Understanding between-cluster variation in prevalence, and limits for how much variation is plausible

In clinical trials and observational studies of clustered binary data, understanding between-cluster variation is essential: in sample size and power calculations of cluster randomised trials, for example, the intra-cluster correlation coefficient is often specified. However, quantifications of between-cluster variation can be unintuitive, and an intra-cluster correlation coefficient as low as 0.04 may correspond to surprisingly large between-cluster differences. We suggest that understanding is improved through visualising the implied distribution of true cluster prevalences – possibly by assuming they follow a beta distribution – or by calculating their standard deviation, which is more readily interpretable than the intra-cluster correlation coefficient. Even so, the bounded nature of binary data complicates the interpretation of variances as primary measures of uncertainty, and entropy offers an attractive alternative. Appealing to maximum entropy theory, we propose the following rule of thumb: that plausible intra-cluster correlation coefficients and standard deviations of true cluster prevalences are both bounded above by the overall prevalence, its complement, and one third. We also provide corresponding bounds for the coefficient of variation, and for a different standard deviation and intra-cluster correlation defined on the log odds scale. Using previously published data, we observe the quantities defined on the log odds scale to be more transportable between studies with different outcomes with different prevalences than the intra-cluster correlation and coefficient of variation. The latter increase and decrease, respectively, as prevalence increases from 0% to 50%, and the same is true for our bounds. Our work will help clinical trialists better understand between-cluster variation and avoid specifying implausibly high values for the intra-cluster correlation in sample size and power calculations

Cytokinin oxidase activity from Phaseolus vulgaris L. cv. Great Northern callus tissues

Cytokinin oxidase activity in callus tissues of Phaseolus vulgaris L. cv. Great Northern has been examined using an assay based on the oxidation of radioactively labeled N⁶ -(Δ² -isopentenyl) adenine (i⁶Ade) to adenine (Ade). Conditions for the quantitative extraction and assay of the enzyme have been established. The substrate specificity of the enzyme appears similar to that reported for cytokinin oxidase preparations from other plant sources. Solutions of exogenous cytokinins applied directly to the surface of Great Northern callus tissues induced relatively rapid (in less than an hour) increases in cytokinin oxidase activity. The cytokinin-induced increase in cytokinin oxidase activity appears to require RNA and protein synthesis. All cytokinin-active compounds tested, including substrates and non-substrates of cytokinin oxidase, were effective in inducing elevated levels of the enzyme in Great Northern callus tissue. The cytokininactive urea derivative, Thidiazuron, was as effective as any adenine derivative in inducing this response. The addition of Cu⁺² to cytokinin oxidase assay mixtures containing imidazole buffer enhanced the in vitro activity of the enzyme more than 20-fold. The effect was enzyme dependent and specific for copper and the cytokinin oxidase catalyzed reaction. In the presence of copper and imidazole, the degradation of i⁶Ade to Ade catalyzed by cytokinin oxidase was observed to proceed under anaerobic conditions. This result suggests that the copper-imidazole complex is substituting for oxygen as an electron accepter in the cytokinin oxidase reaction. The chromatographic properties of the cytokinin oxidase activity have also been investigated. Most of the cytokinin oxidase activity extracted from callus tissues bound to concanavalin A-Sepharose 4B and was specifically eluted with methyl-mannose. This result suggests that the enzyme is a glycoprotein. DEAE-cellulose chromatography resolved the cytokinin oxidase activity into two peaks. The major fraction, which comprised 85% to 90% of the cytokinin oxidase activity extracted from the callus tissues, bound to concanavalin A-Sepharose 4B. The minor peak of cytokinin oxidase activity did not. These results provide evidence for the presence of multiple forms of cytokinin oxidase, but the possibility of artifacts generated during enzyme preparation cannot yet be excluded

Iron status is inversely associated with dietary iron intakes in patients with inactive or mildly active inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) frequently appear iron deplete but whether this is a reflection of dietary iron intakes is not known. METHODS: Dietary data were collected from 29 patients with inactive or mildly-active IBD and 28 healthy controls using a validated food frequency questionnaire that measured intakes of iron and its absorption modifiers. Non-haem iron availability was estimated using a recently developed algorithm. Subjects were classified for iron status based upon data from a concomitant and separately published study of iron absorption. Absorption was used to define iron status because haematological parameters are flawed in assessing iron status in inflammatory conditions such as IBD. RESULTS: Dietary intakes of total iron, non-haem iron and vitamin C were significantly greater in IBD patients who were iron replete compared to those who were iron deplete (by 48%, 48% and 94% respectively; p≤0.05). The predicted percentage of available non-haem iron did not differ between these groups (19.7 ± 2.0% vs 19.3 ± 2.0% respectively; p=0.25). However, because of the difference in iron intake, the overall amount of absorbed iron did (2.4 ± 0.8 mg/d vs 1.7 ± 0.5 mg/d; p=0.013). No such differences were observed in the healthy control subjects. CONCLUSIONS: In IBD, iron status is more closely related to the quality and quantity of dietary iron intake than in the general healthy population.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Dietary fortificant iron intake is negatively associated with quality of life in patients with mildly active inflammatory bowel disease.

