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1.  Risk factors for colonoscopic perforation: A population-based study of 80118 cases 
AIM: To assess the incidence and risk factors associated with colonic perforation due to colonoscopy.
METHODS: This was a retrospective cross-sectional study. Patients were retrospectively eligible for inclusion if they were 18 years and older and had an inpatient or outpatient colonoscopy procedure code in any facility within the Geisinger Health System during the period from January 1, 2002 to August 25, 2010. Data are presented as median and inter-quartile range, for continuous variables, and as frequency and percentage for categorical variables. Baseline comparisons across those with and without a perforation were made using the two-sample t-test and Pearson’s χ2 test, as appropriate.
RESULTS: A total of 50 perforations were diagnosed out of 80118 colonoscopies, which corresponded to an incidence of 0.06% (95%CI: 0.05-0.08) or a rate of 6.2 per 10000 colonoscopies. All possible risk factors associated with colonic perforation with a P-value < 0.1 were checked for inclusion in a multivariable log-binomial regression model predicting 7-d colonic perforation. The final model resulted in the following risk factors which were significantly associated with risk of colonic perforation: age, gender, body mass index, albumin level, intensive care unit (ICU) patients, inpatient setting, and abdominal pain and Crohn’s disease as indications for colonoscopy.
CONCLUSION: The cumulative 7 d incidence of colonic perforation in this cohort was 0.06%. Advanced age and female gender were significantly more likely to have perforation. Increasing albumin and BMI resulted in decreased risk of colonic perforation. Having a colonoscopy indication of abdominal pain or Crohn’s disease resulted in a higher risk of colonic perforation. Colonoscopies performed in inpatients and particularly the ICU setting had substantially greater odds of perforation. Biopsy and polypectomy did not increase the risk of perforation and only three perforations occurred with screening colonoscopy.
PMCID: PMC3691036  PMID: 23801860
Colonoscopic perforation; Colon cancer; Endosocopy
2.  Population risk factor estimates for abdominal aortic aneurysm from electronic medical records: a case control study 
Using abdominal aortic aneurysm (AAA) as a model, this case–control study used electronic medical record (EMR) data to assess known risk factors and identify new associations.
The study population consisted of cases with AAA (n =888) and controls (n =10,523) from the Geisinger Health System EMR in Central and Northeastern Pennsylvania. We extracted all clinical and diagnostic data for these patients from January 2004 to December 2009 from the EMR. From this sample set, bootstrap replication procedures were used to randomly generate 2,500 iterations of data sets, each with 500 cases and 2000 controls. Estimates of risk factor effect sizes were obtained by stepwise logistic regression followed by bootstrap aggregation. Variables were ranked using the number of inclusions in iterations and P values.
The benign neoplasm diagnosis was negatively associated with AAA, a novel finding. Similarly, type 2 diabetes, diastolic blood pressure, weight and myelogenous neoplasms were negatively associated with AAA. Peripheral artery disease, smoking, age, coronary stenosis, systolic blood pressure, age, height, male sex, pulmonary disease and hypertension were associated with an increased risk for AAA.
This study utilized EMR data, retrospectively, for risk factor assessment of a complex disease. Known risk factors for AAA were replicated in magnitude and direction. A novel negative association of benign neoplasms was identified. EMRs allow researchers to rapidly and inexpensively use clinical data to expand cohort size and derive better risk estimates for AAA as well as other complex diseases.
PMCID: PMC4269847  PMID: 25475588
Aortic Aneurysm; Abdominal; Electronic medical record; Neoplasms; Benign; Risk factors; Blood pressure; Diabetes mellitus; Type 2; Case–control studies
3.  Prescription Medication Burden in Patients with Newly-Diagnosed Diabetes: A SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) Study 
To understand the burden of medication use for newly-diagnosed diabetes patients both before and after diabetes diagnosis, and to identify subpopulations of newly-diagnosed diabetes patients who face a relatively high drug burden.
Retrospective cohort.
Eleven U.S. integrated health systems.
196,654 insured adults aged ≥20 diagnosed with newly-diagnosed diabetes from 1/1/2005 – 12/31/2009.
Main Outcome Measure
Number of unique therapeutic classes of drugs dispensed in the 12 months prior to, and 12 months post, the diagnosis of diabetes in 5 categories: overall, antihypertensive, antihyperlipidemic, mental health, and antihyperglycemic (post-period only).
