickle cell patient experiences with care as part of an ongoing and coordinated effort to improve health care quality for this population of patients. We believe that routine and systematic assessments like this are important

because provider training in cultural competence and patient-centered communication techniques have been found to be effective in improving attitudes and communication with patients.67,68 Therefore, routine and systematic assessments of sickle cell patient experiences with care could aid in the identification of health-care-setting–specific communication and training deficits that could be incorporated into the training of the clinicians caring for this patient population. Although poor provider attitudes

Table 3. Studies on Provider Interventions to Improve Provision of Appropriate Pain Management During Vaso-occlusive Crisis Main Improvement Study Study Study Intervention in Pain Study N Subjectsa Components Primary Outcomes Design Location Managementb Mitchell, Pre-post Philadelphia, 27 NS Clinical Utilization (“treat and Potential M.B., 200254 PA protocol release” rates, length of stay) Pre-post, Baltimore, 369 Children Clinical Pain management Co, J.P., Yes CCT MD protocol quality (use of IV fluids, 200355 incentive spirometry, and pain service consultation) Pre-post Greensboro, 204 NS Clinical Patient ratings, utilization Potential Jamison, NC protocol with (length of stay), Costs C., 200256 staff sensitivity training CCT, Cleveland, 67 NS Clinical Pain management Cooper, Yes OH protocol quality (use of G.S., 200057 Pre-post nonguideline narcotic meperedine), utilization (length of stay), costs CCT, Bronx, NY 144 NS Establishment Pain management Benjamin, Potential of day quality (decrease use L.J., 200058 Pre-post hospital of meperidine, increase use of hydromorphone), Utilization (‘treat and release’ rates, length of stay) Pre-post UK 18 NS Audit and Pain management Potential Day, J., feedback quality (decrease use of 199759 intramuscular pethidine, increase use of patientcontrolled analgesia and pain consults) Pre-post Philadelphia, 250 Adults Clinical Utilization (#admissions) Potential Brookoff, PA protocol D., 199260 Fertleman, Pre-post London, UK 72 Children Fast track Pain management Yes C.R., 199761 admission quality (time to analgesia Procedures delivery), patient ratings USA 235 Children Clinical Pain management Yes Treadwell, Pre-post protocol quality (staff use M.J., 200262 of validated pain assessment tools), patient ratings Abbreviations: IV, intravenous; NS, not specified. a

S tudy subjects refers to the group of patients with sickle cell disease who were the intended beneficiaries of the intervention. All of these interventions were targeted at health care providers who were therefore also study subjects.

b

T o be categorized as “improvement,” a study had to demonstrate an effect on a direct outcome (pain management quality and/or patient ratings). Studies with a beneficial effect on indirect outcomes or where we thought there was a considerable risk of bias were rated as “potential improvement.”


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and knowledge related to the use of pain medications during painful VOC may not seem immediately related to use of hydroxyurea or other life-prolonging therapies, patients who have bad experiences in seeking health care while in pain may lose trust in the health care system and therefore be less willing to consider other recommended treatments. Our review also suggests that interventions to improve provision of appropriate pain medications to patients with VOC can be effective. Many types of interventions have been found to be effective (eg, clinical protocols, audit of and feedback to providers, and circumvention of the emergency department through direct admission procedures or a day hospital). Only 1 of these studies addressed negative provider attitudes directly through provider sensitivity training. While provider attitudes may be important targets, shorter-term solutions to improve pain management may be aimed at minimizing the impact of these attitudes. To this end, we rec-

ommend the increased use of sickle cell–specific clinical protocols and pathways, as well as the increased development and proliferation of sickle cell day hospital-type structures of care. These interventions should be structured to meet the specific needs of the health care settings and patient populations in which they would be placed. However, the overall goals of these interventions should be broadly the same—to provide rapid and highquality sickle cell care by knowledgeable clinical staff. To monitor the success of such interventions, we also recommend that direct measures of sickle cell pain management quality be developed and validated. Finally, our review found 1 promising telephone outreach intervention that was effective in improving the attendance of children at routine appointments in a comprehensive sickle cell program.66 Receipt of comprehensive care is essential for patients with SCD to receive other appropriate treatments. As an example, this study

Table 4. Studies on Patient Interventions to Improve Adherence to Medications and Receipt of Routine Care Improvement Study Study Study Main Intervention Type of Relevant in Use of Study Design Location N Subjectsa Components Therapy Outcomes Therapy Desferal day Treadwell, Pre-post California 11 Children Desferal Self-manageNo with SCD camp provided M.J., 200163 ment (selfpeer support and reported education for 4 adherence) days each summer. RCT Toronto, 23 Children Structured Berkovitch, Antibiotic Self-manageNo Canada with SCD presentation of M., 199864 prophylaxis ment (selfinformation to reported parents regarding adherence) antibiotic prophylaxis with weekly telephone calls from social worker RCT US, 37 Children Access to an Health- Self-manageKetchen, Nob Canada with SCD internet-based promoting ment (selfB., 200665 program with activities reported weekly assignments adherence) of educational and social activities and those that encouraged childparent participation. Staff member called caregiver weekly. Patik, M., Pre-post Pittsburgh, 202 Children Telephone-delivered Receipt of Clinic Yes 200666 PA with SCD structured support scheduled attendance and education care (% patients by a nonmedical reporting personnel having not administered every attended 3 months clinic for 2 years) Abbreviation: SCD, sickle cell disease. a

