Nutrient adequacy, dietary patterns and diet quality among children with and without intellectual disabilities.

BACKGROUND: Children with intellectual disabilities (ID) frequently have feeding problems, but there has been limited research on nutrient intake, dietary patterns and diet quality in this population. METHOD: Nutrient intakes, dietary patterns and the Healthy Eating Index were compared between 48 children with ID and 55 typically developing (TD) children aged 3-8 years who participated in the Children's Mealtime Study. Three-day food records that included two weekdays and one weekend day were used to assess dietary intake. Food intake was entered into the Nutrition Data System for Research for analysis of nutrient intake, dietary patterns and diet quality. Height and weight were measured to determine body mass index (BMI). The relation of dietary patterns to weight status was also assessed. RESULTS: Typically developing children and children with ID met the Estimated Average Requirement/Adequate Intake (EAR/AI) for most nutrients. However, a substantial number of children in both groups did not meet the EAR for vitamins E and D and calcium and the AI for vitamin K. Only one TD child met the AI for potassium. A small percentage of children in both groups did not meet the EAR for vitamin A and vitamin C, and in the ID group, a small percentage did not meet the EAR for vitamin B12 . Children in the ID group consumed, on average, fewer servings of vegetables than TD children (0.5 vs. 1.2, P < 0.001), but there was no significant difference in servings of fruit (0.8 vs. 1.1, respectively), fruit juice (less than a half serving in both groups), sugar-sweetened beverages (less than a half serving in both groups) or snacks (1.1 vs. 1.4, respectively) after adjusting for BMI z-score, parental education and race. We found a significant correlation between snack intake and BMI z-score among children with ID but not among TD children (r = 0.48, P < 0.0001 vs. r = 0.19, P = 0.16, respectively). The Healthy Eating Index indicated, on average, poor overall diet quality in both groups (58.2 in the ID group and 59.1 in the TD group). CONCLUSIONS: This study suggests that the diets of children with ID, as in TD children, need improvement. Targeting healthy eating in children with ID would improve diet quality and overall health.

Collaborative Evaluation of the Healthy Habits Program: An Effective Community Intervention to Improve Mobility and Cognition of Chinese Older Adults Living in the U.S.

OBJECTIVES: There is a growing demand to reduce ethnic health disparities. The Healthy Habits Program (HHP) was implemented to provide a community-based physical activity and education intervention for Chinese older adults living in Boston, Massachusetts. This study evaluated the HHP by assessing outcomes that are critical for maintaining independence of older persons. DESIGN, SETTING AND PARTICIPANTS: Quantitative evaluation was performed on 50 Chinese older adults enrolled in the HHP. The community members were trained in data collection and management. MEASUREMENTS: Cognition (Mini Mental State Examination (MMSE), Trail Making Test and Complex Walking Task), mobility (Short Physical Performance Battery (SPPB) and maximal gait speed), depressive symptoms (Patient Health Questionnaire-9), perceived disability (World Health Organization Disability Assessment 2.0), nutritional status (Mini Nutrition Assessment®), and strength (grip and leg strength) were assessed at baseline and at 6 months. All tests were translated into Chinese. RESULTS: Of the 50 participants (mean age 68.4 years; 68% female), 78% achieved the goal of performing exercise ≥3 times/week. After 6 months, clinically meaningful improvements were observed in mobility (mean SPPB score changed from 10.3 to 11.1 points; p=0.01) and cognition (mean MMSE score changed from 26.0 to 27.8 points; p=0.001). There were also statistically significant improvements in executive function, depressive symptoms and perceived disability (p<0.05). CONCLUSION: Culturally sensitive community interventions, such as the HHP, are effective for improving mobility and cognition of Chinese older adults. This reveals the potential of promoting successful aging in minority populations through community settings, and should be advocated to reduce ethnic health disparities in the U.S.

Application and a proposed modification of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Canadian cohort of patients with clinically isolated syndromes.

