James Eckman - Academia.edu (original) (raw)
Papers by James Eckman
Blood
BACKGROUND: Mean life expectancy among adults with sickle cell disease (SCD) remains in the sixth... more BACKGROUND: Mean life expectancy among adults with sickle cell disease (SCD) remains in the sixth decade of life (Elmariah et al. Am J Hem. 2014). We examined the relationship of genetic differences among SCD patients to survival, in order to gain greater understanding of contributors to early mortality. Genetic signatures associated with survival could identify high risk patients who would be optimal candidates for advanced therapies. METHODS: Patient data were previously collected through a multicenter study to identify genetic factors associated with SCD complications. All enrolled patients were 18 years or older, with a diagnosis of SCD (SS, Sβ0, Sβ+, SC). Of the patients enrolled, 542 were followed for a mean of 9.3 years for incidence of death. Genome-wide association study (GWAS) data from the Illumina 610 BeadChips were available for 503 of these individuals. We used the software program IMPUTE2 with a global reference panel from the 1000Genomes Project to impute missing gen...
Blood
Background: Common measures and common data elements (CDEs) for sickle cell disease (SCD) are nee... more Background: Common measures and common data elements (CDEs) for sickle cell disease (SCD) are needed to help improve data quality and data comparability necessary for meta-analyses, guidelines development, and implementation science. In recent years, the National Heart, Lung, and Blood Institute (NHLBI) has undertaken several activities to develop CDEs and measures for SCD. These include developing 1) the Sickle Cell Quality of Life Measurement Information System (ASCQ-Me); 2) clinical practice recommendations for the management of SCD; and 3) a lexicon and consensus definitions for the most frequently occurring complications of SCD. In 2014, the NHLBI funded an Administrative Supplement to the PhenX Toolkit to identify common measures to further promote data comparability across SCD research. The Web-based PhenX Toolkit (consensus measures for Phen otypes and eX posures, https://www.phenxtoolkit.org/) provides a catalog of 449 standard measures and associated interoperability resou...
Blood
2667 Background: Acute pain is the leading cause of hospitalization in both children and adults w... more 2667 Background: Acute pain is the leading cause of hospitalization in both children and adults with sickle cell disease (SCD). Opioid analgesics are used for pain relief, but are associated with significant adverse effects that are bothersome to patients and may predispose to serious sickle-related pulmonary events. Evidence is limited for the most effective opioid administration strategy that maximizes analgesia and minimizes adverse effects. Patient Controlled Analgesia (PCA) has the potential advantage to allow a patient to optimize pain control without dependence on healthcare providers for administration. PCA generally consists of an opioid given by constant infusion with additional demand doses as needed; the proper dosing for each is largely unknown, particularly at high opioid doses. The SCDCRN conducted a multi-center phase III clinical trial comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dos...
Blood
Background: Health services and outcomes research in sickle cell disease (SCD) has been limited b... more Background: Health services and outcomes research in sickle cell disease (SCD) has been limited by inadequate population-based surveillance and reliance on ICD-9 codes to identify individuals with SCD. The accuracy of ICD-9 coding in administrative claims datasets and the extent of miscoding is unknown. GA was one of 7 states funded to participate in the Registry and Surveillance for Hemoglobinopathies (RuSH) Project. The RuSH case definition for confirmed cases required laboratory documentation of SCD by hemoglobin electrophoresis (HEP)/HPLC. The RuSH case definition for probable cases required identification from administrative datasets of ≥ 2 encounters with an SCD ICD-9 code plus ≥ 1 encounter with ICD-9 or CPT codes from a predetermined list of SCD-associated treatments, procedures, and complications (SCD-TPC): eg hydroxyurea, RBC transfusion, cholecystectomy, stroke. We report results of an ancillary study designed to evaluate the accuracy of using administrative claims data f...
Blood
4379 Introduction: Allo- and auto- antibody formation is one of the major and serious complicatio... more 4379 Introduction: Allo- and auto- antibody formation is one of the major and serious complications of RBC transfusion in patients with sickle cell disease. This problem appears to be more common than in other diseases requiring chronic transfusion that leads to acute and delayed hemolytic transfusion reactions, serious morbidity and occasional life threatening problems. Although there have been reports describing prevalence of immunization in SCD patients, data specific for adult population with SCD is lacking. We report the prevalence of allo- and auto-immunization in adult SCD patients. Methods: Patients aged 18 and above with diagnoses of SCD, confirmed by standard hemoglobin electrophoresis, who had at least one type and cross match done from 1995 through 2011 were considered eligible. To facilitate patient management all data on antibody identification, screening and transfusions were routinely recorded in the electronic database of the Georgia Comprehensive Sickle Cell Progra...