The mean number of drug classes used by newly-diagnosed diabetes patients is high before diagnosis (5.0), and increases significantly afterwards (6.6, p<.001). Eighty-one percent of this increase is due to antihyperglycemic initiation and increased use of medications to control hypertension and lipid levels. Multivariate analyses showed that overall drug burden after diabetes diagnosis was higher in female, older, white, and obese patients, as well as among those with higher A1cs and comorbidity levels (p<.001 for all comparisons). The overall number of drug classes used by newly-diagnosed diabetes patients after diagnosis decreased slightly between 2005 and 2009 (p<.001).
Diabetes patients face significant drug burden to control diabetes and other comorbidities, and our data indicate an increased focus on cardiovascular disease risk factor control after diabetes diagnosis. However, total drug burden may be slightly decreasing over time. This information can be valuable to pharmacists working with newly-diagnosed diabetes patients to address their increasing drug regimen complexity.
PMCID: PMC4161641  PMID: 24860866
diabetes; medication burden; surveillance
4.  The New York PTSD Risk Score for Assessment of Psychological Trauma: Male and Female Versions 
Psychiatry research  2012;200(2-3):827-834.
We previously developed a new posttraumatic stress disorder (PTSD) screening instrument – the New York PTSD Risk Score (NYPRS). Since research suggests different PTSD risk factors and outcomes for men and women, in the current study we assessed the suitability of male and female versions of this screening instrument among 3,298 adults exposed to traumatic events. Using diagnostic test methods, including receiver operating curve (ROC) and bootstrap techniques, we examined different prediction domains, including core PTSD symptoms, trauma exposures, sleep disturbances, depression symptoms, and other measures to assess PTSD prediction models for men and women. While the original NYPRS worked well in predicting PTSD, significant interaction was detected by gender, suggesting that separate models are warranted for men and women. Model comparisons suggested that while the overall results appeared robust, prediction results differed by gender. For example, for women, core PTSD symptoms contributed more to the prediction score than for men. For men, depression symptoms, sleep disturbance, and trauma exposure contributed more to the prediction score. Men also had higher cut-off scores for PTSD compared to women. There were other gender-specific differences as well. The NYPRS is a screener that appears to be effective in predicting PTSD status among at-risk populations. However, consistent with other medical research, this instrument appears to require male and female versions to be the most effective.
PMCID: PMC3434234  PMID: 22648009
Posttraumatic stress disorder; Psychological Trauma; Diagnostic testing; Patient screening
6.  Predicting PTSD using the New York Risk Score with genotype data: potential clinical and research opportunities 
We previously developed a post-traumatic stress disorder (PTSD) screening instrument, ie, the New York PTSD Risk Score (NYPRS), that was effective in predicting PTSD. In the present study, we assessed a version of this risk score that also included genetic information.
Utilizing diagnostic testing methods, we hierarchically examined different prediction variables identified in previous NYPRS research, including genetic risk-allele information, to assess lifetime and current PTSD status among a population of trauma-exposed adults.
We found that, in predicting lifetime PTSD, the area under the receiver operating characteristic curve (AUC) for the Primary Care PTSD Screen alone was 0.865. When we added psychosocial predictors from the original NYPRS to the model, including depression, sleep disturbance, and a measure of health care access, the AUC increased to 0.902, which was a significant improvement (P = 0.0021). When genetic information was added in the form of a count of PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (coded 0–6), the AUC increased to 0.920, which was also a significant improvement (P = 0.0178). The results for current PTSD were similar. In the final model for current PTSD with the psychosocial risk factors included, genotype resulted in a prediction weight of 17 for each risk allele present, indicating that a person with six risk alleles or more would receive a PTSD risk score of 17 × 6 = 102, the highest risk score for any of the predictors studied.
Genetic information added to the NYPRS helped improve the accuracy of prediction results for a screening instrument that already had high AUC test results. This improvement was achieved by increasing PTSD prediction specificity. Further research validation is advised.
PMCID: PMC3666578  PMID: 23723703
post-traumatic stress disorder; psychological trauma; diagnostic screening; test development; genotype; single nucleotide polymorphism
7.  The Effects of Prenatal Cocaine-Exposure on Problem Behavior in Children 4-10 Years 
Neurotoxicology and teratology  2010;32(4):443-451.
Children prenatally exposed to cocaine may be at increased risk for behavioral problems due to disruptions of monaminergically regulated arousal systems and/or environmental conditions.
To assess behavioral outcomes of cocaine (CE) and non-cocaine exposed (NCE) children, 4 through 10 years old, controlling for other prenatal drug exposures and environmental factors.
Low socioeconomic status (SES), primarily African-American children (n = 381 (193 (CE), 188 (NCE)) were recruited from birth. Generalized Estimating Equation (GEE) analyses were used to assess the predictive relationship of prenatal cocaine exposure to odds of caregiver reported clinically elevated behavioral problems at 4, 6, 9 and 10 years of age, controlling for confounders.
