Changes in neuropsychological and behavioral functioning in children with and without obstructive sleep apnea following Tonsillectomy.

The most common treatment for sleep disordered breathing (SDB) is adenotonsillectomy (AT). Following AT, SDB resolves in most cases, and gains in cognitive and behavior scores are consistently reported, although persistent neuropsychological deficits or further declines also have been noted. This study presents results of the comprehensive 1-year follow-up neuropsychological examinations for children in the Washtenaw County Adenotonsillectomy Cohort I (95% return rate). After adjusting for normal developmental and practice-effect related changes in control children, significant improvements 1 year following AT were noted in polysomnography and sleepiness, as well as parental reports of behavior, although cognitive outcomes were mixed. Children undergoing AT with and without polysomnography-confirmed obstructive sleep apnea improved across a range of academic achievement measures, a measure of delayed visual recall, short-term attention/working memory, and executive functioning, along with parental ratings of behavior. On the other hand, measures of verbal abstraction ability, arithmetic calculations, visual and verbal learning, verbal delayed recall, sustained attention, and another measure of visual delayed recall demonstrated declines in ability, while other measures did not improve over time. These findings call into question the expectation that AT resolves most or all behavioral and cognitive difficulties in children with clinical, office-based diagnoses of SDB.

Is cervical elongation associated with pelvic organ prolapse?

INTRODUCTION AND HYPOTHESIS: It is commonly believed that pelvic organ prolapse (POP) is associated with cervical elongation. However, cervical lengths have not been formally compared between women with prolapse and those with normal support. METHODS: Cervix and uterine corpus lengths were measured on magnetic resonance images in a case-control study of 51 women with prolapse and 46 women with normal support determined by the Pelvic Organ Prolapse Quantification (POP-Q) examination. Group matching ensured similar demographics in both groups. Ranges for normal cervical lengths were determined from the values in the control group in order to evaluate for cervical elongation amongst women with prolapse. RESULTS: The cervix is 36.4 % (8.6 mm) longer in women with prolapse than in women with normal pelvic support (p < 0.001). Linear regression modeling suggests the feature most highly associated with cervical length is the degree of uterine descent (POP-Q point C). Approximately 40 % of women with prolapse have cervical elongation; 57 % of cervical elongation in prolapse can be explained by a logistic regression-based model including POP-Q point C, body mass index, and menopausal status. CONCLUSIONS: Cervical elongation is found in one third of women with POP, with the extent of elongation increasing with greater degrees of uterine descent.

3D analysis of cystoceles using magnetic resonance imaging assessing midline, paravaginal, and apical defects.

INTRODUCTION AND HYPOTHESIS: This study assesses relative contributions of "midline defects" (widening of the vagina) and "paravaginal defects" (separation of the lateral vagina from the pelvic sidewall). METHODS: Ten women with anterior predominant prolapse and ten with normal support underwent pelvic MR imaging. 3-D models of the anterior vaginal wall (AVW) were generated to determine locations of the lateral AVW margin, vaginal width, and apical position. RESULTS: The lateral AVW margin was farther from its normal position in cases than controls throughout most of the vaginal length, most pronounced midvagina (effect sizes, 2.2-2.8). Vaginal widths differed in the midvagina with an effect size of 1.0. Strong correlations between apical and paravaginal support were evident in mid- and upper vagina (r = 0.77-0.93). CONCLUSIONS: Changes in lateral AVW location were considerably greater than changes in vaginal width in cases vs controls, both in number of sites affected and effect sizes. These "paravaginal defects" are highly correlated with apical descent.

Neuropsychological and behavioral functioning in children with and without obstructive sleep apnea referred for tonsillectomy.

Adenotonsillectomy (AT) is among the most common pediatric surgical procedures and is performed as often for obstructive sleep apnea (OSA) as for recurrent tonsillitis. This study compared behavioral, cognitive, and sleep measures in 27 healthy control children recruited from a university hospital-based pediatric general surgery clinic with 40 children who had OSA (AT/OSA+) and 27 children who did not have OSA (AT/OSA-) scheduled for AT. Parental ratings of behavior, sleep problems, and snoring, along with specific cognitive measures (i.e., short-term attention, visuospatial problem solving, memory, arithmetic) reflected greater difficulties for AT children compared with controls. Differences between the AT/OSA- and control groups were larger and more consistent across test measures than were those between the AT/OSA+ and control groups. The fact that worse outcomes were not clearly demonstrated for the AT/OSA+ group compared with the other groups was not expected based on existing literature. This counterintuitive finding may reflect a combination of factors, including age, daytime sleepiness, features of sleep-disordered breathing too subtle to show on standard polysomnography, and academic or environmental factors not collected in this study. These results underscore the importance of applying more sophisticated methodologies to better understand the salient pathophysiology of childhood sleep-disordered breathing.

