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Sickle Cell Patients Suffer As Disparities In Care, Research Persist

http://www.courant.com/news/connecticut/hc-sickle-cell-20180511-story.html

When 9-year-old Jeremy Brown is in pain, it feels like he is being stabbed. The pain experienced by Deborah Oliver, 40, is like 100 simultaneous charley horses.

Brown, of Bridgeport, and Oliver, of New Haven, have sickle cell disease, a genetic blood disorder that causes excruciating pain, life-threatening complications and a shortened life expectancy. Almost half of sickle cell patients die in their 40s.

The disease affects about 100,000 Americans, about one in 365 African Americans and one out of 16,300 Hispanics, and in lesser numbers, people with Middle Eastern, Indian, Caribbean and Mediterranean ancestries. An estimated 2,000 people in Connecticut have SCD.

But the disease — discovered over 100 years ago — receives little research, funding or attention.

  • Just two medications have been developed to treat the disease: hydroxyurea, approved in 1998; and Endari, approved in 2017.
  • There is no national data registry for tracking the disease.
  • Only four of the state’s 27 acute-care hospitals have sickle cell treatment programs. And the last SCD awareness program by the Department of Public Health was in 2007.
  • A 2013 study in the journal Blood reported that cystic fibrosis, which affects 30,000 people nationally, receives seven to 11 times more funding per patient than sickle cell disease. The amyotrophic lateral sclerosis challenge in 2014 raised more than $115 million for about 20,000 patients in the U.S. The bulk of the funds — $77 million — were allocated for research.

“I think it’s ignored because it’s predominantly a disease of inner-city African Americans,” said Dr. William Zempsky, a pain specialist at Connecticut Children’s Medical Center in Hartford, which treats children with SCD.

The other treatment programs are at Yale New Haven and Bridgeport hospitals and UConn Health in Farmington. In total, they treat about half of the state residents with SCD, estimated Dr. Biree Andemariam, the UConn program director. There are no hard statistics on adults with SCD born before 1990, when the state started testing newborns for it. More than 660 babies were born with the disease from 1990 to 2017, according to DPH.

Andemariam said that about 1,000 patients get no care or go to emergency rooms when in crisis. She and Zempsky created an ER treatment protocol for hospitals without sickle cell programs, but none of the Connecticut ERs they approached use it, she said.

Advocates say poor ER care has caused deaths due to lack of knowledge about SCD. Virginia Pertillar, executive director of Citizens for Quality Sickle Cell Care, said patients endure harmful, “unnecessarily long waits,” are accused of seeking opioids “to get high, not to relieve pain,” and are “mistreated or maltreated.”

“Quite honestly, because this primarily affects people of color in this country, some of the disparities in care and research dollars and pharmaceutical interests are intertwined with our country’s history of the marginalization experienced by people of color,” Andemariam said.

Dr. Gregory Buller, Bridgeport Hospital’s chief of medicine, said most SCD patients don’t have the income or clout to raise awareness, with many on disability or a limited work schedule. “If Warren Buffett had sickle cell disease, then the approach to it might be a whole lot different,” he said.

 

Five Blood Transfusions, One Bone Marrow Transplant — All Before Birth

https://www.nytimes.com/2018/05/25/health/fetal-bone-marrow-transplant.html

SAN FRANCISCO — In the three months before she was even born, Elianna Constantino received five blood transfusions and a bone-marrow transplant. All were given with a needle passed through her mother’s abdomen and uterus, into the vein in her umbilical cord.

Elianna, born Feb. 1 with a robust cry and a cap of gleaming black hair, has a genetic disease that usually kills a fetus before birth. The condition, alpha thalassemia major, leaves red blood cells unable to carry oxygen around the body, causing severe anemia, heart failure and brain damage.

The transfusions in the womb kept her alive, but only treated her illness. The bone-marrow transplant has the potential to cure it. Whether it will succeed is still too soon to tell.

Elianna and her mother, Nichelle Obar, were the first patients in an experiment that pushes the limits of fetal therapy, a field already known for its daring.

If the treatment works, it could open the door to using bone-marrow transplants before birth to cure not just Elianna’s blood disease but also sickle cell anemia, hemophilia and other hereditary disorders, some so severe that the prenatal diagnosis may lead parents to end the pregnancy.

Bone marrow is considered a potential cure because it teems with stem cells, which can create replacements for cells that are missing or defective as a result of genetic flaws.

“This line of work moves the field of fetal surgery, which currently consists of big operations for anatomic disorders, in a new direction of molecular and cellular therapies given non-invasively,” said Dr. Tippi MacKenzie, a pediatric and fetal surgeon who is leading the study at the U.C.S.F. Benioff Children’s Hospital San Francisco, part of the University of California, San Francisco.

Ms. Obar, 40, and her husband, Chris Constantino, 37, are healthy but learned during her first pregnancy that they are thalassemia carriers. There are several forms of the disease, and worldwide about 100,000 children a year are born with severe cases. Millions of people are carriers, most commonly those from Asia, the Mediterranean, Africa or the Middle East.

Carriers are generally healthy, but when two have children together, the children are at risk for the disease. Ms. Obar’s ancestry is Filipino and Puerto Rican; her husband’s is Filipino. They live in Kilauea, on the Hawaiian island of Kauai.

 

IASCNAPA SCHOLARSHIPS

The International Association of Sickle Cell Nurses and Professional Associates, Inc. (IASCNAPA)  has established a college scholarship program to assist individuals living with Sickle Cell Disease who attend an institution of higher learning in the United States.  Applicants for IASCNAPA’s $1,000 Scholarships must be enrolled in, or have been accepted by, a recognized and accredited post- secondary school, including college, university, trade school, or other institution of higher learning. Curriculum choice, age, gender, race, ethnic background, religion and political affiliation will not be used in evaluating applications.  An active IASCNAPA member or a sickle cell disease medical provider must sponsor all applicants.  Applications are accepted from March 1 through July 1 of each year. Awards will be given in August of each year. The number of scholarships awarded each year is dependent on available funds and the quality of applications.

IASCNAPA’s funded scholarship awards include:

The Steven Christy Scholarship Fund was established by his wife in memory of her husband, an individual who lived with sickle cell disease and valued education. He struggled to complete college, but persevered and graduated from Fitchburg State University. He spent his career helping others – first as a social worker at Favarh and then as a counselor and coordinator of newborn hemoglobinopathy screening programs at the combined UCONN/St. Francis sickle cell clinic.

The Christine A. Johnson Scholarship Fund was established by the friends of Dr. Christine A. Johnson in her honor. Dr. Christine A Johnson was a provider and advocate for people with sickle cell disease for most of her adult career. She was the founder and Director of the Pediatric Sickle Cell Program at Wake Forest Baptist Medical Center, and an advocate for sickle cell disease for 30 years.

For more information, to donate to the scholarship fund, or to apply for the scholarship, go to www.Iascnapa.org

 

New video teaching course for CEU/CME

REDUCING COMPLICATIONS OF THERAPEUTIC BLOOD TRANSFUSION IN SICKLE CELL DISEASE at http://ghpc.gsu.edu/cme-course-introduction/

 

June 19 is World Sickle Cell Day

Art T-shits to promote sickle cell awareness by world famous sickle cell artist Hertz Nazaire https://www.amazon.com/s/ref=w_bl_sl_s_ap_web_7141123011?ie=UTF8&node=7141123011&field-brandtextbin=June+19th+World+Sickle+Cell+Day

 

Articles in the Medical Literature

 

Pediatr Blood Cancer. 2018 May 24:e27263. doi: 10.1002/pbc.27263. [Epub ahead of print]

Hematopoietic stem cell transplantation for sickle cell disease: Progress and challenges.