Blood Banking and Transfusion Medicine, 2007
Clinical Trials, 2013
Background The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Althou... more Background The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Although ambulatory pain accounts for most days in pain, pain is also the most common cause of hospitalization and is typically treated with parenteral opioids. The evidence base is lacking for most analgesic practice in SCD, particularly for the optimal opioid dosing for patient-controlled analgesia (PCA), in part because of the challenges of the trial design and conduct for this rare disease. Purpose The purpose of this report is to describe our Network’s experiences with protocol development, implementation, and analysis, including overall study design, the value of pain assessments rather than ‘crisis’ resolution as trial endpoints, and alternative statistical analysis strategies. Methods The Improving Pain Management and Outcomes with Various Strategies (IMPROVE) PCA trial was a multisite inpatient randomized controlled trial comparing two PCA-dosing strategies in adults and children with...
Blood
Over the last three decades there has been improvement in survival in children with sickle cell d... more Over the last three decades there has been improvement in survival in children with sickle cell disease. Overall survival from birth to age 18 of 86% and 95% has been reported in children with sickle cell anemia (HbSS) and sickle hemoglobin C (Hb SC) disease respectively. These encouraging results are secondary to initiation of preventive measures like newborn screening, penicillin prophylaxis, immunization and stroke prevention and other supportive therapies. Ballas (Blood2004;104 supl:Abstr 3743) reported high death rate for young adults with the disease. To determine the death rates and cause of death in our population, we did a retrospective review of our patients who had recently transitioned into adult care. Mortality rate and circumstances of death in a 10 year period of transition from pediatric to adult program in Georgia Comprehensive Sickle Cell Center at Grady Memorial Hospital between 1996 and 2006 were determined. Total number of deaths was obtained from the clinical d...
Blood
The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th ... more The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th decade, but this remains extremely variable. Little is known about the biological factors that protect certain SCD patients from early demise while others never reach mid-adulthood. Recently, McKerrell and colleagues (2004) compared the clinical and laboratory profiles of SCD patients aged 40 years and over with SCD patients who were between 21 and 30 years of age. Similarly, we have compared clinical and genetic correlates of older SCD patients (50 years and over) with those of younger patients (18–30 years). Among 514 patients in our total study population, 49 (10%) were categorized as “older” and 194 (38%) were categorized as “younger.” Older SCD patients had lower hemoglobin (older: 7.8 ± 1.1 vs. younger: 8.5 ± 1.2, p=0.004), platelet count (older: 372 ± 126 vs. younger: 460 ± 225, p=0.02), MCV (older: 92 ± 12 vs. younger: 89 ± 9, p=0.08), MCHC (older: 33.6 ± 1.4 vs. younger: 34.3 ± ...
Blood
In 1994, the average age of death of patients with sickle cell disease (SCD) in the US was 42 yea... more In 1994, the average age of death of patients with sickle cell disease (SCD) in the US was 42 years for males and 48 for females. We theorized that patients who lived appreciably beyond these ages would therefore have lower disease burden than patients overall, and that lack of specific disease complications would be characteristic of such patients. From 2001 until 2006, we enrolled 541 unrelated adult patients (age ≥18) with Hb SS or Hb Sβ0 at three comprehensive sickle cell centers in a study designed to identify factors associated with clinical outcomes in SCD. Our database includes demographic, clinical, and laboratory data on all participants. We identified 61 patients 50 years and older and 32 patients 55 years and older. Among the latter, the average age was 60.6, with a median of 58 years (range 55–83); 65% were female. Although patients with SCD are generally thought to have a low prevalence of hypertension, the mean BP in this older cohort was 142/75, and 55% of patients w...
Blood
Introduction: Renal damage is a progressive complication of sickle cell disease (SCD) that begins... more Introduction: Renal damage is a progressive complication of sickle cell disease (SCD) that begins with hyerfiltration in childhood followed by decline in glomerular filtration rate (GFR) and chronic renal failure in up to 12% of HbSS adults. Albuminuria is a marker of glomerular damage but does not predict GFR. Serum creatinine (SCr) is typically low in SCD despite glomerular damage, in part because tubular dysfunction leads to increased creatinine secretion. Cystatin C (CysC) is a low molecular weight protein, eliminated exclusively by glomerular filtration, and correlates with GFR in children and adults with chronic kidney disease (CKD). Previously, estimated GFR (eGFR) has been compared to measured GFR (mGFR) using equations that incorporate CysC and SCr in young children with SCD; however no studies have examined the precision or accuracy of GFR formulas in adults and older children with SCD. Methods: Adults and children ≥10 years with HbSS and albuminuria (albumin/creatinine ra...
