Cardiometabolic risk factors in siblings from a statewide screening program.

BACKGROUND: The Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project is a state-wide risk factor screening program that operated in West Virginia for 19 years and screened more than 100,000 5th graders for obesity, hypertension, and dyslipidemia. OBJECTIVES: We investigated siblings in the CARDIAC Project to assess whether cardiometabolic risk factors (CMRFs) correlate in siblings. METHODS: We identified 12,053 children from 5752 families with lipid panel, blood pressure, and anthropometric data. A linkage application (LinkPlus from the U.S. Centers for Disease Control and Prevention) matched siblings based on parent names, addresses, telephone numbers, and school to generate a linkage probability curve. Graphical and statistical analyses demonstrate the relationships between CMRFs in siblings. RESULTS: Siblings showed moderate intraclass correlation coefficient of 0.375 for low-density lipoprotein cholesterol (LDL-C), 0.34 for high-density lipoprotein cholesterol (HDL-C), and 0.22 for triglyceride levels. The body mass index (BMI) intraclass correlation coefficient (0.383) is slightly better (2%) than LDL-C or HDL-C, but the standardized beta values from linear regression suggest a 3-fold impact of sibling LDL-C over the child's own BMI. The odds ratio of a second sibling having LDL-C < 110 mg/dL with a first sibling at that level is 3.444:1 (Confidence Limit 3.031-3.915, P < .05). The odds ratio of a sibling showing an LDL-C ≥ 160 mg/dL, given a first sibling with that degree of elevated LDL-C is 29.6:1 (95% Confidence Limit: 15.54-56.36). The individual LDL-C level correlated more strongly with sibling LDL-C than with the individual's own BMI. Seventy-eight children with LDL-C > 160 mg/dL and negative family history would have been missed, which represents more than half of those with LDL-C > 160 mg/dL (78 vs 67 or 54%). CONCLUSIONS: Sibling HDL-C levels, LDL-C levels, and BMIs correlate within a family. Triglyceride and blood pressure levels are less well correlated. The identified CMRF relationships strengthen the main findings of the overall CARDIAC Project: an elevated BMI is not predictive of elevated LDL-C and family history of coronary artery disease poorly predicts cholesterol abnormality at screening. Family history does not adequately identify children who should be screened for cholesterol abnormality. Elevated LDL-C (>160 mg/dL) in a child strongly suggests that additional siblings and parents be screened if universal screening is not practiced.

Foreign Body Aspiration Presenting as Pneumothorax in a Child.

A typical presentation of a foreign body aspiration (FBA) in a child includes witnessed choking, respiratory distress, cyanosis, coughing, wheezing, diminished breath sounds, and/or altered mental status. Following an extensive literature review, we found pneumothorax occurring secondary to FBA is a rare occurrence and should elicit prompt treatment. This 17-month-old female was admitted for respiratory syncytial virus (RSV) bronchiolitis and developed a subsequent pneumothorax during her hospital stay, consequent to aspiration of a cashew fragment two weeks before presentation. In light of the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored expert panel's addended guidelines, published and endorsed by the American Academy of Pediatrics (AAP) in 2017, we highlight a potential complication of increasing encouragement of peanut consumption in children as young as four months.

LDL cholesterol level in fifth-grade schoolchildren associates with stature.

Short stature is associated with increased LDL-cholesterol levels and coronary artery disease in adults. We investigated the relationship of stature to LDL levels in children in the West Virginia Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project to determine whether the genetically determined inverse relationship observed in adults would be evident in fifth graders. A cross-sectional survey of schoolchildren was assessed for cardiovascular risk factors. Data collected at school screenings over 18 years in WV schools were analyzed for 63,152 fifth-graders to determine relationship of LDL to stature with consideration of age, gender, and BMI. The first (shortest) quartile showed an LDL level of 93.6 mg/dl compared with an LDL level of 89.7 mg/dl for the fourth (tallest) quartile. Each incremental increase of 1 SD of height lowered LDL by 0.049 mg/dl (P < 0.0001). Multivariate analysis showed LDL to vary inversely as a function of the first (lowest) quartile of height after controlling for gender, median age, BMI percentile for age and gender, and year of screening. The odds ratio for LDL ≥ 130 mg/dl for shortest versus tallest quartile is 1.266 (95% CL 1.162-1.380). The odds ratio for LDL ≥ 160 mg/dl is 1.456 (95% CL 1.163-1.822). The relationship between short stature and LDL, noted in adults, is confirmed in childhood.