Hulbert ML1, Shenoy S1.

Abstract

Sickle cell disease (SCD) presents challenges to hematopoietic stem cell transplantation (HSCT), including donor availability and morbidity with age/disease severity. However, severe SCD causes irreversible organ damage that HSCT can mitigate. This benefit must be balanced against preparative regimen toxicity, graft-versus-host disease, and mortality risk. We review efforts to balance HSCT complications with the promise of cure, and knowledge gaps that warrant further investigation. We highlight the burden of SCD, HSCT risks and benefits, and SCD families’ approach to this balance. We emphasize the necessity for information exchange to ensure a joint decision-making process between providers and patients.

PMID: 29797658

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Pediatr Blood Cancer. 2018 May 24:e27228. doi: 10.1002/pbc.27228. [Epub ahead of print]

Sickle Cell Clinical Research and Intervention Program (SCCRIP): A lifespan cohort study for sickle cell disease progression from the pediatric stage into adulthood.

Hankins JS1, Estepp JH1, Hodges JR1, Villavicencio MA1, Robison LL2, Weiss MJ1, Kang G3, Schreiber JE4, Porter JS4, Kaste SC5,6,7, Saving KL8, Bryant PC9, Deyo JE10, Nottage KA11, King AA12, Brandow AM13, Lebensburger JD14, Adesina O15, Chou ST16, Zemel BS17, Smeltzer MP18, Wang WC1, Gurney JG18.

Abstract

BACKGROUND:

Previous natural history studies have advanced the understanding of sickle cell disease (SCD), but generally have not included sufficient lifespan data or investigation of the role of genetics in clinical outcomes, and have often occurred before the widespread use of disease-modifying therapies, such as hydroxyurea and chronic erythrocyte transfusions. To further advance knowledge of SCD, St. Jude Children’s Research Hospital established the Sickle Cell Clinical Research and Intervention Program (SCCRIP), to conduct research in a clinically evaluated cohort of individuals with SCD across their lifetime.

PROCEDURES:

Initiated in 2014, the SCCRIP study prospectively recruits patients diagnosed with SCD and includes retrospective and longitudinal collection of clinical, neurocognitive, geospatial, psychosocial, and health outcomes data. Biological samples are banked for future genomics and proteomics studies. The organizational structure of SCCRIP is based upon organ/system-specific working groups and is opened to the research community for partnerships.

RESULTS:

As of August 2017, 1,044 (92.3% of eligible) patients with SCD have enrolled in the study (860 children and 184 adults), with 11,915 person-years of observation. Population demographics included mean age at last visit of 11.3 years (range 0.7-30.1), 49.8% females, 57.7% treated with hydroxyurea, 8.5% treated with monthly transfusions, and 62.9% hemoglobin (Hb) SS or HbSB0 -thalassemia, 25.7% HbSC, 8.4% HbsB+ -Thalassemia, 1.7% HbS/HPFH, and 1.2% other.

CONCLUSIONS:

The SCCRIP cohort will provide a rich resource for the conduct of high impact multidisciplinary research in SCD.

© 2018 Wiley Periodicals, Inc.

PMID: 29797644

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Sports Med Open. 2018 May 23;4(1):19. doi: 10.1186/s40798-018-0131-6.

Sickle Cell Trait and Sudden Death.

Mitchell BL1.

Abstract

Sickle cell trait has long been considered a benign condition but continues to be the leading cause of death in young African Americans in military basic training and civilian organized sports. There continues to be a great deal of controversy surrounding sickle cell trait and its association with exercise-related morbidity and sudden death. Even though sickle cell trait has a high prevalence among African Americans, many clinicians believe the potential adverse consequences should have been mitigated by actions such as universal screening in the USA at birth for sickle hemoglobin, National Collegiate Athletic Association (NCAA) rule changes, and changes in the US Military boot camp system. Sudden death due to periods of extreme physical exertion continues to occur in individuals with sickle cell trait.

PMID: 29796715

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J Music Ther. 2018 May 23. doi: 10.1093/jmt/thy004. [Epub ahead of print]

The Effects of a Single Electronic Music Improvisation Session on the Pain of Adults with Sickle Cell Disease: A Mixed Methods Pilot Study.

Rodgers-Melnick SN1, Matthie N2, Jenerette C3, Griest Pell TJ1, Lane D1, Fu P4, Margevicius S4, Little JA5.

Abstract

Background:

Adults with sickle cell disease (SCD) experience acute pain that is multidimensional. Despite recent improvements in treatment, pain management remains a significant challenge for these individuals. Music therapy interventions have the potential to address several dimensions of SCD pain, but they require systematic investigation.

Objective:

This study investigated feasibility and preliminary efficacy of a single-session electronic music improvisation with a music therapist to diminish pain intensity and improve pain relief and mood in adults with SCD.

Methods:

Using a three-group mixed methods intervention design, we randomized 60 adults with SCD to standard care plus one of three 20-minute study conditions: 1) electronic music improvisation with a music therapist (MT); 2) recorded music listening (ML); or 3) no intervention (control). Measures of pain intensity (VASPI), pain relief (VASPR), and mood (VASMOOD) were assessed before and after the study conditions, with a subset of MT and ML participants interviewed after measure completion.

Results:

Compared to control, MT produced significant improvements in VASPI (odds ratio (OR) = 5.12, P = 0.035) and VASMOOD (OR = 11.60, P = 0.005). ML produced significant improvements in VASMOOD compared to control (OR = 5.76, P = 0.040). Qualitatively, there were two prominent themes directly related to music: 1) ML and MT offered many positive and few negative effects; and 2) music therapists provided comfort beyond the music.

Conclusions:

Preliminary findings were promising and support the need for additional studies evaluating improvisational music therapy interventions for acute pain management in adults with SCD.

PMID: 29796596

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Scand J Pain. 2018 Jan 26;18(1):19-27. doi: 10.1515/sjpain-2017-0140.

Low dose ketamine versus morphine for acute severe vaso occlusive pain in children: a randomized controlled trial.

Lubega FA1, DeSilva MS2, Munube D3, Nkwine R4, Tumukunde J4, Agaba PK4, Nabukenya MT4, Bulamba F5, Luggya TS4.

Abstract

BACKGROUND AND AIMS:

Acute pain episodes associated with sickle cell disease (SCD) are very difficult to manage effectively. Opioid tolerance and side effects have been major roadblocks in our ability to provide these patients with adequate pain relief. Ketamine is cheap, widely safe, readily available drug, with analgesic effects at sub-anesthetic doses and has been used in wide range of surgeries, pediatric burns dressing change and cancer related pain however, literature concerning its use in sickle cell crises is still limited in our setting. This study aimed to establish if 1 mg/kg of intravenous ketamine is non inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain.