Blood
BACKGROUND: Sickle cell disease nephropathy (SCDN) is a common complication of sickle cell diseas... more BACKGROUND: Sickle cell disease nephropathy (SCDN) is a common complication of sickle cell disease (SCD) associated with risk for early mortality (Platt et al., 1994; Elmariah et al, 2014). To identify potential genetic risk factors for SCDN, we performed genome-wide association studies (GWAS) for glomerular filtration rate (GFR) in three well-characterized SCD cohorts and performed in vivo functional analysis of one of the candidate genes in zebrafish. METHODS: Three previously described SCD cohorts were utilized in this analysis: Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) (Elmariah et al, 2014), Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) (Machado et al, 2011) and Pulmonary Hypertension and the Hypoxic Response in Sickle Cell Disease (PUSH) (Minniti et al, 2009). Patients less than 16 years old were excluded from PUSH. GFR was estimated using the…
Blood
Introduction: Sickle cell nephropathy (SCN) is a progressive complication of sickle cell disease ... more Introduction: Sickle cell nephropathy (SCN) is a progressive complication of sickle cell disease (SCD) that begins in childhood and may result in renal failure and early mortality; yet the potential for prevention and reversal of SCN is not known. Urinary albumin/creatinine ratio (ACR) is a biomarker of glomerular damage but may not correlate with renal hemodynamic abnormalities that are indicative of early renal failure, e.g. glomerular filtration rate (GFR), renal plasma flow (RPF), and glomerular membrane permeability. We hypothesized that the angiotensin receptor blocker losartan will improve GFR and decrease excretion of high molecular weight (HMW) proteins that are restricted at the glomerulus, while not affecting abnormalities in markers of tubular injury and ischemia. Methods: Adults and children ≥10 years with HbSS who were on hydroxyurea (HU) for ≥6 months but had persistent microalbuminuria (MiA; ACR ≥30 mg/g) or macroalbuminuria (MA; ACR ≥300 mg/g) on ≥2 consecutive occa...
Blood
Background: Acute chest syndrome (ACS) is one of the most feared complications of sickle cell dis... more Background: Acute chest syndrome (ACS) is one of the most feared complications of sickle cell disease. This syndrome is defined by a clinical constellation of symptoms including fever, infiltrate on lung imaging and hypoxia. ACS is a well-known complication to occur early in the hospitalization of patients for sickle cell vaso-occlusive pain crises (VOP). It is hard to differentiate from pneumonia and its rate of occurrence has not been well characterized. Management of ACS includes exchange or simple transfusion, depending on the severity of its presentation, along with critical care support and pain control. Early recognition of this clinical syndrome can lead to better management and outcomes for patients with sickle cell disease. Methods: The Emory University Georgia Comprehensive Sickle Cell Center at Grady Health System has 1073 sickle cell patients and provides a 24/7 acute care unit (ACU) for the evaluation of patients presenting with pain crises. We conducted a retrospectiv...
Blood
BACKGROUND: Nephropathy is a common and devastating complication of sickle cell disease (SCD) ass... more BACKGROUND: Nephropathy is a common and devastating complication of sickle cell disease (SCD) associated with mortality (Elmariah et al, 2014). However, early detection of SCD nephropathy (SCDN) has proven difficult. Discovery of genetic markers associated with SCDN could greatly improve our ability to identify patients at risk for renal decline. To that end, we have performed a genome-wide association study (GWAS) of glomerular filtration rate (GFR) in our adult SCD cohort. METHODS: Medical history, laboratory values and DNA for genotyping were collected as part of a multicenter study of outcome-modifying genes in SCD. Participating institutions included sickle cell centers at Duke University, University of North Carolina at Chapel Hill, Emory University, and East Carolina University. GFR was estimated using the ‘Modification of Diet in Renal Disease’ (MDRD) study definition (Levey et al, 1999) and dichotomized at the clinically relevant threshold of 90 ml/min/1.73m2. 463 patients ...
Nursing, 2002
Sterling Jackson, 21, who has a history of sickle-cell anemia, is admitted to the medical/surgica... more Sterling Jackson, 21, who has a history of sickle-cell anemia, is admitted to the medical/surgical unit from the emergency department (ED). He developed severe pain in his chest, arms, legs, and back about 10 hours ago. After 4 hours receiving intravenous (I.V.) nalbuphine (Nubain), ketorolac (Toradol), and hydration in the ED, he still rates his pain as 6 on a visual analogue scale, and his blood work shows worsening anemia from his baseline level. The most common genetic disorder in the United States, sickle-cell disease affects about 70,000 people. Although most common in African-Americans, it also affects people whose ancestors came from parts of the world where malaria is endemic. Having one sickle-cell gene (known as sickle-cell trait) provides some protection against malaria, but having two causes sicklecell disease. Years ago, people with sickle-cell disease died in their teens. Today, with improved education and treatment, some live into their 60s, but they’re susceptible to sickle-cell crises all their lives. In this article, we’ll explain what’s causing Mr. Jackson’s problems and how you can help him through the crisis.
