Zinc and multivitamin supplementation have contrasting effects on infant iron status: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: Zinc (Zn) supplementation adversely affects iron status in animal and adult human studies, but few trials have included young infants. The objective of this study was to determine the effects of Zn and multivitamin (MV) supplementation on infant hematologic and iron status. SUBJECTS/METHODS: In a double-blind RCT, Tanzanian infants were randomized to daily, oral Zn, MV, Zn and MV or placebo treatment arms at the age of 6 weeks of life. Hemoglobin concentration (Hb) and red blood cell indices were measured at baseline and at 6, 12 and 18 months of age. Plasma samples from 589 infants were examined for iron deficiency (ID) at 6 months. RESULTS: In logistic regression models, Zn treatment was associated with greater odds of ID (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.0-3.3)) and MV treatment was associated with lower odds (OR 0.49 (95% CI 0.3-0.9)). In Cox models, MV was associated with a 28% reduction in risk of severe anemia (hazard ratio (HR)=0.72 (95% CI 0.56-0.94)) and a 26% reduction in the risk of severe microcytic anemia (HR=0.74 (0.56-0.96)) through 18 months. No effects of Zn on risk of anemia were seen. Infants treated with MV alone had higher mean Hb (9.9 g/dl (95% CI 9.7-10.1)) than those given placebo (9.6 g/dl (9.4-9.8)) or Zn alone (9.6 g/dl (9.4-9.7)). CONCLUSIONS: MV treatment improved iron status in infancy, whereas Zn worsened iron status but without an associated increase in risk for anemia. Infants in long-term Zn supplementation programs at risk for ID may benefit from screening and/or the addition of a MV supplement.

Prospective cohort study comparing transient EUS guided elastography to EUS-FNA for the diagnosis of solid pancreatic mass lesions.

BACKGROUND: Semiquantitative EUS-elastography has been introduced to distinguish between malignant and benign pancreatic lesions. This study investigated whether semiquantitative EUS-guided transient real time elastography increases the diagnostic accuracy for solid pancreatic lesions compared to EUS-FNA. PATIENTS AND METHODS: This single centre prospective cohort study included all patients with solitary pancreatic lesions on EUS during one year. Patients underwent EUS-FNA and semiquantitative EUS-elastography during the same session. EUS and elastography results were compared with final diagnosis which was made on the basis of tissue samples and long-term outcome. RESULTS: 91 patients were recruited of which 68 had pancreatic malignancy, 17 showed benign disease and 6 had cystic lesions and were excluded from further analysis. Strain ratios from malignant lesions were significantly higher (24.00; 8.01-43.94 95% CI vs 44.00; 32.42-55.00 95% CI) and ROC analysis indicated optimal cut-off of 24.82 with resulting sensitivity, specificity and accuracy of 77%, 65% and 73% respectively. B-mode EUS and EUS-FNA had an accuracy for the correct diagnosis of malignant lesions of 87% and 85%. When lowering the cut-off strain ratio for elastography to 10 the sensitivity rose to 96% with specificity of 43% and accuracy of 84%, resulting in the least accurate EUS-based method. This was confirmed by pairwise comparison. CONCLUSION: Semiquantitative EUS-elastography does not add substantial value to the EUS-based assessment of solid pancreatic lesions when compared to B-mode imaging.

Cardiopulmonary exercise testing as a predictor of complications in oesophagogastric cancer surgery.

INTRODUCTION: An anaerobic threshold (AT) of <11 ml/min/kg can identify patients at high risk of cardiopulmonary complications after major surgery. The aim of this study was to assess the value of cardiopulmonary exercise testing (CPET) in predicting cardiopulmonary complications in high risk patients undergoing oesophagogastric cancer resection. METHODS: Between March 2008 and October 2010, 108 patients (83 men, 25 women) with a median age of 66 years (range: 38-84 years) underwent CPET before potentially curative resections for oesophagogastric cancers. Measured CPET variables included AT and maximum oxygen uptake at peak exercise (VO2 peak). Outcome measures were length of high dependency unit stay, length of hospital stay, unplanned intensive care unit (ICU) admission, and postoperative morbidity and mortality. RESULTS: The mean AT and VO2 peak were 10.8 ml/min/kg (standard deviation [SD]: 2.8 ml/min/kg, range: 4.6-19.3 ml/min/kg) and 15.2 ml/min/kg (SD: 5.3 ml/min/kg, range: 5.4-33.3 ml/min/kg) respectively; 57 patients (55%) had an AT of <11 ml/min/kg and 26 (12%) had an AT of <9 ml/min/kg. Postoperative complications occurred in 57 patients (29 cardiopulmonary [28%] and 28 non-cardiopulmonary [27%]). Four patients (4%) died in hospital and 21 (20%) required an unplanned ICU admission. Cardiopulmonary complications occurred in 42% of patients with an AT of <9 ml/min/kg compared with 29% of patients with an AT of ≥9 ml/min/kg but <11 ml/min/kg and 20% of patients with an AT of ≥11 ml/min/kg (p = 0.04). There was a trend that those with an AT of <11 ml/min/kg and a low VO2 peak had a higher rate of unplanned ICU admission. CONCLUSIONS: This study has shown a correlation between AT and the development of cardiopulmonary complications although the discriminatory ability was low.

