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Purpose: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial., Materials and Methods: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months., Results: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports., Conclusions: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.

Objective: Health-related quality of life (HRQOL) impairment may be a central component of chronic prostatitis for men afflicted with this condition. Our objective was to examine HRQOL, and factors associated with HRQOL, using both general and condition-specific instruments., Design: Chronic Prostatitis Cohort (CPC) study., Setting: Six clinical research centers across the United States and Canada., Participants: Two hundred seventy-eight men with chronic prostatitis., Measurements and Main Results: The Short Form 12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS), and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) were measures used. CPC subjects' MCS scores (44.0 +/- 9.8) were lower than those observed in the most severe subgroups of patients with congestive heart failure and diabetes mellitus, and PCS scores (46.4+/-9.5) were worse than those among the general U.S. male population. Decreasing scores were seen in both domains with worsening symptom severity (P < .01). History of psychiatric disease and younger age were strongly associated with worse MCS scores, whereas history of rheumatologic disease was associated with worse PCS scores. Predictors of more severe NIH-CPSI scores included lower educational level and lower income; history of rheumatic disease was associated with higher scores., Conclusions: Men with chronic prostatitis experience impairment in the mental and physical domains of general HRQOL, as well as condition-specific HRQOL. To optimize the care of men with this condition, clinicians should consider administering HRQOL instruments to their patients to better understand the impact of the condition on patients' lives.

We extend the model of Pulkstenis et al. that models binary longitudinal data, subject to informative drop-out through remedication, to the ordinal response case. We present a selection model shared-parameter approach that specifies mixed models for both ordinal response and discrete survival time to remedication. In this fashion, the random parameter present in both models completely characterizes the relationship between response and time to remedication inducing their conditional independence. With a log-log link function for both response and study 'survival', as well as specification of a log-gamma distribution for the random effect, we obtain a closed-form expression for the marginal log-likelihood of response and time to remedication that does not require approximation or numerical integration techniques. A data analysis is performed and simulation results presented which support the consistency of parameter and standard error estimates., (Copyright 2001 John Wiley & Sons, Ltd.)

Purpose: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis., Materials and Methods: A total of 637 eligible patients were entered into the study and followed for symptoms of pain, urgency and urinary frequency. Median followup was 31 months., Results: More than 90% of patients were white women with a median age of 43 years. Using the overall pain-urgency-frequency score 7% of participants presented with mild, 44% with moderate and 49% with severe symptoms. Severe urgency in 41% of cases and severe 24-hour frequency in 41% were more common than severe pain in 29%. Of the patients 51% reported nighttime frequency of 2 or more voids. Median duration of interstitial cystitis symptoms was 8 years and 68% of participants were previously diagnosed with the condition. The 36% of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline. Patterns of change with time suggest initial symptom improvement due to regression to the mean, and an intervention effect associated with the increased followup and care of cohort participants. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity., Conclusions: Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time. These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population.

Purpose: We address the importance of 3 consecutive daily frequency volume charts relative to a single day in research studies for interstitial cystitis. In addition, differences in voiding patterns between weekend days and weekdays were evaluated., Materials and Methods: Longitudinal frequency volume chart data for 305 women enrolled in the National Interstitial Cystitis Data Base Study before December 31, 1995 and meeting protocol specifications were summarized for 3 outcome measures. Longitudinal data methods designed to accommodate different within patient correlation patterns for repeat measures within and among patient contacts were implemented in a generalized estimating equation modeling framework, permitting overall testing of day and weekend effects., Results: Day 2 and day 3 measures were not statistically different (1% level) from day 1 for nocturnal voiding frequency and nocturia. Although statistically significant for 24-hour frequency, the mean difference of -0.36 void daily between days 1 and 3 was not likely to be clinically significant. Also, measures on weekdays were not significantly different from those on weekends for each of the 3 outcome measures., Conclusions: Our results suggest that the current clinical research requirement of 3 consecutive days for frequency volume charts can be reduced to a single day. Furthermore, day selection need not be affected by weekday versus weekend considerations.

Purpose: The lack of a precise working definition of interstitial cystitis may have resulted in the de facto use of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) "research" definition by clinicians. We evaluated these strict criteria in light of the broader inclusion criteria for patients evaluated in the Interstitial Cystitis Database study to determine their utility in clinical practice as a useful basis for the diagnosis of interstitial cystitis., Materials and Methods: A total of 379 women who completed screening for the Interstitial Cystitis Database before January 1, 1996 met the basic criteria of urinary frequency, urgency or pain for at least 6 months in duration without a diagnosable etiology. Of these patients 148 underwent cystoscopy and hydrodistention of the bladder as a part of the evaluation. All patients were followed for a minimum of 1 year. Comparisons were made between patients judged to have a clinical diagnosis of interstitial cystitis and those who met the NIDDK research definition of the syndrome., Results: Almost 90% of patients potentially meeting NIDDK criteria are believed by experienced clinicians to have interstitial cystitis, confirming the research value of these criteria in defining a homogeneous population for study. However, strict application of NIDDK criteria would have misdiagnosed more than 60% of patients regarded by researchers as definitely or likely to have interstitial cystitis., Conclusions: The NIDDK criteria are too restrictive to be used by clinicians as the diagnostic definition of interstitial cystitis.