Fear of blindness in the Collaborative Initial Glaucoma Treatment Study: patterns and correlates over time.

PURPOSE: The objective of this study was to describe the prevalence of fear of blindness (FOB) and the factors associated with FOB during 5 years of follow-up in the Collaborative Initial Glaucoma Treatment Study. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: A total of 607 newly diagnosed patients with open-angle glaucoma were recruited from 14 clinical centers in the United States. METHODS: Patients were assigned randomly either to initial medical therapy or initial trabeculectomy. Study participants received clinical examinations and quality-of-life (QOL) evaluations at baseline and 6-month intervals. The QOL questionnaire was administered by trained telephone interviewers at a centralized interviewing center. MAIN OUTCOME MEASURES: The QOL questionnaire included an assessment of FOB, measures of vision-related functioning, and measures of general physical and psychosocial well being. Ordinal logistic regression analyses were used to assess clinical and QOL measures associated with FOB over time. RESULTS: After being told about the glaucoma diagnosis but before randomization, 34% of patients reported at least a moderate amount of FOB. This percent dropped to 11% at 5 years. In multivariable ordinal logistic regression models, younger age, being white, and having less education and a lower income were associated with increased FOB (all P<0.05). At the 36-month follow-up, visual field progression was associated significantly with increased FOB (P = 0.006); visual acuity loss, although related to increased FOB, did not achieve statistical significance (P = 0.327). Self-reported visual function measures explained more of the variation in FOB over time than did demographic, clinical, or physical or psychosocial measures. Initial treatment assignment (medicine or surgery) was not associated with FOB. The most significant correlate over time with FOB was the perceived impact on an individual's ability to perform visual tasks. CONCLUSIONS: More attention to reducing glaucoma patients' FOB at diagnosis and over time is warranted. Fear of blindness over time is related more to how much an individual is bothered by their inability to perform visual tasks than to their monocular visual acuity or visual field assessments.

Vaginal birth and de novo stress incontinence: relative contributions of urethral dysfunction and mobility.

OBJECTIVE: To evaluate the relative contributions of urethral mobility and urethral function to stress incontinence. METHODS: This was a case-control study with group matching. Eighty primiparous women with self-reported new stress incontinence 9-12 months postpartum were compared with 80 primiparous continent controls to identify impairments specific to stress incontinence. Eighty nulliparous continent controls were evaluated as a comparison group to allow us to determine birth-related changes not associated with stress incontinence. Urethral function was measured with urethral profilometry, and vesical neck mobility was assessed with ultrasound and cotton swab test. Urethral sphincter anatomy and mobility were evaluated using magnetic resonance imaging. The associations among urethral closure pressure, vesical neck movement, and incontinence were explored using logistic regression. RESULTS: Urethral closure pressure (+/-standard deviation) in primiparous incontinent women (62.9+/-25.2 cm H(2)0) was lower than in primiparous continent women (83.9+/-21.0, P<.001; effect size d=0.91) who were similar to nulliparous women (90.3+/-25.0, P=.091). Vesical neck movement measured during cough with ultrasonography was the mobility measure most associated with stress incontinence; 15.6+/-6.2 mm in incontinent women compared with 10.9+/-6.2 in primiparous continent women (P<.001, d=0.76) or nulliparas (9.9+/-5.0, P=.322). Logistic regression disclosed the two-variable model (max-rescaled R(2)=0.37, P<.001) was more strongly associated with stress incontinence than either single-variable model, urethral closure pressure (R(2)=0.25, P<.001) or vesical neck movement (R(2)=0.16 P<.001). CONCLUSION: Lower maximal urethral closure pressure is the measure most associated with de novo stress incontinence after first vaginal birth followed by vesical neck mobility. LEVEL OF EVIDENCE: II.

DSM-IV diagnoses and obstructive sleep apnea in children before and 1 year after adenotonsillectomy.