Prenatal cocaine exposure was associated with increased rates of caregiver reported delinquency (OR=1.93, CI: 1.09-3.42, p<.02). A significant prenatal cocaine exposure by sex interaction was found for delinquency indicating that only females were affected (OR=3.57, CI: 1.67-7.60, p<.001). There was no effect of cocaine on increased odds of other CBCL subscales. Higher prenatal tobacco exposure was associated with increased odds of externalizing symptoms at 4, 9 and 10 years of age. For CE children, those in foster or adoptive care were rated as having more behavior problems than those in biologic mother or relative care. Greater caregiver psychological distress was associated with increased behavioral problems. There were no independent effects of elevated blood lead level on increased behavior problems after control for prenatal drug exposure and other environmental conditions.
Prenatal cocaine and tobacco exposure were associated with greater externalizing behavior after control for multiple prenatal drug exposures, other environmental and caregiving factors and lead exposure from 4 through 10 years of age. Greater caregiver psychological distress negatively affected caregiver ratings of all CBCL domains. Since cocaine and tobacco use during pregnancy and maternal psychological distress have the potential to be altered through prenatal educational, drug treatment and and mental health interventions, they warrant attention in efforts to reduce rates of problem behaviors in children.
PMCID: PMC3586186  PMID: 20227491
behavior; delinquency; prenatal cocaine-exposure; lead exposure; longitudinal
8.  PTSD and Alcohol Use After the World Trade Center Attacks: A Longitudinal Study 
Journal of traumatic stress  2011;24(5):515-525.
Research suggests that posttraumatic stress disorder (PTSD) is associated with increased alcohol use, but the findings have not been consistent. We assessed alcohol use, binge drinking, and psychotropic medication use longitudinally in 1,681 New York City adults, representative of the 2000 census, 2 years after the World Trade Center attacks. We found that, with the exception of a modified CAGE Questionnaire index for alcohol, alcohol use showed a modest increase over time and was related to PTSD symptoms, with an increase of about 1 more drink per month for those with PTSD, even though overall levels appeared to be within the National Institute on Alcohol Abuse and Alcoholism’s safe range. Psychotropic medication use followed a similar trend; those with PTSD used psychotropics about 20 more days over the past year than those without. Because the study analyses adjusted for key psychosocial variables and confounders, it is not clear if the increased alcohol use following trauma exposure is associated with self-medication of PTSD symptoms, whether increased alcohol use prior to exposure is a risk for delayed-onset PTSD, or whether a third unmeasured variable is involved. Further research is warranted.
PMCID: PMC3557517  PMID: 21882246
9.  A brief screening tool for assessing psychological trauma in clinical practice: development and validation of the New York PTSD Risk Score☆,☆☆ 
General hospital psychiatry  2011;33(5):489-500.
The objective was to develop a brief posttraumatic stress disorder (PTSD) screening instrument that is useful in clinical practice, similar to the Framingham Risk Score used in cardiovascular medicine.
We used data collected in New York City after the World Trade Center disaster (WTCD) and other trauma data to develop a new PTSD prediction tool — the New York PTSD Risk Score. We used diagnostic test methods to examine different clinical domains, including PTSD symptoms, trauma exposures, sleep disturbances, suicidal thoughts, depression symptoms, demographic factors and other measures to assess different PTSD prediction models.
Using receiver operating curve (ROC) and bootstrap methods, five prediction domains, including core PTSD symptoms, sleep disturbance, access to care status, depression symptoms and trauma history, and five demographic variables, including gender, age, education, race and ethnicity, were identified. For the best prediction model, the area under the ROC curve (AUC) was 0.880 for the Primary Care PTSD Screen alone (specificity=82.2%, sensitivity=93.7%). Adding care status, sleep disturbance, depression and trauma exposure increased the AUC to 0.943 (specificity=85.7%, sensitivity=93.1%), a significant ROC improvement (P < .0001). Adding demographic variables increased the AUC to 0.945, which was not significant (P=.250). To externally validate these models, we applied the WTCD results to 705 pain patients treated at a multispecialty group practice and to 225 trauma patients treated at a Level I Trauma Center. These results validated those from the original WTCD development and validation samples.
The New York PTSD Risk Score is a multifactor prediction tool that includes the Primary Care PTSD Screen, depression symptoms, access to care, sleep disturbance, trauma history and demographic variables and appears to be effective in predicting PTSD among patients seen in healthcare settings. This prediction tool is simple to administer and appears to outperform other screening measures.
