Publications by authors named "Kenneth E Guire"

26 Publications

  • Page 1 of 1

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

Int J Pediatr Otorhinolaryngol 2016 Jan 10;80:21-5. Epub 2015 Nov 10.

Department of Neurology, Ann Arbor, MI, USA; Neuropsychology Section, Department of Psychiatry, Ann Arbor, MI, USA.

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.
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January 2016

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

Sleep Med 2014 Nov 6;15(11):1362-9. Epub 2014 Jun 6.

Department of Psychiatry, Central Michigan University, Mount Pleasant, MI, USA.

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.
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November 2014

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

J Clin Sleep Med 2014 Aug 15;10(8):903-11. Epub 2014 Aug 15.

Michigan Tech Research Institute, Michigan Technological University, Ann Arbor, MI.

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:, ID: NCT00233194.
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August 2014

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

J Vasc Surg Venous Lymphat Disord 2013 Apr;1(2):117-1125

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.
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April 2013

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

Comp Med 2013 Jun;63(3):244-51

Merck, Rahway, New Jersey, USA.

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.
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June 2013

Is cervical elongation associated with pelvic organ prolapse?

Int Urogynecol J 2012 Aug 14;23(8):1095-103. Epub 2012 Apr 14.

Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.

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.
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August 2012

Esophageal pressures, polysomnography, and neurobehavioral outcomes of adenotonsillectomy in children.

Chest 2012 Jul;142(1):101-110

Neuropsychology Section, Department of Psychiatry, University of Michigan, Ann Arbor, MI.

Background: Esophageal pressure monitoring during polysomnography in children offers a gold-standard, “preferred” assessment for work of breathing, but is not commonly used in part because prospective data on incremental clinical utility are scarce. We compared a standard pediatric apnea/hypopnea index to quantitative esophageal pressures as predictors of apnea-related neurobehavioral morbidity and treatment response.

Methods: Eighty-one children aged 7.8 ± 2.8 (SD) years, including 44 boys, had traditional laboratory-based pediatric polysomnography, esophageal pressure monitoring, multiple sleep latency tests, psychiatric evaluations, parental behavior rating scales, and cognitive testing, all just before clinically indicated adenotonsillectomy, and again 7.2 ± 0.8 months later. Esophageal pressures were used, along with nasal pressure monitoring and oronasal thermocouples, not only to identify respiratory events but also more quantitatively to determine the most negative esophageal pressure recorded and the percentage of sleep time spent with pressures lower than -10 cm H(2)O.

Results: Both sleep-disordered breathing and neurobehavioral measures improved after surgery. At baseline, one or both quantitative esophageal pressure measures predicted a disruptive behavior disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined attention-deficit/hyperactivity disorder, conduct disorder, or oppositional defiant disorder) and more sleepiness and their future improvement after adenotonsillectomy (each P < .05). The pediatric apnea/hypopnea index did not predict these morbidities or treatment outcomes (each P > .10). The addition of respiratory effort-related arousals to the apnea/hypopnea index did not improve its predictive value. Neither the preoperative apnea/hypopnea index nor esophageal pressures predicted baseline hyperactive behavior, cognitive performance, or their improvement after surgery.

Conclusions: Quantitative esophageal pressure monitoring may add predictive value for some, if not all, neurobehavioral outcomes of sleep-disordered breathing.
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July 2012

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

J Int Neuropsychol Soc 2012 Mar 25;18(2):212-22. Epub 2012 Jan 25.

Neuropsychology Section, Department of Psychiatry, University of Michigan, Ann Arbor, MI 48105, USA.

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.
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March 2012

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

Int Urogynecol J 2012 Mar 9;23(3):285-93. Epub 2011 Nov 9.

Pelvic Floor Research Group, University of Michigan, Ann Arbor, MI, USA.

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.
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March 2012

Evaluation of soluble P-selectin as a marker for the diagnosis of deep venous thrombosis.

Clin Appl Thromb Hemost 2011 Aug 17;17(4):425-31. Epub 2011 May 17.

Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, MI, USA.

Objective: The combination of D-dimer and Wells score can exclude, but not confirm, the diagnosis of deep venous thrombosis (DVT). Since thrombosis and inflammation are interrelated, we evaluated the combination of soluble P-selectin (sPsel) with other inflammatory biomarkers for the diagnosis of DVT.

Methods: Sixty-two positive and one hundred and sixteen patients with negative DVT, by duplex scan, were prospectively evaluated for sPsel, D-dimer, C-reactive protein (CRP), microparticles (MPs; total, leukocyte, and platelet-derived and tissue factor positive microparticles), and clinical Wells score.