Background: Conventional cineradiology has been used clinically to detect partially broken outlet struts (single leg separations, SLSs) in normally functioning Björk-Shiley convexo-concave (C/C) heart valves. The value of radiographic screening has, however, been debated in the medical literature. This study uses the same radiographic technique in sheep implanted with known-status C/C valves in combination with a newly developed geometric image magnification radiography system. This study was designed to test whether sensitivity and specificity of radiographic screening of C/C valves in detecting SLSs could be improved through the combination of readers and imaging modalities., Methods: Twenty-one sheep with mitral C/C valves were studied on both systems. Five were used for extensive scanning training. When operators were expert on both systems, 16 blinded study valves (4 intact and 12 with outlet strut SLSs) were scanned twice on both systems, first on a modified conventional and then a prototype geometric image magnification (Feinfocus(TM)) cineradiographic system by two expert physicians working together., Results: Among the 32 scanned valves, the two combined expert physicians were required to evaluate 40 intact legs and 24 with an SLS. For all SLS valves, the conventional and Feinfocus systems separately detected 50 (12/24) and 54% (13/24), respectively. When the two systems were combined, the final consensus score was correct in 67% (16/24) of all SLS valves., Conclusions: Combined modality, paired expert physicians detected 67% of all SLSs. The Feinfocus system might be best reserved for those patients in whom the Siemens screening study demonstrates in minimally suspicious (grade 2) or suspicious (grade 3) appearance of a C/C valve outlet strut leg.

Over a 6-month period, 23 members of the International Microvascular Research Group participated in a prospective survey of their microvascular free-flap practice. Data were recorded with each case for 60 variables covering patient characteristics, surgical technique, pharmacologic treatment, and postoperative outcome. A total of 493 free flaps were reported with a representative demographic distribution for age, sex, indications for surgery, risk factors, flap type, surgical technique, and pharmacologic intervention. Mixed effects logistic regression modeling was used to determine predictors of flap failure and associated complications. The overall incidence of flap failure was 4.1 percent (20 of 493). Reconstruction of an irradiated recipient site and the use of a skin-grafted muscle flap were the only statistically significant predictors of flap failure, with increased odds of failure of 4.2 (p = 0.01) and 11.1 (p = 0.03), respectively. A postoperative thrombosis requiring re-exploration surgery occurred in 9.9 percent of the flaps. The incidence of this complication was significantly higher when the flap was transferred to a chronic wound and when vein grafts were needed, with increased odds of failure of 2.9 (p = 0.02) and 2.5 (p = 0.02), respectively. There was a lower incidence of postoperative thrombosis when rectus/transverse rectus abdominis muscle (TRAM) flaps were used, where odds of failure decreased by 0.36 (p = 0.04), and when subcutaneous heparin was administered in the postoperative period, where odds decreased by 0.27 (p = 0.04). There was an overall 69-percent salvage rate for flaps identified with a postoperative thrombosis. Intraoperative thrombosis occurred in 41 cases (8.3 percent) and was observed more frequently in myocutaneous flaps or when vein grafts were needed (5.5 and 5.0 greater odds, respectively; p < 0.001) but was not associated with higher flap failure (2 of 41 cases; 4.9-percent failure rate). The incidence of a hematoma and/or hemorrhage was increased in obese patients and when vein grafts were needed [2.7 (p = 0.02) and 2.6 (p = 0.03) greater odds, respectively], whereas this complication was significantly decreased in muscle flaps (myocutaneous or skin-grafted muscle), in tobacco users, when a heparinized solution was used for general wound irrigation, and when the attending surgeon performed the arterial anastomosis (in contrast to the resident or fellow on staff) (p < 0.05 for each factor). With the multivariable analysis, many factors were found not to have a significant effect on flap outcome, including the recipient site (e.g., head/neck, breast, lower limb, etc.); indications for surgery (trauma, cancer, etc.); flap transfer in extremes of age, smokers, or diabetics; arterial anastomosis with an end-to-end versus end-to-side technique; irrigation of the vessel without or with heparin added to the irrigation solution; and a wide spectrum of antithrombotic drug therapies. These results present a current baseline for free-flap surgery to which future advances and improvements in technique and practice may be compared.

