Risk-score based strategy to minimize antibiotic exposure in children with sickle cell disease and fever.
Ontology highlight
ABSTRACT:
SUBMITTER: Rincon-Lopez EM
PROVIDER: S-EPMC8484827 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Risk assessment for patients with sickle cell disease (SCD) remains challenging as it depends on an individual physician's experience and ability to integrate a variety of test results. We aimed to provide a new risk score that combines clinical, laboratory, and imaging data. In a prospective cohort of 600 adult patients with SCD, we assessed the relationship of 70 baseline covariates to all-cause mortality. Random survival forest and regularised Cox regression machine learning (ML) methods were used to select top predictors. Multivariable models and a risk score were developed and internally validated. Over a median follow-up of 4·3 years, 131 deaths were recorded. Multivariable models were developed using nine independent predictors of mortality: tricuspid regurgitant velocity, estimated right atrial pressure, mitral E velocity, left ventricular septal thickness, body mass index, blood urea nitrogen, alkaline phosphatase, heart rate and age. Our prognostic risk score had superior performance with a bias-corrected C-statistic of 0·763. Our model stratified patients into four groups with significantly different 4-year mortality rates (3%, 11%, 35% and 75% respectively). Using readily available variables from patients with SCD, we applied ML techniques to develop and validate a mortality risk scoring method that reflects the summation of cardiopulmonary, renal and liver end-organ damage. Trial Registration: ClinicalTrials.gov Identifier: NCT#00011648.
| S-EPMC9123430 | biostudies-literature
Project description:Children with sickle cell disease (SCD) are repeatedly exposed to diagnostic radiation. We identified 938 children with SCD who had 9,246 radiographic tests. Mean number of tests/patient was 9.9 (95% CI: 8.9-10.9) over 8,817 patient-years. Mean rate was 1.5 tests/year (95% CI: 1.3-1.6). On average, a child with SCD will have 26.7 (95% CI: 24.1-29.3) radiographic tests by 18 years of age, and 5% will have ?100 tests. Six percent have ?3 CT scans, which may be associated with an increased risk of cancer. Strong consideration should be given to limiting the exposure of children with SCD to radiation.
| S-EPMC4008662 | biostudies-literature
Project description:Early identification of infants with sickle cell disease (SCD) by newborn screening, now universal in all 50 states in the US, has improved survival, mainly by preventing overwhelming sepsis with the early use of prophylactic penicillin. Routine transcranial Doppler screening with the institution of chronic transfusion decreases the risk of stroke from 10% to 1% in paediatric SCD patients. Hydroxyurea decreases the number and frequency of painful crises, acute chest syndromes and number of blood transfusions in children with SCD. Genetic research continues to be driven toward the prevention and ultimate cure of SCD before adulthood. This review focuses on clinical manifestations and therapeutic strategies for paediatric SCD as well as the evolving topic of gene-focused prevention and therapy.
| S-EPMC3899685 | biostudies-other
Project description:Children with sickle cell anemia (SCA) are at increased risk for invasive pneumococcal disease; antibiotic prophylaxis significantly reduces this risk. We calculated the proportion of children with SCA who received ≥300 days of antibiotic prophylaxis and identified predictors of such receipt. Children aged 3 months to 5 years with SCA were identified by the presence of 3 or more Medicaid claims with a diagnosis of SCA within a calendar year (2005-2012) in Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Receipt of antibiotics was identified through claims for filled prescriptions. The outcome, receipt of ≥300 days of antibiotics, was assessed annually by using varying classifications of antibiotics. By using logistic regression with generalized estimating equations, we estimated the odds of receiving ≥300 days of antibiotics, with potential predictors of age, sex, year, state, and health services use. A total of 2821 children contributed 5014 person-years. Overall, only 18% of children received ≥300 days of antibiotics. Each additional sickle cell disease-related outpatient visit (odds ratio = 1.01, 95% confidence interval: 1.01-1.02) and well-child visit (odds ratio = 1.08, 95% confidence interval: 1.02-1.13) was associated with incrementally increased odds of receiving ≥300 days of antibiotics. Despite national recommendations and proven lifesaving benefit, antibiotic prophylaxis rates are low among children with SCA. Numerous health care encounters may offer an opportunity for intervention; in addition, such interventions likely need to include social factors that may affect the ability for a child to receive and adhere to antibiotic prophylaxis.
| S-EPMC7252515 | biostudies-literature
Project description:Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before-after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 μg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14-18] vs. 13 [13,14] days (p = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% (p = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes.
| S-EPMC7699579 | biostudies-literature
Project description:BackgroundThe Lab-score, based on the combined determination of procalcitonin, C-reactive protein and urinary dipstick results, has been shown accurate in detecting serious bacterial infections (SBI) in children with fever without source (FWS) on retrospective cohorts. We aimed to prospectively assess the utility of the Lab-score in safely decreasing antibiotic prescriptions in children with FWS and to determine its diagnostic characteristics compared to common SBI biomarkers.MethodsRandomized controlled trial in children 7 days to 36 months old with FWS, allocated either to the Lab-score group (Lab-score reported, blinded WBC count) or to the control group (WBC, bands and C-reactive protein determined, blinded procalcitonin and Lab-score), followed up until recovery. Demographic data, antibiotic prescription rate, admission rate and diagnostic properties of the Lab-score were analyzed.Results271 children were analyzed. No statistically significant difference concerning antibiotic prescription rate was observed: 41.2% (54 of 131) in the Lab-score group and 42.1% (59 of 140) in the control group (p = 1.000). If recommendations based on the Lab-score had been strictly applied, a hypothetical 30.6% treatment rate would have been encountered, compared to the overall 41.7% observed rate (p = 0.0095). A Lab-score ≥3 showed the following characteristics: sensitivity 85.1% (95% CI: 76.5-93.6%), specificity 87.3% (95% CI: 82.7-91.8%), positive predictive value 68.7% (95% CI: 58.7-78.7%), negative predictive value 94.1% (95% CI: 91.5-97.9%), positive and negative likelihood ratios: 6.68 and 0.17 respectively. Area under the receiver operating characteristic curve was best for the Lab-score (0.911, 95% CI: 0.871-0.950).DiscussionNo difference regarding antibiotic treatment rate was observed when using the Lab-score, due to lack of adherence to the related recommendations. However, if strictly followed, a significant 26.5% reduction of antibiotic prescriptions would have been encountered. Medical education needs to be reinforced in order to observe rather than treat low-risk well-appearing children with FWS.Trial registrationClinicalTrials.gov NCT02179398.