PMCID: PMC3557518  PMID: 21777981
Posttraumatic stress disorder; Psychological Trauma; Diagnostic testing; Patient screening; Area under receiver operating characteristic (ROC) curve
10.  Death and cardiovascular events after bacteriuria among adult women with chronic kidney disease 
The impact of bacteriuria on mortality and cardiovascular risk has not been previously reported for patients with chronic kidney disease (CKD).
To assess the relationship between outpatient episodes of bacteriuria and mortality and cardiovascular risk among women with CKD.
Retrospective cohort study using an electronic health database from an integrated healthcare system in central Pennsylvania.
Adult women with CKD receiving primary care at Geisinger Health System between January 1, 2004 and December 31, 2009 were eligible, and were followed through December 31, 2010 for study outcomes.
Main measures
The study exposure was bacteriuria, defined as an outpatient urine culture with bacterial growth of 104 cfu/mL. Treatment history (antibiotic prescription within 90 days) was identified. Study outcomes were death and the composite of hospitalization for myocardial infarction, congestive heart failure, or stroke. Multivariate-adjusted Cox models incorporated all bacteriuria episodes and antibiotic prescriptions in time-dependent fashion (in addition to other covariates) to account for the cumulative impact of infections, treatment, and hospitalization during follow-up.
Key results
6807 women were followed for a median (interquartile range) of 5.2 (3.4, 5.9) years. In adjusted models, each untreated bacteriuria episode was associated with an increased risk of death (hazard ratio [HR] 1.56, 95% CI 1.35–1.81) and the composite cardiovascular outcome (HR 1.32, 95% CI 1.05–1.65); treated episodes were not associated with an increased risk of death or cardiovascular events.
Among female patients with CKD, untreated bacteriuria occurring in the outpatient setting is associated with an increased risk of death and cardiovascular morbidity.
PMCID: PMC3508549  PMID: 23204852
bacteriuria; cardiovascular; chronic kidney disease; death; mortality
11.  Effect of Ascaris Lumbricoides specific IgE on tuberculin skin test responses in children in a high-burden setting: a cross-sectional community-based study 
BMC Infectious Diseases  2012;12:211.
M.tuberculosis (M.tb) is associated with enhanced T helper cell type 1 (Th1) immune responses while helminth infection is associated with T helper cell type 2 (Th2) immune responses. Our aim was to investigate whether helminth infection could influence the ability to generate an appropriate Th1 immune response that is characterized by a positive tuberculin skin test (TST), in M.tb exposed children.
We completed a community-based, cross sectional household contact tracing study, using matched enrolment of HIV negative children with and without documented household M.tb exposure. We documented demographics, clinical characteristics, HIV status, M.tb exposure (using a standard contact score) and M.tb infection status (TST > = 10 mm). Ascaris lumbricoides-specific IgE was used as proxy for Ascaris infection/exposure.
Of 271 children (median age 4 years (range: 4 months to 15 years)) enrolled, 65 participants (24%) were serum positive for Ascaris IgE. There were 168 (62%) children with a documented household tuberculosis contact and 107 (40%) were (TST) positive overall.
A positive TST was associated with increasing age (Odds Ratio (OR) =1.17, p < 0.001), increasing M.tb contact score (OR = 1.17, p < 0.001), previous tuberculosis treatment (OR = 4.8, p = 0.06) and previous isoniazid preventive treatment (OR = 3.16, p = 0.01). A visible bacillus Calmette-Guérin (BCG) scar was associated with reduced odds of being TST positive (OR = 0.42, p = 0.01).
Ascaris IgE was not associated with TST status in univariate analysis (OR = 0.9, p = 0.6), but multivariable logistic regression analysis suggested an inverse association between Ascaris IgE status and a positive TST (OR = 0.6, p = 0.08), when adjusted for age, and M.tb contact score. The addition of an age interaction term to the model suggested that the age effect was stronger among Ascaris IgE positive children; the effect of being Ascaris IgE positive significantly reduced the odds of being TST positive amongst younger children while this effect weakened with increasing age.
Our preliminary findings highlight a high prevalence of both Ascaris exposure/infection and M.tb infection in children in an urban setting. Helminth exposure/infection may reduce the immune response following M.tb exposure when controlling for epidemiological and clinical covariates. These findings might be relevant to the interpretation of immunological tests of M.tb infection in children.
PMCID: PMC3482567  PMID: 22966931
Tuberculosis; Helminth infection; Ascaris, M.tb infection; Immune polarization; Paediatric tuberculosis
13.  Predicting Future PTSD using a Modified New York Risk Score: Implications for Patient Screening and Management 
Minerva psichiatrica  2012;53(1):47-59.
