Kenneth E. Guire

Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery

PURPOSE To report interim outcome data, using all available follow-up through 5 years after treatment initiation, in the Collaborative Initial Glaucoma Treatment Study (CIGTS). DESIGN Randomized clinical trial. PARTICIPANTS Six hundred seven newly diagnosed glaucoma patients. METHODS In a randomized clinical trial, 607 patients with newly diagnosed open-angle glaucoma were initially treated with either medication or trabeculectomy (with or without 5-fluorouracil). After treatment onset and early follow-up, patients were evaluated clinically at 6-month intervals. In addition, quality of life telephone interviews were conducted at similar frequency to the clinical visits. Patients in both arms of CIGTS were treated aggressively in an effort to reduce intraocular pressure (IOP) to a level at or below a predetermined target pressure specific for each individual eye. Visual field (VF) scores were analyzed by time-specific comparisons and by repeated measures models. MAIN OUTCOME MEASURES VF loss was the primary outcome variable in CIGTS. Secondary outcomes of visual acuity (VA), IOP, and cataract were also studied. RESULTS On the basis of completed follow-up through 4 years and partially completed through 5 years, VF loss did not differ significantly by initial treatment. Over the entire period of follow-up, surgical patients had a greater risk of substantial VA loss compared with medical patients. However, by 4 years after treatment, the average VA in the two groups was about equal. Over the course of follow-up, IOP in the medicine group has averaged 17 to 18 mmHg, whereas that in the surgery group averaged 14 to 15 mmHg. The rate of cataract requiring removal was greater in the surgically treated group. CONCLUSIONS Both initial medical or initial surgical therapy result in about the same VF outcome after up to 5 years of follow-up. VA loss was greater in the surgery group, but the differences between groups seem to be converging as follow-up continues. When aggressive treatment aimed at substantial reduction in IOP from baseline is used, loss of VF can be seen to be minimal in general. Because 4 to 5 years of follow-up in a chronic disease is not adequate to draw treatment conclusions, these interim CIGTS outcomes do not support altering current treatment approaches to open-angle glaucoma.

Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse.

BACKGROUND: To compare levator ani defects and pelvic floor function among women with prolapse and controls. METHODS: Levator ani structure and function were measured in a case–control study with group matching for age, race, and hysterectomy status among 151 women with prolapse (cases) and 135 controls with normal support (controls) determined by pelvic organ prolapse quantification examination. Magnetic resonance imaging was used to determine whether there were “major” (more than half missing), “minor” (less than half of the muscle missing), or no defects in the levator ani muscles. Vaginal closure force at rest and during maximal pelvic muscle contraction was measured with an instrumented vaginal speculum. RESULTS: Cases were more likely to have major levator ani defects than controls (55% compared with 16%), with an adjusted odds ratio of 7.3 (95% confidence interval 3.9–13.6, P<.001) but equally likely to have minor defects (16% compared with 22%). Of women who reported delivery by forceps, 53% had major defects compared with 28% for the nonforceps women, adjusted odds ratio 3.4 (95% confidence interval 1.95–5.78). Women with prolapse generated less vaginal closure force during pelvic muscle contraction than controls (2.0 Newtons compared with 3.2 Newtons P<.001), whereas those with defects generated less force than women without defects (2.0 Newtons compared with 3.1 Newtons, P<.001). The genital hiatus was 50% longer in cases than controls (4.7±1.4 cm compared with 3.1±1.0 cm, P<.001). CONCLUSION: Women with prolapse more often have defects in the levator ani and generate less vaginal closure force during a maximal contraction than controls. LEVEL OF EVIDENCE: II

Sleep-Disordered Breathing, Behavior, and Cognition in Children Before and After Adenotonsillectomy

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.

