Acupuncture for pain management in children with sickle cell disease

Pain associated with sickle cell disease (SCD) is frequently treated with opioids which have many side effects. There is a need for adjuvant non-opioid therapies that can improve pain control. Acupuncture, an integrative approach, has been shown to be useful in non-SCD pain conditions but has been used to a very limited extent in SCD. In this report we present a single academic pediatric center experience showing acceptability, feasibility and improved pain experience with adjuvant acupuncture therapy in children with SCD and suggest that acupuncture should be explored as a treatment option for managing pain in SCD.     

Opioid doses and acute care utilization outcomes for adults with sickle cell disease: ED versus acute care unit

Background

Acute care units (ACUs) with focused sickle cell disease (SCD) care have been shown to effectively address pain and limit hospitalizations compared to emergency departments (ED), the reason for differences in admission rates is understudied. Our aim was compare effects of usual care for adult SCD pain in ACU and ED on opioid doses and discharge pain ratings, hospital admission rates and lengths of stay.

Integrative approaches to treating pain in sickle cell disease: Pre-clinical and clinical evidence

Sickle cell disease (SCD) is a genetic disorder characterized by hemolysis, end-organ damage, inflammation, and pain. Recurrent and unpredictable episodes of acute pain due to vaso-occlusive crises are a unique feature of SCD. Many patients also develop lifelong chronic pain. Opioids are the primary method of pain treatment in SCD; however, continued use is associated with several adverse effects. Integrative approaches to treating pain in SCD are increasingly being explored to prevent the side effects associated with opioids. In this review, we highlight the mechanisms of pain in SCD and describe mechanism-based integrative approaches for treating pain.     

Vitamin D status and supplementation in pediatric gastrointestinal disease

Purpose. To evaluate vitamin D status and supplementation in the pediatric population with common gastrointestinal diseases. The literature was searched for studies on vitamin D status in children with inflammatory bowel disease (IBD), celiac disease, and liver disease. Vitamin D supplementation in healthy children was also reviewed. Conclusions. Those with gastrointestinal diseases are more likely to have vitamin D deficiency as a result of malabsorption. Current recommendations for supplementation may be too low to achieve optimal levels. Practice Implications. It is important to monitor vitamin D levels in pediatric populations with gastrointestinal diseases and appropriately treat levels that are insufficient.     

Integrative holistic approaches for children,adolescents, and young adults with sickle cell disease: A single center experience

ContextPainful vaso-occlusive crises (VOCs) associated with sickle cell disease (SCD) are the most common cause of morbidity, hospitalizations, and poor quality of life. Additional symptoms such as sleep disturbances, fatigue, and stress are also common. Non-traditional approaches are often used by families, but concerns remain that patients may forgo standard of care effective therapies in favor of dangerous unproven alternatives.ObjectivesTo describe a single center experience related to a multidisciplinary integrative medicine clinic within the division of hematology dedicated to children and young adults with SCD.MethodsThe Sickle Cell Integrative Clinic at Children’s National Hospital services patients with SCD. The main goal of this clinic is to provide access to non-pharmacologic interventions, and to manage patients’ symptoms in a holistic manner along with standard of care management of SCD. This IRB approved study evaluated experiences of both patients and parents who attended this clinic.ResultsThirty-seven unique patients attended this clinic over 2 years and 31 participated in the study. After attending the SCD integrative clinic, the majority of patients reported integrative therapies to be an acceptable way of treating pain and believed these to be effective. Overall, the vast majority (88 %) of patients reported having a positive experience with the therapies offered in the clinic. None of the patients experienced any adverse events related to integrative therapies provided in the clinic.ConclusionOur experience suggests that encouraging conversations and offering safe and potentially effective integrative therapies alongside conventional SCD therapies under medical guidance allows patients to have an open discussion about their beliefs and treatment goals, improves patient satisfaction and can improve outcomes.     