We previously developed a posttraumatic stress disorder (PTSD) screening instrument – the New York PTSD Risk Score – that was effective in predicting PTSD. In the present study, we assessed a 12-month prospective version of this risk score, which is important for patient management, follow-up, and for emergency medicine.
Using data collected in a study of New York City adults after the World Trade Center Disaster (WTCD), we developed a new PTSD prediction tool. Using diagnostic test methods, including receiver operating curve (ROC) and bootstrap procedures, we examined different prediction variables to assess PTSD status 12 months after initial assessment among 1,681 trauma-exposed adults.
While our original PTSD screener worked well in the short term, it was not specifically developed to predict long-term PTSD. In the current study, we found that the Primary Care PTSD Screener (PCPS), when combined with psychosocial predictors from the original NY Risk Score, including depression, trauma exposure, sleep disturbance, and healthcare access, increased the area under the ROC curve (AUC) from 0.707 to 0.774, a significant improvement (p<0.0001). When additional risk-factor variables were added, including negative life events, handedness, self-esteem, and pain status, the AUC increased to 0.819, also a significant improvement (p=0.001). Adding Latino and foreign status to the model further increased the AUC to 0.839 (p=0.007).
A prospective version of the New York PTSD Risk Score appears to be effective in predicting PTSD status 12 months after initial assessment among trauma-exposed adults. Further research is advised to further validate and expand these findings.
PMCID: PMC3298362  PMID: 22408285
Posttraumatic stress disorder; Psychological Trauma; Diagnostic screening; Emergency Medicine
Sleep medicine  2011;12(3):239-245.
Adolescents are predisposed to short sleep duration and irregular sleep patterns due to certain host characteristics (e.g., age, pubertal status, gender, ethnicity, socioeconomic class, and neighborhood distress) and health-related variables (e.g., ADHD, asthma, birth weight, and BMI). The aim of the current study was to investigate the relationship between such variables and actigraphic measures of sleep duration and variability.
Cross-sectional study of 247 adolescents (48.5% female, 54.3% ethnic minority, mean age of 13.7 years) involved in a larger community-based cohort study.
Significant univariate predictors of sleep duration included gender, minority ethnicity, neighborhood distress, parent income, and BMI. In multivariate models, gender, minority status, and BMI were significantly associated with sleep duration (all p<.05), with girls, non-minority adolescents, and those of a lower BMI obtaining more sleep. Univariate models demonstrated that age, minority ethnicity, neighborhood distress, parent education, parent income, pubertal status, and BMI were significantly related to variability in total sleep time. In the multivariate model, age, minority status, and BMI were significantly related to variability in total sleep time (all p<.05), with younger adolescents, non-minority adolescents, and those of a lower BMI obtaining more regular sleep.
These data show differences in sleep patterns in population sub-groups of adolescents which may be important in understanding pediatric health risk profiles. Subgroups that may particularly benefit from interventions aimed at improving sleep patterns include boys, overweight, and minority adolescents.
PMCID: PMC3050885  PMID: 21316300
15.  Candida Skin Testing is a Poor Adjunct to Tuberculin Skin Testing In International Adoptees 
We conducted a prospective longitudinal study evaluating candida skin testing among international adoptees presenting to our clinic between 2000 to 2006. Nineteen (17%) and seventeen (15%) children had negative tests at presentation and at 6-month respectively – only 3 were negative at both points. Our study suggests that candida skin test reactivity is an unstable measure of anergy among international adoptees.
PMCID: PMC3133951  PMID: 19820428
Tuberculosis; tuberculosis testing; adoptees; Bacille Calmette-Guérin vaccination
16.  The Impact of Nutritional Status and Longitudinal Recovery of Motor and Cognitive Milestones in Internationally Adopted Children 
Internationally adopted children often arrive from institutional settings where they have experienced medical, nutritional and psychosocial deprivation. This study uses a validated research assessment tool to prospectively assess the impact of baseline (immediately post adoption) nutritional status on fifty-eight children as measured by weight-for-age, height-for-age, weight-for-height and head circumference-for-age z scores, as a determinant of cognitive (MDI) and psychomotor development (PDI) scores longitudinally. A statistical model was developed to allow for different ages at time of initial assessment as well as variable intervals between follow up visits. The study results show that both acute and chronic measures of malnutrition significantly affect baseline developmental status as well as the rate of improvement in both MDI and PDI scores. This study contributes to the body of literature with its prospective nature, unique statistical model for longitudinal evaluation, and use of a validated assessment tool to assess outcomes.
PMCID: PMC3037064  PMID: 21318018
malnutrition; international adoption; cognitive impairment; developmental delay; nutrition
17.  Relationships Among Sleepiness, Sleep Time, and Psychological Functioning in Adolescents 
Journal of Pediatric Psychology  2009;34(10):1175-1183.