A fundamental goal of orthodontics is to improve the smile, but no objective criteria exist to assess the lip-teeth relationship, establish objectives of treatment or measure treatment outcome. Here we propose a method to digitally measure the smile characteristics of orthodontic patients. Specifically, the 'posed smile' is measured. By definition the posed smile is voluntary and not elicited by an emotion. It can be a learned greeting or a signal of appeasement and can be sustained. The posed smile is reliably repeatable. The multimedia computer program for smile measurement we developed was based on studies of the utility of the smile photograph and the assessment of the lip-teeth characteristics of the posed smile in treated and untreated patients. On the computer screen a grid, or smile mesh, employs horizontal and vertical lines to measure eleven attributes of a smile. Not all orthodontically 'well-treated' patients with exemplary plaster casts exhibit desirable anterior tooth display while smiling. We suggest that the photographic analysis of an unstrained posed smile might be a standard orthodontic record.

Objective: Modified cineradiographic systems have been used clinically to detect partially broken outlet struts in normally functioning Björk-Shiley convexo-concave heart valves. Almost all such valves were explanted, presuming that full failure would likely follow. Inasmuch as the clinical setting only rarely permits examination of normally rated valves, the accuracy of radiographic detection cannot be clinically defined. This study uses the clinical radiographic technique in sheep implanted with known-status convexo-concave valves, comparing its accuracy and that of a newly developed, geometric image magnification radiography system., Methods: Twenty-one sheep with mitral convexo-concave valves were studied on both systems. Five were used for extensive training. When operators were expert with both systems, images of four intact valves and 12 valves with outlet strut single leg separations, along with a seventeenth single leg separation valve used for calibration, were integrated into 112 image sets organized into a balanced incomplete block design for evaluation by eight trained, blinded reviewers., Results: Cineradiography sensitivity was 24% versus 31% for direct image magnification. The odds ratio for detection of single leg separation by direct image magnification versus cineradiography was 2.0 (95% confidence interval, 0.76 to 5.9; p = 0.13). Cineradiography specificity was 93% versus 90% for direct image magnification. Sensitivity and specificity varied markedly by reviewer, with sensitivity ranging from 8% to 55% and specificity from 51% to 100% for the combined technologies., Conclusions: The data support the need for more intensive training for convexo-concave valve imaging and further investigation of unconventional radiographic technologies. Clinical cineradiography of convexo-concave valves may detect as little as 25% of valves having a single leg separation, underestimating the prevalence of single leg separations and thereby implying more rapid progression to full fracture than is actually the case.

A shared parameter model with logistic link is presented for longitudinal binary response data to accommodate informative drop-out. The model consists of observed longitudinal and missing response components that share random effects parameters. To our knowledge, this is the first presentation of such a model for longitudinal binary response data. Comparisons are made to an approximate conditional logit model in terms of a clinical trial dataset and simulations. The naive mixed effects logit model that does not account for informative drop-out is also compared. The simulation-based differences among the models with respect to coverage of confidence intervals, bias, and mean squared error (MSE) depend on at least two factors: whether an effect is a between- or within-subject effect and the amount of between-subject variation as exhibited by variance components of the random effects distributions. When the shared parameter model holds, the approximate conditional model provides confidence intervals with good coverage for within-cluster factors but not for between-cluster factors. The converse is true for the naive model. Under a different drop-out mechanism, when the probability of drop-out is dependent only on the current unobserved observation, all three models behave similarly by providing between-subject confidence intervals with good coverage and comparable MSE and bias but poor within-subject confidence intervals, MSE, and bias. The naive model does more poorly with respect to the within-subject effects than do the shared parameter and approximate conditional models. The data analysis, which entails a comparison of two pain relievers and a placebo with respect to pain relief, conforms to the simulation results based on the shared parameter model but not on the simulation based on the outcome-driven drop-out process. This comparison between the data analysis and simulation results may provide evidence that the shared parameter model holds for the pain data.

Objectives: To describe the design, patient population, and data and specimen collection aspects of the interstitial Cystitis Data Base (ICDB) Study and to provide preliminary descriptive statistics and inferential results from an interim analysis., Methods: All 424 study participants successfully enrolled in the ICDB Study prior to December 31, 1995, were selected for an interim analysis and were classified into 1 of 3 symptom severity subgroups. Statistical tests for associations among these symptom severity subgroups and a broad range of baseline characteristics were conducted using Mantal-Haenszel procedures to adjust for variation among clinical centers., Results: ICDB Study patients are predominantly female (91.5%), white (91.0%), with an average age at enrollment of 44.3 years. Nearly 45% of these patients underwent a cystoscopy at baseline screening, among whom there was an overall prevalence of 10.5% for Hunner's patch and 90% for glomerulations. Urodynamic evaluation for the entire 424 patients demonstrated that volumes at first sensation and at maximal capacity were inversely associated with symptom severity subgroups. A broad range of symptoms were analyzed, indicating that nearly 40% of patients reported urinating 15 times or more during awake hours, and more than 20% reported voiding at least 4 times per night. Almost half (47.9%) reported constant urgency and 23.6% reported having severe pain. Patients in the severe symptom subgroup reported greater limitations in selected quality-of-life indicators than those with less severe symptoms., Conclusions: This interim analysis of the ICDB Study data was compared to previous epidemiologic studies of IC and provides an essential foundation for further analytic investigations of baseline associations and longitudinal trends.