OBJECTIVE: Obstructive sleep apnea, a common indication for adenotonsillectomy in children, has been linked to behavioral morbidity. We assessed psychiatric diagnoses in children before and after adenotonsillectomy and examined whether baseline sleep apnea predicted improvement after surgery. METHOD: Subjects of this prospective cohort study were children ages 5.0 to 12.9 years old who had been scheduled for adenotonsillectomy (n = 79) or care for unrelated surgical conditions (n = 27, among whom 13 had surgery after baseline assessment). Before intervention and 1 year later, subjects underwent structured diagnostic interviews and polysomnography. The main outcome measure was frequency of DSM-IV attention and disruptive behavior disorder diagnoses at baseline and follow-up. RESULTS: At baseline, attention and disruptive behavior disorders were diagnosed in 36.7% of adenotonsillectomy subjects and 11.1% of controls (p < .05); attention-deficit/hyperactivity disorder was found in 27.8% and 7.4%, respectively (p < .05). One year later, group differences were nonsignificant; attention and disruptive behavior disorders were diagnosed in only 23.1% (p < .01), and 50% of subjects with baseline attention-deficit/hyperactivity disorder no longer met diagnostic criteria. Obstructive sleep apnea on polysomnography at baseline did not predict concurrent psychiatric morbidity or later improvement. CONCLUSIONS: Attention and disruptive behavior disorders, diagnosed by DSM-IV criteria, were more common before clinically indicated adenotonsillectomy than 1 year later. Surgery may be associated with reduced morbidity, even among subjects lacking polysomnographic evidence of obstructive sleep apnea.

Symptoms of anal incontinence and difficult defecation among women with prolapse and a matched control cohort.

OBJECTIVE: The purpose of this study was to quantify the risk for anal incontinence and difficult defecation among women with prolapse by comparing them with women without prolapse of similar age, body mass index, race, and hysterectomy status, and to determine whether there are characteristics or findings in women with prolapse that are associated with greater symptom severity. STUDY DESIGN: Women with primary pelvic organ prolapse (n = 151) were compared with women without prolapse (n = 135). All subjects underwent pelvic examination and completed symptom questionnaires regarding how frequently anal incontinence and difficult defecation were experienced. Incontinence of flatus was considered to be present if it occurred on "most" or "every" day; difficult defecation was considered to be present if it was experienced with "most" or "every" bowel movement. Symptoms that occurred "on occasion" or "never" were considered to be absent. RESULTS: Incontinence of flatus was reported by 23.1% of cases vs 8.3% of control subjects (P = .006). Incontinence of liquid or solid stool was present in 4.7% and 3.5%, respectively, and was not reported by control subjects (P < .001 and .009, respectively). Difficult defecation, which was characterized by pushing on the vaginal walls to complete defecation, was present in 19.7% vs 4.4% of control subjects (P = .001). Cases that reported symptoms were compared with those that did not report symptoms. Among those reporting difficult defecation, the length of the perineal body length was greater when straining (4.0 vs 3.4 cm; P = .020). Among those reporting incontinence of flatus, mean parity was higher (3.3 vs 2.5; P = .012), and a positive standing cough stress test was more likely (39.3% vs 18.5%; P = .025). Symptoms of anal incontinence and/or difficult defecation were present in 35.3% of subjects (52/147). CONCLUSION: Women with prolapse are more likely than control subjects to have symptoms of anal incontinence or difficult defecation; approximately one-third of these women will have symptoms.

Pediatric sleep questionnaire: prediction of sleep apnea and outcomes.

OBJECTIVES: To further validate a questionnaire about symptoms of childhood obstructive sleep apnea (OSA) and to compare the questionnaire with polysomnography in their ability to predict outcomes of adenotonsillectomy. DESIGN: Retrospective analysis of data from a longitudinal study. SETTING: University-based sleep disorders laboratory. PARTICIPANTS: The Washtenaw County Adenotonsillectomy Cohort, comprising 105 children aged 5.0 to 12.9 years at entry. Intervention Parents completed the 22-item Sleep-Related Breathing Disorder (SRBD) scale of the Pediatric Sleep Questionnaire, and children underwent polysomnography before and 1 year after clinically indicated adenotonsillectomy (n = 78, usually for suspected OSA) or unrelated surgical care (n = 27). MAIN OUTCOME MEASURES: Findings from commonly used hyperactivity ratings, attention tests, and sleepiness tests. RESULTS: At baseline, a high SRBD scale score (1 SD above the mean) predicted an approximately 3-fold increased risk of OSA on polysomnography (odds ratio, 2.80; 95% confidence interval, 1.68-4.68). One year later, OSA and symptoms had largely resolved, but a high SRBD score still predicted an approximately 2-fold increased risk of residual OSA on polysomnography (odds ratio, 1.89; 95% confidence interval, 1.13-3.18). Compared with several standard polysomnographic measures of OSA, the baseline SRBD scale better predicted initial hyperactivity ratings and 1-year improvement, similarly predicted sleepiness and its improvement, and similarly failed to predict attention deficit or its improvement. CONCLUSIONS: The SRBD scale predicts polysomnographic results to an extent useful for research but not reliable enough for most individual patients. However, the SRBD scale may predict OSA-related neurobehavioral morbidity and its response to adenotonsillectomy as well or better than does polysomnography.

