C. Patrick Carroll

Mortality Rates and Age at Death from Sickle Cell Disease: U.S., 1979-2005

Objectives. Improvements in survival for children with sickle cell disease (SCD) during the last 30 years have been well established. Whether similar improvements for adults with the disease have occurred is unknown. We investigated mortality rates for children and adults with SCD. Methods. We used the National Center for Health Statistics multiple-cause-of-death files to examine age at death and calculate mortality rates from 1979 to 2005. We examined trends in mortality rates using negative binomial regression, and we examined age at death using t-tests and linear regression. Results. We identified 16,654 sickle cell-related deaths. Mean age at death was significantly different for males (33.4 years, 95% confidence interval [CI] 33.0, 33.7) than for females (36.9 years, 95% CI 36.5, 37.4). In a regression model controlling for gender, the mean age at death increased by 0.36 years for each year of the study. The median age at death in 2005 was 42 years for females and 38 years for males. The overall mortality rate increased 0.7% (p<0.001) each year during the time period studied. The adult (>19 years of age) mortality rate increased by 1% (p<0.001) each year during the time period studied. The pediatric mortality rate decreased by 3% (p<0.001) each year during the time period studied. Conclusions. These data confirm prior findings of a significant decrease in mortality for children with SCD The mortality rate for adults appears to have increased during the same time period It seems unlikely that this increase is due merely to an influx of younger patients surviving to adulthood and may reflect a lack of access to high-quality care for adults with SCD.

The course and correlates of high hospital utilization in sickle cell disease: Evidence from a large, urban Medicaid managed care organization

Although most patients with sickle cell disease (SCD) are hospitalized infrequently and manage painful crises at home, a small subpopulation is frequently admitted to emergency departments and inpatient units. This small group accounts for the majority of health care expenses for patients with SCD. Using inpatient claims data from a large, urban Medicaid MCO for 5 consecutive years, this study sought to describe the course of high inpatient utilization (averaging four or more admissions enrolled per year for at least 1 year) in members with a diagnosis of SCD and a history of hospitalizations for vaso‐occlusive crisis. High utilizers were compared with the other members with SCD on demographics, medical and psychiatric comorbidity, and use of other health care resources. Members who were high utilizers had more diagnostic mentions of sickle cell complications than low utilizers. However, the pattern of high inpatient utilization was likely to moderate over successive years, and return to the pattern after moderation was uncommon. Despite this, a small subpopulation engaged in exceptional levels of inpatient utilization over multiple years. Am. J. Hematol., 2009.

Perceived Discrimination in Health Care Is Associated With a Greater Burden of Pain in Sickle Cell Disease

CONTEXT Perceived discriminatory experiences in society have been associated with a higher burden of pain among some minority patient populations. OBJECTIVES To describe the extent to which patients with sickle cell disease (SCD) perceive discrimination from health care providers and to examine the association of these experiences with the burden of chronic SCD pain. METHODS Cross-sectional analysis of data collected at baseline of a prospective cohort study of SCD patient experiences of care (n = 291). Perceived race-based and disease-based discrimination from health care providers were measured using subscales adapted from the Interpersonal Processes of Care Survey. Discrimination scores were examined for their association with patient characteristics and measures of pain burden using descriptive, bivariate, and multivariate analytic techniques. RESULTS Respondents reported a greater burden of race-based discrimination from health care providers than has been previously reported by African Americans, and they reported a greater amount of disease-based vs. race-based discrimination. Age and having difficulty persuading providers about pain were the only patient characteristics independently associated with race-based discrimination, whereas older age, greater emergency room utilization, having difficulty persuading providers about pain, daily chronic pain, fewer good days during a week, and a higher severity of pain on their good days were independently associated with greater disease-based discrimination. CONCLUSION Perceived disease-based, but not race-based, discrimination was found to be associated with a greater range of self-reported pain among patients with SCD. If causal, this finding could signal an important new approach to mitigating the burden of pain experienced by persons with SCD.

Prediction of onset and course of high hospital utilization in sickle cell disease

BACKGROUND Although sickle cell disease (SCD) patients typically manage their pain at home, a small subgroup is frequently hospitalized and accounts for the majority of costs. OBJECTIVES 1) To identify prospective diagnostic and demographic markers of new periods of high utilization; 2) To identify demographic and diagnostic markers of a persistent rather than moderating course of high utilization; 3) To replicate the finding that high utilization tends to moderate. DESIGN The State Inpatient Databases for California, 2004-2007, were used. Patients with new onset periods of high utilization were compared with non-high utilizers, and new high utilizers who moderated were compared with those who had a persistent course. SETTING All hospitals in the state of California. PATIENTS Patients age 13 years or older in 2004 with a recorded diagnosis of sickle cell disease and at least one hospitalization for crisis during the study period. MEASURES METHODS Groups from hospitals throughout California were compared on demographics and discharge diagnoses of SCD complications and comorbidities. Patients age 13 years or older in 2004 with a recorded diagnosis of sickle cell disease and at least 1 hospitalization for crisis during the study period were included. RESULTS New periods of high utilization were associated with more prior hospitalizations and previous diagnoses of aseptic necrosis and renal disease. High utilization typically moderated. A persistent course was associated with slightly more hospitalizations during the initial year of high utilization, and, subsequently, by more mentions of septicemia and mood disorders. CONCLUSIONS Overall, high utilization was difficult to predict, as was its course. The diagnoses most associated with high utilization indicated more severe sickle cell disease. Septicemia deserves further investigation as a preventable cause for high utilization, as do mood disorders.

