1022 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009

o r i g i n a l c o m m u n i c a t i o n

IntroductIon

Sickle cell disease (SCD) is a group of genetic dis-orders in which hemoglobin polymerizes when deoxygenated, which leads to hemolysis, obstruc-

tion of blood vessels by sickled red blood cells, tissue hypoxia, and clinical complications. In 2006 the 59th World Health Assembly adopted a resolution that empha-sized 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 com-plications 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, meaning-ful access to these treatments can improve patient out-comes.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

Beach, associate professor of medicine and health, behavior, and society; Dr Lanzkron, assistant professor of medicine and director, Adult Sickle Cell Cen-ter; Dr Strouse, assistant professor of pediatrics; Dr Bass, professor of medicine; Dr Segal, associate professor of medicine; Ms Wilson, research program coor-dinator, 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 Profes-sor 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 (mcbeach@jhmi.edu).

A Systematic Review of Barriers and Interventions to Improve Appropriate Use of Therapies for Sickle Cell DiseaseCarlton 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

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

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 Ser-vices. 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 sup-ported 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 underutiliza-tion of sickle cell disease (SCD) therapies, including hydroxy-urea, 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 interven-tions 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 mea-sures. One intervention improved receipt of routine ambula-tory 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

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009 1023

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 hydroxy-urea reduced morbidity in clinical trials and was approved by the Food and Drug Administration in 1998 for the treat-ment 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 com-missioned 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 treat-ment of patients with SCD as found in its 2002 guide, The Management of Sickle Cell Disease. Specifically, we exam-ined: (1) hydroxyurea, which is a pharmacologic agent that induces the production of fetal hemoglobin and is recom-mended for adults, adolescents, and children with sickle cell anemia or SCD-S ßo thalassemia disease who experi-ence frequent pain episodes (≥3 per year), history of acute chest syndrome, other severe vaso-occlusive events, or severe symptomatic anemia; (2) appropriate pain manage-ment, 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 pre-vent 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 chron-ically (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 main-tenance 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.

MethodSThe 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 criteriaWe searched MEDLINE and EMBASE, TOXLine

and CINAHL through June 30, 2007, to identify litera-

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 ref-erence 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 associa-tion with use of an indicated therapy. For evidence of the effectiveness of interventions to improve use of thera-pies, 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 extractionWe 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 review-er’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 discus-sion between the reviewers or, if necessary, through con-sensus 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 deci-sions,” 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 prin-ciple-based individualized care), audit and feedback (ie,

1024 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009

BARRIERS TO CARE IN SICKLE CELL DISEASE

retrospective audit of sickle cell care as indicated in medi-cal records, followed by the provision of feedback to cli-nicians about positive or negative data or trends noted in the audit), or establishment of fast-track admission proce-dures. We also determined the extent to which the mea-sured study outcomes were direct measures of our out-comes of interest (eg, provision of appropriate pain management or receipt of routine, scheduled care). For example, in the pain management interventions, we con-sidered utilization outcomes (eg, duration of hospitaliza-tion, 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 cate-gorized intervention studies as “improvement” if any measure of direct evidence showed statistically significant improvement and no outcomes (direct or indirect) wors-ened. 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 sup-port 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 design-based 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 out-comes worsened and no outcomes improved.

table 1. Detailed Description of Studies on Barriers to Receipt of Appropriate Pain Management During Vaso-occlusive Crisis

Study Study designStudy Population/ Location n

Summary of reported Barriers detailed description of reported Barriers

Booker, M.J., 200641

Qualitative: Focus groups Patients (adults)/UK 10 NA, PPK 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.

Rouse, C.M., 200442

Qualitative: Observations made while performing anthropological research on two children’s hospitals

Nurses, doctors, patients/California and Pennsylvania

Not reported NA 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.

Pack-Mabien, A., 200136

Quantitative: Written 31-item multiple choice survey to obtain information on nurses’ attitudes and perceived barriers to pain management

Nurses/USA 200 NA, PPK, T, IAT 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%).