Objective This study examined associations among adolescent sleepiness, sleep duration, variability in sleep duration, and psychological functioning (symptoms of anxiety, depression, externalizing behaviors, and perceived health). Methods This was a cross-sectional analysis of data from a community-based cohort study of sleep and health. Participants were 247 adolescents (48.6% female, 54.3% ethnic minority, mean age of 13.7 years). Sleep duration and variability in sleep duration were measured by actigraphy and sleepiness was measured by adolescent questionnaire. Primary outcomes were measured by parent, teacher, and adolescent questionnaires. Results Sleepiness was associated with higher scores on measures of anxiety (Adjusted partial r2 = .28, p < .001), depression (Adjusted partial r2 = .23, p < .001), and perceived health (indicating more negative outcomes) (Adjusted partial r2 = .19, p < .01). Significant associations between sleep duration or variability in sleep duration with psychological variables were not found. Conclusions Findings highlight the inter-relationships between sleepiness and psychological functioning and the potential importance of addressing sleepiness in health and psychological evaluations of adolescents.
PMCID: PMC2782255  PMID: 19494088
adolescents; sleep; psychosocial functioning.
18.  PEDS and ASQ Developmental Screening Tests May Not Identify the Same Children 
Pediatrics  2009;124(4):e640-e647.
In analyzing data from a larger study, we noticed significant disagreement between results of 2 commonly used developmental screening tools (Parents’ Evaluation of Developmental Status [PEDS; parent concern questionnaire] and Ages & Stages Questionnaires [ASQ; parent report of developmental skills]) delivered to children at the same visit in primary care. The screens have favorable reported psychometric properties and can be efficient to use in practice; however, there is little comparative information about the relative performance of these tools in primary care. We sought to describe the agreement between the 2 screens in this setting.
Parents of 60 children aged 9 to 31 months completed PEDS and ASQ screens at the same visit. Concordance (PEDS and ASQ results agree) and discordance (results differ) for the 2 screens were determined.
The mean age of children was 17.6 months, 77% received Medicaid, and 50% of parents had a high school education or less. Overall, 37% failed the PEDS and 27% failed the ASQ. Thirty-one children passed (52%) both screens; 9 (15%) failed both; and 20 (33%) failed 1 but not the other (13 PEDS and 7 ASQ). Agreement between the 2 screening tests was only fair, statistically no different from agreement by chance.
There was substantial discordance between PEDS and ASQ developmental screens. Although these are preliminary data, clinicians need to be aware that in implementing revised American Academy of Pediatrics screening guidelines, the choice of screening instrument may affect which children are likely to be identified for additional evaluation.
PMCID: PMC2764374  PMID: 19736268
developmental screening; primary care; well-child visit
19.  Cognitive Development and Low-Level Lead Exposure in Poly-Drug Exposed Children 
Neurotoxicology and teratology  2009;31(4):225-231.
The impact of early postnatal lead exposure measured at age 4 on children’s IQ and academic achievement at 4, 9, and 11 years of age was examined. The sample consisted of 278 inner-city, primarily African American children who were polydrug exposed prenatally. Regression analyses indicated a linear effect of lead exposure on outcomes and no moderating effects of polydrug exposure. An IQ loss of about 4.1–5.4 Full Scale IQ points was estimated for each 10 ug/dl increase in blood lead level at ages 4, 9, and 11 years as a function of blood lead level at age 4. Decrements in scores on tests of non-verbal reasoning were consistently associated with higher lead levels at age 4, while verbal decrements became apparent only at age 11. Lower reading summary scores at 9 and 11 years were consistently associated with higher lead exposure, while decrements in mathematics were not apparent until 11 years. Subgroup analyses on children with blood lead levels < 10 μg/dL showed detrimental lead effects even at the 5 μg/dL level, providing additional evidence of adverse effects occurring at blood lead levels below the current 10 μg/dL public health blood lead action level.
PMCID: PMC2693288  PMID: 19345261
lead; cognitive development; school achievement; prenatal drug exposure; restricted cubic splines
20.  Comparing Diary and Retrospective Reports of Pain and Activity Restriction in Children and Adolescents with Chronic Pain Conditions 
The Clinical journal of pain  2009;25(4):299-306.
The current study investigated the daily relationship between pain, activity restriction and depression in children and adolescents with chronic pain, and compared participants’ responses on diary and retrospective assessment measures.