Subjective sleepiness and polysomnographic correlates in children scheduled for adenotonsillectomy vs other surgical care.

STUDY OBJECTIVE: To compare a validated subjective measure of childhood sleepiness to an objective determination, assess the frequency of problematic sleepiness among children with suspected sleep-disordered breathing (SDB), and examine what standard or investigational polysomnographic measures of SDB predict subjective sleepiness. DESIGN: Prospective, cross-sectional. SETTING: University-based sleep disorders laboratory. PARTICIPANTS: Washtenaw County Adenotonsillectomy Cohort. INTERVENTION: Polysomnography followed by Multiple Sleep Latency Tests (MSLTs) in 103 children aged 5 to 12 years old: 77 were scheduled for clinically indicated adenotonsillectomy, usually for suspected SDB, and 26 for unrelated surgical care. Parents completed the previously validated, 4-item Pediatric Sleep Questionnaire-Sleepiness Subscale (PSQ-SS). RESULTS: Thirty-three (43%) of the children scheduled for adenotonsillectomy had high PSQ-SS scores, in comparison with only 3 (12%) of the controls (p = .004). The PSQ-SS scores correlated inversely with mean sleep latencies on the MSLTs (rho = -0.23, p = .006). The obstructive apnea index, apnea-hypopnea index, and respiratory disturbance index (which included respiratory event-related arousals identified by esophageal pressure monitoring) each correlated similarly with PSQ-SS scores, as did investigational quantification of esophageal pressures and respiratory cycle-related electroencephalographic changes (each rho approximately 0.30, p < .02). A stepwise regression identified sigma-frequency respiratory cycle-related electroencephalographic changes as the strongest independent predictor of subjective sleepiness among all subjects and particularly among those without obstructive sleep apnea. CONCLUSIONS: Sleepiness is a frequent problem among children with suspected SDB. Subjective sleepiness (PSQ-SS) reflects MSLT results to a limited extent, as in adults. Standard polysomnographic measures of SDB predict subjective sleepiness, but respiratory cycle-related electroencephalographic changes may offer additional clinical utility.

Levator plate angle in women with pelvic organ prolapse compared to women with normal support using dynamic MR imaging.

OBJECTIVE: The purpose of this study was to determine whether the levator plate is (1) horizontal in women with normal support, (2) different between women with and without prolapse, (3) related to levator hiatus and perineal body descent. STUDY DESIGN: Cohorts of cases with prolapse at least 1 cm below the hymen and normal controls with all points 1 cm or more above the hymen were prospectively enrolled in a study of pelvic organ support to be of similar age, race, and parity. Subjects underwent supine midsagittal dynamic magnetic resonance imaging (MRI) during Valsalva. Levator plate angle (LPA) was measured relative to a horizontal reference line. Levator hiatus length (LH) and perineal body location (PB) were also measured. Student t tests and Pearson correlation coefficients (r) were performed. RESULTS: Sixty-eight controls and 74 cases were analyzed. During Valsalva, controls had a mean LPA of 44.3 degrees . Cases, compared to controls, had 9.1 degrees (21%) more caudally directed LPA (53.4 degrees vs 44.3 degrees , P < .01), 15% larger LH length (7.8 cm vs 6.8 cm, P < .01), and 24% more caudal PB location (6.8 cm vs 5.5 cm, P < .01). Increases in LPA were correlated with increased LH length (r = 0.42, P < .0001) and PB location (r =.51, P < .0001). CONCLUSION: The measured levator plate angle in women with normal support is 44.3 degrees . During Valsalva, women with prolapse have a modest (9.1 degrees) though statistically greater levator plate angle compared to controls. This larger angle showed moderate correlation with larger levator hiatus length and greater displacement of the perineal body in women with prolapse compared to controls.