Maxwell, K., 199943

Qualitative: 18 semistructured interviews with 15 individuals and 8 focus groups

Patients (adults)/London

57 NA 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).

Waters, J., 199550

Mixed: Questionnaires with qualitative analysis of open-ended responses.

Nurses (inpatient), patients (adults)/UK

26 (9 patients and 17 nurses)

NA, PPK, T, IAT 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”

Tucker, C., 199544

Qualitative: Focus groups Patients (adults)/California

Not reported NA, PPK 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.

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009 1025

BARRIERS TO CARE IN SICKLE CELL DISEASE

Quality AssessmentWe 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 iden-tify 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.

data SynthesisWe 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 meta-analysis because of the substantial heterogeneity among the studies in terms of their target populations of inter-est, study designs, and outcome measures.

Grading of evidenceWe graded the quantity, quality, and consistency of the

evidence by adapting an evidence grading scheme recom-mended 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 evi-dence 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 substan-tially. For this body of literature, we first judged the quan-tity of the evidence on the basis of the number of studies that identified a particular factor as a barrier, facilitator, or

table 1. Detailed Description of Studies on Barriers to Receipt of Appropriate Pain Management During Vaso-occlusive Crisis

Study Study designStudy Population/ Location n

Summary of reported Barriers detailed description of reported Barriers

Booker, M.J., 200641

Qualitative: Focus groups Patients (adults)/UK 10 NA, PPK 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.

Rouse, C.M., 200442

Qualitative: Observations made while performing anthropological research on two children’s hospitals

Nurses, doctors, patients/California and Pennsylvania

Not reported NA 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.

Pack-Mabien, A., 200136

Quantitative: Written 31-item multiple choice survey to obtain information on nurses’ attitudes and perceived barriers to pain management

Nurses/USA 200 NA, PPK, T, IAT 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%).

Maxwell, K., 199943

Qualitative: 18 semistructured interviews with 15 individuals and 8 focus groups

Patients (adults)/London

57 NA 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).

Waters, J., 199550

Mixed: Questionnaires with qualitative analysis of open-ended responses.

Nurses (inpatient), patients (adults)/UK

26 (9 patients and 17 nurses)

NA, PPK, T, IAT 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”

Tucker, C., 199544

Qualitative: Focus groups Patients (adults)/California

Not reported NA, PPK 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.

1026 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009

BARRIERS TO CARE IN SICKLE CELL DISEASE

neither: high (>10), moderate (6-10), low (3-5), or insuffi-cient (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 confound-ers (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 associa-tion with the therapy of interest. The score was raised by 1 level if 100% of the studies examining any particular inde-pendent variable found it to be a barrier, facilitator, or have no association with the therapy of interest.

role of the Funding SourceThis 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 evidence-based 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 evi-dence report. AHRQ did not directly participate in the literature search; determination of study eligibility crite-ria; data analysis or interpretation; or preparation, review, or approval of the manuscript for publication.

reSuLtS

data SynthesisOur 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 stud-ies evaluated interventions to improve use of therapies.54-66

table 1. Detailed Description of Studies on Barriers to Receipt of Appropriate Pain Management During Vaso-occlusive Crisis (contd)

Study Study designStudy Population/ Location n

Summary of reported Barriers detailed description of reported Barriers

Alleyne, J., 199445

Qualitative: In-depth semistructured individual and group interviews

Nurses (inpatient), patients (adults)/UK

20 (10 nurses and 10 patients)

NA, R 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.

Shelley, B., 199446

Qualitative: Phone interviews Patients (adults, SCD self-help group leaders)/USA

11 NA, PPK 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.

Strickland, O. L., 200147

Qualitative: Focus groups Patients (adults), family members/USA

21 (10 patients and 11 family members)

NA 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.