METHODS:

We performed an institutional review board-approved randomized, prospective, double-blinded, active-control, non-inferiority trial at the national referral sickle cell center. Children between 7 and 18 years of age with severe painful sickle cell crisis, defined by numerical rating scale score of greater or equal to 7 were enrolled. Patients were consented and randomized to receive, either IV ketamine (LDK) 1 mg/kg or IV morphine (MOR) 0.1 mg/kg as an infusion over 10 min. The primary endpoint is maximal change in Numerical Rating Scale (NRS) pain score. Secondary outcomes were, incidence of adverse effects, optimal time to and duration of action of ketamine and incidence of treatment failures by treatment group. A clinically meaningful difference in validated pain scores was defined as 1.3 units. Assuming both treatments are on average equal, a sample size of 240 patients (120 per group) provided 95% power to demonstrate that IV LDK is non-inferior to IV morphine with a 0.05 level of significance and a 10% non-inferiority margin. All analyses were based on a modified intention to treat. This trial was registered with clinicaltrials.gov NCT02434939.

RESULTS:

Two hundred and forty patients were enrolled (LDK120, MOR120). Demographic variables and baseline NRS scores (8.9 vs. 9.2) were similar. LDK was comparable to MOR in the maximum change in NRS scores, 66.4% vs. 61.3% (MD 5.5; 95% CI -2.2 to -13.2). Time to achieve maximum reduction in NRS pain scores was at 19.8 min for LDK and 34.1 min for MOR. The average duration of action for LDK was 60 min. MOR had more patients still at maximum effect at 120 min (45.8% vs. 37.5%; RR 1.2; 95% CI 0.9-1.7). LDK patients were 11.3 times more likely to develop side effects, though were transient, anticipated and non-life threatening (37.5% vs. 3.3%). MOR had significantly more treatment failures 40% vs. 28.3% (RR 0.7; 95% CI 0.5-1.03, p=0.07) Vital signs and sedation scores were similar in both groups.

CONCLUSIONS:

Intravenous LDK at 1 mg/kg provides comparable analgesic effectiveness as IV MOR in the acute treatment of severe painful sickle cell crisis in children in the day care sickle cell center. However, it is associated with a high incidence of several transient, non-life threatening mild side effects.

IMPLICATIONS:

Intravenous ketamine at 1 mg/kg can be a reliable alternative to morphine in the management of severe painful sickle cell crisis especially in a resource limited area where morphine is not readily available.

PMID: 29794277

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J Pain Palliat Care Pharmacother. 2018 May 23:1-7. doi: 10.1080/15360288.2018.1468383. [Epub ahead of print]

Low-Dose Ketamine Infusion for Adjunct Management during Vaso-occlusive Episodes in Adults with Sickle Cell Disease: A Case Series.

Palm N, Floroff C, Hassig TB, Boylan A, Kanter J.

Abstract

The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.

PMID: 29791238

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BMC Musculoskelet Disord. 2018 May 22;19(1):158. doi: 10.1186/s12891-018-2067-x.

Use of autologous bone marrow stem cell implantation for osteonecrosis of the knee in sickle cell disease: a preliminary report.

Daltro G1, Franco BA1, Faleiro TB1, Rosário DAV1, Daltro PB2, Meyer R2, Fortuna V3.

Abstract

BACKGROUND:

The purpose of our study was to evaluate safety, feasibility and clinical results of bone marrow mononuclear cell (BMC) implantation for early-stage osteonecrosis of the knee (OK) secondary to sickle cell disease.

METHODS:

Thirty-three SCD patients (45 knees) with OK treated with BMC implantation in the osteonecrotic lesion were clinically and functionally evaluated through the American Knee Society Clinical Score (KSS), Knee Functional Score (KFS) and Numeric Rating Scale (NRS) pain score. MRI and radiographic examinations of the knee were assessed during a period of five years after intervention.

RESULTS:

No complications or serious adverse event were associated with BMC implantation. From preoperative assessment to the latest follow-up, there was a significant (p < 0.001) improvement of clinical KSS (64.3 ± 9.7, range: 45-80 and 2.2 ± 4.1, range: 84-100, respectively), KFS (44.5 ± 8.0, range: 30-55 and 91.6 ± 5.8, range: 80-100, respectively) and reduction of NRS pain score (6.7 ± 1.2, range: 4-9 and 3.4 ± 1.0, range: 2-5, respectively). In total, 87% of patients (29/33) consistently experienced improvements in joint function and activity level as compared to preoperative score. No patient had additional surgery following BMC implantation. Radiographic assessment showed joint preservation and no progression to subchondral collapse at most recent follow-up.

CONCLUSIONS:

The technique of BMC implantation is a promising, relatively simple and safe procedure for OK in SCD patients. Larger and long-term controlled trials are needed to support its clinical effectiveness.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02448121 . Retrospectively registered 19 May 2015.

PMCID: PMC5964644 Free PMC Article

PMID: 29788942

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Glob Pediatr Health. 2018 May 14;5:2333794X18774970. doi: 10.1177/2333794X18774970. eCollection 2018.

Stroke Prevalence in Children With Sickle Cell Disease in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Marks LJ1, Munube D2, Kasirye P2, Mupere E2, Jin Z3, LaRussa P3, Idro R2, Green NS3.

Abstract

Objectives. The prevalence of stroke among children with sickle cell disease (SCD) in sub-Saharan Africa was systematically reviewed. Methods. Comprehensive searches of PubMed, Embase, and Web of Science were performed for articles published between 1980 and 2016 (English or French) reporting stroke prevalence. Using preselected inclusion criteria, titles and abstracts were screened and full-text articles were reviewed. Results. Ten full-text articles met selection criteria. Cross-sectional clinic-based data reported 2.9% to 16.9% stroke prevalence among children with SCD. Using available sickle gene frequencies by country, estimated pediatric mortality, and fixed- and random-effects model, the number of affected individuals is projected as 29 800 (95% confidence interval = 25 571-34 027) and 59 732 (37 004-82 460), respectively. Conclusion. Systematic review enabled the estimation of the number of children with SCD stroke in sub-Saharan Africa. High disease mortality, inaccurate diagnosis, and regional variability of risk hamper more precise estimates. Adopting standardized stroke assessments may provide more accurate determination of numbers affected to inform preventive interventions.

PMCID: PMC5954575 Free PMC Article

PMID: 29785408

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

 

 

Health Qual Life Outcomes. 2018 May 21;16(1):99. doi: 10.1186/s12955-018-0930-y.

Systematic literature review and assessment of patient-reported outcome instruments in sickle cell disease.

Sarri G1, Bhor M2, Abogunrin S3, Farmer C3, Nandal S2, Halloway R2, Revicki DA4.

Author information:

Abstract

BACKGROUND:

Sickle cell disease (SCD) is a chronic condition associated with high mortality and morbidity. It is characterized by acute clinical symptoms such as painful vaso-occlusive crises, which can impair health-related quality of life (HRQL). This study was conducted to identify validated patient-reported outcome (PRO) instruments for use in future trials of potential treatments for SCD.

METHODS:

A systematic literature review (SLR) was performed using MEDLINE and EMBASE to identify United States (US)-based studies published in English between 1997 and 2017 that reported on validated PRO instruments used in randomized controlled trials and real-world settings. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the quality of PRO instruments.

RESULTS:

The SLR included 21 studies assessing the psychometric properties of 24 PRO instruments. Fifteen of those instruments were developed and validated for adults and 10 for children (one instrument was used in both children and young adults aged up to 21 years). Only five of the 15 adult instruments and three of the 10 pediatric instruments were developed specifically for SCD. For most instruments, there were few or no data on validation conducted in SCD development cohorts. Of the 24 PRO instruments identified, 16 had strong internal reliability (Cronbach’s α ≥0.80). There was often insufficient information to assess the content validity, construct validity, responsiveness, or test-retest reliability of the instruments identified for both child and adult populations. No validated PRO instruments measuring caregiver burden in SCD were identified.

