Highly Irregular Functional Generalized Linear Regression with Electronic Health Records

This work presents a new approach, called MISFIT, for fitting generalized functional linear regression models with sparsely and irregularly sampled data. Current methods do not allow for consistent estimation unless one assumes that the number of observed points per curve grows sufficiently quickly with the sample size. In contrast, MISFIT is based on a multiple imputation framework, which has the potential to produce consistent estimates without such an assumption. Just as importantly, it propagates the uncertainty of not having completely observed curves, allowing for a more accurate assessment of the uncertainty of parameter estimates, something that most methods currently cannot accomplish. This work is motivated by a longitudinal study on macrocephaly, or atypically large head size, in which electronic medical records allow for the collection of a great deal of data. However, the sampling is highly variable from child to child. Using MISFIT we are able to clearly demonstrate that the development of pathologic conditions related to macrocephaly is associated with both the overall head circumference of the children as well as the velocity of their head growth.Comment: 5 figures, 17 tables (including supplementary material), 34 pages (including supplementary material

Differing prevalence of microcephaly and macrocephaly in male and female fetuses

ObjectiveTo compare the proportion of female and male fetuses classified as microcephalic (head circumference [HC] < 3rd percentile) and macrocephalic (>97th percentile) by commonly used sex-neutral growth curves.MethodsFor fetuses evaluated at a single center, we retrospectively determined the percentile of the first fetal HC measurement between 16 and 0/7 and 21–6/7 weeks using the Hadlock, Intergrowth-21st, and NICHD growth curves. The association between sex and the likelihood of being classified as microcephalic or macrocephalic was evaluated with logistic regression.ResultsFemale fetuses (n = 3,006) were more likely than male fetuses (n = 3,186) to be classified as microcephalic using the Hadlock (0.4% male, 1.4% female; odds ratio female vs. male 3.7, 95% CI [1.9, 7.0], p < 0.001), Intergrowth-21st (0.5% male, 1.6% female; odds ratio female vs. male 3.4, 95% CI [1.9, 6.1], p < 0.001), and NICHD (0.3% male, 1.6% female; odds ratio female vs. male 5.6, 95% CI [2.7, 11.5], p < 0.001) curves. Male fetuses were more likely than female fetuses to be classified as macrocephalic using the Intergrowth-21st (6.0% male, 1.5% female; odds ratio male vs. female 4.3, 95% CI [3.1, 6.0], p < 0.001) and NICHD (4.7% male, 1.0% female; odds ratio male vs. female 5.1, 95% CI [3.4, 7.6], p < 0.001) curves. Very low proportions of fetuses were classified as macrocephalic using the Hadlock curves (0.2% male, < 0.1% female; odds ratio male vs. female 6.6, 95% CI [0.8, 52.6]).ConclusionFemale fetuses were more likely to be classified as microcephalic, and male fetuses were more likely to be classified as macrocephalic. Sex-specific fetal head circumference growth curves could improve interpretation of fetal head circumference measurements, potentially decreasing over- and under-diagnosis of microcephaly and macrocephaly based on sex, therefore improving guidance for clinical decisions. Additionally, the overall prevalence of atypical head size varied using three growth curves, with the NICHD and Intergrowth-21st curves fitting our population better than the Hadlock curves. The choice of fetal head circumference growth curves may substantially impact clinical care

Accuracy of physician-estimated probability of brain injury in children with minor head trauma

Objective: To evaluate the accuracy of physician estimates of the probability of intracranial injury in children with minor head trauma. Methods: This is a subanalysis of a large prospective multicentre cohort study performed from July 2001 to November2005. During data collection for the derivation of a clinical prediction rule for children with minor head trauma, physicians indicated their estimate of the probability of brain injury visible on computed tomography (P-Injury) and the probability of injury requiring intervention (P-Intervention) by choosing one of the following options: 0%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 90%, and 100%. We compared observed frequencies to expected frequencies of injury using Pearson’s χ2-test in analyses stratified by the level of each type of predicted probability and by year of age. Results: In 3771 eligible subjects, the mean predicted risk was 4.6% (P-Injury) and 1.4% (P-Intervention). The observed frequency of injury was 4.1% (any injury) and 0.6% (intervention). For all levels of P-Injury from 1% to 40%, the observed frequency of injury was consistent with the expected frequency. The observed frequencies for the 50%, 75%, and 90% levels were lower than expected (p\u3c0.05). For estimates of P-Intervention, the observed frequency was consistently higher than the expected frequency. Physicians underestimated risk for infants (mean P-Intervention 6.2%, actual risk 12.3%, p\u3c0.001). Conclusions: Physician estimates of probability of any brain injury in children were collectively accurate for children with low and moderate degrees of predicted risk. Risk was underestimated in infants