Machine learning-based coreference resolution of concepts in clinical documents.

OBJECTIVE: Coreference resolution of concepts, although a very active area in the natural language processing community, has not yet been widely applied to clinical documents. Accordingly, the 2011 i2b2 competition focusing on this area is a timely and useful challenge. The objective of this research was to collate coreferent chains of concepts from a corpus of clinical documents. These concepts are in the categories of person, problems, treatments, and tests. DESIGN: A machine learning approach based on graphical models was employed to cluster coreferent concepts. Features selected were divided into domain independent and domain specific sets. Training was done with the i2b2 provided training set of 489 documents with 6949 chains. Testing was done on 322 documents. RESULTS: The learning engine, using the un-weighted average of three different measurement schemes, resulted in an F measure of 0.8423 where no domain specific features were included and 0.8483 where the feature set included both domain independent and domain specific features. CONCLUSION: Our machine learning approach is a promising solution for recognizing coreferent concepts, which in turn is useful for practical applications such as the assembly of problem and medication lists from clinical documents.

Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation.

Selenium-deficiency cardiomyopathy is a known secondary complication from long-term treatment with a ketogenic diet for medical refractory epilepsy. Our patient, a 5-year-old boy on a ketogenic diet for intractable seizures, had a normal selenium level before starting the diet, but he shortly thereafter developed acute reversible cardiomyopathy and ventricular tachycardia, which was unmasked during a hospitalization for an elective operative procedure. His cardiomyopathy was suspected to be secondary to a selenium-deficient state and was confirmed by way of a markedly low serum selenium level and supported by rapid improvement with the initiation of selenium supplementation and cessation of the ketogenic diet. For patients being initiated on a ketogenic diet, current screening guidelines call for baseline and follow-up selenium levels every 3 months during the first year along with RDA selenium supplementation, which is 30 mcg/day. Most of the new ketogenic diet formulas meet this requirement. Our patient underwent elective surgery before his planned 3-month selenium level check and had potentially preventable complications. Secondary to this experience, we suggest that all patients initiated on a ketogenic diet should have a preoperative electrocardiogram (EKG), an echocardiogram, and selenium level determined before any elective surgery. These steps would prevent unnecessary perioperative morbidity and mortality.

Impact of a Multimodal Antimicrobial Stewardship Program on Pseudomonas aeruginosa Susceptibility and Antimicrobial Use in the Intensive Care Unit Setting.

Objective. To study the impact of our multimodal antibiotic stewardship program on Pseudomonas aeruginosa susceptibility and antibiotic use in the intensive care unit (ICU) setting. Methods. Our stewardship program employed the key tenants of published antimicrobial stewardship guidelines. These included prospective audits with intervention and feedback, formulary restriction with preauthorization, educational conferences, guidelines for use, antimicrobial cycling, and de-escalation of therapy. ICU antibiotic use was measured and expressed as defined daily doses (DDD) per 1,000 patient-days. Results. Certain temporal relationships between antibiotic use and ICU resistance patterns appeared to be affected by our antibiotic stewardship program. In particular, the ICU use of intravenous ciprofloxacin and ceftazidime declined from 148 and 62.5 DDD/1,000 patient-days to 40.0 and 24.5, respectively, during 2004 to 2007. An increase in the use of these agents and resistance to these agents was witnessed during 2008-2010. Despite variability in antibiotic usage from the stewardship efforts, we were overall unable to show statistical relationships with P. aeruginosa resistance rate. Conclusion. Antibiotic resistance in the ICU setting is complex. Multimodal stewardship efforts attempt to prevent resistance, but such programs clearly have their limits.

Acute subdural hematoma: potential soccer injury in an otherwise healthy child.

A 16-year-old adolescent boy presented with headache, dizziness, loss of consciousness, and a tonic-clonic seizure after heading a soccer ball in a competitive match. A computed tomographic scan of the head revealed an acute subdural hematoma with a mass effect. The patient was emergently referred to a tertiary care facility where he eventually recovered completely with conservative care. No predisposing medical conditions were found. To the best of our knowledge, this is the first report of an intracranial hemorrhage secondary to the heading of a soccer ball alone in an otherwise healthy child without any underlying predisposing central nervous system abnormalities.