Improved behavior after adenotonsillectomy in children with higher and lower IQ.

OBJECTIVES: To examine whether high intellectual ability, in comparison to average or lower performance, reflects the consequences of sleep-disordered breathing and limits behavioral benefit observed 6 months after adenotonsillectomy. METHODS: Children aged 3-12 years (n=147) recruited from otolaryngology practices at two hospitals and assessed with Conners' Parent Rating Scales and an age range-appropriate intellectual measure, the Stanford-Binet Intelligence Scale at baseline and 6 months after clinically-indicated adenotonsillectomy. Subjects were classified as having high (IQ≥110), average (90≤IQ<110), or low (IQ<90) cognitive ability. RESULTS: After adenotonsillectomy, improvements in Conners' internalizing, externalizing, hyperactivity, and cognitive domains were observed across IQ groups (main effects for time, all p<0.01 or better), with no evidence for differential improvements among the groups (no significant time by IQ group interactions). The magnitude of behavioral improvement among children with high IQ resembled that observed among the other two groups. Changes in the Conners' domains were not significantly correlated with baseline IQ, age, socioeconomic status, body mass index z-score, or respiratory disturbance index. CONCLUSION: Behavioral function can improve after adenotonsillectomy even among children with relatively high intellectual ability at baseline. Diagnosis and treatment with expectation of neurobehavioral benefit should be considered among high-performing children as readily as it is more traditionally among their lower-performing peers.

D-dimer, P-selectin, and microparticles: novel markers to predict deep venous thrombosis. A pilot study.

Current plasma markers for diagnosis of deep venous thrombosis (DVT) allow for exclusion of the diagnosis, but lack adequate specificity to establish the diagnosis. Thus, a prospective study was performed to determine the sensitivity and specificity of plasma assays for D-dimer, soluble P-selectin (P-selectin), and total microparticles in patients with documented DVT by duplex ultrasound. Three groups of individuals were examined: 30 normals; 22 positive for DVT on duplex ultrasound (Group 2); and 21 symptomatic, but negative on duplex ultrasound for DVT (Group 3). Group 1 individuals had D-dimer values of 1.53 +/- 0.12 mg/l and P-selectin values of 0.34 +/- 0.05 ng/mg total protein. Group 2 vs. Group 3 individuals had D-dimer values of 7.57 +/- 2.03 vs. 3.19 +/- 0.79 mg/l, p = 0.02; P-selectin values of 0.98 +/- 0.11 vs. 0.55 +/- 0.08 ng/mg total protein, p < 0.01; and micro-particle values of 129 +/- 17% vs. 99 +/- 12% of control, p = ns. Using a logistic regression model with dichotomous variables, we determined a sensitivity of 73%, specificity of 81%, and accuracy of 77% when combining D-dimer, soluble P-selectin, and total microparticles to differentiate Group 2 from Group 3 patients. Logistic regression using continuous variables yielded similar results (p = 0.05). This study demonstrates that plasma markers for DVT can be developed and achieve moderate sensitivity and specificity in diagnosing DVT. However for clinical applicability, the sensitivity/specificity will need to be improved. These studies also suggest the importance of soluble P-selectin in assessing DVT in humans.

Perioperative complications of trabeculectomy in the collaborative initial glaucoma treatment study (CIGTS).

PURPOSE: To describe the incidence of, and risk factors for, surgical complications reported during and within the first post-operative month after trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS). DESIGN: Review of prospectively collected data from a multicenter, randomized clinical trial. METHODS: Complications were tabulated for the 300 CIGTS patients randomized to surgery. Logistic regression analyses were used to identify risk factors for complications. RESULTS: Among the 300 patients randomized to initial surgery, 465 trabeculectomies were performed. Intraoperative complications were reported in 55 eyes (12%). The most frequent reported complications were anterior chamber bleeding during surgery (37 eyes, 8%) and conjunctival buttonhole (five eyes, 1%). Early post-operative complications were reported in 232 eyes (50%). Complications with a frequency over 10% included shallow or flat anterior chamber (62 eyes, 13%), encapsulated bleb (56 eyes, 12%), ptosis (55 eyes, 12%), serous choroidal detachment (52 eyes, 11%), and anterior chamber bleeding or hyphema (48 eyes, 10%). There were three localized suprachoroidal hemorrhages (0.7%) and no cases of endophthalmitis. Older patients were more likely to experience serous choroidal detachment, new anterior or posterior synechiae, and wound leak. Blacks were less likely to experience anterior chamber bleeding, but more likely to experience post-operative ptosis. The number of subjects experiencing bilateral complications was higher than that which would have been predicted by chance alone. CONCLUSIONS: The incidence of transient and self-limiting complications was high in the perioperative period, but we observed few complications with the potential to cause severe sustained vision loss in this group of previously untreated eyes.