CONCLUSIONS:

The evidence on the psychometric properties of PRO instruments was limited. However, the results of this SLR provide key information on such tools to help inform the design of future clinical trials for patients with SCD in the US.

Free Article

PMID: 29784054

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Pediatr Blood Cancer. 2018 May 21:e27113. doi: 10.1002/pbc.27113. [Epub ahead of print]

Diastolic dysfunction is associated with exercise impairment in patients with sickle cell anemia.

Alsaied T1,2, Niss O3, Powell AW1, Fleck RJ4, Cnota JF1, Chin C1, Malik P3,5, Quinn CT3, Taylor MD1.

Abstract

BACKGROUND:

Left ventricular diastolic dysfunction (DD) is an independent risk factor for mortality in sickle cell anemia (SCA) and is associated with increased extracellular volume (ECV) on cardiac MRI (CMR). Exercise impairment is common in SCA, but its causes and prognostic value are not well understood.

OBJECTIVE:

To study the effects of DD and ECV on cardiopulmonary exercise test (CPET) in patients with SCA.

METHODS AND RESULTS:

As part of a prospective study to characterize the cardiomyopathy of SCA (NCT02410811), 20 children and adults with SCA underwent CMR, echocardiography, and cycle ergometer CPET (age range 8-43 years). Maximum exercise was reached in 18 patients and 17 (94%) had reduced exercise capacity (%predicted VO2 less than 80%). Six patients had DD and none had systolic dysfunction. Patients with DD had lower exercise capacity compared to patients with normal diastolic function (%predicted VO2 48.2 ± 9.1% vs. 61.2 ± 11.7%; P = 0.01). The z-score of left ventricular lateral E/e’ ratio, which is a marker of DD, was negatively associated with %predicted VO2 (r = -0.61, P = 0.01). All patients with moderate-to-severe exercise impairment (%predicted VO2  < 60%) had lateral E/e’ z-score > 2. In a multivariate analysis, lateral E/e’ z-score was independently associated with %predicted VO2 (P = 0.02). All participants had elevated ECV but the degree of elevation was not associated with exercise parameters.

CONCLUSION:

Left ventricular DD is associated with decreased exercise capacity in SCA. Interventions to prevent or delay DD could improve exercise capacity, quality of life, and long-term outcomes in SCA.

© 2018 Wiley Periodicals, Inc.

PMID: 29781568

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Blood Cells Mol Dis. 2018 May 16. pii: S1079-9796(18)30173-6. doi: 10.1016/j.bcmd.2018.05.001. [Epub ahead of print]

Biomarker signatures of sickle cell disease severity.

Du M1, Van Ness S2, Gordeuk V3, Nouraie SM4, Nekhai S5, Gladwin M6, Steinberg MH7, Sebastiani P8.

Abstract

Identifying sickle cell disease patients at high risk of complications could lead to personalized treatment and better prognosis but despite many advances prediction of the clinical course of these patients remains elusive. We propose a system-type approach to discover profiles of multiple, common biomarkers that correlate with morbidity and mortality in sickle cell disease. We used cluster analysis to discover 17 signatures of 17 common circulating biomarkers in 2320 participants of the Cooperative Study of Sickle Cell Disease, and evaluated the association of these signatures with risk for stroke, pain, leg ulceration, acute chest syndrome, avascular necrosis, seizure, death, and trend of fetal hemoglobin and hemolysis using longitudinally collected data. The analysis shows that some of the signatures are associated with reduced risk for complications, while others are associated with increased risk for complications. We also show that these signatures repeat in two more contemporary studies of sickle cell disease and correlate with recently discovered biomarkers of pulmonary vascular disease. With replication and further study, these biomarker signatures could become an important and affordable precision medicine tool to aid treatment and management of the disease.

PMID: 29778312

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J Pain Res. 2018 May 8;11:947-953. doi: 10.2147/JPR.S151198. eCollection 2018.

Pain catastrophizing is associated with poorer health-related quality of life in pediatric patients with sickle cell disease.

Bakshi N1, Lukombo I1,2, Belfer I3, Krishnamurti L1.

Background:

Sickle cell disease (SCD) is an inherited disorder of the red blood cells and is associated with chronic multisystem involvement. While SCD has been associated with poorer health-related quality of life (HRQoL), there is a paucity of data on the relationship of psychological covariates other than anxiety and depression and quality of life (QoL) in children with SCD.

Materials and methods:

We performed a cross-sectional study of psychological factors, HRQoL, and pain-related outcomes in participants with SCD and race-matched controls as part of a larger study of experimental pain phenotyping.

Results:

Pain catastrophizing was inversely correlated with HRQoL measured by the PedsQL™ Generic Core Scale in children with SCD, while this was not noted in control participants. Psychological factors, such as anxiety and depressive symptoms, were also associated with poorer HRQoL in both children with SCD and controls. We did not find an association of psychological factors with prior health care utilization. Psychological factors such as anxiety and depressive symptoms were inversely correlated with pain interference, but not pain intensity in SCD.

Conclusion:

Catastrophizing is associated with poorer HRQoL in SCD, but in this study, it was not associated with pain intensity or interference and health care utilization in children with SCD. Further studies are needed to fully define the association of psychological factors including catastrophizing with QoL, pain burden, and SCD outcomes.

PMCID: PMC5947835 Free PMC Article

PMID: 29773954

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Soc Work Public Health. 2018 May 16:1-18. doi: 10.1080/19371918.2018.1469064. [Epub ahead of print]

Knowledge, beliefs, attitudes, and behaviors regarding sickle cell disease: Implications for prevention.

Smith M1, Brownell G1.

Abstract

Sickle cell disease (SCD) is a widespread inherited blood disorder, which leaves lasting effects on the health, social functioning, and finances of individuals, families, communities, and health care systems. A nonexperimental, cross-sectional research design was used to assess 415 college students’ knowledge about SCD. Data was obtained through an online survey derived from a modified version of the SCD Knowledge Assessment Tool. The majority of participants (79%) reported previous SCD knowledge; however, 21% of the participants reported no previous SCD knowledge. Results support the need for improved education and awareness for at risk groups. The lack of SCD knowledge among African Americans shows a need for improved, nongendered specific education, awareness, and screening efforts geared toward at-risk populations.

PMID: 29768104

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Br J Haematol. 2018 May 16. doi: 10.1111/bjh.15270. [Epub ahead of print]

Risk factors for vitamin D deficiency in sickle cell disease.

Han J1,2,3, Zhang X2, Saraf SL2, Gowhari M2, Molokie RE2,4, Hassan J2, Jain S2, Shah BN2, Abbasi T2, Machado RF5, Gordeuk VR2.