The Effects of Sugars Intake and Frequency of Ingestion on Dental Caries Increment in a Three-year Longitudinal Study

A three-year longitudinal study was carried out with a group of children, initially aged 11-15, residing in non-fluoridated rural communities in south-central Michigan. This report analyzes the relation between caries increment and consumption of sugars from all sources to see if accepted relationships have changed with the caries decline in the United States. There were 499 children who provided three or more 24-hour dietary recall interviews, and who received dental examinations at baseline and after three years. Caries increment averaged 2.91 DMFS over the three years, with 81 % of new lesions on pit-and-fissure surfaces. Consumption of sugars from all sources averaged 156 g per day for males and 127 g per day for females, an average of 52 kg per person per year. Sugars constituted one-quarter of total caloric intake for both boys and girls, and the average number of eating occasions per day was 4.3. Children who consumed a higher proportion of their total energy intake as sugars had a higher increment of approximal caries, though there was little relation to pit-and-fissure caries. The average number of daily eating occasions was not related to caries increment, nor was the average number of sugary snacks (defined as foods with 15% or more of sugars) consumed between meals, but the average consumption of between-meal sugars was related to the approximal caries increment. When children were categorized by high caries increment compared with no caries increment, a tendency toward more frequent snacks was seen in the high-caries children. In an age of generally declining caries, it was concluded that higher average daily consumption of sugars, and higher between-meal consumption of sugars, was still a risk factor for children susceptible to approximal caries. Overall frequency of eating and frequency of ingestion of sugary foods between meals, however, were both poorly related to approximal caries increment. Pit-and-fissure caries could not be related to any aspect of sugars consumption.

The Collaborative Initial Glaucoma treatment study: Interim quality of life findings after Initial medical or surgical treatment of Glaucoma

OBJECTIVE To present interim quality of life (QOL) findings in the Collaborative Initial Glaucoma Treatment Study (CIGTS) using all available follow-up through 5 years from treatment initiation. DESIGN Randomized controlled clinical trial. PARTICIPANTS Six hundred seven newly diagnosed patients with open-angle glaucoma from 14 clinical centers. INTERVENTION Patients were randomly assigned to either initial medical therapy or initial trabeculectomy. After treatment initiation and early follow-up, patients received clinical and QOL evaluations at 6-month intervals. QOL assessments were administered by telephone at a centralized interviewing center. MAIN OUTCOME MEASURES The CIGTS collected comprehensive QOL information that included both generic and vision-specific QOL measures. This article focuses on initial treatment group differences related to symptom reporting, as measured by a Symptom and Health Problem Checklist, and changes in daily visual functioning, as measured by the Visual Activities Questionnaire (VAQ). RESULTS Across both treatment groups, there was an overall decline in the percent of participants reporting symptoms over time. Of 43 possible symptoms, 12 symptoms were reported with greater frequency by the surgically treated group and 7 symptoms more frequently by the medically-treated group. The surgical patients reported more total Symptom Impact Glaucoma (P = 0.005) and, in particular, more bother related to local eye symptoms. Very few treatment group differences were noted in visual functioning, although surgical patients reported more problems with activities related to their visual acuity (P = 0.024). The percentage of patients across treatment groups reporting worry about blindness was 50% at baseline but declined to approximately 25% over time. CONCLUSIONS Overall, the QOL impact reported by the two treatment groups as measured by instruments used in this study is remarkably similar, with relatively few significant study group differences observed after up to 5 years of follow-up in the CIGTS. When significant differences in visual function have been detected using the VAQ, they are consistent with the clinical outcomes. To date, the most persistent QOL finding is the increased impact of local eye symptoms reported by the surgical group compared with the medical group. Although no changes are recommended in the treatment of newly diagnosed glaucoma patients at the time of this interim report, further follow-up will allow for more definitive answers to the QOL impact of these two treatment approaches.