Natural language processing framework to assess clinical conditions.

OBJECTIVE The authors developed a natural language processing (NLP) framework that could be used to extract clinical findings and diagnoses from dictated physician documentation. DESIGN De-identified documentation was made available by i2b2 Bio-informatics research group as a part of their NLP challenge focusing on obesity and its co-morbidities. The authors describe their approach, which used a combination of concept detection, context validation, and the application of a variety of rules to conclude patient diagnoses. RESULTS The framework was successful at correctly identifying diagnoses as judged by NLP challenge organizers when compared with a gold standard of physician annotations. The authors overall kappa values for agreement with the gold standard were 0.92 for explicit textual results and 0.91 for intuited results. The NLP framework compared favorably with those of the other entrants, placing third in textual results and fourth in intuited results in the i2b2 competition. CONCLUSIONS The framework and approach used to detect clinical conditions was reasonably successful at extracting 16 diagnoses related to obesity. The system and methodology merits further development, targeting clinically useful applications.

Assessment of commercial NLP engines for medication information extraction from dictated clinical notes.

PURPOSE: We assessed the current state of commercial natural language processing (NLP) engines for their ability to extract medication information from textual clinical documents. METHODS: Two thousand de-identified discharge summaries and family practice notes were submitted to four commercial NLP engines with the request to extract all medication information. The four sets of returned results were combined to create a comparison standard which was validated against a manual, physician-derived gold standard created from a subset of 100 reports. Once validated, the individual vendor results for medication names, strengths, route, and frequency were compared against this automated standard with precision, recall, and F measures calculated. RESULTS: Compared with the manual, physician-derived gold standard, the automated standard was successful at accurately capturing medication names (F measure=93.2%), but performed less well with strength (85.3%) and route (80.3%), and relatively poorly with dosing frequency (48.3%). Moderate variability was seen in the strengths of the four vendors. The vendors performed better with the structured discharge summaries than with the clinic notes in an analysis comparing the two document types. CONCLUSION: Although automated extraction may serve as the foundation for a manual review process, it is not ready to automate medication lists without human intervention.

Pharmacological management of acute bronchiolitis.

This article reviews the current knowledge base related to the pharmacological treatments for acute bronchiolitis. Bronchiolitis is a common lower respiratory illness affecting infants worldwide. The mainstays of therapy include airway support, supplemental oxygen, and support of fluids and nutrition. Frequently tried pharmacological interventions, such as ribavirin, nebulized bronchodilators, and systemic corticosteroids, have not been proven to benefit patients with bronchiolitis. Antibiotics do not improve the clinical course of patients with bronchiolitis, and should be used only in those patients with proven concurrent bacterial infection. Exogenous surfactant and heliox therapy also cannot be recommended for routine use, but surfactant replacement holds promise and should be further studied.

Infantile Kawasaki disease and peripheral gangrene.

We report a 1-month-old infant with Kawasaki disease and peripheral gangrene. We advocate using the newly published American Heart Association guidelines advising early laboratory and echocardiogram investigations in infants with fever but without other classic manifestations of Kawasaki disease. Initiation of early therapy may prevent this serious complication with its permanent sequelae.

Octreotide efficacy in the treatment of chylothoraces following cardiac surgery in infants and children.

OBJECTIVE: To examine the efficacy of octreotide in resolving chylothoraces in infants and children following cardiac surgery. DESIGN: Retrospective chart review. SETTING: Pediatric intensive care unit of a tertiary care center. PATIENTS: All children who received octreotide for the treatment of chylothoraces following surgery for congenital heart disease over a 30-month period between 2001-2004. INTERVENTIONS: Octreotide infusion. MEASUREMENTS AND MAIN RESULTS: Eight courses of octreotide treatment were identified in seven patients who met our inclusion criteria. The median duration of therapy was 5 days, and dosing ranged from 1 to 4 microg/kg/hr. Treatment did not result in an overall decrease in average chest tube output after 3 days of therapy. However, in two patients (29%) the chylothoraces ultimately resolved during the octreotide infusion. Treatment was well tolerated, and no serious side effects were noted. CONCLUSION: In contrast to previously published reports, we find octreotide therapy for postoperative chylothoraces to be successful in only a minority of cases.