Blood, 2005
The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th ... more The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th decade, but this remains extremely variable. Little is known about the biological factors that protect certain SCD patients from early demise while others never reach mid-adulthood. Recently, McKerrell and colleagues (2004) compared the clinical and laboratory profiles of SCD patients aged 40 years and over with SCD patients who were between 21 and 30 years of age. Similarly, we have compared clinical and genetic correlates of older SCD patients (50 years and over) with those of younger patients (18–30 years). Among 514 patients in our total study population, 49 (10%) were categorized as “older” and 194 (38%) were categorized as “younger.” Older SCD patients had lower hemoglobin (older: 7.8 ± 1.1 vs. younger: 8.5 ± 1.2, p=0.004), platelet count (older: 372 ± 126 vs. younger: 460 ± 225, p=0.02), MCV (older: 92 ± 12 vs. younger: 89 ± 9, p=0.08), MCHC (older: 33.6 ± 1.4 vs. younger: 34.3 ± 1.8, p=0.05), and WBC (older: 10.2 ± 2.7 vs. younger: 13.1 ± 4.1, p<0.001). Older patients also had lower total bilirubin (p=0.01), and increased alkaline phosphatase (p=0.0002) and creatinine (p=0.0002), which was associated with poorer creatinine clearance (p<0.0001). The older SCD patients also had increased systolic (p<0.0001) and diastolic (p=0.008) blood pressure, decreased O2 saturation (p=0.03), and a history of fewer pain episodes per year requiring medical treatment (p<0.0001). Many of our findings are consistent with those of McKerrell et al. (2004). In order to identify genetic factors associated with longevity in SCD, we examined 155 SNPs in a total of 41 genes, primarily involved in red blood cell adhesion and inflammation pathways. Chi Square tests of association were constructed for the genotypes of each SNP with the two clinical categories: “older” and “younger.” When the number of rare homozygotes was less than 5 individuals, we combined those individuals with the heterozygote individuals for analysis. All p-values are uncorrected for multiple testing. We found putative associations with 5 SNPs in 3 genes. Three non-coding SNPs in Klotho, not in linkage disequilibrium, exhibited different genotype frequencies in the older versus younger SCD patients (p=0.007, p=0.01 and p=0.01). Similarly, a single non-coding SNP in NOS2A (p=0.02) and TGFBR2 (p=0.02) also exhibited significantly different genotype frequencies in the older versus younger patients. These data support the clinical findings in aging SCD patients reported by McKerrell and colleagues (2004), and they also suggest that genetic factors contribute to variability in longevity in SCD. Interestingly, multiple SNPs in Klotho exhibited differing genotype frequencies in older versus younger patients. Mutations in Klotho have been previously associated with aging-related phenotypes in mice. A better understanding of the biological mechanisms associated with longevity in SCD may help identify those at risk for early demise and in need of more specialized medical care.
The Journal of bone and joint surgery. American volume, 1988
We studied the effect of indomethacin on the prevention of formation of heterotopic bone after to... more We studied the effect of indomethacin on the prevention of formation of heterotopic bone after total hip replacement. In a randomized, double-blind clinical trial involving 201 patients, 102 patients received twenty-five milligrams of indomethacin three times daily for the first six postoperative weeks, and the other ninety-nine patients received a placebo. One year after the operation, eighty-nine of those who had received indomethacin had no sign of heterotopic ossification, and the remaining thirteen had a grade-I lesion. In the group that had received a placebo, twenty-seven had no heterotopic ossification; twenty-four, a grade-I lesion; thirty, a grade-II lesion; and eighteen, a grade-III lesion. Significantly fewer patients who had received indomethacin had formation of heterotopic bone compared with those who had been given a placebo (chi-square test, p less than 0.0005). Only patients who had grade-III formation of heterotopic bone had a significant reduction in movement of ...
Screening, 1992
... A. Davidson, J. Eckman, WH Hannon, MA Henson, M. Hillard, S. Kling, HL Levy, FJ Meaney, ERB M... more ... A. Davidson, J. Eckman, WH Hannon, MA Henson, M. Hillard, S. Kling, HL Levy, FJ Meaney, ERB McCabe, V. Mordaunt, K. Pass, E. Shapira and J. Tuerck CORN Newborn Screening Committee, Council of Regional Networks for Genetic Services, Cornell University Medical ...