Abstract

Vitamin D deficiency (VDD), 25-OHD levels <20 ng/ml, is prevalent among patients with sickle cell disease (SCD) and is linked to acute and chronic pain and bone fracture in this population. There is limited literature regarding VDD-associated risk factors for SCD. We examined potential clinical and genomic parameters associated with VDD in 335 adults with SCD in a cross-sectional study. VDD was present in 65% of adult SCD patients, and 25-OHD levels independently and positively correlated with older age (P < 0·001) and vitamin D supplementation (P < 0·001). 25-OHD levels were higher in SCD patients over 40 years of age compared to the general African-American population. Both lower 25-OHD levels and increased pain frequency were associated with increased expression of SLC6A5 encoding glycine transporter-2 (GlyT2), a protein involved in neuronal pain pathways. Lower 25-OHD levels were also associated with increased expression of CYP3A4, and with decreased expression of GC (also termed DBP) and VDR, three genes involved in vitamin D metabolism. We conclude that vitamin D supplementation should be an almost universal feature of the care of young adults with SCD, and that further research is warranted into genomic factors that regulate vitamin D metabolism in SCD.

PMID: 29767851

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Br J Haematol. 2018 May 16. doi: 10.1111/bjh.15396. [Epub ahead of print]

Hydroxycarbamide adherence and cumulative dose associated with hospital readmission in sickle cell disease: a 6-year population-based cohort study.

Zhou J1, Han J1,2,3, Nutescu EA1, Gordeuk VR3, Saraf SL3, Calip GS1,4.

Abstract

Sickle cell disease (SCD) is a congenital haemoglobinopathy that causes frequent acute care/emergency room visits and hospital admissions for affected individuals. Evidence from population-based studies demonstrating the role of hydroxycarbamide (HC, also termed hydroxyurea) in reducing hospital readmission rates is limited. Our objective was to describe the use of HC and its association with acute care utilization and readmission rates using a large, nationally-representative US health insurance claims database over a 6-year period between 2009 and 2014. We identified 20 721 SCD-related inpatient and acute care encounters. Patients had been exposed to HC within 6 months prior to admission in 4263 (21%) of SCD-related admission events. HC use was more common among children aged 10-17 years and young adults aged 18-29 years. HC was associated with lower 30-day all-cause readmission rates in adults treated with average daily doses ≥1 g (odds ratio [OR], 0·72, 95% confidence interval [CI] 0·52-0·99) and doses of 0·5-1 g (OR, 0·73, 95% CI 0·57-0·93), compared to HC treatment with average daily doses of <0·5 g; adherence to HC with proportion of days covered of ≥0·80 was also associated with significantly lower 30-day all-cause readmission risks (OR, 0·59, 95% CI 0·41-0·84). Optimal therapeutic dosing and adherence to HC treatment significantly reduces 30-day readmissions among patients with SCD.

PMID: 29767446

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Blood. 2018 May 15. pii: blood-2018-03-822593. doi: 10.1182/blood-2018-03-822593. [Epub ahead of print]

How we diagnose and treat venous thromboembolism in sickle cell disease.

Shet AS1, Wun T2.

Abstract

The incidence of venous thromboembolism (VTE) in adult patients with sickle cell disease (SCD) is high. However, overlapping features between the clinical presentation of VTE and SCD complications and a low index of suspicion for thrombosis can influence patient management decisions. VTE in SCD can therefore present management challenges to the clinical hematologist. Herein, we present three distinct clinical vignettes that are representative of our clinical practice with SCD patients. These vignettes are discussed with specific reference to the hypercoagulable state in SCD patients, recent VTE diagnosis and anticoagulant therapy guidelines from the general population, and evaluation of the risk of bleeding as a result of long term exposure to anticoagulant therapy. We examine current diagnostic and treatment options, highlight limitations of the existing clinical prognostic models that offer personalized guidance regarding the duration of anticoagulation, and propose a clinical approach to guide the decision to extend anticoagulation beyond 3 months.

PMID: 29764840

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Echocardiography. 2018 May 14. doi: 10.1111/echo.14028. [Epub ahead of print]

Echocardiographic parameters to identify sickle cell patients with cardio-pathology.

Chiadika S1, Lim-Fung M1, Llanos-Chea F2, Serauto Canache A2, Yang W2, Paruthi C1, Zhang X3, McPherson DD1, Idowu M4.

Abstract

BACKGROUND:

Sickle cell disease (SCD) affects millions of people and causes chronic hemolytic anemia leading to vasculopathies such as pulmonary hypertension and abnormalities in cardiac function that increase complications and mortality. It is therefore crucial to identify cardiac abnormalities in SCD. We aimed to assess the prevalence of echocardiographic parameters in SCD to help identify cardiopulmonary risk.

METHODS:

Ninety-one patients (53% male), median age of 30, body surface area (BSA) of 1.79 m2 , hemoglobin of 8.8 g/dL, and creatinine of 0.7 mg/dL identified. We retrospectively measured laboratory and echocardiographic parameters in patients with SCD : left ventricular (LV) dimensions, LV ejection fraction (LVEF), LV Myocardial Performance Index (MPI), LV Mass Index (MI), Left Atrial Volume Index (LAVI), Tricuspid Regurgitation Velocity (TRV), tricuspid annular plane systolic excursion (TAPSE), right heart dimensions.

RESULTS:

Prevalence of left heart abnormalities was 32%: increased LV end-diastolic diameter (EDD), 78%: LV MPI, 21%: diastolic dysfunction, 38%: decreased LVEF, 24%: increased LVMI, and 47%: increased LAVI. Right heart abnormalities were 39%: TAPSE, 38%: increased TRV, and 59%: increased pulmonary systolic pressure (PASP). Multivariate logistic regression analysis was significant for increased LVMI and LAVI in those with hemoglobin ≤8 g/dL (odds ratio (OR) 7.4, 95% confidence interval (CI) 2.23-24.6, P = .001) and (OR 3.32, 95% CI 1.18-9.33, P = .023).

CONCLUSIONS:

We confirmed increased prevalence of abnormal LVEDD, LVMI, diastolic function, LAVI, and PASP in SCD. In addition, we identified abnormal LV MPI (78%), TAPSE (29%). These parameters may be useful and readily accessible echocardiographic prognostic tools in this population.

© 2018 Wiley Periodicals, Inc.

PMID: 29756358

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Mediterr J Hematol Infect Dis. 2018 May 1;10(1):e2018032. doi: 10.4084/MJHID.2018.032. eCollection 2018.

Perioperative Management of Sickle Cell Disease.

Adjepong KO1, Otegbeye F2, Adjepong YA3.

Abstract

Over 30 million people worldwide have sickle cell disease (SCD). Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlusive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury. Pre-operative assessment must include a careful review of the patient’s known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and opioid use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss. Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged.

PMCID: PMC5937979 Free PMC Article

PMID: 29755709

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Pediatr Blood Cancer. 2018 May 11:e27084. doi: 10.1002/pbc.27084. [Epub ahead of print]

Management of severe chronic pain with methadone in pediatric patients with sickle cell disease.

LeBlanc Z1, Vance C2, Payne J3, Zhang J4, Hilliard L3, Lebensburger JD1,2,3,4, Howard TH3.

Abstract

Vasocclusive pain crises are common among pediatric patients with sickle cell disease (SCD). Some patients with repeated pain crises develop chronic pain. We performed a retrospective cohort study of pediatric patients with SCD with chronic pain treated with methadone. We identified a significant reduction in pain hospitalizations following methadone treatment (0.35 ± 0.19 vs. 0.19 ± 0.17 hospitalizations/month, P = 0.016). In addition, we did not observe overt organ toxicity nor symptoms of opioid withdrawal during methadone wean. We suggest that methadone is safe and has some clinical benefit, which should be proven in prospective randomized trials for pediatric patients with SCD and chronic pain.