BACKGROUND: The 2005 and 2010 McDonald criteria utilize magnetic resonance imaging (MRI) to provide evidence of disease dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis (MS) in patients who have clinically isolated syndromes (CIS). METHODS: Data from 109 CIS patients not satisfying the 2005 criteria at entry into a randomized controlled minocycline trial were analyzed to determine the proportion who would have been diagnosed with MS at screening based on 2010 criteria. The impact of including symptomatic, as well as asymptomatic, MRI lesions to confirm DIT was also explored. RESULTS: Thirty percent (33/109) of patients, retrospectively, met the 2010 criteria for a diagnosis of MS at baseline. When both symptomatic and asymptomatic lesions were used to confirm DIT, three additional patients met the 2010 criteria. There was a significant 10.1% increase in the proportion of patients who met the 2010 DIS criteria, compared with the 2005 DIS criteria; however, two patients satisfied the 2005 DIS but not 2010 DIS criteria. CONCLUSION: Using 2010 McDonald criteria, 30% of the CIS patients could be diagnosed with MS using a single MRI scan. Inclusion of symptomatic lesions in the DIT criteria further increases this proportion to 33%.

Effects of intermittent hypoxia on erythropoietin, soluble erythropoietin receptor and ventilation in humans.

Erythropoietin (EPO) and soluble EPO receptors (sEPOR) have been proposed to play a central role in the ventilatory acclimatisation to continuous hypoxia in mice. In this study, we demonstrated for the first time in humans (n = 9) that sEPOR is downregulated upon daytime exposure to 4 days of intermittent hypoxia (IH; 6 h·day⁻¹, cycles of 2 min of hypoxia followed by 2 min of reoxygenation; peak end-tidal oxygen tension (P(ET,O2)) 88 Torr, nadir P(ET,O2)) 45 Torr), thereby allowing EPO concentration to rise. We also determined the strength of the association between these haematological adaptations and alterations in the acute hypoxic ventilatory response (AHVR). We observed a nadir in sEPOR on day 2 (-70%), concomitant with the peak in EPO concentration (+50%). Following exposure to IH, tidal volume (V(T)) increased, respiratory frequency remained unchanged, and minute ventilation (V'(E)) was increased. There was a negative correlation between EPO and sEPOR (r = -0.261; p = 0.05), and between sEPOR and V(T) (r = -0.331; p = 0.02). EPO was positively correlated with V'(E) (r = 0.458; p = 0.001). In conclusion, the downregulation of sEPOR by IH modulates the subsequent EPO response. Furthermore, the alterations in AHVR and breathing pattern following IH appear to be mediated, at least in part, by the increase in EPO.

Reliability of visual temporal thresholds.

BACKGROUND: Visual processing deficits involving temporal characteristics are typically not captured by the widely used outcome measures (i.e., Expanded Disability Status Scale, Multiple Sclerosis Functional Composite) in multiple sclerosis (MS). Visual temporal thresholds (i.e., measurements of the temporal aspects in visual processing) are typically significantly higher (i.e., prolonged) in MS patients when compared to controls. The test-retest reliability of these thresholds was examined in patients with MS. METHODS: Visual temporal thresholds were measured in 21 stable MS patients during two separate test sessions. Test-retest reliability and the standard error of measurement were calculated. The threshold of change in visual temporal thresholds in MS patients that would correspond to real change beyond measurement error with 95% certainty was also calculated. For comparisons, a control group (n = 10) was included. RESULTS: The test-retest reliability of this measure of visual temporal thresholds was 0.97. The threshold indicating change beyond chance or measurement error with 95% certainty was 11 ms. Higher thresholds were significantly correlated with longer durations of disease. CONCLUSIONS: This measure of visual temporal thresholds has excellent test-retest reliability and a change of greater than 11 ms is highly likely to represent real change in MS patients. The findings indicate that these measurements may provide useful clinical information about functional changes regarding the temporal aspects of the visual system, which is currently not captured by the Extended Disability Status Scale.

Acute ischemic lesions of varying ages predict risk of ischemic events in stroke/TIA patients.

