Poor Health Related Quality of Life Among Patients of Sickle Cell Disease

Background:

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and vascular occlusion, causing recurrent painful episodes, neuro-cognitive deficits, organ failures and death in early adulthood. Besides the medical consequences, most of the families with a child of SCD have to cope with financial and social crisis. Quality of life (QOL) is a broad multidimensional concept that usually includes subjective evaluations of both positive and negative aspects of life. Other than health; emotional well being, social dysfunction, chronic pain and fatigability are also important aspects of overall quality of life that add to the complexity of its measurement.

Aim:

The present case control study was designed to determine the health related quality of life (HRQoL) in patients of sickle cell disease and to compare it with patients of other chronic non-communicable diseases.

Setting and Design:

Case control study conducted at tertiary health care facility of Central India.

Material and Methods:

The present study conducted to measure HRQoL among patients of SCD and patients of other chronic non-communicable diseases. A translated and pretested version of WHO SF-36 questionnaire was used to measure HRQoL.

Results:

We observed that there was significantly lower HRQoL among SCD patients.

Conclusion:

Besides merely pharmacotherapy, restoration of overall quality of life should be the mainstay of management of patients with SCD.     

HLA Haploidentical Stem Cell Transplant with Pretransplant Immunosuppression for Patients with Sickle Cell Disease

Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD), but a significant number of patients lack an HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report we describe a favorable haploidentical HCT approach in a limited cohort of SCD patients with significant comorbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit antithymocyte globulin, busulfan, and fludarabine preceded with 2 courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine and dexamethasone. Graft-versus-host disease (GVHD) prophylaxis consisted of PTCY on days +3 and +4 followed by tacrolimus and mycophenolate mofetil starting on day +5. Four patients (ages 13, 19, 19, and 23 years) received T cell–replete haploidentical stem cell infusion. All patients engrafted with 99.9% to 100% donor chimerism, and all patients continued with stable engraftment at the last follow-up (5 to 11 months post-transplant). Time to neutrophil engraftment was 14 to 26 days. Two patients had high levels of donor-specific anti-HLA antibodies, which required the implementation of an antibody management protocol. This facilitated neutrophil engraftment on day +16 and day +26, respectively. One patient developed grade I acute GVHD, which resolved. Three patients developed mild, limited skin GVHD that responded to conventional immunosuppressive therapy. Human herpesvirus-6 viremia was detected in 3 patients but resolved without treatment. One patient developed asymptomatic cytomegalovirus viremia that responded appropriately to standard therapy with ganciclovir. The prompt, stable engraftment and low toxicity in the post-transplant period makes PTIS with haploidentical transplant a promising option for patients with SCD.     

Outcomes of Unrelated Donor Stem Cell Transplantion with Post-Transplant Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients with Severe Sickle Cell Disease

Unrelated donor (URD) hematopoietic cell transplantation (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft-versus-host disease (GVHD). We report on the first 4 patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen composed of busulfan, fludarabine, and antithymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Three patients engrafted and remain disease-free after a median follow-up period of 2.5 years. One patient had primary graft failure attributed to low stem cell content of the graft. Of interest, none of the engrafted patients developed acute or chronic GVHD. This preparative regimen along with the use of post-transplant cyclophosphamide offers a promising approach for unrelated donor transplants in patients with SCD and needs further corroboration in larger number of patients.     

Vitamin D Deficiency in Adult Sickle Cell Patients

Introduction

Vitamin D levels in adult black Americans with sickle cell disease (SCD) are comparatively lower than those found in the general population of black Americans. The objectives of this study were to examine the prevalence of Vitamin D deficiency (VDD) in adults with various subtypes of sickle cell disease and identify risk factors for vitamin D deficiency.

Ethical Challenges in Hematopoietic Cell Transplantation for Sickle Cell Disease

Hematopoietic cell transplantation (HCT) using an HLA-identical sibling donor offers a very high likelihood of cure with good outcomes for patients with sickle cell disease (SCD), and alternative donor HCT for SCD is an area of active clinical research. Thus, HCT is a potential option for a growing number of patients with SCD. This expanded use of HCT has raised several ethical questions. Who is eligible for HCT, in terms of both disease severity and psychosocial factors? Should affected children with matched sibling donors undergo HCT only when they have declared themselves as having significant symptomatology? Regarding donors, special ethical challenges include the use of preimplantation genetic diagnosis to conceive an HLA-identical sibling. In this review, we critically analyze various ethical challenges related to HCT for SCD, and offer recommendations to guide clinical care.     