Stress Urinary Incontinence: Relative Importance of Urethral Support and Urethral Closure Pressure

PURPOSE Treatment strategies for stress incontinence are based on the concept that urethral mobility is the predominant causal factor with sphincter function a secondary contributor. To our knowledge the relative importance of these 2 factors has not been assessed in properly controlled studies. MATERIALS AND METHODS The Research on Stress Incontinence Etiology project is a case-control study that compared 103 women with stress incontinence and 108 asymptomatic controls in groups matched for age, race, parity and hysterectomy. Urethral closure pressure, urethral and pelvic organ support, levator ani muscle function and intravesical pressure were measured and analyzed using logistic regression and multivariable modeling. RESULTS Mean +/- SD maximal urethral closure pressure was 42% lower in cases (40.8 +/- 17.1 vs 70.2 +/- 22.4 cm H(2)O, d = 1.47). Lesser effect sizes were seen for support parameters, including resting urethral axis and urethrovaginal support (d = 0.41 and 0.50, respectively). Other pelvic floor parameters, including genital hiatus size and urethral axis during muscle contraction (d = 0.60 and 0.58, respectively), differed but levator strength and levator defect status did not. Maximum cough pressure, which is an assessment of stress on the continence mechanism, was also different (d = 0.43). After adjusting for body mass index the maximal urethral closure pressure alone correctly classified 50% of cases. Adding the best predictors for urethrovaginal support and cough strength to the model added 11% of predictive ability. CONCLUSIONS The finding that maximal urethral closure pressure and not urethral support is the factor most strongly associated with stress incontinence implies that improving urethral function may have therapeutic promise.

Differential diagnosis of Class II malocclusions: Part 1. Facial types associated with Class II malocclusions

By means of computer-based statistical methods, several types of Class II malocclusion have been discovered with defining horizontal and vertical characteristics. Of the six horizontal types, four are severe syndromes, one is a loose, ill-defined grouping of cases with mild skeletal features, and one has only the dental features of Class II. Five vertical types associates with Class II were also revealed, although each vertical is not associated with all horizontal types. A simplified simulation of the computerized procedures has been developed for routine use in clinical practice.

Carpal length in children: A useful measurement in the diagnosis of rheumatoid arthritis and some congenital malformation syndromes

The distance between the midpoint of the distal radial epiphyseal growth plate and the proximal end of the third metacarpal offers a useful measure for determining wrist size. Standards of this distance as compared to intermetacarpal width and second metacarpal length are presented. These measures (or ratios) should be useful in evaluating patients with juvenile rheumatoid arthritis and a number of congenital malformation syndromes, particularly when the carpals are still not fully ossified. Shortening of the carpus occurs in multiple epiphyseal dysplasia, the otopalatodigital syndromes, Turner syndrome, arthrogryposis, and in juvenile rheumatoid arthritis. A relatively large carpus is present in achondroplasia.

Metabolic consequences of sepsis-induced acute lung injury revealed by plasma 1H-nuclear magnetic resonance quantitative metabolomics and computational analysis

Metabolomics is an emerging component of systems biology that may be a viable strategy for the identification and validation of physiologically relevant biomarkers. Nuclear magnetic resonance (NMR) spectroscopy allows for establishing quantitative data sets for multiple endogenous metabolites without preconception. Sepsis-induced acute lung injury (ALI) is a complex and serious illness associated with high morbidity and mortality for which there is presently no effective pharmacotherapy. The goal of this study was to apply ¹H-NMR based quantitative metabolomics with subsequent computational analysis to begin working towards elucidating the plasma metabolic changes associated with sepsis-induced ALI. To this end, this pilot study generated quantitative data sets that revealed differences between patients with ALI and healthy subjects in the level of the following metabolites: total glutathione, adenosine, phosphatidylserine, and sphingomyelin. Moreover, myoinositol levels were associated with acute physiology scores (APS) (ρ = -0.53, P = 0.05, q = 0.25) and ventilator-free days (ρ = -0.73, P = 0.005, q = 0.01). There was also an association between total glutathione and APS (ρ = 0.56, P = 0.04, q = 0.25). Computational network analysis revealed a distinct metabolic pathway for each metabolite. In summary, this pilot study demonstrated the feasibility of plasma ¹H-NMR quantitative metabolomics because it yielded a physiologically relevant metabolite data set that distinguished sepsis-induced ALI from health. In addition, it justifies the continued study of this approach to determine whether sepsis-induced ALI has a distinct metabolic phenotype and whether there are predictive biomarkers of severity and outcome in these patients.

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.