The test characteristics of head circumference measurements for pathology associated with head enlargement: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The test characteristics of head circumference (HC) measurement percentile criteria for the identification of previously undetected pathology associated with head enlargement in primary care are unknown.</p> <p>Methods</p> <p>Electronic patient records were reviewed to identify children age 3 days to 3 years with new diagnoses of intracranial expansive conditions (IEC) and metabolic and genetic conditions associated with macrocephaly (MGCM). We tested the following HC percentile threshold criteria: ever above the 95^th, 97^th, or 99.6^thpercentile and ever crossing 2, 4, or 6 increasing major percentile lines. The Centers for Disease Control and World Health Organization growth curves were used, as well as the primary care network (PCN) curves previously derived from this cohort.</p> <p>Results</p> <p>Among 74,428 subjects, 85 (0.11%) had a new diagnosis of IEC (n = 56) or MGCM (n = 29), and between these 2 groups, 24 received intervention. The 99.6^thpercentile of the PCN curve was the only threshold with a PPV over 1% (PPV 1.8%); the sensitivity of this threshold was only 15%. Test characteristics for the 95th percentiles were: sensitivity (CDC: 46%; WHO: 55%; PCN: 40%), positive predictive value (PPV: CDC: 0.3%; WHO: 0.3%; PCN: 0.4%), and likelihood ratios positive (LR+: CDC: 2.8; WHO: 2.2; PCN: 3.9). Test characteristics for the 97th percentiles were: sensitivity (CDC: 40%; WHO: 48%; PCN: 34%), PPV (CDC: 0.4%; WHO: 0.3%; PCN: 0.6%), and LR+ (CDC: 3.6; WHO: 2.7; PCN: 5.6). Test characteristics for crossing 2 increasing major percentile lines were: sensitivity (CDC: 60%; WHO: 40%; PCN: 31%), PPV (CDC: 0.2%; WHO: 0.1%; PCN: 0.2%), and LR+ (CDC: 1.3; WHO: 1.1; PCN: 1.5).</p> <p>Conclusions</p> <p>Commonly used HC percentile thresholds had low sensitivity and low positive predictive value for diagnosing new pathology associated with head enlargement in children in a primary care network.</p

Clinician diagnoses of failure to thrive before and after switch to World Health Organization growth curves.

OBJECTIVE: To evaluate change in the incidence of failure to thrive (FTT) based on selected growth percentile criteria and diagnostic codes before and after a switch in growth curves. METHODS: We performed a retrospective cohort study of children 2 to 24 months of age in a large primary care network that switched its default growth curve from the Centers for Disease Control and Prevention (CDC) reference to the World Health Organization (WHO) standards in 2012. We compared the incidence of FTT defined by growth percentile criteria (using the default growth curve at the time of each measurement) and by International Classification of Diseases, Ninth Revision, codes in the 3 years before and after the CDC-WHO switch using an interrupted time series analysis. We performed these analyses stratified by age group (≤6 months and \u3e6-24 months). RESULTS: We evaluated 83,299 children. Among those ≤6 months, increases in FTT incidence were found in both growth-percentile and clinician-diagnosis criteria at the CDC-WHO switch (P \u3c .05). Among those \u3e6 to 24 months, decreases in FTT incidence were found by growth-percentile criteria at the CDC-WHO switch (P \u3c .05), but no significant changes were found in FTT incidence by diagnostic codes. CONCLUSIONS: When switching from the CDC to the WHO growth curves, changes in the incidence of FTT by growth-percentile and clinician-diagnosis criteria differed for younger versus older infants. Factors beyond growth likely influence the decision to diagnose a child as having FTT and may differ in younger compared to older infants

Evaluation of Income and Food Insecurity as Risk Factors for Failure to Thrive: An Analysis of National Survey Data.

Limited data exist regarding the relationship between socioeconomic risk factors and failure to thrive (FTT). Using data from the National Health and Nutrition Examination Survey (NHANES) from years 1999 to 2014, we sought to determine whether there was a higher prevalence of underweight ([WFA], weight-for-length [WFL], or body mass index-for-age [BFA]), and, therefore, likely a higher risk of FTT, in US childrenchildren, there were no significant differences in the prevalence of underweight by adjusted household income quintile, food security, household Women, Infants, and Children (WIC) status, or federal poverty income ratio. These findings do not support a link between low income or food security and underweight in children and, therefore, do not provide support for an association between low income or food security and FTT

Intraarticular steroids as DMARD-sparing agents for juvenile idiopathic arthritis flares: Analysis of the Childhood Arthritis and Rheumatology Research Alliance Registry.

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) who achieve a drug free remission often experience a flare of their disease requiring either intraarticular steroids (IAS) or systemic treatment with disease modifying anti-rheumatic drugs (DMARDs). IAS offer an opportunity to recapture disease control and avoid exposure to side effects from systemic immunosuppression. We examined a cohort of patients treated with IAS after drug free remission and report the probability of restarting systemic treatment within 12 months. METHODS: We analyzed a cohort of patients from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry who received IAS for a flare after a period of drug free remission. Historical factors and clinical characteristics and of the patients including data obtained at the time of treatment were analyzed. RESULTS: We identified 46 patients who met the inclusion criteria. Of those with follow up data available 49% had restarted systemic treatment 6 months after IAS injection and 70% had restarted systemic treatment at 12 months. The proportion of patients with prior use of a biologic DMARD was the only factor that differed between patients who restarted systemic treatment those who did not, both at 6 months (79% vs 35%, p \u3c 0.01) and 12 months (81% vs 33%, p \u3c 0.05). CONCLUSION: While IAS are an option for all patients who flare after drug free remission, it may not prevent the need to restart systemic treatment. Prior use of a biologic DMARD may predict lack of success for IAS. Those who previously received methotrexate only, on the other hand, are excellent candidates for IAS