Biochemical and …, 1996
JOBNAME: BM 57#2 96 PAGE: 1 SESS: 15 OUTPUT: Fri May 31 05:51:55 1996 /xypage/worksmart/tsp000/69... more JOBNAME: BM 57#2 96 PAGE: 1 SESS: 15 OUTPUT: Fri May 31 05:51:55 1996 /xypage/worksmart/tsp000/69087h/9pu ... Guidelines for the Retention, Storage, and Use of Residual Dried ... Blood Spot Samples after Newborn Screening Analysis:
Blood
BACKGROUND: Mean life expectancy among adults with sickle cell disease (SCD) remains in the sixth... more BACKGROUND: Mean life expectancy among adults with sickle cell disease (SCD) remains in the sixth decade of life (Elmariah et al. Am J Hem. 2014). We examined the relationship of genetic differences among SCD patients to survival, in order to gain greater understanding of contributors to early mortality. Genetic signatures associated with survival could identify high risk patients who would be optimal candidates for advanced therapies. METHODS: Patient data were previously collected through a multicenter study to identify genetic factors associated with SCD complications. All enrolled patients were 18 years or older, with a diagnosis of SCD (SS, Sβ0, Sβ+, SC). Of the patients enrolled, 542 were followed for a mean of 9.3 years for incidence of death. Genome-wide association study (GWAS) data from the Illumina 610 BeadChips were available for 503 of these individuals. We used the software program IMPUTE2 with a global reference panel from the 1000Genomes Project to impute missing gen...
Blood
Background: Common measures and common data elements (CDEs) for sickle cell disease (SCD) are nee... more Background: Common measures and common data elements (CDEs) for sickle cell disease (SCD) are needed to help improve data quality and data comparability necessary for meta-analyses, guidelines development, and implementation science. In recent years, the National Heart, Lung, and Blood Institute (NHLBI) has undertaken several activities to develop CDEs and measures for SCD. These include developing 1) the Sickle Cell Quality of Life Measurement Information System (ASCQ-Me); 2) clinical practice recommendations for the management of SCD; and 3) a lexicon and consensus definitions for the most frequently occurring complications of SCD. In 2014, the NHLBI funded an Administrative Supplement to the PhenX Toolkit to identify common measures to further promote data comparability across SCD research. The Web-based PhenX Toolkit (consensus measures for Phen otypes and eX posures, https://www.phenxtoolkit.org/) provides a catalog of 449 standard measures and associated interoperability resou...
Blood
2667 Background: Acute pain is the leading cause of hospitalization in both children and adults w... more 2667 Background: Acute pain is the leading cause of hospitalization in both children and adults with sickle cell disease (SCD). Opioid analgesics are used for pain relief, but are associated with significant adverse effects that are bothersome to patients and may predispose to serious sickle-related pulmonary events. Evidence is limited for the most effective opioid administration strategy that maximizes analgesia and minimizes adverse effects. Patient Controlled Analgesia (PCA) has the potential advantage to allow a patient to optimize pain control without dependence on healthcare providers for administration. PCA generally consists of an opioid given by constant infusion with additional demand doses as needed; the proper dosing for each is largely unknown, particularly at high opioid doses. The SCDCRN conducted a multi-center phase III clinical trial comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dos...
Blood
Background: Health services and outcomes research in sickle cell disease (SCD) has been limited b... more Background: Health services and outcomes research in sickle cell disease (SCD) has been limited by inadequate population-based surveillance and reliance on ICD-9 codes to identify individuals with SCD. The accuracy of ICD-9 coding in administrative claims datasets and the extent of miscoding is unknown. GA was one of 7 states funded to participate in the Registry and Surveillance for Hemoglobinopathies (RuSH) Project. The RuSH case definition for confirmed cases required laboratory documentation of SCD by hemoglobin electrophoresis (HEP)/HPLC. The RuSH case definition for probable cases required identification from administrative datasets of ≥ 2 encounters with an SCD ICD-9 code plus ≥ 1 encounter with ICD-9 or CPT codes from a predetermined list of SCD-associated treatments, procedures, and complications (SCD-TPC): eg hydroxyurea, RBC transfusion, cholecystectomy, stroke. We report results of an ancillary study designed to evaluate the accuracy of using administrative claims data f...
Blood
4379 Introduction: Allo- and auto- antibody formation is one of the major and serious complicatio... more 4379 Introduction: Allo- and auto- antibody formation is one of the major and serious complications of RBC transfusion in patients with sickle cell disease. This problem appears to be more common than in other diseases requiring chronic transfusion that leads to acute and delayed hemolytic transfusion reactions, serious morbidity and occasional life threatening problems. Although there have been reports describing prevalence of immunization in SCD patients, data specific for adult population with SCD is lacking. We report the prevalence of allo- and auto-immunization in adult SCD patients. Methods: Patients aged 18 and above with diagnoses of SCD, confirmed by standard hemoglobin electrophoresis, who had at least one type and cross match done from 1995 through 2011 were considered eligible. To facilitate patient management all data on antibody identification, screening and transfusions were routinely recorded in the electronic database of the Georgia Comprehensive Sickle Cell Progra...