Cineradiography can identify patients with single-leg fractured Björk-Shiley Convexo-Concave valves, although little is known about the sensitivity and specificity of this technique. We evaluated three normal and six (0 microm gap) single-leg fractured Björk-Shiley valves that were placed in a working phantom model. Valves were randomly imaged a total of 33 times and duplicated into a 120-valve series with a 1:9 ratio of abnormal/normal valves. Six reviewers independently graded each valve and demonstrated markedly different rates of identifying the fractured valves. Average sensitivity at the grade that clinically results in valve explanation was 47%. Among the normal valves, a correct identification was made 96% (range 91% to 99%) of the time. Present radiographic technology may have significant difficulty in identifying true single-leg fracture in Björk-Shiley valves with limb separations that are common among clinically explanted valves.

We compare population-averaged and cluster-specific models for clustered ordinal data. We consider generalized estimating equations and constrained equations maximum likelihood estimation of population-averaged cumulative logit regression models, and mixed effects estimation of cluster-specific cumulative logit regression models. A previously reported relationship between population-averaged and cluster-specific parameters for the binary logistic link appears to hold for analogous parameters under the cumulative logit link. We address these issues in the context of data from two cross-over clinical trials.

Purpose: A dosimetric evaluation of a new device dedicated to intravascular irradiation, associating a beta source and a centering device, was carried out before initiation of a clinical pilot study., Methods and Materials: A 29-mm-long 90Y coil, coated with titanium and fixed to the end of a thrust wire, was introduced into the inner lumen of purpose-built centering balloons of different diameters (2.5, 3, 3.5, and 4 mm). Dose homogeneity was evaluated by studying both axial and circumferential dose variations, based on readings from thermoluminescent dosimeters (TLDs) placed on the balloon surface. Axial homogeneity was determined by comparing the readout values of dosimeters located on peripheral balloon segments with those located on segments adjacent to the midpoint of the source. The centering ability of the device was studied by comparing measurements on opposing surfaces of the balloon. The dose attenuation by water and contrast medium was evaluated and compared with that in air. The balloon contamination was studied using a contamination counter. The total 90Y coil activity was measured by liquid scintillation to relate activity to surface dose., Results: Activity-surface dose correlation showed that for a linear coil activity of 1 mCi/mm, the mean dose rate at the surface of a 2.5-mm balloon filled with contrast medium was 8.29 Gy/min. The doses at the surface of larger balloons (3, 3.5, and 4 mm) filled with contrast were 78%, 59%, and 47%, respectively, of the dose measured at the surface of the 2.5-mm balloon. The coefficient of variation (CV) in surface dose for 2.5-, 3-, 3.5-, and 4-mm centering devices filled with contrast medium were 9%, 8%, 9%, and 12%, respectively. There was no statistically significant difference between readouts from central and peripheral balloon segments or among rows of dosimeters facing each other. For a 2.5-mm balloon, compared with air the dose attenuation by water and contrast medium was similar (0.70 and 0.69, respectively), but a significant difference was seen between the readouts of water- and contrast-filled balloons when the diameter was larger than 3 mm (p < 0.001). No contamination was found in the balloon shaft after source retrieval., Conclusion: The dosimetric tests showed very good surface dose homogeneity, demonstrating satisfactory centering of the source within the centering balloons. The achievable dose rates will permit intravascular irradiation within a short time interval. The absence of residual balloon contamination after source retrieval meets the requirements for a sealed source used in a clinical setting.

Objective: To 1) assess the degree of agreement among physicians on the cause of previously flagged adverse outcomes and 2) relate the findings to systems of quality assurance and performance assessment and proposals for no-fault compensation for medical injuries., Design: Observational study of 7533 pairs of "structured implicit" reviews (subjective opinions based on guidelines) of medical records done by 127 physicians working independently., Setting: Random sample of 51 inpatient facilities in New York State., Patients: Random sample of inpatient medical records from the selected facilities., Measurements: 1) Number of agreed-upon adverse events compared with the number of cases of extreme disagreement and 2) internally and indirectly standardized rates at which physician reviewers found adverse events (injuries to patients caused at least in part by medical management)., Results: In 12.9% of cases (971 of 7533), the two physicians in a pair had extreme disagreement about the occurrence of an adverse event. These cases outnumbered those in which both reviewers found an adverse event (10%; n = 757). Agreement was highest for wound infections and lowest for adverse events attributed to failure to diagnose or lack of therapy. The amount of experience the physicians had in reviewing records tended to increase the level of agreement. Even after standardization to the results of the entire sample, individual physicians' rates of finding at least slight evidence of an adverse event varied widely (range, 9.9% to 43.7%) (P < 0.001)., Conclusions: Structured implicit reviews produced disagreement on the causes of adverse patient outcomes. If systems of quality assurance, performance audits, or no-fault patient compensation are to succeed, methods for overcoming the common tendency toward disagreement among experts must be developed.