Results: Biomarkers and clinical scores that differentiated DVT positives from negatives were sPsel (87.3 vs 53.4 ng/mL, P < .0001), D-dimer (5.8 vs 2.1 mg/ L, P < .0001), CRP (2.1 vs 0.8 μg/mL, P < .0005), and Wells score (3.2 vs 2.0, P < .0001). For MP analysis, platelet-derived MPs were found to differentiate DVT from negatives. Using multivariable logistic regression, a combination of sPsel and Wells score could establish the diagnosis of DVT (cut point ≥ 90 ng/mL + Wells ≥ 2), with a specificity of 96% and positive predictive value (PPV) of 100%, and could exclude DVT diagnosis (cut point ≤ 60 ng/mL and Wells <2) with a sensitivity of 99%, a specificity of 33%, and a negative predictive value (NPV) of 96%.

Conclusion: This study establishes a biomarker and clinical profile combination that can both confirm and exclude the diagnosis of DVT.
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August 2011

Proteomics of microparticles after deep venous thrombosis.

Thromb Res 2010 Jun 13;125(6):e269-74. Epub 2010 Feb 13.

Jobst Vascular Research Laboratory, Section of Vascular Surgery, Cardiovascular Center, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Background: Microparticles (MP) are submicron size membrane vesicles released from activated cells that are associated with thrombosis and inflammation. MP present diverse biological expressions that may be linked to a unique subset of proteins derived from their origin cells.

Methods: To identify these proteins, plasma samples were taken from 9 patients with deep venous thrombosis (DVT) documented by duplex ultrasound, 9 with leg pain but negative for DVT by duplex, and 6 healthy controls without a history of thrombosis, for fold variation. MP were extracted from platelet-poor plasma, digested separately with trypsin and tagged using iTRAQ reagents. The digests were subjected to 2-D LC separation followed by MALDI tandem mass spectrometry. Peak lists were generated and searched against all human sequences. For protein identification, a minimum of two peptides at 95% confidence was required. Later, iTRAQ ratios were generated comparing relative protein levels of DVT patients to baseline. The proteomic analysis was performed twice for each blood sample. Proteins were considered elevated or depressed if the iTRAQ ratio (R) deviated by 20% change from normal and a p-value less than 0.05.

Results: Two proteins (Galectin-3 Binding Protein, [Gal3BP], R=1.76 and Alpha-2 macroglobulin [A2M] R=1.57) were differentially expressed on DVT patients. Nine proteins were depleted including fibrinogen beta and gamma chain precursors (R=0.65).

Conclusions: These proteins influence thrombosis through inflammation, cell shedding, inhibition of fibrinolysis and hemostatic plug formation. Further studies are needed to confirm the mechanistic role of these proteins in the pathogenesis of venous thrombosis in humans.
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June 2010

Contrasting the use of 2 vision-specific quality of life questionnaires in subjects with open-angle glaucoma.

J Glaucoma 2009 Jun-Jul;18(5):403-11

Department of Wellness, Health Promotion, and Injury Prevention, School of Health Sciences, Oakland University, Rochester, MI 48309, USA.

Purpose: To compare 2 vision-specific functional status measures to each other and to clinical parameters in the Collaborative Initial Glaucoma Treatment Study (CIGTS).

Methods: CIGTS participants completed the Visual Activities Questionnaire (VAQ) and the National Eye Institute-Visual Function Questionnaire (NEI-VFQ) and were tested for visual field (VF) and visual acuity (VA). In all, 426 subjects contributed the VAQ and NEI-VFQ scores at 54 months. Pearson correlations were used to assess associations.

Results: The VAQ subscales (range, 0 to 100) that assessed light-dark adaptation (mean=66.1), glare disability (66.4), and acuity/spatial vision (67.7) indicated vision-related functions that CIGTS participants found most difficult. On the NEI-VFQ, subjects reported high levels of visual functioning, with mean >/=90 (out of 100) on the total score and in 9 of 12 subscales. General vision (mean=82.6) received the lowest subscale score. Two subscales common to both questionnaires were highly correlated: VA (r=0.68) and peripheral vision (r=0.77) (both P<0.0001). Correlations between participants' perceptions and clinical measures of visual function were in the expected direction, but weaker. Stronger associations were found between clinical measures and the NEI-VFQ than the VAQ. Better eye VF and worse eye VA had the highest number of significant correlations with subjects' perceptions of their visual function. Increasing VF loss was associated with a significant decrease in the overall and peripheral vision subscale scores from both questionnaires, and also several other subscales.

Conclusions: CIGTS patients reported excellent visual function on both the NEI-VFQ and VAQ. These findings will help researchers interested in assessing patients' perceptions of their visual function make an informed selection when choosing between the VAQ and the NEI-VFQ.
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September 2009

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

J Int Neuropsychol Soc 2008 Jul;14(4):571-81

Neuropsychology Section, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48105-0716, USA.

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.
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July 2008

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

J Am Acad Child Adolesc Psychiatry 2007 Nov;46(11):1425-36

Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Michigan Medical School, Ann Arbor, USA.

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.
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November 2007

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

Am J Obstet Gynecol 2007 Nov 21;197(5):509.e1-6. Epub 2007 Aug 21.

Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI 48109-0276, USA.