Review/overview of pain in sickle cell disease

Sickle cell disease (SCD) is a highly complex inherited disorder of hemoglobin structure. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Its manifestations could be acute, chronic, nociceptive, neuropathic that could occur singly or in various combinations. Pain continues to be the major factor of SCD phenotypic complications and the most common cause of admissions to the Emergency Department and/or the hospital. Although progress has been made in understanding the pathophysiology of SCD as well as in developing curative therapies such as hematopoietic stem cell transplantation and gene therapy, effective pain management continues to lag behind. Palliative therapies continue to be the major approach to the management of SCD and its complications. The advent of hydroxyurea made partial success in preventing the frequency of vaso-occlusive crises and l-glutamine awaits post-trial confirmation of benefits. The search for additional pharmacotherapeutic agents that could be used singly or in combination with hydroxyurea and/or l-glutamine awaits their dawn hopefully in the near future. The purpose of this review is to describe the various manifestations of SCD, their pathophysiology and their current management. Recent impressive advances in understanding the pathophysiology of pain promise the determination of agents that could replace or minimize the use of opioids.     

Relationship between Vitamin D levels and pain and disease activity in patients with newly diagnosed axial spondyloarthritis

ObjectivesTo explore the relationship between Vitamin D levels and pain and disease activity in patients with newly diagnosed axial spondyloarthritis (axSpA).MethodsA convenience sample of 131 newly diagnosed axSpA patients and 60 healthy controls was recruited from July 2016 to December 2018. Serum 25-hydroxyvitamin D [25(OH)D] was measured to assess vitamin D levels. Disease activity was assessed by objective indicators [Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the Bath Ankylosing Spondylitis Metrology Index (BASMI)], patient-reported questionnaires [the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Bath Ankylosing Spondylitis Functional Index (BASFI)]. Pain intensity and interference were also assessed.ResultsVitamin D insufficiency [serum 25(OH) D levels<50 nmol/L]was found in 46 (35.1%) and 25 (43.3%) of the axSpA patients and the healthy controls, respectively. Female patients had higher risk (OR:4.928; 95% CI: 1.921–12.642) for vitamin D insufficiency than male patients. Vitamin D was positively correlated with CRP, ESR level, the BASFI, and the BASMI. Logistic regression showed that vitamin D levels were not associated with pain, or disease activity in the newly diagnosed axSpA patients. Gender was the only predictive variable for vitamin D levels.ConclusionsVitamin D insufficiency was prevalent in both newly diagnosed axSpA patients and healthy controls. There was no association between vitamin D and pain and disease activity in the newly diagnosed axSpA patients. Monitoring vitamin D levels is important and early intervention for vitamin D insufficiency is needed, especially in female patients.     

Injury patterns in children with frequent emergency department visits

Objectives

To compare injury patterns in children with many and few emergency department (ED) visits in order to reveal the causes for the frequent visits.

Methods

Three cohorts of Danish children (total 579 721 children) were followed for three years when their ages were 0–2, 6–8, and 12–14 years. Information on all ED visits was obtained from the Danish National Patient Registry. Injury type, place of accident, injury mechanism, admission, and distance to ED were compared between children with frequent ED visits (five or more during the three years) and children with only one visit.

Results

Children with frequent visits had a different injury pattern with 0–46% more superficial injuries and 25–82% more dislocations, sprains, and strains. There was 20–30% fewer fractures and 12% fewer falls from a higher level. 15–51% fewer were admitted.

Conclusions

Children with many ED visits had less severe injuries and more dislocations, sprains, and strains.     

Transfusion support for patients with sickle cell disease

Red blood cell (RBC) transfusion is an essential treatment for many patients with sickle cell disease (SCD), whose RBCs express hemoglobin S (HbS), a mutated form of hemoglobin A (HbA). Transfusion goals include increasing blood oxygen carrying capacity and decreasing the relative amount of HbS to HbA to mitigate vaso-occlusion in small blood vessels. In situations where correction of severe anemia and reduction in HbS may be achieved without removal of RBCs, simple transfusion may be utilized. Partial manual RBC exchange, which removes blood containing HbS by phlebotomy and replaces with donor blood transfusion sequentially allows for larger changes in the ratio of HbS to HbA when compared to simple transfusion. Automated RBC exchange by apheresis is useful in situations where a rapid and drastic HbS reduction is indicated. Vascular access is an important consideration for transfusion. Although peripheral access may be sufficient, central venous catheters and implantable venous access devices may be necessary for adequate access over time. Blood bank considerations include adequate RBC antigen matching to mitigate the risk of RBC alloimmunization, of which patients with SCD are at risk of developing. Transfusion may be utilized in efforts to intervene in the evolution of potentially life-threatening complications of SCD such as acute stroke, severe acute anemia and acute chest syndrome. Transfusion is also useful in several non-acute settings, such as stroke prevention, pregnancy, pre-surgery, and transfusion support for curative therapies. Individualized treatment plans are an essential component of patient care. Continuous evaluation of clinical indications and evolution of guidelines will continue to optimize care for patients with SCD.     