Blood Banking and Transfusion Medicine, 2007
Clinical Trials, 2013
Background The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Althou... more Background The hallmark of sickle cell disease (SCD) is pain from a vaso-occlusive crisis. Although ambulatory pain accounts for most days in pain, pain is also the most common cause of hospitalization and is typically treated with parenteral opioids. The evidence base is lacking for most analgesic practice in SCD, particularly for the optimal opioid dosing for patient-controlled analgesia (PCA), in part because of the challenges of the trial design and conduct for this rare disease. Purpose The purpose of this report is to describe our Network’s experiences with protocol development, implementation, and analysis, including overall study design, the value of pain assessments rather than ‘crisis’ resolution as trial endpoints, and alternative statistical analysis strategies. Methods The Improving Pain Management and Outcomes with Various Strategies (IMPROVE) PCA trial was a multisite inpatient randomized controlled trial comparing two PCA-dosing strategies in adults and children with...
Blood
Over the last three decades there has been improvement in survival in children with sickle cell d... more Over the last three decades there has been improvement in survival in children with sickle cell disease. Overall survival from birth to age 18 of 86% and 95% has been reported in children with sickle cell anemia (HbSS) and sickle hemoglobin C (Hb SC) disease respectively. These encouraging results are secondary to initiation of preventive measures like newborn screening, penicillin prophylaxis, immunization and stroke prevention and other supportive therapies. Ballas (Blood2004;104 supl:Abstr 3743) reported high death rate for young adults with the disease. To determine the death rates and cause of death in our population, we did a retrospective review of our patients who had recently transitioned into adult care. Mortality rate and circumstances of death in a 10 year period of transition from pediatric to adult program in Georgia Comprehensive Sickle Cell Center at Grady Memorial Hospital between 1996 and 2006 were determined. Total number of deaths was obtained from the clinical d...
Blood
The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th ... more The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th decade, but this remains extremely variable. Little is known about the biological factors that protect certain SCD patients from early demise while others never reach mid-adulthood. Recently, McKerrell and colleagues (2004) compared the clinical and laboratory profiles of SCD patients aged 40 years and over with SCD patients who were between 21 and 30 years of age. Similarly, we have compared clinical and genetic correlates of older SCD patients (50 years and over) with those of younger patients (18–30 years). Among 514 patients in our total study population, 49 (10%) were categorized as “older” and 194 (38%) were categorized as “younger.” Older SCD patients had lower hemoglobin (older: 7.8 ± 1.1 vs. younger: 8.5 ± 1.2, p=0.004), platelet count (older: 372 ± 126 vs. younger: 460 ± 225, p=0.02), MCV (older: 92 ± 12 vs. younger: 89 ± 9, p=0.08), MCHC (older: 33.6 ± 1.4 vs. younger: 34.3 ± ...
Blood
In 1994, the average age of death of patients with sickle cell disease (SCD) in the US was 42 yea... more In 1994, the average age of death of patients with sickle cell disease (SCD) in the US was 42 years for males and 48 for females. We theorized that patients who lived appreciably beyond these ages would therefore have lower disease burden than patients overall, and that lack of specific disease complications would be characteristic of such patients. From 2001 until 2006, we enrolled 541 unrelated adult patients (age ≥18) with Hb SS or Hb Sβ0 at three comprehensive sickle cell centers in a study designed to identify factors associated with clinical outcomes in SCD. Our database includes demographic, clinical, and laboratory data on all participants. We identified 61 patients 50 years and older and 32 patients 55 years and older. Among the latter, the average age was 60.6, with a median of 58 years (range 55–83); 65% were female. Although patients with SCD are generally thought to have a low prevalence of hypertension, the mean BP in this older cohort was 142/75, and 55% of patients w...
Blood
Introduction: Renal damage is a progressive complication of sickle cell disease (SCD) that begins... more Introduction: Renal damage is a progressive complication of sickle cell disease (SCD) that begins with hyerfiltration in childhood followed by decline in glomerular filtration rate (GFR) and chronic renal failure in up to 12% of HbSS adults. Albuminuria is a marker of glomerular damage but does not predict GFR. Serum creatinine (SCr) is typically low in SCD despite glomerular damage, in part because tubular dysfunction leads to increased creatinine secretion. Cystatin C (CysC) is a low molecular weight protein, eliminated exclusively by glomerular filtration, and correlates with GFR in children and adults with chronic kidney disease (CKD). Previously, estimated GFR (eGFR) has been compared to measured GFR (mGFR) using equations that incorporate CysC and SCr in young children with SCD; however no studies have examined the precision or accuracy of GFR formulas in adults and older children with SCD. Methods: Adults and children ≥10 years with HbSS and albuminuria (albumin/creatinine ra...