Computerized antimicrobial decision support: an offline evaluation of a database-driven empiric antimicrobial guidance program in hospitalized patients with a bloodstream infection.

INTRODUCTION: We developed a computerized antimicrobial guidance program based on the last 5 years of our laboratory culture data augmented by expert infectious disease logic. The program is designed to assist physicians with the targeting of empiric antimicrobials for hospitalized patients by tracking pathogenic bacteria and their evolving antimicrobial resistance profiles. Costs, toxicities, and environmental impact of antimicrobial use also influence the final recommendations. We undertook the following analysis to verify its potential safety and efficacy in hospitalized patients with a bloodstream infection. METHODS: We retrospectively enrolled all inpatients with a positive blood culture for a previously undetermined pathogen during the first 6 months of 2002 and determined the empiric therapy initiated within the 12h before and after the time of culture. Antimicrobial recommendations from the microbiologic decision support tool were then determined by matching specimen (blood), hospital unit, community- versus hospital-acquired category, age category, and gender. Generated antimicrobial recommendations were tailored to patient allergies, age category, and presence of pregnancy, lactation, or hepatic impairment. RESULTS: The microbiology laboratory recorded 226 unique patient/pathogen blood cultures during the study period. Physicians initiated effective empiric therapy in 150 of the 226 cases, for an effectiveness rate of 66%. The computer-guided therapy was effective in 195 of the 226 cases for a rate of 86%. A contingency table analysis showed 55 cases where the computer recommendation was effective but the physicians' selection was not, and eight cases where the physicians' antimicrobials were effective but the computer's were not (P < 0.0001). DISCUSSION: For patients with a bloodstream infection, we found that our computer-guided statistically-derived antimicrobial therapy would potentially improve the rate of effectiveness of empirically chosen antimicrobials.

Left-sided CHILD syndrome caused by a nonsense mutation in the NSDHL gene.

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is a rare X-linked dominant malformation syndrome characterized by unilaterally distributed ichthyosiform nevi, often sharply delimited at the midline, and ipsilateral limb defects. At least two-thirds of cases demonstrate involvement of the right side. Mutations in an essential enzyme of cholesterol biosynthesis, NAD(P)H steroid dehydrogenase-like [NSDHL], have been reported in five unrelated patients with right-sided CHILD syndrome and in a sixth patient with bilaterally, symmetric nevi and mild skeletal anomalies, but not with CHILD syndrome as originally defined. Although all of the molecularly diagnosed cases with the CHILD phenotype to date have had right-sided disease, we report here a novel nonsense mutation (E151X) of NSDHL in an infant with left-sided CHILD syndrome. This result demonstrates that both right- and left-sided CHILD syndrome can be caused by mutations in the same gene.

Computerized antimicrobial decision support for hospitalized patients with a bloodstream infection.

We developed a computerized antimicrobial decision support program founded on our local bacterial susceptibility data. In a retrospective analysis of patients with a bloodstream infection, we compared the actual antimicrobials prescribed to the antimicrobials recommended by the program. We found the computer-guided therapy to be clinically and statistically more effective than the therapy initiated by the physicians. We conclude that computerized decision support can improve the targeting of empiric antimicrobial therapy.

Database-driven computerized antibiotic decision support: novel use of expert antibiotic susceptibility rules embedded in a pathogen-antibiotic logic matrix.

To better serve an antibiotic guidance program, we hypothesized that the relatively few antibiotic susceptibility measurements conducted in the microbiology laboratory could be extended to predict antibiotic susceptibilities for all antibiotics on the hospital formulary using expert infectious disease logic. With the assistance of infectious disease specialists, we developed these logic rules and then applied them to 26,196 unique patient culture specimens and the accompanying 334,131 antibiotic susceptibility measurements generating 804,809 additional predicted bug-drug susceptibility data points. From the resulting data set, the antibiotic susceptibility profile for one pathogen, Streptococcus pneumoniae, is highlighted herein. We then incorporated the extended susceptibility profiles into a computerized antibiotic guidance program that matches current patients of interest with the positive cultures from past similar patients and calculates predicted effective antibiotic therapy. We conclude that this method successfully derives antibiotic predictions and merits further testing to evaluate its potential use in the hospital environment.