| S-EPMC4263728 | biostudies-literature
Project description:Hydroxyurea therapy offers promise for ameliorating the clinical course of children with sickle cell disease (SCD). Hydroxyurea is a prototypic therapeutic option; it can be administered with minimal side effects, has a relatively wide therapeutic window, and has mechanisms of action that address pathophysiologic pathways of sickling, vaso-occlusion, hemolysis, and organ damage. There are limited data regarding hydroxyurea's ability to prevent or diminish organ dysfunction, and the long-term risks of hydroxyurea therapy remain incompletely defined. Although clinical trials are underway to address long-term issues, hydroxyurea remains an effective but underutilized therapy for SCD.
| S-EPMC4765496 | biostudies-other
Project description:We developed a risk score to predict event-free survival (EFS) after allogeneic hematopoietic cell transplantation for sickle cell disease. The study population (n = 1425) was randomly split into training (n = 1070) and validation (n = 355) cohorts. Risk factors were identified and validated via Cox regression models. Two risk factors of 9 evaluated were predictive for EFS: age at transplantation and donor type. On the basis of the training cohort, patients age 12 years or younger with an HLA-matched sibling donor were at the lowest risk with a 3-year EFS of 92% (score, 0). Patients age 13 years or older with an HLA-matched sibling donor or age 12 years or younger with an HLA-matched unrelated donor were at intermediate risk (3-year EFS, 87%; score, 1). All other groups, including patients of any age with a haploidentical relative or HLA-mismatched unrelated donor and patients age 13 years or older with an HLA-matched unrelated donor were high risk (3-year EFS, 57%; score, 2 or 3). These findings were confirmed in the validation cohort. This simple risk score may guide patients with sickle cell disease and hematologists who are considering allogeneic transplantation as a curative treatment relative to other available contemporary treatments.
| S-EPMC7393258 | biostudies-literature
Project description:Sickle cell disease (SCD) is caused by a pathogenic hemoglobin (Hb) mutation, yet patients can have dramatically variable clinical manifestations. Here we address the genetic basis of this clinical heterogeneity. Using a systems genetics approach, we performed whole blood gene expression analysis and eQTL analysis on different clinical phenotypes in SCD patients. We generated whole blood gene expression profiles for 311 West-African children recruited from the National Sickle Cell Disease Centre in Cotonou, Benin which included 250 patients with varying degrees of SCD severities and 61 age-matched controls. SCD is caused by a point-mutation in the beta-hemoglobin gene that changes the normal HbAA protein into, most often, an abnormal HbSS or HbSC protein. The SCD patients recruited in the study either had HbSS or HbSC phenotypes and were categorized into different 3 clinical states based on follow-up status (Rahimy, MC, et al. Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in sub-Saharan African setting. Bood 102, 834-838. 2002). When patients are refered to the clinic, they are enrolled when they are in steady-state condition, and are labeled as entry (E). Patients followed at the SCD clinic are labeled as FU. Control patients were recruited and are labeled as C. Patients were also assigned a severity score (Sebastiani, P. et al. A network model to predict the risk of death in sickle cell disease. Blood 110, 2727-2735, 2007). Hemoglobin protein status (Hb phenotype) was confirmed for each patient using standard electrophoretic techniques. We generated genotypes for 263 of these individuals and performed principal component analysis (PCA) which identified 2 signigicant genotypic principal components (gPC1 and gPC2). Using the gene expression and genotyping data, we performed an eSNP analysis. . Gene expression data presented in this study.
2014-07-01 | E-GEOD-35007 | biostudies-arrayexpress
Project description:Despite efforts to control for confounding variables using stringent sampling plans, selection bias typically exists in observational studies, resulting in unbalanced comparison groups. Ignoring selection bias can result in unreliable or misleading estimates of the causal effect.Generalized boosted models were used to estimate propensity scores from 42 confounding variables for a sample of 361 neonates. Using emergent neonatal attention and orientation skills as an example developmental outcome, we examined the impact of tobacco exposure with and without accounting for selection bias. Weight at birth, an outcome related to tobacco exposure, also was used to examine the functionality of the propensity score approach.Without inclusion of propensity scores, tobacco-exposed neonates did not differ from their nonexposed peers in attention skills over the first month or in weight at birth. When the propensity score was included as a covariate, exposed infants had marginally lower attention and a slower linear change rate at 4 weeks, with greater quadratic deceleration over the first month. Similarly, exposure-related differences in birth weight emerged when propensity scores were included as a covariate.The propensity score method captured the selection bias intrinsic to this observational study of prenatal tobacco exposure. Selection bias obscured the deleterious impact of tobacco exposure on the development of neonatal attention. The illustrated analytic strategy offers an example to better characterize the impact of prenatal tobacco exposure on important developmental outcomes by directly modeling and statistically accounting for the selection bias from the sampling process.
| S-EPMC2991623 | biostudies-literature