BACKGROUND: Multiple ischemic lesions identified by diffusion-weighted imaging (DWI) have been shown to predict high risk of future ischemic events. However, the importance of lesion age has not been factored into this risk. Our goal was to evaluate whether the presence of ischemic lesions of varying ages identified by DWI and apparent diffusion coefficient (ADC) suggests a higher risk of future ischemic events. METHODS: Patients with acute stroke and TIA presenting within 12 hours of symptom onset who had a baseline and 1-month follow-up MRI were enrolled in the study. Acute ischemic lesions were divided into DWI positive with ADC low lesions and DWI positive with ADC normalized lesions. The baseline MRI and the presence of new lesions on the follow-up MRI were analyzed. RESULTS: A total of 360 patients were prospectively enrolled, and all had appropriate imaging. Two hundred twenty-three were excluded as there were no DWI lesions, they received recombinant tissue plasminogen activator, or they did not have the 30-day follow-up MRI. One hundred seventeen patients had DWI lesions of one age (DWI positive with either ADC low lesions or ADC normalized lesions alone) and 20 had lesions of varying ages (DWI positive lesions with reduced and normalized ADC) on the baseline MRI. Patients with multiple DWI lesions of varying ages were at more risk of having new lesions on the 30-day MRI compared with those having lesions of the same age (relative risk = 3.6; 95% CI 1.9 to 6.8). Multiple DWI lesions of varying ages (odds ratio [OR] 6.6; 95% CI 2.3 to 19.1) and cardioembolic stroke subtype (OR 3.2; 95% CI 1.1 to 8.7) were independently associated with new lesion recurrence by multiple logistic regression analysis. CONCLUSION: The presence of multiple diffusion-weighted imaging lesions of varying ages suggests very active early recurrence over time and portends a higher early risk of future ischemic events.

Duration and distance of exposure are important predictors of transmission among community contacts of Ontario SARS cases.

We report attack rates and contact-related predictors among community contacts of severe acute respiratory syndrome (SARS) cases from the 2003 Toronto-area outbreak. Community contact data was extracted from public health records for single, well-defined exposures to a SARS case. In total, 8662 community-acquired exposures resulted in 61 probable cases; a crude attack rate of 0.70% [95% confidence interval (CI) 0.54-0.90]. Persons aged 55-69 years were at higher risk of acquiring SARS (1.14%) than those either younger (0.60%) or older (0.70%). In multivariable analysis exposures for at least 30 min at a distance of

Identifying reliable change in tactile temporal thresholds in multiple sclerosis: test-retest reliability.

BACKGROUND: Tactile temporal thresholds are typically significantly higher (ie, prolonged) in multiple sclerosis (MS) patients when compared to controls and increase significantly during relapses, probably reflecting integrity of conduction across a portion of the corpus callosum. As part of an ongoing validation study of tactile temporal thresholds, the test-retest reliability of these thresholds was examined in patients with MS. METHODS: Tactile temporal thresholds were measured in 61 MS patients during two separate test sessions within three weeks. Test-retest reliability and the standard error of measurement were calculated. The threshold of change in tactile temporal thresholds in MS patients that would correspond to real change beyond measurement error with 95% certainty was also calculated. RESULTS: The test-retest reliability of this measure of tactile temporal thresholds was 0.93. The threshold indicating change beyond chance or measurement error with 95% certainty was 19 ms. CONCLUSIONS: This measure of tactile temporal thresholds has excellent test-retest reliability and a change of greater than 19 ms is highly likely to represent real change. This measure is promising as a precise, reliable outcome measure in MS.

Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging.