PMID: 29749702

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Hemoglobin. 2018 May 10:1-5. doi: 10.1080/03630269.2018.1452760. [Epub ahead of print]

Prevalence and Characteristics of Priapism in Sickle Cell Disease.

Arduini GAO1, Trovó de Marqui AB2..

Abstract

Priapism is a pathological condition of persistent penile erection in the absence of sexual arousal or desire. It is an urological emergency and its identification is important as lack of prompt treatment can result in erectile dysfunction. The aim of this study was to estimate and describe the characteristics (number of episodes, duration, time of occurrence and evolution) of priapism in patients with sickle cell disease. A bibliographical research was carried out in PubMed, searching for papers published in the last 5 years. Thirteen scientific articles were included in this review. The main results were: 1) the highest prevalence of priapism in males reported was 48.0% and the lowest 0.67%; 2) six studies were carried out on the African Continent (46.1%), three in America (23.1%), two in Europe (15.4%) and two in Asia (15.4%); 3) the main goal of ∼50.0% of the studies was to determine the rate of priapism in patients with sickle cell disease; 4) there was predominance of sickle cell anemia patients [homozygous Hb S (HBB: c.20A>T) genotype]; 5) the minimum age of patients with priapism was 7 years old and the maximum 30 years. In general, the episodes of priapism occurred during sleep, were recurrent and had variable duration. The prevalence of priapism are not real and the explanations include underreporting by patients, lack of awareness by physicians and lack of proper prospective studies. Priapism is a complication that deserves close attention due to its significant impact on the life of the patient with sickle cell disease and, therefore, should be further clarified.

PMID: 29745276

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J Am Med Inform Assoc. 2018 May 7. doi: 10.1093/jamia/ocy036. [Epub ahead of print]

Technology use and preferences to support clinical practice guideline awareness and adherence in individuals with sickle cell disease.

Utrankar A1, Mayo-Gamble TL2, Allen W3, Novak L4, Kassim AA5, Bonnet K6, Schlundt D6, Murry VM7, Jackson GP4,8,9, DeBaun M10, Cronin RM4,8,11.

Abstract

Objective:

Sickle cell disease (SCD) is a chronic condition affecting over 100 000 individuals in the United States, predominantly from vulnerable populations. Clinical practice guidelines, written for providers, have low adherence. This study explored knowledge about guidelines; desire for guidelines; and how technology could support guideline awareness and adherence, examining current technology uses, and user preferences to inform design of a patient-centered guidelines application in a chronic disease.

Methods:

This cross-sectional mixed-methods study involved semi-structured interviews, surveys, and focus groups of adolescents and adults with SCD. We evaluated interest, preferences, and anticipated benefits or barriers of a patient-centered adaptation of SCD practice guidelines; prospective technology uses for health; and barriers to technology utilization.

Results:

Forty-seven individuals completed surveys and interviews, and 39 participated in three separate focus groups. Most participants (91%) were unaware of SCD guidelines, but almost all (96%) expressed interest in a guidelines application, identifying benefits (knowledge, activation, individualization, and rewards), and barriers (poor information, low motivation, and resource limitations). Current technology health uses included information access, care coordination, and reminders about health-related actions. Prospective technology uses included informational messaging and timely alerts. Barriers to technology use included lack of interest, lack of utility, and preference for direct communication.

Conclusions:

This study’s findings can inform the design of clinical practice guideline applications, suggesting a promising role for technology to engage patients, facilitate care decisions and actions, and improve outcomes.

PMID: 29741695

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Cochrane Database Syst Rev. 2018 May 8;5:CD012349. doi: 10.1002/14651858.CD012349.pub2. [Epub ahead of print]

Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia.

Fortin PM1, Fisher SA, Madgwick KV, Trivella M, Hopewell S, Doree C, Estcourt LJ.

Abstract

BACKGROUND:

Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia (who are transfusion-dependent or non-transfusion-dependent) are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands; which can be prevented and treated with iron chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and well-being, which may affect adherence.

OBJECTIVES:

To identify and assess the effectiveness of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) to improve adherence to iron chelation therapy in people with SCD or thalassaemia.

SEARCH METHODS:

We searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, Psychology and Behavioral Sciences Collection, Web of Science Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (01 February 2017). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register (12 December 2017).

SELECTION CRITERIA:

For trials comparing medications or medication changes, only randomised controlled trials (RCTs) were eligible for inclusion.For studies including psychological and psychosocial interventions, educational Interventions, or multi-component interventions, non-RCTs, controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion.

DATA COLLECTION AND ANALYSIS:

Three authors independently assessed trial eligibility, risk of bias and extracted data. The quality of the evidence was assessed using GRADE.

MAIN RESULTS:

We included 16 RCTs (1525 participants) published between 1997 and 2017. Most participants had β-thalassaemia major; 195 had SCD and 88 had β-thalassaemia intermedia. Mean age ranged from 11 to 41 years. One trial was of medication management and 15 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral-chelating agents, deferiprone and deferasirox.We rated the quality of evidence as low to very low across all outcomes identified in this review.Three trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL.Deferiprone versus deferoxamineWe are uncertain whether deferiprone increases adherence to iron chelation therapy (four trials, very low-quality evidence). Results could not be combined due to considerable heterogeneity (participants’ age and different medication regimens). Medication adherence was high (deferiprone (85% to 94.9%); deferoxamine (71.6% to 93%)).We are uncertain whether deferiprone increases the risk of agranulocytosis, risk ratio (RR) 7.88 (99% confidence interval (CI) 0.18 to 352.39); or has any effect on all-cause mortality, RR 0.44 (95% CI 0.12 to 1.63) (one trial; 88 participants; very low-quality evidence).Deferasirox versus deferoxamineWe are uncertain whether deferasirox increases adherence to iron chelation therapy, mean difference (MD) -1.40 (95% CI -3.66 to 0.86) (one trial; 197 participants; very-low quality evidence). Medication adherence was high (deferasirox (99%); deferoxamine (100%)). We are uncertain whether deferasirox decreases the risk of thalassaemia-related serious adverse events (SAEs), RR 0.95 (95% CI 0.41 to 2.17); or all-cause mortality, RR 0.96 (95% CI 0.06 to 15.06) (two trials; 240 participants; very low-quality evidence).We are uncertain whether deferasirox decreases the risk of SCD-related pain crises, RR 1.05 (95% CI 0.68 to 1.62); or other SCD-related SAEs, RR 1.08 (95% CI 0.77 to 1.51) (one trial; 195 participants; very low-quality evidence).Deferasirox film-coated tablet (FCT) versus deferasirox dispersible tablet (DT)Deferasirox FCT may make little or no difference to adherence, RR 1.10 (95% CI 0.99 to 1.22) (one trial; 173 participants; low-quality evidence). Medication adherence was high (FCT (92.9%); DT (85.3%)).We are uncertain if deferasirox FCT increases the incidence of SAEs, RR 1.22 (95% CI 0.62 to 2.37); or all-cause mortality, RR 2.97 (95% CI 0.12 to 71.81) (one trial; 173 participants; very low-quality evidence).Deferiprone and deferoxamine combined versus deferiprone alone We are uncertain if deferiprone and deferoxamine combined increases adherence to iron chelation therapy (very low-quality evidence). Medication adherence was high (deferiprone 92.7% (range 37% to 100%) to 93.6% (range 56% to 100%); deferoxamine 70.6% (range 25% to 100%).Combination therapy may make little or no difference to the risk of SAEs, RR 0.15 (95% CI 0.01 to 2.81) (one trial; 213 participants; low-quality evidence).We are uncertain if combination therapy decreases all-cause mortality, RR 0.77 (95% CI 0.18 to 3.35) (two trials; 237 participants; very low-quality evidence).Deferiprone and deferoxamine combined versus deferoxamine aloneDeferiprone and deferoxamine combined may have little or no effect on adherence to iron chelation therapy (four trials; 216 participants; low-quality evidence). Medication adherence was high (deferoxamine 91.4% to 96.1%; deferiprone: 82.4%)Deferiprone and deferoxamine combined, may have little or no difference in SAEs or mortality (low-quality evidence). No SAEs occurred in three trials and were not reported in one trial. No deaths occurred in two trials and were not reported in two trials.Deferiprone and deferoxamine combined versus deferiprone and deferasirox combinedDeferiprone and deferasirox combined may improve adherence to iron chelation therapy, RR 0.84 (95% CI 0.72 to 0.99) (one trial; 96 participants; low-quality evidence). Medication adherence was high (deferiprone and deferoxamine: 80%; deferiprone and deferasirox: 95%).We are uncertain if deferiprone and deferasirox decreases the incidence of SAEs, RR 1.00 (95% CI 0.06 to 15.53) (one trial; 96 participants; very low-quality evidence).There were no deaths in the trial (low-quality evidence).Medication management versus standard careWe are uncertain if medication management improves health-related QoL (one trial; 48 participants; very low-quality evidence). Adherence was only measured in one arm of the trial.