Efficient Clinical Counseling for Sickle Cell Disease

Sickle cell anemia (SCA) is a chronic illness that requires frequent health care visits for preventative management. Adherence to national guidelines such as the National Heart Lung and Blood Institute (NHLBI) Expert Panel Report on the Evidence-Based Management of Sickle Cell Disease can be challenging to both the clinician and the patient. Utilizing effective communication strategies with patients and their families can improve clinician/patient relationships, as well as adherence to national guidelines. Aims of this overview are to review challenges faced in outpatient subspecialty medicine and describe evidence-based techniques for more effective communication for patients with sickle cell anemia.     

Menstrual Type,Pain and Psychological Distress in Adult Women with Sickle Cell Disease (SCD)

ObjectiveWe evaluated the effects of menstrual types inclusive of PMS on reports of chronic pain intensity and psychopathology in twenty-eight women (mean age 38.93 ± 13.51) with Sickle Cell disease (SCD).MethodsUsing the Menstrual Symptoms Questionnaire, we compared women with PMS to those with less distressing spasmodic cycle types.ResultsThirty-four percent of the sample used oral contraception; there were no significant effects of birth control use on reports of pain. Women with PMS characterized the sensory (p = .04) and affective (p = .04) experiences of their SCD-related chronic pain, including their current pain intensity (p = .03), as significantly greater than women with primary spasmodic menstrual type. Further, there was a trend towards significance for women with PMS to report greater levels of overall pain intensity (p = .07) and average pain intensity over the past month (p = .08).ConclusionsThe authors interpret these results to suggest that there may be a complex interaction of neurohormonal, biological, and psychological factors associated with PMS that influence manifestation and experience of chronic pain in patients with SCD.     

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease

We report on the screening and development of haploidentical hematopoietic stem cell transplantation (HSCT) for adult patients with clinically aggressive sickle cell disease (SCD) at our institution. Of 50 adult SCD patients referred for HSCT between January 2014 and March 2017, 20% were denied by insurance. Of 41 patients initially screened, 10% lacked an available haploidentical donor, 29% had elevated donor-specific antibodies (DSAs), and 34% declined to proceed to HSCT. All 10 patients who were transplanted received peripheral blood stem cells. The initial 2 were conditioned with alemtuzumab/total body irradiation (TBI) 3?Gy followed by post-transplant cyclophosphamide and failed to engraft. The next 8 patients received the regimen developed at Johns Hopkins University with TBI 3?Gy. Granulocyte colony-stimulating factor was administered from day +12 in those with HbS < 30%. All 8 patients engrafted with a median time to neutrophil >.5 × 10⁹/L of 22 days (range, 18 to 23). One patient subsequently lost the graft, and 7 (87.5%) maintained >95% donor cell chimerism at 1-year post-HSCT. Two patients developed acute graft-versus-host disease (GVHD) of at least grade II. One had chronic GVHD and died >1 year after HSCT of unknown causes. With a median follow-up of 16 months (range, 11 to 29), 7 patients (87.5%) are alive. Our findings suggest that limited insurance coverage, high rate of DSAs, and patient declining HSCT may limit the availability of haploidentical HSCT in adult SCD patients. The modified Hopkins regimen used here demonstrates high engraftment and low morbidity rates and should be tested in larger, multicenter, prospective clinical trials.     

Renal Medullary Carcinoma and Sickle Cell Trait: A Push for Early Diagnosis and Intervention Report of Two Cases

Renal medullary carcinoma (RMC) is a rare but highly aggressive neoplasm that primarily affects young African Americans with sickle cell trait. Most patients present with macroscopic hematuria and have metastases at diagnosis. Chemotherapy, biologics directed against the more common renal cell carcinomas and radiation have all shown limited efficacy in treating patients with advanced RMC. We report two patients with RMC. Both had Stage IV disease. One underwent radical nephrectomy followed by radiation and biologic drug therapy but died five months later; the other underwent multiple cycles of chemotherapy plus anti-angiogenesis treatment but died 15 months after diagnosis. Review of the literature suggests that early diagnosis and surgical intervention while the tumor is confined to the kidney offer the best prospect for long term survival. Since newborn screening for sickle cell is now mandated in the US, the at-risk population for RMC could be identified and followed by yearly urine dipstick testing for microscopic hematuria. Those who test positive can be further evaluated to rule out RMC.     