Murray, N., 198837

Quantitative: Questionnaires Patients (adults)/UK 102 NA 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.

Harris, A, 199848

Qualitative: Standardized, structured open-ended interviews

Patients (adults)/UK 27 NA 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”).

Labbe, E., 200551

Quantitative: Questionnaires Doctors/Alabama 109 NA, IAT 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.

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 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.

Abbreviations: IAT, inadequate assessment tools; NA, negative attitudes; PPK, poor provider knowledge; R, patient race; SCD, sickle cell disease; T, lack of time.

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009 1027

BARRIERS TO CARE IN SICKLE CELL DISEASE

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 pro-vision of pain management during vaso-occlusive crisis (VOC) and patient adherence to prophylactic antibiotics. A comprehensive listing of all factors (barriers and facili-tators) reported in the literature about these 2 therapies is included in Appendix A. In terms of appropriate pain man-agement (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 suspi-cious of drug abuse or addiction,36,41-43,46,47,50,51 provider stig-matization 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 pro-phylactic antibiotics was that patient sex was not associ-ated with the use of antibiotics in any of the 3 studies in which it was examined. We concluded there was moder-ate evidence that patient sex was not related to use of pro-phylactic antibiotics (Table 2). Patient age, frequent hos-pital 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 fac-tors were sufficiently and consistently studied or identi-fied as barriers or facilitators to any of the other recom-mended therapies for SCD that we studied.

table 1. Detailed Description of Studies on Barriers to Receipt of Appropriate Pain Management During Vaso-occlusive Crisis (contd)

Study Study designStudy Population/ Location n

Summary of reported Barriers detailed description of reported Barriers

Alleyne, J., 199445

Qualitative: In-depth semistructured individual and group interviews

Nurses (inpatient), patients (adults)/UK

20 (10 nurses and 10 patients)

NA, R 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.

Shelley, B., 199446

Qualitative: Phone interviews Patients (adults, SCD self-help group leaders)/USA

11 NA, PPK 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.

Strickland, O. L., 200147

Qualitative: Focus groups Patients (adults), family members/USA

21 (10 patients and 11 family members)

NA 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.

Murray, N., 198837

Quantitative: Questionnaires Patients (adults)/UK 102 NA 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.

Harris, A, 199848

Qualitative: Standardized, structured open-ended interviews

Patients (adults)/UK 27 NA 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”).

Labbe, E., 200551

Quantitative: Questionnaires Doctors/Alabama 109 NA, IAT 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.

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 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.

Abbreviations: IAT, inadequate assessment tools; NA, negative attitudes; PPK, poor provider knowledge; R, patient race; SCD, sickle cell disease; T, lack of time.

1028 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009

BARRIERS TO CARE IN SICKLE CELL DISEASE

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 stud-ies also had a concurrent control group. Three of the 9 stud-ies included only children with SCD; 1, only adults; and the remainder did not specify. Seven of the 9 studies were con-ducted 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 proto-col to affect provider practice patterns, 1 involved conduct-ing 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 admis-sion 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 provider-targeted interventions can improve appropriate provision of pain medications to SCD patients with VOC.

Four studies evaluated the impact of patient interven-tions (Table 4): 3 of these attempted to improve self-management, such as adherence to prophylactic antibi-otics (n = 1), desferoxamine (n = 1), and health-promoting activities (n = 1), and 1 study evaluated the effect of tele-phone 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 interven-tions 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 ambu-latory care, and we concluded that there was moderate evidence that patient-targeted interventions can improve receipt of routine ambulatory care for SCD.