BACKGROUND AND OBJECTIVES: Controversy exists about the optimal imaging technique in acute stroke. It was hypothesised that CT is comparable with DWI, when both are read systematically using quantitative scoring. METHODS: Ischaemic stroke patients who had CT within six hours and DWI within seven hours of onset were included. Five readers used a quantitative scoring system (ASPECTS) to read the baseline (b) and follow up CT and DWI. Use of MRI in acute stroke was also assessed in patients treated with tissue plasminogen activator (tPA) by prospectively recording reasons for exclusion. Patients were followed clinically at three months. RESULTS: bDWI and bCT were available for 100 consecutive patients (admission median NIHSS = 9). The mean bDWI and bCT ASPECTS were positively related (p<0.001). The level of interrater agreement ranged from good to excellent across all modalities and time periods. Bland-Altman plots showed more variability between bCT and bDWI than at 24 hours. The difference between bCT and bDWI was < or =2 ASPECTS points. Of bCT scans with ASPECTS 8-10, 81% had DWI ASPECTS 8-10. Patients with bCT ASPECTS of 8-10 were 1.9 times more likely to have a favourable outcome at 90 days than those with a score of 0-7 (95% CI 1.1 to 3.1, p = 0.002). The relative likelihood of favourable outcome with a bDWI ASPECTS 8-10 was 1.4 (95% CI 1.0 to 1.9, p = 0.10). Of patients receiving tPA 45% had contraindications to urgent MRI. CONCLUSION: The differences between CT and DWI in visualising early infarction are small when using ASPECTS. CT is faster and more accessible than MRI, and therefore is the better neuroimaging modality for the treatment of acute stroke.

Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke.

BACKGROUND AND PURPOSE: Early studies showed that carotid endarterectomy (CEA) carried a high risk if performed within days after a large ischemic stroke. Therefore, many surgeons delay CEA for 4 to 6 weeks after any stroke. To determine the effect of delay to CEA on operative risk and benefit, we pooled data from the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial. METHODS: Risk of ipsilateral ischemic stroke in the medical group, operative risk of stroke and death, and overall benefit from surgery were determined in relation to the time from the last symptomatic event to randomization. Operative risk of stroke and death was also determined in relation to the time to surgery. Analyses were stratified by sex and type of presenting event. RESULTS: The 30-day perioperative risk of stroke and death was unrelated to the time since the last symptomatic event and was not increased in patients operated <2 weeks after nondisabling stroke. In contrast, the risk of ipsilateral ischemic stroke in the medical group fell rapidly with time since event (P<0.001), as did the absolute benefit from surgery (P=0.001). This decline in benefit with time was unrelated to the type of presenting event but was more pronounced in women than men (difference P<0.001). Benefit in women was confined to those randomized <2 weeks after their last event, irrespective of severity of stenosis. CONCLUSIONS: CEA can be performed safely within 2 weeks of nondisabling ischemic stroke. Benefit from endarterectomy declines rapidly with increasing delay, particularly in women.

Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery.

BACKGROUND: Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery. METHODS: We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups. RESULTS: 5893 patients with 33000 patient-years of follow-up were analysed. Sex (p=0.003), age (p=0.03), and time from the last symptomatic event to randomisation (p=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials. INTERPRETATION: Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.

Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis.

BACKGROUND: Endarterectomy reduces risk of stroke in certain patients with recently symptomatic internal carotid stenosis. However, investigators have made different recommendations about the degree of stenosis above which surgery is effective, partly because of differences between trials in the methods of measurement of stenosis. To accurately assess the overall effect of surgery, and to increase power for secondary analyses, we pooled trial data and reassessed carotid angiograms. METHODS: We pooled data from the European Carotid Surgery Trial (ECST), North American Symptomatic Carotid Endarterectomy Trial, and Veterans Affairs trial 309 from the original electronic data files. Outcome events were re-defined, if necessary, to achieve comparability. Pre-randomisation carotid angiograms from ECST were re-measured by the method used in the other two trials. RESULTS: Risks of main outcomes in both treatment groups and effects of surgery did not differ between trials. Data for 6092 patients, with 35000 patient-years of follow-up, were therefore pooled. Surgery increased the 5-year risk of ipsilateral ischaemic stroke in patients with less than 30% stenosis (n=1746, absolute risk reduction -2.2%, p=0.05), had no effect in patients with 30-49% stenosis (1429, 3.2%, p=0.6), was of marginal benefit in those with 50-69% stenosis (1549, 4.6%, p=0.04), and was highly beneficial in those with 70% stenosis or greater without near-occlusion (1095, 16.0%, p<0.001). There was a trend towards benefit from surgery in patients with near-occlusion at 2 years' follow-up (262, 5.6%, p=0.19), but no benefit at 5 years (-1.7%, p=0.9). INTERPRETATION: Re-analysis of the trials with the same measurements and definitions yielded highly consistent results. Surgery is of some benefit for patients with 50-69% symptomatic stenosis, and highly beneficial for those with 70% symptomatic stenosis or greater but without near-occlusion. Benefit in patients with carotid near-occlusion is marginal in the short-term and uncertain in the long-term.