S tudy subjects refers to the group of patients with sickle cell disease who were the intended beneficiaries of the intervention. In most cases of interventions targeted at children, the parents or other caregivers were also involved.

b

This intervention had beneficial effects on other outcomes but not on patient adherence to health promotion activities.




also demonstrated an increase in the proportion of patients who received recommended annual screening with transcranial Doppler ultrasound.66 Although not measured in this study, improvements in appropriate use of many other therapies and recommended preventive services might be expected with use of such outreach programs. The limitations of available studies provide a road

map for future research. First, in terms of studies describing barriers, only 2 studies directly addressed barriers to hydroxyurea treatment; more studies are needed on this important and underutilized medication. Second, studies examined a diverse group of potential barriers and did not consistently report on any 1 type of barrier, which made comparisons across studies difficult. Third, only

Appendix A. Barriers and Facilitators to Use of Appropriate Therapy Identified in Studies of Patients With Sickle Cell Disease Type of Therapy (No. Studies Examining) Prophylactic antibiotics (7 studies)

Barriers and Facilitators (# Studies Demonstrating) Patient Provider/Health Care System Barriers

Facilitators

Neither

Pain management during vasoocclusive crisis (15 studies)

More children at home (1) Forgetting medicine (2) Dislike taste (1) Concern about side effects (1) Caregiver being busy (1) Child falling asleep (1) Running out of medicine (1) Private insurance (2) Patient/caregiver knowledge (2) Hospital visits (1) More adults in home (1) Having a car (1) No prior history of transfusions (1) Younger patient age (1) Intent to adhere (1) Perceived benefits (1) Family employment (1) Patient/caregiver knowledge (1) Non-preventive outpatient visits (1) Patient sex (3) Patient age (3) Urban residence (1) Parental education (1) SCD type (1) Number of children (1) Years on therapy (1) History of stroke (1) Hospital visits (2) Number of missed appointments (1)

Academic medical setting (1)

Provider knowledge (1) Provider specialty (pediatrics) (1)

Provider years in practice (1) Provider gender (1) Cost sharing (1)

Barriers

Hospital visits (1) Patient race (1)

Negative attitudes (13) Lack of knowledge (5) Lack of time (2) Inadequate pain assessment tools (2)

Facilitators

Dispositional optimism (1)

Neither

Patient age (1) Patient sex (1) Patient education (1)

Female sex (1) Fewer years in practice (1) Attitudes towards pain (1) Professional experience/training (1)


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half of the cross-sectional studies used multivariate or design-based techniques to control for the effects of potential confounders, which made inferences uncertain. Fourth, the majority of the potential barriers examined in cross-sectional studies (eg, those chosen by the researcher) were patient-related factors. Since the majority of barriers identified in qualitative studies (eg, those brought up spontaneously by patients and providers) were provider-related factors, there ought to be a greater attention to provider and health care system barriers to treatments for SCD. Finally, only children were included in 13 of the 18 cross-sectional studies examining barriers to treatment. More research is needed on the barriers to treatment in adults, especially given the rapid growth in the number of adults with SCD in the last 30 years. No studies examined interventions to increase use of hydroxyurea. Among the intervention studies, there were only 2 randomized controlled trials, several studies were very small and were probably underpowered, and many studies did not report the statistical significance of the apparent improvement. In addition, many of the studies on interventions to improve pain management quality used indirect outcomes of improvements, such as length of stay or total hospital costs. There are some limitations of our review process that should be considered. Due to limited resources, we restricted our literature review to studies published in English. Therefore, our conclusions concerning barriers to care and interventions to overcome these barriers may not reflect the experiences of persons with SCD that have been described in foreign-language journals. We created our own quality assessment tools to assess the quality of nonrandomized study designs. These tools have not been formally validated. Therefore, it is possible that our measures are not truly indicative of article quality. Despite the lack of formal validation, our tools were based on expert recommendations found in the literature and included items that have been used previously and are widely thought to be indicators of high-quality research reporting. Finally, we did not exclude studies from our review on the basis of low-quality scores. One could argue that articles of low quality should not contribute to a formal review of the evidence of barriers to sickle cell care. However, given the relatively sparse nature of the literature on barriers to sickle cell care, we thought it necessary to be as inclusive as possible in our review. In conclusion, interventions to improve pain management quality for patients with painful VOC should be implemented and should address provider attitudes or minimize the impact of harmful attitudes. Individual health care providers need to be more aware of how their attitudes may interfere with use of appropriate therapies for patients with SCD. Specific indicators of health care quality (eg, provision of appropriate treatments and patient experiences surveys) for patients with SCD ought to be routinely measured, and barriers to high-quality health care identi1032 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION

fied. One promising telephone outreach intervention to improve receipt of ambulatory care should be replicated, and more studies are needed to identify effective interventions to improve receipt of all other SCD therapies. Such work will require increased support from health plans, government funding agencies, and foundations interested in improving the care of patients with SCD.

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