Data collection included the administration of diary and retrospective measures of pain, activity restriction, and depression to 93 children with recurrent headache, juvenile chronic arthritis, and sickle cell disease. The study used HLM to examine the relationship between daily pain and activity restriction, and analyses compared participants’ responses on diary and retrospective assessment measures.
Using diary measures, daily pain intensity was related to children’s levels of activity restriction. Diary completion was predicted by age and diary-type, with younger children and children utilizing electronic diaries demonstrating higher compliance. Pain intensity was significantly higher on retrospective compared to diary measures, demonstrating inflation in retrospective reports of pain. No significant differences between measures of activity restriction emerged.
These preliminary results suggest that while retrospective reports of activity restriction may be an acceptable alternative to daily diary assessment for children with chronic pain, retrospective measures of pain intensity may show inflated pain levels. To provide support for the findings, longitudinal research comparing responses to diary versus retrospective measures is recommended.
PMCID: PMC2709738  PMID: 19590478
chronic pain; activity restriction; depression; children; adolescents
21.  The association of prenatal cocaine use and childhood trauma with psychological symptoms over 6 years 
Archives of women's mental health  2008;11(3):181-192.
The use of cocaine and other drugs during pregnancy may have serious public health consequences. The objective of this study was to determine if the use of cocaine prenatally identifies women for ongoing risk of psychological symptoms. Four hundred and two women (207 cocaine using [C], 195 non-cocaine using [NC]) were assessed for rates of clinically elevated psychological symptoms shortly after childbirth, 6.5 months and 1, 2, 4 and 6 years after using the Brief Symptom Inventory (BSI). Generalized estimating equation modeling (GEE) was used to compare psychological symptom severity, controlling for confounding factors including early childhood trauma. Results indicated that women identified as having used cocaine during pregnancy had clinically elevated psychological distress (OR=1.76, 95%CI=1.15–2.71, p=0.01), psychoticism (OR=1.97, 95%CI=1.41–2.76, p=0.001), interpersonal sensitivity (OR=2.34; 95%CI=1.65–3.34; p<0.0001) and phobic anxiety (OR=1.86; 95%CI=1.24– 2.79) across all assessments compared to NC women. Childhood emotional abuse was also independently associated with psychological distress. Women who use cocaine during pregnancy should be recognized as at very high risk of ongoing clinically elevated psychological symptoms and should receive early and regular assessments and intervention for mental health and substance use problems.
PMCID: PMC2844662  PMID: 18463942
Psychological distress; Childhood trauma; Longitudinal; Prenatal cocaine use
22.  Communication About Child Development During Well-Child Visits: Impact of Parents’ Evaluation of Developmental Status Screener With or Without an Informational Video 
Pediatrics  2008;122(5):e1091-e1099.
The American Academy of Pediatrics recommends periodic administration of standardized developmental screening instruments during well-child visits to facilitate timely identification of developmental delay. However, little is known about how parents and physicians communicate about child development or how screening impacts communication.
Our goal was to examine whether parent-physician communication about child development is affected by (1) administration of a developmental screen or (2) video presentation on child development before well-child visits.
Six primary care pediatricians in a practice serving predominantly Medicaid-insured children participated. Fifteen parents of children 9 to 31 months of age per pediatrician were assigned to 1 of 3 previsit conditions (n = 89): (1) usual care; (2) parent completed the Parents’ Evaluation of Developmental Status screen; or (3) parent viewed 5-minute "activation" video before completing the Parents’ Evaluation of Developmental Status. Visits were audiorecorded and coded by blinded raters using a classification system that assesses communication content. Outcomes included visit length, physicians’ questions, information giving, reassurance or counseling about development, and parents’ concerns and requests for developmentally related services.
Mean visit duration was similar for the 3 groups (22.5 minutes). Physicians made more information-giving and counseling statements about development and raised more developmental concerns in group 3 (video plus the Parents’ Evaluation of Developmental Status) than in group 1 (usual care) visits. A trend toward increased use of such communication was also seen in group 2 (Parents’ Evaluation of Developmental Status only). Parents were more likely to raise a developmental concern in group 3 than in group 1. No parent requested early intervention, therapy, or other related services.
Use of a validated screening test did not increase average visit duration, an important consideration in primary care. Although use of the Parents’ Evaluation of Developmental Status alone led to some increase in parent-physician communication about development and developmental concerns, additional increase in communication was seen with the addition of a brief parent activation video shown before the Parents’ Evaluation of Developmental Status was completed.
PMCID: PMC2727627  PMID: 18977959
developmental screening; parent activation; primary care; well-child visit
23.  Prenatal and Neonatal Risk Factors for Sleep Disordered Breathing in School-Aged Children Born Preterm 
The Journal of pediatrics  2008;153(2):176-182.