The Intensive Treatment Unit: A brief inpatient detoxification facility demonstrating good postdetoxification treatment entry.

Inpatient detoxification is frequently used to treat substance use disorders, despite consistent findings that drug use soon after detoxification is the norm. A number of lines of evidence suggest the most rational means of improving outcomes after detoxification is to improve postdetoxification treatment entry. This report presents outcomes from the Intensive Treatment Unit (ITU), a brief inpatient detoxification unit in Baltimore, MD, found to have good postdischarge treatment entry outcomes. The patients followed were predominantly male African Americans in early middle age who were sequentially admitted to the unit (N = 134) and demonstrated severe social disruption and psychiatric comorbidity. More than 80% of the patients discharged from the ITU were admitted to treatment postdetoxification, with most going to long-term residential settings or recovery houses. Success was associated with seeking residential treatment, and failure was concentrated among the minority discharged with no plan for aftercare and those seeking outpatient treatments. The report explores patient and process factors associated with these outcomes and discusses the possibility that the ITU may be a model system for improving outcomes postdetoxification.

A Preliminary Study of Psychiatric, Familial, and Medical Characteristics of High Utilizing Sickle Cell Disease Patients

Objectives:To identify demographic, medical, and psychosocial characteristics that distinguished sickle cell disease (SCD) patients who were frequent utilizers of urgent or emergent care resources from low-utilizing patients. Methods:Patients at a large urban comprehensive SCD treatment center were recruited from clinic or during urgent care visits. Participants who were high utilizers, defined as having >4 acute or emergency care visits in the prior 12 months, were compared with patients with more typical utilization patterns on lifetime complications of SCD, family background, psychiatric history, occupational function, coping, depressive symptoms, and personality. Results:High utilizers were nearly a decade younger on average; despite this they had a similar lifetime history of SCD complications. High-utilizing patients’ parents seemed to have greater educational achievement overall. High utilizers reported a nearly 3-fold greater prevalence of psychiatric illness in family members than low utilizers. On other measures, including coping strategies, social support, and personality, the 2 groups were comparable. Discussion:The study strengthens emerging evidence that disease severity, familial factors related to greater parental education, and psychiatric illness are important factors in high care utilization in patients with SCD.

Impact of a Dedicated Infusion Clinic for Acute Management of Adults with Sickle Cell Pain Crisis

Most adults with sickle cell disease (SCD) receive care for their acute painful episodes in an emergency department (ED) setting. The purpose of this article is to describe the impact of opening a dedicated treatment center for adults with SCD [Sickle Cell Infusion Clinic (SCIC)] on patient outcomes and on hospital discharges for SCD. Descriptive data including demographics, time to first dose of narcotic, and pain scores were collected on patients presenting to the SCIC and ED. Maryland hospital discharge data were obtained from the Maryland Health Services Cost Review Commission. Analyses were conducted using T tests, χ2 tests, and simple generalized estimating equation regression models accounting for the clustered nature of observations, as appropriate. There were 3,874 visits to the SCIC by 361 unique patients; 85% of those visits resulted in the patient being sent home. During the same time period, there were 3,408 visits to the ED by 558 unique patients with SCD. The overall admission rate from the ED for these patients was 35.9% but decreased significantly over the time period with a rate of 20% in December 2011. There was a significant decrease in readmissions over time for the entire Baltimore Metro area with the likelihood of readmission decreasing by 7% over time. The SCIC model provides adults with SCD access to high quality care that decreases the need for hospital admission. Further research needs to be done to evaluate the cost effectiveness of this model. Am. J. Hematol. 90:376–380, 2015.

Assessment of agonist and antagonist effects of tramadol in opioid-dependent humans.

The subjective, behavioral, and physiologic effects of racemic tramadol, an analgesic with low abuse liability and dual mu-opioid agonist and monoamine reuptake actions, were evaluated in 2 clinical pharmacology studies in dependent opioid abusers. In the withdrawal precipitation study, participants (N = 8) were maintained on methadone 60 mg/day orally and challenged with intramuscular tramadol, hydromorphone, naloxone, and placebo 20 hr after methadone administration. In the withdrawal suppression study, participants (N = 6) were maintained on hydromorphone given orally 10 mg 4 times daily, and spontaneous opioid withdrawal was produced by withholding doses for 23 hr. During the experimentally induced withdrawal, oral tramadol, hydromorphone, naltrexone, and placebo were given. In both studies a comprehensive panel of participant-rated, observer-rated, and physiologic measures were collected. In both studies, naloxone and naltrexone significantly increased measures of opioid withdrawal, whereas tramadol showed no discernible antagonist effects. In contrast, tramadols pattern of effects was more similar to that of hydromorphone and suggestive of mild opioid-agonist effects (withdrawal suppression), though not to a statistically significant degree.

Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls

Abstract Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not.