Objective: To compare and contrast a managed care program's analysis of differences in hospital mortality with results obtained by accepted statistical methods., Design: A re-analysis of computerized discharge data using the same method used by a managed care program, and using conventional methods of categorical data analysis. One thousand computer simulations of a method for comparing hospitals by severity-adjusted mortality were done to determine the probability of falsely identifying hospitals as high-mortality outliers., Setting: 22 acute care hospitals in central Pennsylvania., Patients: All adult patients with pneumonia (n = 4587; diagnosis-related groups 089-090) less than 65 years of age who were discharged from the 22 hospitals in 1989, 1990, and 1991, excluding patients with the acquired immunodeficiency syndrome and transplant recipients., Measurements: In-hospital mortality adjusted for age and severity of illness using MedisGroups admission severity group score., Results: The hospital that had the highest mortality for adult pneumonia according to the managed care program's analysis did not, according to an appropriate analysis, differ significantly from other area hospitals (likelihood ratio test, P = 0.23). Random variation in this sample of patients with a low average mortality rate (3.5%) showed a 60% chance that 1 or more of the 22 hospitals would be falsely identified as a "high-mortality outlier" when simplistic statistical methods were used., Conclusion: Organizations seeking to compare the quality of hospitals and physicians through outcome data need to recognize that simplistic methods applicable to large samples fail when applied to the outcomes of typical patients, such as those admitted for pneumonia. Although these comparisons are much in demand, careful attention must be paid to their statistical methods to ensure validity and fairness.

To determine whether elastase levels in gingival crevicular fluid (GCF) could serve as a marker for the progression of periodontitis, we monitored GCF elastase and periodontal status in selected sites in 32 periodontally healthy volunteers and 31 periodontitis patients at intervals over a 6-month period. Clinical measurements included plaque index, gingival index, bleeding on probing, suppuration, probing depth, clinical attachment level, and relative attachment level measured with an automated disk probe. GCF elastase, detected by reaction with a fluorescent substrate, was assessed visually against fluorescence standards and quantitatively with a fluorometer. Bone loss was detected by subtraction radiography of standardized vertical bite-wing radiographs at baseline and 6 months. Mean visual elastase scores (VES) and quantitative elastase measurements were significantly higher (P < 0.001) in sites from periodontitis patients than in sites from healthy volunteers. When bone loss was used as the criterion for disease progression, significantly higher (P < 0.001) visual and quantitative GCF elastase levels were found at progressing sites than in nonprogressing sites in the periodontitis patients. The odds ratios (OR) for the event of developing bone loss with positive 4-minute and 8-minute VES tests were 4.2 (P < 0.001) and 7.4 (P < 0.001), respectively. When corrected for the tendency of progressing sites to be clustered within a subpopulation of patients, the OR for developing bone loss with the 4-minute and 8-minute VES tests were 3.1 (P < 0.007) and 4.9 (P < 0.001), respectively. These data indicate that sites with high levels of elastase are at significantly greater risk for progressive bone loss as assessed by digital subtraction radiography.

Diet of the Swiss population has probably changed over the last 10 years, but these changes have not been recorded yet by nutritional studies. In the present study, 3 registered dieticians interviewed over the telephone 626 adults, resident of Canton Geneva, using a 24 hour recall. Interviews were performed during the 7 days of the week. Participants were randomly selected according to their age, sex and nationality. Participation was 80%. The following caloric (C) and nutritional intakes in proteins (P), lipids (L), carbohydrates (CH) and alcohol (A) were recorded: In non Swiss men: C = 2464 kcal/j., P = 16.2%, L = 32.4%, CH = 44.4%, A = 7.0%; in Swiss men: C = 2752 kcal/j., P = 15.3%, L = 34.0%, CH = 43.5%, A = 7.1%; in non Swiss women: C = 1897 kcal/j., P = 16.4%, L = 35.1%, CH = 46.5%, A = 2.4%; in Swiss women: C = 1865 kcal/j., P = 15.0%, L = 35.3%, CH = 46.0%, A = 3.2%. Total caloric intake and iron intake decreased with age. Older women ate less calcium than younger. In summary, the most important determinants of diet are age and sex. Proportion of lipids is relatively low in both men and women. Small differences related to nationality were observed in men.