Assessing Knowledge of Sickle Cell Trait/Disease Inheritance in Metropolitan Detroit

Sickle cell disease (SCD) is an autosomal recessive disease not specific to one race. This study aims to assess knowledge about the inheritance pattern of sickle cell disease among college students in the Metropolitan Detroit area. An electronic survey was administered to undergraduate students at Oakland University, and first through fourth year medical students at Oakland University William Beaumont School of Medicine (OUWB). The primary analysis compared knowledge of sickle cell disease inheritance pattern between different demographic categories. A total of 146 Oakland University (27.4%) and OUWB (72.6%) students responded to the survey. The average age of the respondents was 24.27 ± 4.09. The majority of respondents were female (61%) and white (72.6%). In total, three (3) respondents - 1 white, 1 Asian and 1 African American, reported knowing that they have sickle cell disease/trait. In addition, one (1) white female respondent reported having an infant carrying the sickle cell trait. Most respondents (95.9%) knew that sickle cell disease/trait is genetically inherited, but a majority believed that it is associated only with African-Americans (67.8%). Respondents who were college graduates were more likely to correctly identify SCD inheritance patterns (98% compared to 85% of undergraduates; p = 0.002) and less likely to correctly answer the question “Who gets the disease?” (24% compared to 63%; p < 0.001). Most respondents (75%) think people should know if they have sickle cell trait/disease before marriage. The result shows that most respondents believe sickle cell disease is specific to African-Americans. However, because it is equally possible for all races to inherit this disease, knowing one's status could help prevent sickle cell-related deaths during rigorous exercises and enable individuals of reproductive age to make informed reproductive decisions in order to decrease sickle cell disease prevalence, and its associated financial and psychosocial burdens.     

Opioid Utilization by Pregnant Women with Sickle Cell Disease and the Risk of Neonatal Abstinence Syndrome

Background

Pregnant women with sickle cell disease (SCD) are at increased risk of maternal and fetal complications. There are limited data on the outcome of the treatment of VOCs with opioids in relation to neonatal complications during pregnancy.

A Qualitative Study of Chronic Pain and Self-Management in Adults with Sickle Cell Disease

Acute, intermittent vaso-occlusive pain is the hallmark of sickle cell disease (SCD) and is associated with substantial morbidity and impaired quality of life (QOL). The subgroup of adults with SCD who transition from recurrent, acute pain to chronic, persistent pain have even greater QOL impairment and higher rates of healthcare utilization. Self-management is central to SCD management; however, its role in chronic pain management is not established. This qualitative study was conducted to answer the following research questions: (1) What is the chronic pain experience of adults with SCD? (2) What self-management strategies do adults with SCD use for chronic pain? and (3) Do adults with SCD have any needs in the self-management of chronic pain? Eighteen Black adults with SCD completed a demographics questionnaire and an interview. The majority of the participants were 21–30 years of age (mean 33.5, SD 7.6), female (61.1%), employed at least part-time (61.1%), single/never married (72.2%), and had a SCD type of sickle cell anemia (55.5%). Interview analysis revealed three major themes: (1) the chronic pain experience; (2) strategies for managing chronic pain; and (3) challenges and needs in managing chronic pain. Study findings can be used to support chronic pain management among adults with SCD. Further research is needed to devise and implement effective strategies for the prevention and management of chronic SCD pain.     

Bone Marrow Transplantation after Nonmyeloablative Treosulfan Conditioning Is Curative in a Murine Model of Sickle Cell Disease

Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for patients with sickle cell disease (SCD). However, morbidity associated with myeloablative conditioning and graft-versus-host disease has limited its utility. To this end, autologous HSCT for SCD using lentiviral gene-modified bone marrow (BM) or peripheral blood stem cells has been undertaken, although toxicities of fully ablative conditioning with busulfan and incomplete engraftment have been encountered. Treosulfan, a busulfan analog with a low extramedullary toxicity profile, has been used successfully as part of a myeloablative conditioning regimen in the allogeneic setting in SCD. To further minimize toxicity of conditioning, noncytotoxic monoclonal antibodies that clear stem cells from the marrow niche, such as anti-c-Kit (ACK2), have been considered. Using a murine model of SCD, we sought to determine whether nonmyeloablative conditioning followed by transplantation with syngeneic BM cells could ameliorate the disease phenotype. Treosulfan and ACK2, in a dose-dependent manner, decreased BM cellularity and induced cytopenia in SCD mice. Conditioning with treosulfan alone at nonmyeloablative dosing (3.6?g/kg), followed by transplantation with syngeneic BM donor cells, permitted long-term mixed-donor chimerism. Level of chimerism correlated with improvement in hematologic parameters, normalization of urine osmolality, and improvement in liver and spleen pathology. Addition of ACK2 to treosulfan conditioning did not enhance engraftment. Our data suggests that pretransplant conditioning with treosulfan alone may allow sufficient erythroid engraftment to reverse manifestations of SCD, with clinical application as a preparative regimen in SCD patients undergoing gene-modified autologous HSCT.     

Sickle Cell Disease Pain in Children and Adolescents: Change in Pain Frequency and Coping Strategies Over Time

Examined 9-month follow-up data obtained from children and adolescentswith sickle cell disease (SCD) and their parents participatingin a longitudinal study of pain coping strategies. Of 87 subjectscompleting the baseline assessment of pain coping strategies,70 (80%) of their parents completed a structured pain interviewassessing their child's health care use and activity reductionduring painful episodes over the follow-up period. Regressionanalyses controlling for age and pain frequency revealed thatbaseline Coping Attempts were associated with higher levelsof school, household, and social activity during painful episodes.Baseline Passive Adherence was associated with more frequenthealth care contacts during the subsequent 9 months. Increasesin Negative Thinking over time were associated with furtherincreases in health care contacts during the follow-up period.Comparing pain coping strategies assessed at baseline to paincoping strategies measured at follow-up revealed that pain copingstrategies were relatively stable over time for younger childrenbut changed more for adolescents.     

Hospital Admissions,Mortality and Comorbidities Among New York State Sickle Cell Patients, 2005-2013

Analyses of administrative and large data sources in Sickle Cell Disease (SCD) can answer questions not suitable for prospective study but have been hampered by lack of validated methods to adjust for individual comorbidities and lack of baseline utilization data over time. We sought to develop a database to characterize inpatient SCD care across New York State and generate a re-weighted sickle-cell specific Charlson Comorbidity index (S-CCI) for use in future large data SCD research. We identified 18,541 individual SCD patients admitted to New York State hospitals between 2005 and 2013 from the SPARCS database. We present data from both a randomly selected derivation cohort, used to develop the S-CCI and a validation cohort, The S-CCI resulted in small improvements in model fit and discrimination while using fewer covariates, allowing a more parsimonious model. Despite being the most common comorbidity, chronic pulmonary disease was not predictive of mortality. Mortality per hospitalization was 0.61%. Many patients (32%) were admitted only once during the nine year period. However, the majority was admitted more frequently with over 15% of patients being admitted more than once per year.     

情志护理用于中风患者生活质量研究

目的 研究情志护理对中风患者生活质量的影响。方法 选择2016年1月~7月来陕西中医药大学附属医院就诊的中风患者102例,随机分为干预组和对照组,每组51例。对照组常规健康指导,干预组在对照组基础上施行情志护理,评估两组生活质量的差异。结果 干预后,直方图显示干预组的生活质量在力量、记忆思维、情绪、交流、日常生活活动能力（ADL）、行动能力、手功能和社会参与方面高于对照组,差异有统计学意义（P＜0.05）。结论 情志护理可以用于改善中风患者的生活质量。     

Psychosocial Adjustment in Children and Adolescents with Sickle Cell Disease

This study investigated the degree to which the stress of chronicillness impacted on adjustment of a sample of 50 children andadolescents with sickle cell disease. The sample was selectedfrom patients seen in a Sickle Cell Center over an extendedperiod of time, with symptoms ranging from mild to severe. Thecharacteristics of the illness in terms of perceived pain, hospitalizations,and emergency room visits was evaluated, as well as the natureof presenting symptoms and levels of adjustment. Results indicatedthat there were problems in a range of adjustment variables,particularly for adolescent males, and most significantly inthe areas of behavior problems and social adjustment. The implicationsfor adaptive coping with adolescent developmental processeswere noted.