AUTHORS’ CONCLUSIONS:

The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects.Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation.Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy.Due to lack of evidence this review cannot comment on intervention strategies for different age groups.

PMID: 29737522

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Hematol Oncol Clin North Am. 2018 Jun;32(3):535-550. doi: 10.1016/j.hoc.2018.01.014.

Key Components of Pain Management for Children and Adults with Sickle Cell Disease.

Brandow AM1, DeBaun MR2.

Abstract

Sickle cell disease pain manifests as severe acute pain episodes and a debilitating chronic pain syndrome. Acute pain episodes are the most common reason for health care use; however, acute pain episodes are also frequently managed at home. Chronic pain syndrome develops in 30% to 40% of individuals with sickle cell disease, with an increasing incidence and severity with age. We review the critical aspects of pain management that are integral to the comprehensive approach to sickle cell disease pain and are rooted in the biopsychosocial model. The review focuses on opioid pharmacology and psychosocial comorbidities.

PMID: 29729787

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Bone Marrow Transplant. 2018 May 4. doi: 10.1038/s41409-018-0193-6. [Epub ahead of print]

Hematopoietic stem cell transplantation for adult sickle cell disease in the era of universal donor availibility.

Aslam HM1, Yousuf S2, Kassim A3, Iqbal SM4, Hashmi SK5.

Abstract

Current projections estimate that the number of newborns with sickle cell disease (SCD) globally will exceed 400,000 by 2050. Over the last three decades, increased newborn screening, supportive care, and use of hydroxyurea therapy, have decreased early childhood mortality among individuals affected with SCD. Despite hematopoietic cell transplantation (HCT) being curative in SCD, its impact on disease free survival remains unknown, especially in adults, partly due to previous limitations in donor options and perceived mortality in adults using myeloablative conditioning. Novel non-myeloablative or reduced intensity conditioning regimens have made HCT safer and applicable to adults with SCD who were previously excluded. Other reasons for limited use of HCT in SCD includes referral bias, provider preference, poor education of patient/families, perceived procedure risks, costs and limited logistic resources in both low income, middle income, and high income countries. Current data from landmark studies indicate that both the long-term disease-free survival and overall survival exceed 90% after matched sibling donor HCT in children. Improving transplant outcomes and expanding donor pool will increase the use of transplant for SCD, especially in affected adults. On-going investigations using matched umbilical cord units, unrelated matched donor, and related haploidentical donors, promises to make HCT a viable option for nearly all eligible patients with SCD. This systematic review focuses on the recent data for HCT for patients with adult SCD with particular emphasis on donor sources and availability as illustrated by a case presentation exhibiting real world issues.

PMID: 29728697

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Expert Rev Clin Pharmacol. 2018 May 18:1-10. doi: 10.1080/17512433.2018.1473760. [Epub ahead of print]

Efficacy and safety of iron chelators in thalassemia and sickle cell disease: a multiple treatment comparison network meta-analysis and trial sequential analysis.

Sridharan K1, Sivaramakrishnan G2.

Abstract

BACKGROUND:

To compare the efficacy and safety of desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) and silymarin in patients with either thalassemia or sickle cell disorder through network meta-analysis.

METHODS:

Electronic databases were searched for appropriate randomized clinical trials comparing iron chelators in patients with iron overload. Random effects model was used to generate direct, indirect and mixed treatment comparison pooled estimates for the following outcomes: serum ferritin, liver iron concentration (LIC), changes in serum ferritin, mortality, urine iron excretion, adverse events, neutropenia, agranulocytosis and number of patients withdrawing the chelating therapy.

RESULTS:

Thirty-two clinical trials were included in the meta-analysis. DFX/DFO was associated with better serum ferritin levels compared to DFO, DFX, DFO/Silymarin and DFP/DFO. DFX/DFO also lower LIC significantly compared to DFO. DFP/DFO was associated with higher LVEF, low risk of adverse events and reduced end of serum ferritin compared to DFO. Combination of silymarin with either DFP or DFX was observed with reduced end of treatment serum ferritin compared to using either of the drugs alone. DFP was observed with better effects in sickle cell disease. The strength of evidence was very low for most of the comparisons.

CONCLUSION:

Relative estimates between the individual iron chelators have been established. However, this evidence should be considered preliminary and may change with the results of future head-to-head clinical trials.

PMID: 29727586

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Blood. 2018 May 3. pii: blood-2018-02-785964. doi: 10.1182/blood-2018-02-785964. [Epub ahead of print]

How I safely transfuse patients with sickle cell disease and manage delayed hemolytic transfusion reactions.

Pirenne F1, Yazdanbakhsh K2.

Abstract

Transfusions can be a life-saving treatment for patients with sickle cell disease (SCD). However, availability of matched units can be limiting due to distinctive blood group polymorphisms in patients of African descent. Development of antibodies against the transfused red blood cells (RBCs), resulting in delayed hemolytic transfusion reactions (DHTRs), can be life-threatening and pose unique challenges for this population with regard to treatment strategies and transfusion management protocols. In cases where the transfused cells as well as patient’s own RBCs are destroyed, diagnosis of DHTR can be difficult because symptoms may mimic vaso-occlusive crisis, and frequently antibodies are undetectable. Guidelines are needed for early diagnosis of DHTR since treatment may need to include temporarily withholding any new transfusions to avoid further hemolysis. Also needed are case-control studies to optimally tailor treatments based on the severity of DHTR and develop preventive transfusion strategies for patients at DHTR risk. Here, we will review gaps in knowledge and describe through case studies our recommended approach to prevent alloimmunization, and to diagnose and treat symptomatic DHTRs for which complementary mechanistic studies to understand their pathogenesis are sorely needed.