Previously published data from the Cleveland Children’s Sleep and Health Study (CCSHS) demonstrated that preterm infants are especially vulnerable both to sleep disordered breathing (SDB) and its neurocognitive sequelae at age 8–11 years. In this analysis, we aimed to identify the components of the neonatal medical history associated with childhood SDB among children born prematurely.
Study design
This analysis focuses on the 383 children in the population-based CCSHS cohort who were born <37 weeks gestational age and who had technically acceptable sleep studies performed at ages 8–11 years (92% of all preterm children). Logistic regression was used to evaluate the associations between candidate perinatal and neonatal risk factors and the presence of childhood SDB by sleep study.
Twenty-eight preterm children (7.3%) met the definition for SDB at age 8–11 years. Having a single mother and mild maternal pre-eclampsia were strongly associated with SDB in unadjusted and race-adjusted models. Unadjusted analyses also identified xanthine use and CPR and/or intubation in the delivery room as potential risk-factors for SDB. We did not find a significant link between traditional markers of severity of neonatal illness -- such as gestational age, birth weight, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or duration of ventilation -- and childhood SDB at school age.
These results represent a first step in identifying prenatal and neonatal characteristics which place preterm infants at higher risk for childhood SDB. The strong association between mild pre-eclampsia and childhood SDB underscores the importance of research aimed at understanding in utero risk factors for neurorespiratory development.
PMCID: PMC2753386  PMID: 18534222
sleep disordered breathing (SDB); obstructive sleep apnea (OSA); pre-eclampsia; snoring; neonate
24.  A Measure of Ventilatory Variability at Wake-Sleep Transition Predicts Sleep Apnea Severity 
Chest  2008;134(1):73-78.
Increased variability in ventilation may contribute to the pathogenesis of obstructive sleep apnea (OSA) by promoting ventilatory instability, fluctuations of neuromuscular output to the upper airway, and pharyngeal collapsibility. We assessed the association of a measure of ventilatory variability measured at the wake-sleep transition with OSA and associated covariates.
485 participants in the Cleveland Family Study underwent overnight polysomnography with independent derivation of the Ventilatory Variability Index and the Apnea Hypopnea Index. The Ventilatory Variability Index was calculated from the variability in the power spectrum of the abdominal inductance signal over a 2-minute period beginning at sleep onset.
The Ventilatory Variability Index was strongly correlated with the Apnea Hypopnea Index (r=0.43, p<0.001). After adjusting for age, body mass index, sex, and race, the Ventilatory Variability Index remained significantly associated with Apnea Hypopnea Index (p<0.001). The adjusted odds ratio for obstructive sleep apnea (Apnea Hypopnea Index ≥ 15) with each half standard deviation increase in Ventilatory Variability Index was 1.41 [1.25–1.59]. In a subgroup analysis of obese snorers, to limit analyses to those with a presumed anatomic predisposition for apnea, Ventilatory Variability Index remained associated with an elevated Apnea Hypopnea Index.
Increased ventilatory variability may be a useful phenotype in characterizing obstructive sleep apnea.
PMCID: PMC2672201  PMID: 18347208
Sleep apnea syndromes; sleep disordered breathing; polysomnography; apnea
25.  Prenatal Cocaine Exposure: Drug and Environmental Effects at 9 years 
The Journal of pediatrics  2008;153(1):105-111.
To assess school age cognitive and achievement outcomes after prenatal cocaine exposure, controlling for confounding drug and environmental factors.
Study design
At 9 years, 371 children (192 cocaine exposure, CE; 179 non-exposure, NCE) were assessed for IQ and school achievement in a longitudinal, prospective study from birth. An extensive number of confounding variables were controlled, including quality of caregiving environment, polydrug exposure, lead, iron deficiency anemia (IDA), and foster/adoptive care.
CE predicted poorer Perceptual Reasoning IQ with a linear relationship of the concentration of the cocaine metabolite, benzoylecgonine, to degree of impairment. Effects were mediated through birth head circumference, indicating a relationship with fetal brain growth. Negative effects of alcohol, lead, and marijuana exposure and positive effects of home environment were additive. Children with CE in foster/adoptive care had better home environments and lower lead levels. School achievement was not affected.
There were persistent teratologic effects of CE on specific cognitive functions and additive effects of alcohol, lead, marijuana, IDA, and home environment. Documenting environmental factors in behavioral teratology studies is important because in this sample, CE was associated with better home environments and lower environmental risk for a substantial number of children.
PMCID: PMC2581925  PMID: 18571546
Lead; alcohol; marijuana; iron deficiency anemia; home environment; cognition; school achievement; poverty; behavioral teratogen

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