BACKGROUND: Iron deficiency anaemia and oral iron supplementation have been associated negatively with quality of life, and with adverse effects, respectively, in subjects with inflammatory bowel disease (IBD). Hence, the risk-benefit ratio of oral iron is not understood in this patient group. The present case-control study investigated whether dietary iron intake impacts on quality of life in IBD patients. METHODS: Quality of life, habitual dietary iron intakes and iron requirements were assessed in 29 patients with inactive or mildly active IBD as well as in 28 healthy control subjects. RESULTS: As expected, quality of life was worse in IBD patients as a whole in comparison to healthy controls according to EuroQol score and EuroQol VAS percentage (6.9 ± 1.6 vs 5.3 ± 0.6; p< 0.0001 and 77 ± 14% vs 88 ± 12%; p=0.004 respectively). For IBD subjects, 21/29 were iron deplete based upon serum iron responses to oral iron but, overall, were non-anaemic with mean haemoglobin of 13.3 ± 1.5 g/dL, and there was no difference in their quality of life compared to 8/29 iron replete subjects (Hb 14.0 ± 0.8 g/dL). Interestingly, total dietary iron intake was significantly negatively associated with quality of life in IBD patients, specifically for non-haem iron and, more specifically, for fortificant iron. Moreover, for total non-haem iron the negative association disappeared when fortificant iron values were subtracted. Finally, further sub-analysis indicated that the negative association between (fortificant) dietary iron intake and quality of life in IBD patients is driven by findings in patients with mildly active disease rather than in patients with quiescent disease. CONCLUSIONS: Iron deficiency per se (i.e. without concomitant anaemia) does not appear to further affect quality of life in IBD patients with inactive or mildly active disease. However, in this preliminary study, dietary iron intake, particularly fortificant iron, appears to be significantly negatively associated with quality of life in patients with mildly active disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The reliability of assigning individuals to cognitive states using the Mini Mental-State Examination: a population-based prospective cohort study.

BACKGROUND: Previous investigations of test re-test reliability of the Mini-Mental State Examination (MMSE) have used correlations and statistics such as Cronbach's α to assess consistency. In practice, the MMSE is usually used to group individuals into cognitive states. The reliability of this grouping (state based approach) has not been fully explored. METHODS: MMSE data were collected on a subset of 2,275 older participants (≥ 65 years) from the population-based Medical Research Council Cognitive Function and Ageing Study. Two measurements taken approximately two months apart were used to investigate three state-based categorisations. Descriptive statistics were used to determine how many people remained in the same cognitive group or went up or down groups. Weighted logistic regression was used to identify predictive characteristics of those who moved group. RESULTS: The proportion of people who remained in the same MMSE group at screen and follow-up assessment ranged from 58% to 78%. The proportion of individuals who went up one or more groups was roughly equal to the proportion that went down one or more groups; most of the change occurred when measurements were close to the cut-points. There was no consistently significant predictor for changing cognitive group. CONCLUSION: A state-based approach to analysing the reliability of the MMSE provided similar results to correlation analyses. State-based models of cognitive change or individual trajectory models using raw scores need multiple waves to help overcome natural variation in MMSE scores and to help identify true cognitive change.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The comparative cost of food and beverages at remote Indigenous communities, Northern Territory, Australia

OBJECTIVE: To determine the average price difference between foods and beverages in remote Indigenous community stores and capital city supermarkets and explore differences across products. METHODS: A cross-sectional survey compared prices derived from point-of-sale data in 20 remote Northern Territory stores with supermarkets in capital cities of the Northern Territory and South Australia for groceries commonly purchased in remote stores. Average price differences for products, supply categories and food groups were examined. RESULTS: The 443 products examined represented 63% of food and beverage expenditure in remote stores. Remote products were, on average, 60% and 68% more expensive than advertised prices for Darwin and Adelaide supermarkets, respectively. The average price difference for fresh products was half that of packaged groceries for Darwin supermarkets and more than 50% for food groups that contributed most to purchasing. CONCLUSIONS: Strategies employed by manufacturers and supermarkets, such as promotional pricing, and supermarkets\u27 generic products lead to lower prices. These opportunities are not equally available to remote customers and are a major driver of price disparity. IMPLICATIONS: Food affordability for already disadvantaged residents of remote communities could be improved by policies targeted at manufacturers, wholesalers and/or major supermarket chains

Clostridium difficile Infection and Proton Pump Inhibitor Use in Hospitalized Pediatric Cystic Fibrosis Patients

Children with cystic fibrosis (CF) often take proton pump inhibitors (PPIs), which helps improve efficacy of fat absorption with pancreatic enzyme replacement therapy. However, PPI use is known to be associated with Clostridium difficile-(C. diff-) associated diarrhea (CDAD). We retrospectively evaluated the incidence of C. diff infection from all pediatric hospital admissions over a 5-year period at a single tertiary children's hospital. We found significantly more C. diff-positive stool tests in hospitalized patients with CF compared to patients with no diagnosis of CF. However, use of a PPI was not associated with an increased risk of CDAD in hospitalized CF patients. In summary, C. diff infection is more common in hospitalized pediatric CF patients although PPI use may not be a risk factor for CDAD development in this patient population