Haploidentical stem cell transplantation for patients with sickle cell disease: current status

For patients with high-risk sickle cell disease (SCD) without any available matched sibling or unrelated donor, haploidentical stem cell transplantation (haploHCT) expands the availability of this life-saving intervention to nearly all patients who may benefit from HCT. The greatest challenge in haploHCT has been the significant risk of graft failure. Developing a treatment modality which sustains engraftment without increasing the incidence of debilitating graft-versus-host disease (GvHD) remains the ultimate goal. A number of modifications have been explored to overcome the high incidence of graft rejection and severe GvHD including: (1) ex-vivo T-cell depletion (via CD34⁺ selection, CD3⁺/CD19⁺, or TCRαβ⁺/CD19⁺ depletion), and (2) in vivo T-cell depletion using unmanipulated grafts followed by post-transplant cyclophosphamide (PTCy) for GvHD prophylaxis. Furthermore, the presence of donor-specific anti-HLA antibodies (DSA) has been associated with an increased risk of both graft failure and poor graft function. Several approaches for desensitization ameliorate this risk when a suitable donor without DSA is not available. In addition to advances in supportive care, the recent demonstration that stable mixed chimerism post-HCT sufficiently sustains symptom-free status has opened the door for less toxic treatment approaches yielding excellent survival outcomes. Though late effects remain uncertain, the goal of finding the least toxic conditioning regimen while providing the highest rate of donor engraftment draws closer within reach. In this review, the authors aim to present the latest findings, challenges, and treatment modalities of this life-saving modality.     

Risk factors for early return visits to the emergency department in patients with urinary tract infection

Background

Optimal management of urinary tract infections (UTIs) in the emergency department (ED) is challenging due to high patient turnover, decreased continuity of care, and treatment decisions made in the absence of microbiologic data. We sought to identify risk factors for return visits in ED patients treated for UTI.

大连市儿童血清25-羟维生素D水平分析

目的：通过对该地区儿童血清25-羟维生素 D 水平检测,为佝偻病防治提供依据。方法选取2012年3月至2013年3月儿保科门诊就诊儿童共445例。取清晨空腹血,采用串联质谱法检测其血清25-羟维生素 D水平。结果大连市儿童各年龄组血清25-羟维生素 D 水平均呈偏态分布,以中位数表示,分别为0～1岁组34．4 ng/mL（27．9～42．9 ng/mL）;1～3岁组32．5 ng/mL（25．6～38．8 ng/mL）;3～6岁组24．9 ng/mL（16．3～31．2）ng/mL;＞6岁组19．7 ng/mL（13．2～29．1）ng/mL;经秩和检验,不同年龄组维生素水平差异有统计学意义（P ＜0．01）。各年龄组除0～1岁组男性高于女性（P ＜0．05）外,其他年龄组男女性别无统计学意义（P ＞0．05）。445例儿童中,维生素 D 严重缺乏（＜5 ng/mL）占0．23％（1/445）;缺乏（5．1～15 ng/mL）占8．76％（39/445）;不足或以下（15．1～20 ng/mL）占6．97％（31/445）;充足（20．1～100 ng/mL）占84．04％（374/445）;过量（＞100 ng/mL）为0。维生素 D 不足（＜20 ng/mL）的儿童占15．95％（71/445）,其中0～1岁组为5．79％（8/138）;1～3岁组为5．20％（9/173）;3～6岁组为32．05％（25/78）;＞6岁组为51．78％（29/56）,以3岁以上儿童为主,各组间存在显著性差异（P＜0．01）。不同季节血清维生素 D 值差异有统计学意义（P ＜0．01）。结论大连市儿童维生素 D 营养状况良好,血清25-羟维生素 D 水平随着年龄波动,3岁以上儿童需重视维生素 D 的补充,特别是冬季春季节。     

Cholecystosonography in children with sickle cell disease: technical approach and clinical results

Forty-five children with sickle cell anemia were studied with meticulous cholecystosonograms using a 5-MHz thyroid transducer. Good-quality images were obtained. The most informative and useful view was the left-side-down decubitus study with the ultrasound gantry angled 45% to the anteroposterior axis. Rotating the patient rapidly through 360 degrees did not increase the information content of the examination. We found that one third of a random group fo children with sickle cell anemia will have gallstones and one fifth will have"sludge". A kinked deformity of the gallbladder may simulate a gallstone. Neither age, sex, weight, physical findings (except for hepatomegaly), nor a variety of biochemical measurements of the blood will be of much value in predicting gallbladder disease in any given patient.     