Occurrence of hemispheric and retinal ischemia in atrial fibrillation compared with carotid stenosis.

BACKGROUND AND PURPOSE: The goal of this study was to examine the hypotheses that retinal ischemia is caused more often by carotid atherosclerosis than by atrial fibrillation and that the odds of retinal events compared with hemispheric events increase with worsening carotid stenosis. METHODS: We used data from the Stroke Prevention in Atrial Fibrillation (SPAF) I through III trials and North American Symptomatic Carotid Endarterectomy Trial (NASCET), calculating hemispheric:retinal (H:R) odds for the territory of ischemic events during follow-up in patients with atrial fibrillation and medically treated 50% to 99% carotid stenosis or occlusion in the respective trials. RESULTS: The H:R odds were 25:1 in the SPAF aspirin-assigned patients and 2:1 for NASCET vessels. In NASCET patients, the H:R odds of recurrent ischemic events were 1:4 for vessels randomized initially for retinal symptoms compared with 6:1 for those randomized for hemispheric events (significant difference; P<0.001). Moreover, the H:R odds of first events in the territory of the contralateral asymptomatic artery were 1:1 if the randomized vessel had retinal symptoms compared with 4:1 if the randomized vessel had hemispheric symptoms (significant difference; P<0.01). Increasing carotid stenosis in the 50% to 99% range had no effect on H:R odds (P=0.8). CONCLUSIONS: These findings confirm that retinal symptoms are more typical of carotid stenosis. Hemodynamic effects do not appear to be more important in the pathogenesis of retinal events than hemispheric ones in carotid stenosis. The retinal versus hemispheric location of initial symptoms is strongly predictive of the location of subsequent events in patients with carotid stenosis, even when new symptoms are contralateral to the original ones.

Clinically important change in quality of life in epilepsy.

BACKGROUND: Health related quality of life (HRQOL) is increasingly recognised as an important outcome in epilepsy. However, interpretation of HRQOL data is difficult because there is no agreement on what constitutes a clinically important change in the scores of the various instruments. OBJECTIVES: To determine the minimum clinically important change, and small, medium, and large changes, in broadly used epilepsy specific and generic HRQOL instruments. METHODS: Patients with difficult to control focal epilepsy (n = 136) completed the QOLIE-89, QOLIE-31, SF-36, and HUI-III questionnaires twice, six months apart. Patient centred estimates of minimum important change, and of small, medium, and large change, were assessed on self administered 15 point global rating scales. Using regression analysis, the change in each HRQOL instrument that corresponded to the various categories of change determined by patients was obtained. The results were validated in a subgroup of patients tested at baseline and at nine months. RESULTS: The minimum important change was 10.1 for QOLIE-89, 11.8 for QOLIE-31, 4.6 for SF-36 MCS, 3.0 for SF-36 physical composite score, and 0.15 for HUI-III. All instruments differentiated between no change and minimum important change with precision, and QOLIE-89 and QOLIE-31 also distinguished accurately between minimum important change and medium or large change. Baseline HRQOL scores and the type of treatment (surgical or medical) had no impact on any of the estimates, and the results were replicated in the validation sample. CONCLUSIONS: These estimates of minimum important change, and small, medium, and large changes, in four HRQOL instruments in patients with epilepsy are robust and can distinguish accurately among different levels of change. The estimates allow for categorisation of patients into various levels of change in HRQOL, and will be of use in assessing the effect of interventions in individual patients.