In recent years, methods have been developed for modelling repeated observations of a categorical response obtained over time on the same individual. Although situations in which the repeated response is binary or Poisson have been studied extensively, relatively little attention has been given to polytomous categorical response variable. In this paper, we extend the estimating equations initially developed for clustered discrete data by Liang and Zeger (1986, Biometrika 73, 13-22), and subsequently extended by Prentice (1988, Biometrics 44, 1033-1048), to polytomous response variables. Under certain assumptions, we illustrate that these estimating equations simplify to the weighted least squares (WLS) equations formalized by Koch et al. (1977, Biometrics 33, 133-158). This connection provides a formal framework for obtaining iterated weighted least squares model parameter estimates. Cumulative logit models are developed and applied to a representative longitudinal data set. Simulation results comparing WLS, an iterative form of WLS, and independence estimating equations using a robust estimate of the variance are presented.

Objective: To evaluate the effect of calcium supplementation on bone acquisition in adolescent white girls., Design: A randomized, double-blind, placebo-controlled trial of the effect of 18 months of calcium supplementation on bone density and bone mass., Subjects: Ninety-four girls with a mean age of 11.9 + 0.5 years at study entry., Setting: University hospital in a small town., Interventions: Calcium supplementation, 500 mg/d calcium as calcium citrate malate; controls received placebo pills., Main Outcome Measures: Bone mineral density and bone mineral content of the lumbar spine and total body were measured by dual-energy x-ray absorptiometry and calcium excretion from 24-hour urine specimens., Results: Calcium intake from dietary sources averaged 960 mg/d for the entire study group. The supplemented group received, on average, an additional 354 mg/d of calcium. The supplemented group compared with the placebo group had greater increases of lumbar spine bone density (18.7% vs 15.8%; P = .03), lumbar spine bone mineral content (39.4% vs 34.7%; P = .06), total body bone mineral density (9.6% vs 8.3%; P = .05), and 24-hour urinary calcium excretion (90.4 vs 72.9 mg/d; P = .02), respectively., Conclusions: Increasing daily calcium intake from 80% of the recommended daily allowance to 110% via supplementation with calcium citrate malate resulted in significant increases in total body and spinal bone density in adolescent girls. The increase of 24 g of bone gain per year among the supplemented group translates to an additional 1.3% skeletal mass per year during adolescent growth, which may provide protection against future osteoporotic fracture.

Objective: To investigate whether an association exists between the probability of a cesarean delivery and the level of malpractice claims risk faced by hospitals and physicians., Design: Survey of computerized discharge data linked with physician and hospital malpractice claims records based on stratified, random sample of hospitals., Setting: Acute care hospitals in New York State in 1984., Population: All deliveries (60 490) at 31 hospitals., Results: After controlling for the clinical risk of a cesarean delivery, patient socioeconomic status, and physician and hospital characteristics, cesarean delivery was positively associated with physician malpractice premiums (odds ratio [OR], 3.00; 95% confidence interval [CI], 2.13 to 4.24 for the difference between upstate and New York City levels), with the number of physician claims opened per 100 physicians at the hospital level (OR, 1.15; 95% CI, 1.02 to 1.30 for a 1-SD change), and with the number of hospital claims opened per 1000 discharges (OR, 1.26; 95% CI, 1.10 to 1.43 for a 1-SD change). Measures of physician-perceived risk of suit also showed a significant association with cesarean delivery (OR, 1.96; 95% CI, 1.53 to 2.52, upstate vs New York City). Within hospitals, there was no significant association (OR, 1.15; P = .126) between the odds of cesarean delivery and the claims history (none vs one or more) of an individual physician., Conclusion: Results support previous speculations of a positive association between malpractice claims risk and the rate of cesarean delivery.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to measure adenosine triphosphate (ATP) concentration and pH in vivo in rabbits subjected to a 40-minute period of unilateral renal ischemia to determine the effect of infusing ATP-magnesium chloride (MgCl2, 100 mumol/kg) versus saline at the initiation of reperfusion. Data were compared initially by analysis of variance and then analyzed further using a general linear model with covariate adjustment. ATP-MgCl2-treated animals did not have higher ATP levels during recovery but did have significantly higher renal blood flow (p less than 0.05), a significantly decreased rate of recovery from acidosis (p less than 0.05), and significantly higher urinary output (p less than 0.01) than saline-treated animals during the recovery period. Therefore, treatment with ATP-MgCl2 improves postischemic functional parameters in this model of moderate injury without functioning as a direct source of ATP or its precursors. These data add support to the emerging concept that intracellular acidosis protects cells from reperfusion injury.