recommendations and conclusionsOur review found that patients and providers consis-

tently report that negative provider attitudes and poor pro-vider 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 sug-gests that interventions to improve the quality of pain man-agement 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 pro-viders and experienced by patients. This suggests that future efforts to measure and improve upon these attitudes and knowledge may involve a combination of provider self-report 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…

type of therapy FactorBarrier

(n)Facilitator

(n)neither

(n) evidence GradePain management during vaso-occlusive crisis

Negative provider attitudes

13 0 0 High that negative provider attitudes are a barrier to provider provision of

pain medication

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

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009 1029

BARRIERS TO CARE IN SICKLE CELL DISEASE

generic instruments to evaluate patient experiences exist and should be implemented, it may also be necessary to develop instruments specifically for patients with pain sec-ondary to VOC. Using generic or sickle cell–specific instru-ments, 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 communi-cation 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–spe-cific 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

StudyStudy

designStudy

Location nStudy

Subjectsa

Main Intervention components Primary outcomes

Improvement in Pain

Managementb

Mitchell, M.B., 200254

Pre-post Philadelphia, PA

27 NS Clinical protocol

Utilization (“treat and release” rates, length of

stay)

Potential

Co, J.P., 200355

Pre-post, CCT

Baltimore, MD

369 Children Clinical protocol

Pain management quality (use of IV fluids, incentive spirometry,

and pain service consultation)

Yes

Jamison, C., 200256

Pre-post Greensboro, NC

204 NS Clinical protocol with staff sensitivity

training

Patient ratings, utilization (length of stay), Costs

Potential

Cooper, G.S., 200057

CCT, Pre-post

Cleveland, OH

67 NS Clinical protocol

Pain management quality (use of

nonguideline narcotic meperedine), utilization (length of stay), costs

Yes

Benjamin, L.J., 200058

CCT, Pre-post

Bronx, NY 144 NS Establishment of day

hospital

Pain management quality (decrease use

of meperidine, increase use of hydromorphone),

Utilization (‘treat and release’ rates, length of

stay)

Potential

Day, J., 199759

Pre-post UK 18 NS Audit and feedback

Pain management quality (decrease use of intramuscular pethidine, increase use of patient-

controlled analgesia and pain consults)

Potential

Brookoff, D., 199260

Pre-post Philadelphia, PA

250 Adults Clinical protocol

Utilization (#admissions) Potential

Fertleman, C.R., 199761

Pre-post London, UK 72 Children Fast track admission

Procedures

Pain management quality (time to analgesia delivery), patient ratings

Yes

Treadwell, M.J., 200262

Pre-post USA 235 Children Clinical protocol

Pain management quality (staff use of validated pain

assessment tools), patient ratings

Yes

Abbreviations: IV, intravenous; NS, not specified.a Study 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 To 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.”

1030 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009

BARRIERS TO CARE IN SICKLE CELL DISEASE

and knowledge related to the use of pain medications dur-ing 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 inter-ventions have been found to be effective (eg, clinical protocols, audit of and feedback to providers, and cir-cumvention 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 solu-tions to improve pain management may be aimed at min-imizing 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 devel-opment and proliferation of sickle cell day hospital-type structures of care. These interventions should be struc-tured to meet the specific needs of the health care set-tings 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 high-quality sickle cell care by knowledgeable clinical staff. To monitor the success of such interventions, we also recommend that direct measures of sickle cell pain man-agement quality be developed and validated.

Finally, our review found 1 promising telephone out-reach intervention that was effective in improving the attendance of children at routine appointments in a com-prehensive sickle cell program.66 Receipt of comprehen-sive 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

StudyStudy

designStudy

Location nStudy

Subjectsa

Main Intervention components

type of therapy

relevant outcomes

Improvement in use of therapy

Treadwell, M.J., 200163

Pre-post California 11 Children with SCD

Desferal day camp provided

peer support and education for 4

days each summer.

Desferal Self-manage-ment (self-reported

adherence)

No

Berkovitch, M., 199864

RCT Toronto, Canada

23 Children with SCD

Structured presentation of information to

parents regarding antibiotic

prophylaxis with weekly telephone calls from social

worker

Antibiotic prophylaxis

Self-manage-ment (self-reported

adherence)

No

Ketchen, B., 200665

RCT US, Canada

37 Children with SCD

Access to an internet-based program with

weekly assignments of educational and

social activities and those that

encouraged child-parent participation. Staff member called

caregiver weekly.