Prognosis after transient monocular blindness associated with carotid-artery stenosis.

BACKGROUND: Transient monocular blindness associated with internal-carotid-artery stenosis is a risk factor for stroke. The effect of carotid endarterectomy in patients who present with transient monocular blindness has not been determined. METHODS: We compared the risk of stroke among patients presenting with transient monocular blindness with the risk among patients presenting with hemispheric transient ischemic attack. The effect of endarterectomy was assessed in patients with transient monocular blindness. The analyses were based on data from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: A total of 198 medically treated patients with transient monocular blindness had a three-year risk of ipsilateral stroke that was approximately half of that among 417 medically treated patients with hemispheric transient ischemic attack (adjusted hazard ratio, 0.53; 95 percent confidence interval, 0.30 to 0.94). Six factors were associated with a higher risk of stroke in patients with monocular blindness--an age of 75 years or more, male sex, a history of hemispheric transient ischemic attack or stroke, a history of intermittent claudication, stenosis of 80 to 94 percent of the luminal diameter, and the absence of collateral circulation. The three-year risk of stroke with medical treatment for patients with zero or one risk factor was 1.8 percent, with two risk factors 12.3 percent, and with three or more risk factors 24.2 percent (P=0.003). The three-year absolute reduction in the risk of stroke associated with endarterectomy was -2.2 percent (i.e., a 2.2 percent increase in risk) among patients with zero or one risk factor, 4.9 percent among those with two risk factors, and 14.3 percent among those with three or more risk factors (P=0.23 by a test for interaction). CONCLUSIONS: Among patients with internal-carotidartery stenosis, the prognosis was better for those presenting with transient monocular blindness than for those presenting with hemispheric transient ischemic attack. Among patients with transient monocular blindness, carotid endarterectomy may be beneficial when other risk factors for stroke are also present.

A randomized, controlled trial of surgery for temporal-lobe epilepsy.

BACKGROUND: Randomized trials of surgery for epilepsy have not been conducted, because of the difficulties involved in designing and implementing feasible studies. The lack of data supporting the therapeutic usefulness of surgery precludes making strong recommendations for patients with epilepsy. We conducted a randomized, controlled trial to assess the efficacy and safety of surgery for temporal-lobe epilepsy. METHODS: Eighty patients with temporal-lobe epilepsy were randomly assigned to surgery (40 patients) or treatment with antiepileptic drugs for one year (40 patients). Optimal medical therapy and primary outcomes were assessed by epileptologists who were unaware of the patients' treatment assignments. The primary outcome was freedom from seizures that impair awareness of self and surroundings. Secondary outcomes were the frequency and severity of seizures, the quality of life, disability, and death. RESULTS: At one year, the cumulative proportion of patients who were free of seizures impairing awareness was 58 percent in the surgical group and 8 percent in the medical group (P<0.001). The patients in the surgical group had fewer seizures impairing awareness and a significantly better quality of life (P<0.001 for both comparisons) than the patients in the medical group. Four patients (10 percent) had adverse effects of surgery. One patient in the medical group died. CONCLUSIONS: In temporal-lobe epilepsy, surgery is superior to prolonged medical therapy. Randomized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects.

A general goodness-of-fit approach for inference procedures concerning the kappa statistic.

The kappa statistic is frequently used as a measure of agreement among two or more raters. Although considerable research on statistical inferences for this statistic has been published for the case of two raters and a binary outcome, relatively little work has appeared on inference problems for the case of multiple raters and/or polytomous nominal outcome categories. In this paper we propose a new procedure for constructing inferences for the kappa statistic that may be applied to this general case. The procedure is based on a chi-square goodness-of-fit test as applied to the Dirichlet multinomial model, and is a natural extension of previously proposed procedures that apply to more restricted cases. A simulation study shows that the new procedure provides confidence interval coverage levels and type I error rates close to nominal over a wide range of parameter combinations. We also present a sample size formula which may be used to determine the required number of subjects and raters for a given number of outcome categories.