Blood
BACKGROUND: Sickle cell disease nephropathy (SCDN) is a common complication of sickle cell diseas... more BACKGROUND: Sickle cell disease nephropathy (SCDN) is a common complication of sickle cell disease (SCD) associated with risk for early mortality (Platt et al., 1994; Elmariah et al, 2014). To identify potential genetic risk factors for SCDN, we performed genome-wide association studies (GWAS) for glomerular filtration rate (GFR) in three well-characterized SCD cohorts and performed in vivo functional analysis of one of the candidate genes in zebrafish. METHODS: Three previously described SCD cohorts were utilized in this analysis: Outcome Modifying Genes in Sickle Cell Disease (OMG-SCD) (Elmariah et al, 2014), Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) (Machado et al, 2011) and Pulmonary Hypertension and the Hypoxic Response in Sickle Cell Disease (PUSH) (Minniti et al, 2009). Patients less than 16 years old were excluded from PUSH. GFR was estimated using the…
Blood
Introduction: Sickle cell nephropathy (SCN) is a progressive complication of sickle cell disease ... more Introduction: Sickle cell nephropathy (SCN) is a progressive complication of sickle cell disease (SCD) that begins in childhood and may result in renal failure and early mortality; yet the potential for prevention and reversal of SCN is not known. Urinary albumin/creatinine ratio (ACR) is a biomarker of glomerular damage but may not correlate with renal hemodynamic abnormalities that are indicative of early renal failure, e.g. glomerular filtration rate (GFR), renal plasma flow (RPF), and glomerular membrane permeability. We hypothesized that the angiotensin receptor blocker losartan will improve GFR and decrease excretion of high molecular weight (HMW) proteins that are restricted at the glomerulus, while not affecting abnormalities in markers of tubular injury and ischemia. Methods: Adults and children ≥10 years with HbSS who were on hydroxyurea (HU) for ≥6 months but had persistent microalbuminuria (MiA; ACR ≥30 mg/g) or macroalbuminuria (MA; ACR ≥300 mg/g) on ≥2 consecutive occa...
Blood
Background: Acute chest syndrome (ACS) is one of the most feared complications of sickle cell dis... more Background: Acute chest syndrome (ACS) is one of the most feared complications of sickle cell disease. This syndrome is defined by a clinical constellation of symptoms including fever, infiltrate on lung imaging and hypoxia. ACS is a well-known complication to occur early in the hospitalization of patients for sickle cell vaso-occlusive pain crises (VOP). It is hard to differentiate from pneumonia and its rate of occurrence has not been well characterized. Management of ACS includes exchange or simple transfusion, depending on the severity of its presentation, along with critical care support and pain control. Early recognition of this clinical syndrome can lead to better management and outcomes for patients with sickle cell disease. Methods: The Emory University Georgia Comprehensive Sickle Cell Center at Grady Health System has 1073 sickle cell patients and provides a 24/7 acute care unit (ACU) for the evaluation of patients presenting with pain crises. We conducted a retrospectiv...
Blood
BACKGROUND: Nephropathy is a common and devastating complication of sickle cell disease (SCD) ass... more BACKGROUND: Nephropathy is a common and devastating complication of sickle cell disease (SCD) associated with mortality (Elmariah et al, 2014). However, early detection of SCD nephropathy (SCDN) has proven difficult. Discovery of genetic markers associated with SCDN could greatly improve our ability to identify patients at risk for renal decline. To that end, we have performed a genome-wide association study (GWAS) of glomerular filtration rate (GFR) in our adult SCD cohort. METHODS: Medical history, laboratory values and DNA for genotyping were collected as part of a multicenter study of outcome-modifying genes in SCD. Participating institutions included sickle cell centers at Duke University, University of North Carolina at Chapel Hill, Emory University, and East Carolina University. GFR was estimated using the ‘Modification of Diet in Renal Disease’ (MDRD) study definition (Levey et al, 1999) and dichotomized at the clinically relevant threshold of 90 ml/min/1.73m2. 463 patients ...
Nursing, 2002
Sterling Jackson, 21, who has a history of sickle-cell anemia, is admitted to the medical/surgica... more Sterling Jackson, 21, who has a history of sickle-cell anemia, is admitted to the medical/surgical unit from the emergency department (ED). He developed severe pain in his chest, arms, legs, and back about 10 hours ago. After 4 hours receiving intravenous (I.V.) nalbuphine (Nubain), ketorolac (Toradol), and hydration in the ED, he still rates his pain as 6 on a visual analogue scale, and his blood work shows worsening anemia from his baseline level. The most common genetic disorder in the United States, sickle-cell disease affects about 70,000 people. Although most common in African-Americans, it also affects people whose ancestors came from parts of the world where malaria is endemic. Having one sickle-cell gene (known as sickle-cell trait) provides some protection against malaria, but having two causes sicklecell disease. Years ago, people with sickle-cell disease died in their teens. Today, with improved education and treatment, some live into their 60s, but they’re susceptible to sickle-cell crises all their lives. In this article, we’ll explain what’s causing Mr. Jackson’s problems and how you can help him through the crisis.