Health-promoting activities

Self-manage-ment (self-reported

adherence)

Nob

Patik, M., 200666

Pre-post Pittsburgh, PA

202 Children with SCD

Telephone-delivered structured support

and education by a nonmedical

personnel administered every

3 months

Receipt of scheduled

care

Clinic attendance (% patients reporting

having not attended clinic for 2

years)

Yes

Abbreviation: SCD, sickle cell disease.a Study 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.

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009 1031

BARRIERS TO CARE IN SICKLE CELL DISEASE

also demonstrated an increase in the proportion of patients who received recommended annual screening with trans-cranial 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 describ-ing 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) Barriers and Facilitators (# Studies demonstrating)

Patient Provider/health care SystemProphylactic antibiotics (7 studies)

Barriers More children at home (1) Academic medical setting (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)Facilitators Private insurance (2) Provider knowledge (1)

Patient/caregiver knowledge (2) Provider specialty (pediatrics) (1)

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)

Neither Patient/caregiver knowledge (1) Provider years in practice (1) Non-preventive outpatient visits (1) Provider gender (1) Patient sex (3) Cost sharing (1) 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)

Pain management during vaso-occlusive crisis(15 studies)

Barriers Hospital visits (1) Negative attitudes (13) Patient race (1) Lack of knowledge (5) Lack of time (2) Inadequate pain assessment

tools (2)

Facilitators Dispositional optimism (1) Female sex (1) Fewer years in practice (1)

Neither Patient age (1) Attitudes towards pain (1) Patient sex (1)

Patient education (1)Professional experience/training (1)

1032 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009

BARRIERS TO CARE IN SICKLE CELL DISEASE

half of the cross-sectional studies used multivariate or design-based techniques to control for the effects of potential confounders, which made inferences uncer-tain. Fourth, the majority of the potential barriers exam-ined in cross-sectional studies (eg, those chosen by the researcher) were patient-related factors. Since the major-ity 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 barri-ers 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 mea-sures 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 manage-ment quality for patients with painful VOC should be implemented and should address provider attitudes or min-imize 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 experi-ences surveys) for patients with SCD ought to be routinely measured, and barriers to high-quality health care identi-

fied. One promising telephone outreach intervention to improve receipt of ambulatory care should be replicated, and more studies are needed to identify effective interven-tions 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.