PMID: 29724898

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JAMA Neurol. 2018 Apr 23. doi: 10.1001/jamaneurol.2018.0571. [Epub ahead of print]

Association of Sickle Cell Trait With Ischemic Stroke Among African Americans: A Meta-analysis.

Hyacinth HI1, Carty CL2, Seals SR3, Irvin MR4, Naik RP5, Burke GL6, Zakai NA7,8, Wilson JG9, Franceschini N10, Winkler CA11, David VA11, Kopp JB12, Judd SE4, Adams RJ13, Longstreth WT Jr14, Egede L15, Lackland DT13, Taylor H16, Manson JE17, Howard V4, Allison M18, Gee BE19, Correa A20, Safford MM21, Arnett DK22, Howard G23, Reiner AP24, Cushman M7,8.

Abstract

Importance:

African Americans and individuals of African ancestry have a higher risk of stroke compared with non-Hispanic white individuals. Identifying the source of this disparity could provide an opportunity for clinical stroke risk stratification and more targeted therapy. Whether sickle cell trait (SCT) is an indicator of increased risk of ischemic stroke among African Americans is still unclear.

Objective:

To examine whether SCT is associated with a higher risk of incident ischemic stroke among African Americans.

Design, Setting, and Participants:

This meta-analysis assessed the association of SCT with the risk of incident ischemic stroke. Four large, prospective, population-based studies with African American cohorts were assessed: Jackson Heart Study (September 1, 2005, through December 31, 2012), Multi-Ethnic Study of Atherosclerosis (July 1, 2002, through December 31, 2012), Reasons for Geographic and Racial Differences in Stroke (January 1, 2003, through December 31, 2014), and Women’s Health Initiative (October 1, 1998, through December 31, 2012). Using a Cox proportional hazards regression model adjusted for major stroke risk factors, this study estimated the hazard ratio for incident ischemic stroke associated with SCT. Data analysis was performed from July 10, 2016, to February 2, 2017.

Interventions or Exposures:

Participants’ SCT status determined by polymerase chain reaction assay genotyping or a combination of whole-exome sequencing and imputation.

Main Outcomes and Measures:

Incident ischemic stroke.

Results:

This meta-analysis included 19 464 African American individuals (1520 with SCT, 17 944 without SCT, and 620 with ischemic stroke) from 4 studies, with a mean (SD) age of 60.0 (13.0) years (5257 [27.0%] men and 14 207 [73.0%] women). No differences were found in the distribution of risk factors for ischemic stroke comparing participants with and those without SCT at study visit 1 in each cohort. The crude incidence of ischemic stroke was 2.9 per 1000 person-years (95% CI, 2.2-4.0 per 1000 person-years) among those with SCT and 3.2 per 1000 person-years (95% CI, 2.7-3.8 per 1000 person-years) among those without SCT. After stroke risk factors were adjusted for, the hazard ratio of incident ischemic stroke independently associated with SCT in the meta-analysis of all 4 cohorts was 0.80 (95% CI, 0.47-1.35; P = .82). The results of the meta-analysis were similar to those of individual cohorts, in which the results were also similar.

Conclusions and Relevance:

Sickle cell trait may not be associated with incidence of ischemic stroke among African Americans. The results of this study suggest performing a more thorough clinical evaluation of a stroke patient with SCT rather than assuming that SCT is the etiologic factor for the stroke.

PMID: 29710269

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Sickle Cell Conferences and Events

 

June 9th 2018: Hope Gala & Awards 2018

The Sickle Cell Awareness Group of Ontario (SCAGO) will be holding its annual Hope Gala & Awards in Toronto, Ontario. At this event, youths with Sickle Cell Disease in post-secondary institutions will receive the Sunday Afolabi Scholarship and the Sholape Scholarship grants. A few distinguished individuals who have supported the cause in the province will also be presented with awards under different categories including the Medical, Nursing, Allied Health, Community, Media, Humanitarian and the Volunteer Awards of Excellence.

 

 

National Sickle Cell Awareness Day (June 19) is Law in Canada

Through advocacy of the Sickle Cell Disease International Organisation (SCDIO), the support of the Republic of Congo and the Republic of Senegal, and the commitment in the scientific world, the African Union (in 2005), the UNESCO (2005), WHO (2006), and the United Nations (2008),  sickle cell disease is recognized as a public health priority and the 19 of June has been chosen to celebrate every year the World Sickle Cell Day in order to raise awareness of the disease in the world.

Through the advocacy of the Sickle Cell Disease Association of Canada (SCDAC) and its member associations including the Sickle Cell Awareness Group of Ontario (SCAGO), Bill S-211-An Act recognizing the June 19th as National Sickle Cell Day became law on Dec. 12th 2017- The Bill S-211 has made Canada the first country in the world to legally recognize June 19th and we are proud of this achievement!

Mark your Calendar: The SCDAC will be hosting a National Sickle Cell Awareness Day Celebrations at the Parliament Hill on June 18th and the SCAGO will be hosting a provincial event in Toronto at the council chamber in the City Hall, on 100 Queen St. W Toronto.

Background on the SCAGO:

Sickle Cell Awareness Group of Ontario (SCAGO) was established in 2005 to:

  • Improve treatment and care received by patients living with SCD by supporting knowledge translation among care providers
  • Improve self-management of disease by patients and families through its Learning for Life Education Program
  • Educate the community on SCD and sickle cell trait with the expected outcome of reducing the number of new births with the disease.
  • Support patients and families by providing access to peer support group meetings, networking, scholarships, grants, and advocating on their behalf with the Ministry of Health, Schools and Workplaces.

To learn more about SCAGO or register for one of our workshops, visit: www.sicklecellanemia.ca

 

 

The Second Biennial Pediatric-Adult Regional Sickle Cell Disease Conference

“A New Era In Sickle Cell Disease” will be held Saturday, May 19th, 2018 at St. Jude Children’s Research Hospital, Memphis, TN. 

This conference is open to all health care providers, social workers, counselors, and others who provide health care for those with sickle cell disease. It is also open to sickle cell consumers, caregivers, and the public. Speakers include Drs. Kenneth Ataga, Jane Hankins, Patricia Kavanaugh, and many others.  Registration is free, but pre-registration is required. To view the full agenda and register, go to www.stjude.org/sickle-cell-disease-conference

 

 

46TH ANNUAL NATIONAL CONVENTION THEME ANNOUNCED

This year’s theme for the conference is Celebrating the Diversity Within the Sickle Cell Community: Commitment, Innovation, and Practice

With over 600 researchers, physicians, nurses, social workers, individuals living with SCD & SCT in attendance, last year’s year’s convention was a major success and our largest to date. We are excited to unite again with you at the 46th Annual National Convention in Baltimore, MD on October 10-13, 2018! https://www.sicklecelldisease.org/2017/03/07/46th-annual-national-convention/

 

 

12TH ANNUAL SICKLE CELL DISEASE RESEARCH AND EDUCATIONAL SYMPOSIUM!

June 15 -17

WASHINGTON MARRIOTT WARDMAN PARK

2660 WOODLEY ROAD NW WASHINGTON, DC  20008 – https://fscdr.org/events/2018-symposium/

 

 

The 4th Annual Sickle Cell Disease Symposium for Carolinas Healthcare System

Atrium Health

The symposium will be held on Saturday, October 27, 2018 at the Speedway Club in Charlotte, NC. The theme this year is: “4th Annual SCD Symposium: Racing to Improve the Access to Care & Outcomes for SCD.”