THIS STUDY SOUGHT TO EVALUATE the ability of gingival crevicular fluid (GCF) elastase to predict attachment and bone loss in human periodontitis. Thirty subjects who were medically healthy and had a history of progressive periodontitis were studied with an automated probe. Five sites in each patient were monitored bi-monthly for a 6-month period for attachment loss. Subtraction radiography was utilized at the beginning and end of the study to monitor bone loss. GCF elastase was measured at 0 month and then bi-monthly by collecting GCF on paper strips impregnated with PMN leukocyte elastase substrate inserted into the gingival crevice for 15 seconds. After 8 minutes of reaction time, the strips were scored relative to fluorescent standards in an ultraviolet view box. Strips were then eluted in methanol and total elastase measured by spectrofluorometry. Total elastase was significantly higher in sites demonstrating progressive attachment loss than in inactive sites (2.81 +/- .29 versus 2.03 +/- .07, P less than 0.0005) and sites demonstrating bone loss (2.32 +/- .17 versus 2.01 +/- .08 P less than 0.05). When considering the joint presence of bone loss and attachment loss of 1.0 mm or greater in the 6-month period following a visual elastase kit score of 2 or greater, the test kit shows a sensitivity and specificity of 82% and 66%, respectively. This study demonstrated that GCF elastase levels are significantly higher in sites demonstrating progressive periodontal attachment and bone loss assessed 6 months later and may serve as a predictor of future bone and attachment loss.

The most commonly used laboratory test for predicting malignant hyperthermia susceptibility is the caffeine halothane contracture test. However, the specificity and sensitivity of proposed North American diagnostic guidelines for this test have never been evaluated in a large, human study population. Therefore, the authors conducted a multiinstitutional, prospective study of skeletal muscle contracture responses in a subject population at low risk for malignant hyperthermia susceptibility to help determine the specificity of the proposed guidelines. Subjects were selected arbitrarily from a population of patients undergoing surgery unrelated to performance of a diagnostic muscle biopsy. Subjects were admitted to this study and were presumed nonsusceptible if there was no evidence of any of the following malignant hyperthermia risk factors: prior abnormal response to triggering anesthetic agents, myopathy, or family history of malignant hyperthermia susceptibility. The authors suggested rejection of the proposed diagnostic guidelines if an 85% specificity estimate among subjects could not be obtained. The authors analyzed the responses of 1,022 muscle fascicles, derived from 176 subjects, to the following: 1) separate administration of 3% halothane or incremental caffeine concentrations, or 2) the joint administration of 1% halothane and incremental caffeine concentrations. The following contracture results were obtained. First, for individual fascicles, 9.2% exceeded a greater than 0.7 g threshold for 3% halothane, 15.2% exceeded a greater than or equal to 0.2 g threshold for 2 mM caffeine, 32.4% exceeded a 1-g increase for less than 4 mM caffeine, 2.6% had a greater than 7% maximal increase in tension at 2 mM caffeine, and 63.5% had a "halothane caffeine-specific concentration" at less than or equal to 1 mM caffeine. Second, the percentages of subjects with 1 or more fascicles exceeding the proposed threshold were as follows: 45.8% for the four-component, 28.8% for the three-component, and 32.7% for the two-component contracture test. Third, the percentages of subjects with 1 or more fascicles exceeding the proposed threshold for both halothane and caffeine were as follows: 9.5% for 3% halothane and 2 mM caffeine, 2.0% for 3% halothane and 7% maximal increase in tension at 2 mM caffeine, and 11.0% for 1% halothane and 2 mM caffeine. Fourth, center-to-center differences were the major source of variation in the rate that subjects exceeded proposed thresholds. These data demonstrate that proposed diagnostic guidelines must be modified to improve specificity estimates before adoption by diagnostic centers.(ABSTRACT TRUNCATED AT 400 WORDS)

The gallbladder and biliary system were scanned by real-time ultrasound in 2274 patients undergoing diagnostic ultrasound for other than gallbladder disease. Patients (212) with previous gallbladder symptoms or with nonvisualization of their gallbladder were excluded from the study. Obesity is the most important risk factor for the development of asymptomatic gallstones in women (P less than .01), although it is not a significant factor in men. Increasing age is an important risk factor for both sexes, and the only significant risk factor in men (P less than .01). While few men have asymptomatic gallstones before the age of 40, 5% of women aged 20-29 and 9% aged 30-39 do. In the 40 and over age group, men (14%) and women (11%) had insignificantly different prevalences. In women, the number of previous pregnancies is a significant risk factor (chi-square = 5.4, P = .02). For instance, there is a 3%, 8%, and 17% overall frequency of gallstones in women with 0, 3, and 6 or more previous pregnancies, respectively. A stepwise logistic regression analysis, after adjusting for age, body mass index, and for women, number of pregnancies, found no significant increased risk related to race (P = .40), high blood pressure (P = .43), heart disease (P = .47), or diabetes (P = .46). After age adjustment, there is no significant gender effect (P = .25). Asymptomatic gallstones are a relatively common occurrence in men over 40 and women over 30. While age is the only significant risk factor in men, obesity, parity, and to a lesser extent age were significant risk factors in women.