Social and emotional impact of strabismus surgery on quality of life in children.

PURPOSE: Improved quality of life after strabismus surgery has been demonstrated in adults, but has not been extensively studied in children. The purpose of this study was to evaluate the psychosocial effects of childhood strabismus surgery. METHODS: This was a prospective interventional study. A modified version of the RAND Health Insurance Study quality of life instrument was administered to parents or guardians of children with strabismus. The questionnaire was administered by telephone interviews conducted by trained staff before and 2 months after corrective surgery. RESULTS: Ninety-eight children with a mean age of 4.5 (+/-3.3) years were studied. Reliability measures (Cronbach's alpha coefficients) indicate that the questionnaire has good internal consistency (alpha > 0.7 in most subscales). Compared with before surgery, significant improvements were noted after surgery, especially within the functional limitations (paired Student's t -test, P = 0.01), social relations ( P < 0.01), general health perceptions ( P < 0.01), and developmental satisfaction ( P < 0.01) subscales. CONCLUSIONS: Parental proxies can provide meaningful measures of children's response to strabismus surgery. Statistically significant improvements were observed in social, emotional, and functional measures of the children's health status. As previously documented for adults, this study shows that psychosocial benefits afforded by strabismus surgery also contribute to an improvement in quality of life for children.

The collaborative initial glaucoma treatment study: baseline visual field and test-retest variability.

PURPOSE: To compare the baseline Collaborative Initial Glaucoma Treatment Study (CIGTS) visual field (VF) score and mean deviation (MD), investigate test-retest variability, and identify variables associated with VF loss and VF measurement variability. METHODS: Baseline data from a randomized clinical trial of 607 patients with newly diagnosed open-angle glaucoma were collected at 14 clinical centers. The CIGTS VF score and MD were obtained from 24-2 VF tests (Zeiss-Humphrey Systems, Dublin, CA) at two visits approximately 2 weeks apart. RESULTS: Although most baseline CIGTS VF scores showed limited field loss, 15% (91/607) of patients showed a substantial deficit (VF score >10 on a 0-20 scale). A small but significant learning effect was seen over the two baseline measures for CIGTS VF score and MD. CIGTS VF score and MD correlate highly (r = -0.93); both have high test-retest correlation (0.83 and 0.91, respectively). Variables associated with greater baseline VF loss for both CIGTS VF score and MD include (probabilities for VF only): male sex (P = 0.018), black race (P

Periodic leg movements during sleep in children scheduled for adenotonsillectomy: frequency, persistence, and impact.

OBJECTIVE: The aim of this study was to assess the frequency and potential clinical impact of periodic leg movements during sleep (PLMS), with or without arousals, as recorded incidentally from children before and after adenotonsillectomy (AT). METHODS: Children scheduled for AT for any clinical indications who participated in the Washtenaw County Adenotonsillectomy Cohort II were studied at enrollment and again 6 months thereafter. Assessments included laboratory-based polysomnography, a Multiple Sleep Latency Test (MSLT), parent-completed behavioral rating scales, neuropsychological testing, and psychiatric evaluation. RESULTS: Participants included 144 children (81 boys) aged 3-12 years. Children generally showed mild to moderate obstructive sleep apnea (median respiratory disturbance index 4.5 (Q1 = 2.0, Q3 = 9.5)) at baseline, and 15 subjects (10%) had at least five periodic leg movements per hour of sleep (PLMI ≥ 5). After surgery, 21 (15%) of n = 137 subjects who had follow-up studies showed PLMI ≥ 5 (p = 0.0067). Improvements were noted after surgery in the respiratory disturbance index; insomnia symptoms; sleepiness symptoms; mean sleep latencies; hyperactive behavior; memory, learning, attention, and executive functioning on NEPSY assessments; and frequency of attention-deficit/hyperactivity disorder (DSM-IV criteria). However, PLMI ≥ 5 failed to show associations with worse morbidity in these domains at baseline or follow-up. New appearance of PLMI ≥ 5 after surgery failed to predict worsening of these morbidities (all p > 0.05), with only one exception (NEPSY) where the magnitude of association was nonetheless negligible. Similar findings emerged for periodic leg movements with arousals (PLMAI ≥ 1). CONCLUSION: PLMS, with and without arousals, become more common after AT in children. However, results in this setting did not suggest substantial clinical impact.

Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. METHODS: Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS: Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). CONCLUSION: Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT00233194.

Soluble P-selectin for the diagnosis of lower extremity deep venous thrombosis.

OBJECTIVE: Although duplex ultrasound is the standard for the diagnosis of lower extremity deep venous thrombosis (LE-DVT), imaging is not always available. The use of D-dimer can exclude (high-sensitivity), but not rule in (low-specificity) LE-DVT. Previously, we demonstrated that soluble P-selectin (sP-sel) in combination with the Wells score, establishes the diagnosis of LE-DVT with a specificity of 96% and a positive predictive value of 100%. In order to validate our previous results, we applied the model to a separate but similar patient cohort. Additionally, we analyzed the role of biomarkers for diagnosing upper extremity DVT (UE-DVT). METHODS: Between April 2009 and March 2012, all patients presenting for a duplex ultrasound exam with concern of DVT were screened. Demographics, clinical data, D-dimer, sP-sel, C-reactive protein, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, and von Willebrand factor levels were prospectively collected in 279 patients (234 LE-DVT, 45 UE-DVT). Continuous and categorical variables among patients with DVT were compared with patients without DVT. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were then calculated using our previously derived cut points to rule in or exclude DVT. RESULTS: Among 234 patients evaluated for LE-DVT, 112 (48%) patients had a confirmed LE-DVT with significant differences in all biomarkers. When Wells score ≥2, sP-sel could rule in LE-DVT with a specificity of 97.5% and a positive predictive value of 91%, which was more accurate than Wells score ≥2 and D-dimer (specificity, 65%; positive predictive value, 69%). When Wells score was <2, D-dimer was superior to sP-sel for excluding the diagnosis of LE-DVT (sensitivity, 98%; negative predictive value, 95% vs sensitivity, 91%; negative predictive value, 79%). The use of additional biomarkers did not increase accuracy. Had imaging not been available, we could have correctly ruled in or ruled out LE-DVT in 29% (67/234) of patients. The use of sP-sel in UE-DVT was nondiagnostic. CONCLUSIONS: We demonstrate that when Wells score ≥2, sP-sel is an excellent biomarker to rule in LE-DVT. Different from our previous study, D-dimer and a Wells score <2 was most sensitive at excluding a diagnosis of LE-DVT. Combined, Wells score, sP-sel, and D-dimer can both rule in and exclude LE-DVT in approximately one-third of patients.

Prothrombotic effects of thrombolytic therapy in a rat (Rattus norvegicus) model of venous thrombolysis.

The use of thrombolytic agents has greatly improved patient outcomes, but the prothrombotic response to these drugs in vivo is unknown. Approximately 24 h after we induced thrombosis in male Sprague-Dawley rats, we placed an infusion line in the inferior vena cava and administered either saline or a thrombolytic agent (tissue plasminogen activator [tPA] or plasmin) for 30 min. Blood was drawn immediately after infusion; rats were euthanized 24 h after infusion for collection of blood and tissue (inferior vena cava and thrombus). Thrombus size was decreased in the tPA-treated rats but not in those that received saline or plasmin; this change correlated with the significant rise in D-dimer levels noted immediately after infusion in the tPA-treated rats. Plasma soluble P-selectin, a prothrombotic marker, was elevated at 24 h in the plasmin group compared with the other treatment groups. There were no significant differences in plasma C3a, C5a, or C5b9 levels or in thrombus C3 levels between groups. According to ultrastructural analysis, thrombus structure and vein wall effects did not differ between groups. Local tPA did not induce a prothrombotic state during acute DVT or after thrombolytic therapy in a rodent model of venous thrombolysis. Conversely, levels of the prothrombotic marker plasma soluble P-selectin increased when plasmin was administered.