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.
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November 2007

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

Obstet Gynecol 2007 Aug;110(2 Pt 1):354-62

Department of Obstetrics and Gynecology, Pelvic Floor Research Group, and School of Nursing, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.

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.
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August 2007

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

Ophthalmology 2007 Dec 9;114(12):2213-20. Epub 2007 May 9.

Department of Health Behavior and Health Education, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109-2029, USA.

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.
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December 2007

Pediatric sleep questionnaire: prediction of sleep apnea and outcomes.

Arch Otolaryngol Head Neck Surg 2007 Mar;133(3):216-22

Sleep Disorders Center, Department of Neurology, School of Public Health, University of Michigan, Ann Arbor, USA.

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.
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March 2007

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

Sleep 2006 Apr;29(4):495-503

Sleep Disorders Center, Department of Neurology, University of Michigan, Ann Arbor, MI, USA.

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.
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April 2006

Sleep-disordered breathing, behavior, and cognition in children before and after adenotonsillectomy.

Pediatrics 2006 Apr;117(4):e769-78

Sleep Disorders Center, Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.

Objectives: Most children with sleep-disordered breathing (SDB) have mild-to-moderate forms, for which neurobehavioral complications are believed to be the most important adverse outcomes. To improve understanding of this morbidity, its long-term response to adenotonsillectomy, and its relationship to polysomnographic measures, we studied a series of children before and after clinically indicated adenotonsillectomy or unrelated surgical care.

Methods: We recorded sleep and assessed behavioral, cognitive, and psychiatric morbidity in 105 children 5.0 to 12.9 years old: 78 were scheduled for clinically indicated adenotonsillectomy, usually for suspected SDB, and 27 for unrelated surgical care. One year later, we repeated all assessments in 100 of these children.

Results: Subjects who had an adenotonsillectomy, in comparison to controls, were more hyperactive on well-validated parent rating scales, inattentive on cognitive testing, sleepy on the Multiple Sleep Latency Test, and likely to have attention-deficit/hyperactivity disorder (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) as judged by a child psychiatrist. In contrast, 1 year later, the 2 groups showed no significant differences in the same measures. Subjects who had an adenotonsillectomy had improved substantially in all measures, and control subjects improved in none. However, polysomnographic assessment of baseline SDB and its subsequent amelioration did not clearly predict either baseline neurobehavioral morbidity or improvement in any area other than sleepiness.

Conclusions: Children scheduled for adenotonsillectomy often have mild-to-moderate SDB and significant neurobehavioral morbidity, including hyperactivity, inattention, attention-deficit/hyperactivity disorder, and excessive daytime sleepiness, all of which tend to improve by 1 year after surgery. However, the lack of better correspondence between SDB measures and neurobehavioral outcomes suggests the need for better measures or improved understanding of underlying causal mechanisms.
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April 2006

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

Am J Obstet Gynecol 2006 May 31;194(5):1427-33. Epub 2006 Mar 31.

Department of Obstetrics and Gynecology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.

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.
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May 2006

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

Thromb Haemost 2005 Dec;94(6):1312-7

Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, Michigan, USA.

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.
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December 2005

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

Am J Ophthalmol 2005 Jul;140(1):16-22

Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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.
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July 2005

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

J AAPOS 2005 Apr;9(2):148-51

Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105. USA.

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.
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April 2005

Colorectal cancer screening attitudes and behavior: a population-based study.

Prev Med 2003 Dec;37(6 Pt 1):627-34

Department of Health Behavior and Health Education, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

Background: Even though colorectal cancer (CRC) screening tests for persons 50 years of age or over are recommended to reduce colorectal cancer mortality, screening rates remain disturbingly low.

Methods: Using random digit dialing, 355 telephone interviews were conducted with black and white men and women, 50-79 years of age, who resided in Genesee County, Michigan. The Health Belief Model provided the framework to assess attitudes and practices regarding CRC screening.

Results: For both endoscopic procedures, significantly higher percentages of whites than blacks were aware of the screening procedure (P < 0.05). Overall, fewer than 30% of respondents were adherent to current CRC screening guidelines. Adherence was lowest for black females: 21% for fecal occult blood test, 20% for flexible sigmoidoscopy, and 12% for colonoscopy. Black males compared to black females were about 2.8 times more likely to have had either flexible sigmoidoscopy or colonoscopy (P < 0.05). Physician recommendation was a powerful motivator to screening. Two consistent barriers to screening were the belief that: (a) the test is not needed; and (b) the test is embarrassing.

Conclusions: Interventions directed at physicians and patients are essential to enhance CRC screening rates. CRC survival rates may be improved by physician-guided promotion of screening that focuses on identified barriers.
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December 2003

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

Invest Ophthalmol Vis Sci 2003 Jun;44(6):2613-20

Department of Biostatistics, Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.

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
Conclusions: The CIGTS VF score provides a measure of VF strikingly similar to the MD. Variables associated with VF loss and VF variability may help identify patients who need greater clinical scrutiny.
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June 2003