A generalized variance component model is proposed for the analysis of a categorical response variable with extra-multinomial variation. Categorical data obtained from research designs such as randomized multicenter clinical trials or complex sample surveys with clustering frequently exhibit extra-variation resulting from intracluster correlation. General correlation patterns are accounted for by utilizing a mixed-effects modelling approach, estimating the cluster variance components through the method of moments and modelling functions of the observed proportions through the use of estimating equations. A flexible set of assumptions characterizing the underlying covariance structure for the proportions can be accommodated. The importance of accounting for extra-variation when performing hypothesis tests is highlighted with an application to data from a multi-investigator clinical trial.

Studies examining animal models of genetic obesity have identified defects in adipocyte hormone-stimulated lipolysis that involve the adenylate cyclase transmembrane signaling system, specifically those components that decrease adenylate cyclase activity. To determine whether obese people demonstrate alterations in adenylate cyclase activity that could contribute to the maintenance of obesity by inhibiting lipolysis, we examined human adipocytes from patients who were lean, obese, or formerly obese. Fat samples were obtained from the lower abdomen of 14 women who were morbidly obese (obese group), from 10 women who were formerly morbidly obese and had lost weight after gastric stapling (postobese group), and from 10 similarly aged women of normal weight (controls). Adipocyte adenylate cyclase activity was determined under ligand-free (no stimulatory or inhibitory influences present), hormone-stimulated (isoproterenol, 10(-6) mmol/L), and maximal (cells stimulated with 10 mumol/L forskolin) conditions by measuring cyclic adenosine monophosphate (cAMP) levels by radioimmunoassay. The activity of adenylate cyclase was significantly different (p less than 0.01) in the three groups. Adipocytes from obese women had lower levels of cyclase activity under both ligand-free (5% vs 16% of maximal) and hormone-stimulated conditions (76% vs 100% of maximal) than adipocytes from normal women. Postobese women had levels of hormone-stimulated cAMP identical to those of normal women but still had abnormal ligand-free levels (under 5%). These results suggest the presence of an alteration in adipocyte adenylate cyclase regulation in morbidly obese women that is not entirely corrected when weight is lost after food intake is reduced by gastric stapling. This alteration in ligand-free cAMP activity may contribute to the development and maintenance of obesity.

The effect of empiric antiarrhythmic therapy with quinidine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), quinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p less than 0.05), and for sudden death was 69, 69 and 89% (p less than 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.

Predictors of chronic obstructive pulmonary disease (COPD) have been identified in the prospective epidemiologic study of the population of Tecumseh, Michigan. Risk of developing COPD within 10 yr can be estimated from a profile that includes as risk factors age, sex, cigarette smoking habits, and forced expiratory volume in one second (FEV1). The index of risk placed 63% of male incidence cases and 64% of female incidence cases in the top 10% of the risk distribution and 81% of male and 86% of female COPD cases in the top 20% of the risk distribution for Tecumseh. The validity of the Tecumseh index of risk for other populations was determined in a collaborative investigation of data collected in longitudinal epidemiologic studies in Baltimore, Boston, Framingham, Louisiana, Staveley, and Tucson. The extent to which the risk model fitted these data sets was assessed by comparing predicted (or expected) onsets of COPD in each population with observations made in each study. The predictors of COPD identified in Tecumseh were shown to be the most important risk factors in the other populations as well. The goodness-of-fit of the index was satisfactory overall. In all populations, a high risk score was associated with an increased incidence of COPD, thus confirming the predictive ability of the risk index. The Tecumseh index of risk provides a practical method for developing a risk profile from answers to standard questions and simple tests of lung function. Risks are greatest for heavy cigarette smokers with reduced lung function, lower in smokers who stop smoking or reduce their cigarette consumption, and lowest of all in nonsmokers with above average lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

Percentage distributions for variables in the Michigan Ambulatory Medical Care Survey (MAMCS), both for the Detroit Standard Metropolitan Statistical Area (SMSA) and the State as a whole, are compared with those from the National Ambulatory Medical Care Survey (NAMCS). The MAMCS data are a subset of the NAMCS data, since the MAMCS was carried out by augmenting the NAMCS in Michigan. Differences in the impact of survey results for the three areas are examined in the context of planning and developing ambulatory health care services. A specific application of survey data is examined, namely, its use in planning the Health Care Institute of Wayne State University and the Detroit Medical Center. The survey results for the three areas are similar enough to warrant the use of data from the national survey in the planning and evaluation of health services locally, although special studies of a few items such as X-ray usage may be needed. To reestablish local credibility for national results, or to detect changes in patterns which may develop, another Statelevel survey is suggested at the time of a census. Based on the experience with the MAMCS, augmentation of the NAMCS or other national surveys would be used in other States.