Association between ambient PM2.5 and emergency department visits for psychiatric emergency diseases

BackgroundWhether or not short-term exposure to particulate matter <2.5 μm in diameter (PM_2.5) increases the risk of psychiatric emergency diseases is unclear.MethodsThe study was performed in a metropolis from January 2015 to December 2016. The exposure was PM_2.5, and the confounders were weather (temperature and humidity) and other pollutants (PM₁₀, SO₂, CO, O₃, and NO₂). The outcomes were emergency department (ED) visits with psychiatric disease codes (F00-F99 in ICD10 codes). General additive models were used for the statistical analysis to calculate the adjusted relative risks (ARRs) and 95% confidence intervals (95% CIs) for the daily number of ED visits with a lag of 1 to 3 days following a 10 μg/m³ increase in PM_2.5.ResultsDuring the study period, a total of 67,561 ED visits for psychiatric diseases were identified and tested for association with PM_2.5. Daily ED visits for all psychiatric diseases were not associated with PM_2.5 in the model that was not adjusted for other pollutants. The ARR (95% CI) in the model adjusted for SO₂ was 1.011 (1.002–1.021) by 10 μg/m³ of PM_2.5 on Lag 1 for all psychiatric diseases (F00-F99). The ARR (95% CI) in the model adjusted for O₃ was 1.015 (1.003–1.029) by 10 μg/m³ of PM_2.5 on Lag 1 for F40-F49 (Neurotic, stress-related and somatoform disorders).ConclusionAn increase in PM_2.5 showed a significant association with an increase in ED visits for all psychiatric diseases (F00-F99) and for neurotic, stress-related and somatoform disorders (F40-F49) on lag day 1.     

The effects of glutamine supplementation on markers of apoptosis and autophagy in sickle cell disease peripheral blood mononuclear cells

ObjectivesL-Glutamine was FDA-approved for sickle cell disease (SCD) in 2017, yet the mechanism(s)-of-action are poorly understood. This study investigates the potential activation of autophagy as a previously unexplored mechanism-of-benefit.DesignProspective, open-label, 8-week, phase-2 trial of oral L-glutamine (10 g TID) in patients with SCD at risk for pulmonary hypertension identified by Doppler-echocardiography by an elevated tricuspid-regurgitant-jet-velocity (TRV)≥ 2.5 m/s. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples taken from SCD patients at baseline, two, four, six and eight weeks of glutamine therapy, and from controls at baseline; BAX (pro-apoptotic marker) and LC3-II/LC3-I (autophagy marker) were measured via western blot analysis to assess apoptosis and autophagy respectively.SettingComprehensive SCD Center in Oakland, California.ResultsPatients with SCD (n = 8) had a mean age of 44 ± 16, 50% were male; 63% Hb-SS, and mean TRV= 3.1 ± 0.7 m/s. Controls’ mean age (n = 5) was 32 ± 12% and 57% were male; all were Hb-AA with a mean TRV= 1.8 ± 0.6. At baseline, SCD-PBMCs had 2-times higher levels of BAX and LC3-I versus controls (both p = 0.03). Levels of BAX expression increased by 300% after 8-weeks of glutamine supplementation (p = 0.005); LC3-I protein levels decreased while LC3-II levels increased by 70%, giving a significant increase in the LC3-II/LC3-I ratio (p = 0.02).ConclusionPBMCs from glutamine-supplemented SCD patients have upregulated apoptotic and autophagy proteins. The parallel increase in BAX and the LC3-II / LC3-I ratio with glutamine supplementation suggest a possible role of autophagic cell death. The increase in apoptotic markers provide insight into a possible mechanism used by peripheral PBMCs during glutamine supplementation in patients with SCD.