Blood, 2005
The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th ... more The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th decade, but this remains extremely variable. Little is known about the biological factors that protect certain SCD patients from early demise while others never reach mid-adulthood. Recently, McKerrell and colleagues (2004) compared the clinical and laboratory profiles of SCD patients aged 40 years and over with SCD patients who were between 21 and 30 years of age. Similarly, we have compared clinical and genetic correlates of older SCD patients (50 years and over) with those of younger patients (18–30 years). Among 514 patients in our total study population, 49 (10%) were categorized as “older” and 194 (38%) were categorized as “younger.” Older SCD patients had lower hemoglobin (older: 7.8 ± 1.1 vs. younger: 8.5 ± 1.2, p=0.004), platelet count (older: 372 ± 126 vs. younger: 460 ± 225, p=0.02), MCV (older: 92 ± 12 vs. younger: 89 ± 9, p=0.08), MCHC (older: 33.6 ± 1.4 vs. younger: 34.3 ± 1.8, p=0.05), and WBC (older: 10.2 ± 2.7 vs. younger: 13.1 ± 4.1, p<0.001). Older patients also had lower total bilirubin (p=0.01), and increased alkaline phosphatase (p=0.0002) and creatinine (p=0.0002), which was associated with poorer creatinine clearance (p<0.0001). The older SCD patients also had increased systolic (p<0.0001) and diastolic (p=0.008) blood pressure, decreased O2 saturation (p=0.03), and a history of fewer pain episodes per year requiring medical treatment (p<0.0001). Many of our findings are consistent with those of McKerrell et al. (2004). In order to identify genetic factors associated with longevity in SCD, we examined 155 SNPs in a total of 41 genes, primarily involved in red blood cell adhesion and inflammation pathways. Chi Square tests of association were constructed for the genotypes of each SNP with the two clinical categories: “older” and “younger.” When the number of rare homozygotes was less than 5 individuals, we combined those individuals with the heterozygote individuals for analysis. All p-values are uncorrected for multiple testing. We found putative associations with 5 SNPs in 3 genes. Three non-coding SNPs in Klotho, not in linkage disequilibrium, exhibited different genotype frequencies in the older versus younger SCD patients (p=0.007, p=0.01 and p=0.01). Similarly, a single non-coding SNP in NOS2A (p=0.02) and TGFBR2 (p=0.02) also exhibited significantly different genotype frequencies in the older versus younger patients. These data support the clinical findings in aging SCD patients reported by McKerrell and colleagues (2004), and they also suggest that genetic factors contribute to variability in longevity in SCD. Interestingly, multiple SNPs in Klotho exhibited differing genotype frequencies in older versus younger patients. Mutations in Klotho have been previously associated with aging-related phenotypes in mice. A better understanding of the biological mechanisms associated with longevity in SCD may help identify those at risk for early demise and in need of more specialized medical care.
The Journal of bone and joint surgery. American volume, 1988
We studied the effect of indomethacin on the prevention of formation of heterotopic bone after to... more We studied the effect of indomethacin on the prevention of formation of heterotopic bone after total hip replacement. In a randomized, double-blind clinical trial involving 201 patients, 102 patients received twenty-five milligrams of indomethacin three times daily for the first six postoperative weeks, and the other ninety-nine patients received a placebo. One year after the operation, eighty-nine of those who had received indomethacin had no sign of heterotopic ossification, and the remaining thirteen had a grade-I lesion. In the group that had received a placebo, twenty-seven had no heterotopic ossification; twenty-four, a grade-I lesion; thirty, a grade-II lesion; and eighteen, a grade-III lesion. Significantly fewer patients who had received indomethacin had formation of heterotopic bone compared with those who had been given a placebo (chi-square test, p less than 0.0005). Only patients who had grade-III formation of heterotopic bone had a significant reduction in movement of ...
Screening, 1992
... A. Davidson, J. Eckman, WH Hannon, MA Henson, M. Hillard, S. Kling, HL Levy, FJ Meaney, ERB M... more ... A. Davidson, J. Eckman, WH Hannon, MA Henson, M. Hillard, S. Kling, HL Levy, FJ Meaney, ERB McCabe, V. Mordaunt, K. Pass, E. Shapira and J. Tuerck CORN Newborn Screening Committee, Council of Regional Networks for Genetic Services, Cornell University Medical ...
Biochemical and …, 1996
JOBNAME: BM 57#2 96 PAGE: 1 SESS: 15 OUTPUT: Fri May 31 05:51:55 1996 /xypage/worksmart/tsp000/69... more JOBNAME: BM 57#2 96 PAGE: 1 SESS: 15 OUTPUT: Fri May 31 05:51:55 1996 /xypage/worksmart/tsp000/69087h/9pu ... Guidelines for the Retention, Storage, and Use of Residual Dried ... Blood Spot Samples after Newborn Screening Analysis: