Influenza vaccine effectiveness and disease burden in children and adolescents with sickle cell disease: 2012-2017.
- 作者列表："Kao CM","Lai K","McAteer JM","Elmontser M","Quincer EM","Yee MEM","Tippet A","Jerris RC","Lane PA","Anderson EJ","Bakshi N","Yildirim I
BACKGROUND:Data are limited on the burden of influenza and seasonal influenza vaccine effectiveness (VE) in children with sickle cell disease (SCD). METHODS:We used a prospectively collected clinical registry of SCD patients 6 months to 21 years of age to determine the influenza cases per 100 patient-years, vaccination rates, and a test-negative case-control study design to estimate influenza VE against medically attended laboratory-confirmed influenza infection. Influenza-positive cases were randomly matched to test-negative controls on age and influenza season in 1:1 ratio. We used adjusted logistic regression models to compare odds ratio (OR) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimate. RESULTS:There were 1037 children with SCD who were tested for influenza, 307 children (29.6%) had at least one influenza infection (338 infections, incidence rate 3.7 per 100 person-years; 95% CI, 3.4-4.1) and 56.2% of those tested received annual influenza vaccine. Overall VE pooled over five seasons was 22.3% (95% CI, -7.3% to 43.7%). Adjusted VE estimates ranged from 39.7% (95% CI, -70.1% to 78.6%) in 2015/2016 to -5.9% (95% CI, -88.4% to 40.4%) in the 2016/17 seasons. Influenza VE varied by age and was highest in children 1-5 years of age (66.6%; 95% CI, 30.3-84.0). Adjusted VE against acute chest syndrome during influenza infection was 39.4% (95% CI, -113.0 to 82.8%). CONCLUSIONS:Influenza VE in patients with SCD varies by season and age. Multicenter prospective studies are needed to better establish and monitor influenza VE among children with SCD.
背景: 关于镰状细胞病 (SCD) 儿童的流感负担和季节性流感疫苗有效性 (VE) 的数据有限。 方法: 我们使用前瞻性收集的6个月至21岁SCD患者的临床登记，以确定每100患者年的流感病例，疫苗接种率，以及测试阴性病例对照研究设计，以评估流感VE对医疗实验室确诊的流感感染的影响。流感阳性病例在年龄和流感季节以1:1的比例与测试阴性对照随机匹配。我们使用调整后的逻辑回归模型来比较病例和对照中疫苗接种的比值比 (OR)。我们计算VE为 [100% × (1-校正OR)]，并计算估计值周围的95% 置信区间 (ci)。 结果: 有1037名SCD儿童接受了流感检测，307名儿童 (29.6%) 至少有一种流感感染 (338例感染，发病率3.7/100人年; 95% CI，3.4-4.1)，56.2% 的受试儿童每年接受流感疫苗接种。五个季节汇总的总体VE为22.3% (95% CI，-7.3% 至43.7%)。在39.7% 个季节中，95% 至-70.1% (78.6% CI，-2015/2016至5.9%) 的VE估计值范围为95% (88.4% CI，-40.4% 至2016/17)。流感VE因年龄而异，在1-5岁儿童中最高 (66.6%; 95% CI，30.3-84.0)。流感感染期间急性胸部综合征的校正VE为39.4% (95% CI，-113.0至82.8%)。 结论: SCD患者的流感VE因季节和年龄而异。需要多中心前瞻性研究来更好地建立和监测SCD儿童中的流感VE。
METHODS:BACKGROUND:Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE:In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN:In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS:As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION:Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.
METHODS:OBJECTIVES:Sickle cell disease (SCD) is a serious illness with disabling acute and chronic pain that needs better therapies, but insufficient patient participation in research is a major impediment to advancing SCD pain management. The purpose of this article is to discuss the challenges of conducting an SCD study and approaches to successfully overcoming those challenges. DESIGN:In a repeated-measures, longitudinal study designed to characterize SCD pain phenotypes, we recruited 311 adults of African ancestry. Adults with SCD completed 4 study visits 6 months apart, and age- and gender-matched healthy controls completed 1 visit. RESULTS:We recruited and completed measures on 186 patients with SCD and 125 healthy controls. We retained 151 patients with SCD with data at 4 time points over 18 months and 125 healthy controls (1 time point) but encountered many challenges in recruitment and study visit completion. Enrollment delays often arose from patients' difficulty in taking time from their complicated lives and frequent pain episodes. Once scheduled, participants with SCD cancelled 49% of visits often because of pain; controls canceled 30% of their scheduled visits. To facilitate recruitment and retention, we implemented a number of strategies that were invaluable in our success. CONCLUSION:Patients' struggles with illness, chronic pain, and their life situations resulted in many challenges to recruitment and completion of study visits. Important to overcoming challenges was gaining the trust of patients with SCD and a participant-centered approach. Early identification of potential problems allowed strategies to be instituted proactively, leading to success.
METHODS:OBJECTIVES:Sickle cell anemia is the commonest genetic disorder in India, and the frequency of the sickle cell gene is very high in the remote tribal areas where facilities are generally limited. Therefore, a rapid and affordable point-of-care test for sickle cell disease is needed. METHODS:The diagnostic accuracy of HemoTypeSC was evaluated against automated high-performance liquid chromatography (HPLC) as the gold standard for its efficacy in a newborn screening program. RESULTS:A total of 1,559 individuals (980 newborns and 579 adults) from four participating centers were analyzed by both methods. HemoTypeSC correctly identified 209 of 211 total hemoglobin (Hb) SS cases, for a 99.1%/99.9% total HbSS sensitivity/specificity. Overall, HemoTypeSC exhibited sensitivity and specificity of 98.1% and 99.1% for all possible phenotypes (HbAA, HbAS, and HbSS) detected. HPLC is relatively expensive and not available in most laboratories in remote tribal areas. CONCLUSIONS:We conclude that the rapid, point-of-care testing device HemoTypeSC test is suitable for population and newborn screening for the HbS phenotype.