reFerenceS1. World Health Organization: The 59th World Health Assembly. Sickle-cell anaemia. WHA.59.20. 2006.2. Weatherall D, Akinyanju O, Fucharoen S. Inherited Disorders of Hemoglo-bin. In: Disease Control Priorities in Developing Countries. New York: Oxford University Press. 2006;663-680. 3. Platt OS, Brambilla DJ, Rosse WF et al. Mortality in sickle cell dis-ease. Life expectancy and risk factors for early death. N Engl J Med. 1994;330(23):1639-1644. 4. US Preventive Services Task Force. Screening for Hemoglobinopathies US Preventive Services Task Force, Guidelines from Guide to Clinical Preven-tive Services. 2nd ed. Williams and Wilkens; 1996.5. McClish DK, Penberthy LT, Bovbjerg VE et al. Health related quality of life in sickle cell patients: the PiSCES project. Health Qual Life Outcomes. 2005;3:50. 6. Shapiro BS, Benjamin LJ, Payne R, Heidrich G. Sickle cell-related pain: per-ceptions of medical practitioners. J Pain Symptom Manage. 1997;14:168-174. 7. Department of Health and Human Services: National Heart, Lung, and Blood Institute. People Science Health. 2008. 8. Smith WR, Bovbjerg VE, Penberthy LT et al. Understanding pain and improving management of sickle cell disease: the PiSCES study. J Natl Med Assoc. 2005;97(2):183-193. 9. Davis H, Gergen PJ, Moore RM Jr. Geographic differences in mortality of young children with sickle cell disease in the United States. Public Health Rep. 1997;112(1):52-58. 10. Sox CM, Cooper WO, Koepsell TD, DiGiuseppe DL, Christakis DA. Provi-sion of pneumococcal prophylaxis for publicly insured children with sickle cell disease. JAMA. 2003;290(8):1057-1061.11. Lanzkron S, Haywood C Jr, Segal JB, and Dover GJ. Hospitalization rates and costs of care of patients with sickle-cell anemia in the state of Mary-land in the era of hydroxyurea. Am J Hematol. 2006;81 (12):927-932. 12. Segal JB, Strouse JJ, Beach MC et al. Hydroxyurea for the Treatment of Sickle Cell Disease. Evid Rep Technol Assess (Summ). (in press)13. Berlin JA. Does blinding of readers affect the results of meta-analyses? University of Pennsylvania Meta-analysis Blinding Study Group. Lancet. 1997;350(9072):185-186. 14. Jadad AR, Moore RA, Carroll D et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1-12. 15. Lincoln TM, Reif W. How much do sample characteristics affect the effect size? An investigation of studies testing the treatment effects for social phobia. J Anxiety Disord. 2004;18(4). 16. Tobin GA and Begley CM. Methodological rigour within a qualitative framework. J Adv Nurs. 2004;48(4):388-396. 17. Horsburgh D. Evaluation of qualitative research. J Clin Nurs. 2003;12(2):307-312. 18. Ratanawongsa N, Thomas PA, Marinopoulos SS et al. Reliability of Meth-ods for Evaluating Continuing Medical Education: A Systematic Review. Acad Med. In press. 19. Atkins D, Best D, Briss PA et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328(7454):1490. 20. Methods Reference Manual for Comparative Effectiveness Reviews. 2007;1-127.21. Hankins J, Hinds P, Day S et al. Therapy preference and decision-making among patients with severe sickle cell anemia and their families&. Pediatr Blood Cancer. 2007;48(7):705-710. 22. Treadwell MJ, Law AW, Sung J et al. Barriers to adherence of deferox-amine usage in sickle cell disease. Pediatr Blood Cancer 2005;44(5):500-507. 23. Wurst KE and Sleath BL. Physician knowledge and adherence to pre-

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 101, NO. 10, OCTOBER 2009 1033

BARRIERS TO CARE IN SICKLE CELL DISEASE

scribing antibiotic prophylaxis for sickle cell disease. Int J Qual Health Care. 2004;16(3):245-251. 24. Elliott V, Morgan S, Day S, Mollerup LS, and Wang W. Parental health beliefs and compliance with prophylactic penicillin administration in chil-dren with sickle cell disease. J Pediatr Hematol Oncol. 2001;23(2):112-116. 25. Teach SJ, Lillis KA, and Grossi M. Compliance with penicillin pro-phylaxis in patients with sickle cell disease. Arch Pediatr Adolesc Med. 1998;152(3):274-278. 26. Jensen SA, Elkin DT, Hilker K, Jordan S, Iyer R, and Smith MG. Caregiver knowledge and adherence in children with sickle cell disease: Knowing is not doing. J. Clin Psychol Med Settings. 2005;12 (4):333-337. 27. Armstrong FD, Pegelow CH, Gonzalez JC, and Martinez A. Impact of children’s sickle cell history on nurse and physician ratings of pain and medication decisions. J Pediatr Psychol. 1992;17(5):651-664. 28. Pence L, Valrie CR, Gil KM, Redding-Lallinger R, and Daeschner C. Opti-mism Predicting Daily Pain Medication Use in Adolescents with Sickle Cell Disease. J. Pain Symptom Manage. 2007;33(3):302-309. 29. Telfair J, Haque A, Etienne M, Tang S, Strasser S. Rural/urban differences in access to and utilization of services among people in Alabama with sickle cell disease. Public Health Rep. 2003;118(1):27-36. 30. Logan DE, Radcliffe J, and Smith-Whitley K. Parent factors and adoles-cent sickle cell disease: associations with patterns of health service use. J Pediatr Psychol. 2002;27(5):475-484. 31. Wojciechowski EA, Hurtig A, and Dorn L. A natural history study of adoles-cents and young adults with sickle cell disease as they transfer to adult care: a need for case management services. J Pediatr Nurs. 2002;17(1):18-27. 32. Haque A and Telfair J. Socioeconomic distress and health status: the urban-rural dichotomy of services utilization for people with sickle cell disor-der in North Carolina. J Rural Health. 2000;16(1):43-55. 33. Barakat LP, Smith-Whitley K, and Ohene-Frempong K. Treatment adher-ence in children with sickle cell disease: Disease-related risk and psychoso-cial resistance factors. J. Clin. Psychol. Med. Settings. 2002;9(3):201-209. 34. Belgrave FZ and Lewis DM. The role of social support in compliance and other health behaviors for African Americans with chronic illnesses. J Health Soc Policy. 1994;5(3-4):55-68. 35. Zumberg MS, Reddy S, Boyette RL, Schwartz RJ, Konrad TR, and Lotten-berg R. Hydroxyurea therapy for sickle cell disease in community-based practices: a survey of Florida and North Carolina hematologists/oncolo-gists. Am J Hematol. 2005 ;79(2):107-113. 36. Pack-Mabien A, Labbe E, Herbert D, and Haynes J Jr. Nurses’ atti-tudes and practices in sickle cell pain management. Appl Nurs Res. 2001;14(4):187-192. 37. Murray N and May A. Painful crises in sickle cell disease--patients’ per-spectives. BMJ. 1988;297( 6646):452-454. 38. Telfair J, Myers J, and Drezner S. Does race influence the provision of care to persons with sickle cell disease? Perceptions of multidisciplinary providers. J Health Care Poor Underserved. 1998;9(2):184-195. 39. Vichinsky E, Rust D, and Lubin B. A possible disparity between standard of care and delivery of care in sickle cell disease, as assessed from sickle cell centers. Int J Pediatr. Hematol Oncol. 1999;6(3):189-197. 40. Walters MC, Patience M, Leisenring W et al. Barriers to bone mar-row transplantation for sickle cell anemia. Biol Blood Marrow Transplant 1996;2(2):100-104. 41. Booker MJ, Blethyn KL, Wright CJ, and Greenfield SM. Pain manage-ment in sickle cell disease. Chronic Illn. 2006;2(1):39-50. 42. Rouse CM. Paradigms and politics: shaping health care access for sick-le cell patients through the discursive regimes of biomedicine. Cult Med Psychiatry. 2004;28(3):369-399. 43. Maxwell K, Streetly A, and Bevan D. Experiences of hospital care and treatment seeking for pain from sickle cell disease: qualitative study. BMJ. 1999;318(7198):1585-1590. 44. Tucker C, Spencer J, Dowling PT, and Allman L. Developing a com-munity for patients with sickle cell anemia at Harbor-UCLA. Emphasis Nurs. 1995;5(1):19-27. 45. Alleyne J and Thomas VJ. The management of sickle cell crisis pain as experienced by patients and their carers. J Adv Nurs 1994;19(4):725-732.

46. Shelley B, Kramer KD, and Nash KB. Sickle cell mutual assistance groups and the health services delivery system. J Health Soc Policy. 1994;5(3-4):243-259. 47. Strickland OL, Jackson G, Gilead M, McGuire DB, and Quarles S. Use of focus groups for pain and quality of life assessment in adults with sickle cell disease. J Natl Black Nurses Assoc. 2001;12(2):36-43. 48. Harris A, Parker N, and Barker C. Adults with sickle cell disease: Psycho-logical impact and experience of hospital services. Psychol. Health Med. 1998;3(2):171-179. 49. Butler DJ and Beltran LR. Functions of an adult sickle cell group: educa-tion, task orientation, and support. Health Soc Work. 1993;18(1):49-56. 50. Waters J and Thomas V. Pain from sickle-cell crisis. Nurs Times. 1995;91(16):29-31. 51. Labbe E, Herbert D, and Haynes J. Physicians’ attitude and practices in sickle cell disease pain management. J Palliat Care. 2005;21(4):246-251. 52. Witherspoon D and Drotar D. Correlates of adherence to prophylac-tic penicillin therapy in children with sickle cell disease. Child Health Care. 2006;35(4):281-296. 53. Pejaver RK, Ahmed FE, and Al Hifzi I. Compliance to penicillin prophy-laxis amongst Saudi children with sickle cell disease. J Ir Coll Phys Surg. 1997;26(4):268-270. 54. Mitchell MB, Lambright WD, Breish R et al. Meeting the challenge of managing vaso-occlusive crisis. J Healthc Qual. 2002;24(3):4-8, 56. 55. Co JP, Johnson KB, Duggan AK, Casella JF, and Wilson M. Does a clini-cal pathway improve the quality of care for sickle cell anemia? Jt Comm J Qual Saf. 2003;29 (4 ):181-190. 56. Jamison C and Brown HN. A special treatment program for patients with sickle cell crisis. Nurs Econ. 2002;20(3):126-132. 57. Cooper GS, Armitage KB, Ashar B et al. Design and implementation of an inpatient disease management program. Am J Manag Care. 2000;6(7): 793-801. 58. Benjamin LJ, Swinson GI, and Nagel RL. Sickle cell anemia day hospital: an approach for the management of uncomplicated painful crises. Blood. 2000;95(4 ):1130-1136. 59. Day J. An audit of pain management in acute sickle cell crisis. Nurs Times. 1997;93(2):33-34. 60. Brookoff D and Polomano R. Treating sickle cell pain like cancer pain. Ann Intern Med. 1992;116(5):364-368. 61. Fertleman CR, Gallagher A, and Rossiter MA. Evaluation of fast track admission policy for children with sickle cell crises: questionnaire survey of parents’ preferences. BMJ. 1997;315(7109):650. 62. Treadwell MJ, Franck LS, and Vichinsky E. Using quality improvement strategies to enhance pediatric pain assessment. Int J Qual Health Care. 2002;14(1):39-47. 63. Treadwell MJ and Weissman L. Improving adherence with deferox-amine regimens for patients receiving chronic transfusion therapy. Semin Hematol. 2001;38(1 suppl 1):77-84. 64. Berkovitch M, Papadouris D, Shaw D, Onuaha N, Dias C, and Olivieri NF. Trying to improve compliance with prophylactic penicillin therapy in chil-dren with sickle cell disease. Br J Clin Pharmacol. 1998;45(6):605-607. 65. Ketchen B, Hazzard A, Lassiter S et al. STARBRIGHT World: A pilot study of a home-based sickle cell psychoeducational intervention. Child Health Care. 2006;35(4):321-338. 66. Patik M, Phillips L, Kladny B, Captain A, Gettig E, and Krishnamurti L. Structured telephone-based outreach using nonmedical personnel can improve adherence to comprehensive care in families of children with sickle cell disease. Am J Hematol. 2006;81(6):462-464. 67. Beach MC, Price EG, Gary TL et al. Cultural competence: a systematic review of health care provider educational interventions. Med Care. 2005; 43(4):356-373.68. Lewin SA, Skea ZC, Entwistle V, Zwarenstein M, Dick J. Interventions for providers to promote a patient-centred approach in clinical consultations. Cochrane Database Syst Rev. 2001; (4):CD003267. n