Preliminary analysis of the cost-effectiveness of the National Bowel Cancer Screening Program: demonstrating the potential value of comprehensive real world data.

BACKGROUND/AIM: The complexity and cost of treating cancer patients is escalating rapidly and increasingly difficult decisions are being made regarding which interventions provide value for money. BioGrid Australia supports collection and analysis of comprehensive treatment and outcome data across multiple sites. Here, we use preliminary data regarding the National Bowel Cancer Screening Program (NBCSP) and stage-specific treatment costs for colorectal cancer (CRC) to demonstrate the potential value of real world data for cost-effectiveness analyses (CEA). METHODS: Data regarding the impact of NBCSP on stage at diagnosis were combined with stage-specific CRC treatment costs and existing literature. An incremental CEA was undertaken from a government healthcare perspective, comparing NBCSP with no screening. The 2008 invited population (n= 681,915) was modelled in both scenarios. Effectiveness was expressed as CRC-related life years saved (LYS). Costs and benefits were discounted at 3% per annum. RESULTS: Over the lifetime and relative to no screening, NBCSP was predicted to save 1265 life years, prevent 225 CRC cases and cost an additional $48.3 million, equivalent to a cost-effectiveness ratio of $38,217 per LYS. A scenario analysis assuming full participation improved this to $23,395. CONCLUSIONS: This preliminary CEA based largely on contemporary real world data suggests population-based faecal occult blood test screening for CRC is attractive. Planned ongoing data collection will enable repeated analyses over time, using the same methodology in the same patient populations, permitting an accurate analysis of the impact of new therapies and changing practice. Similar CEA using real world data related to other disease types and interventions appears desirable.

Long-term follow-up of endoscopic Histoacryl glue injection for the management of gastric variceal bleeding.

BACKGROUND: Variceal bleeding is an acute medical emergency with high mortality. Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding is more severe and more difficult to control. The optimal therapy for gastric variceal bleeding remains unclear although endoscopic injection of N-Butyl-2-Cyanoacrylate (Histoacryl) glue is often used. However, its long-term efficacy is poorly described. We studied the immediate and long-term effects of Histoacryl glue injection as treatment for bleeding gastric varices in a large UK hospital. METHOD: Endoscopy records and case notes were used to identify patients receiving Histoacryl injection for gastric variceal bleeding over a 4-year period. RESULTS: Thirty-one patients received Histoacryl for gastric variceal bleeding. Seventy-four per cent patients had alcohol-related liver disease and 61% of cirrhotics were Childs Pugh grade B or C. Fifty-eight per cent were actively bleeding during the procedure with 100% haemostasis rates achieved. Two patients developed pyrexia within 24 h of injection settling with antibiotics. No other complications were encountered. Mean overall follow-up was 35 months, with mean follow-up of survivors 57 months. Forty-eight per cent patients had endoscopic ultrasound assessment of varices during follow-up with no effect on rebleeding rates. Thirteen per cent required subsequent transjugular intrahepatic portosystemic shunt placement. Gastric variceal rebleeding rate was 10% at 1 year and 16% in total. One- and two-year mortality was 23% and 35%, respectively. CONCLUSION: Endoscopic injection of Histoacryl glue appears to be a safe and effective treatment for gastric variceal bleeding. Further data are required to compare it with other therapies in this situation.

An assessment of microbiological water quality of six water source categories in north-east Uganda.

Target 7C of the Millennium Development Goals is to "halve, by 2015, the proportion of people without sustainable access to safe drinking water and basic sanitation". However, the corresponding indicator measures the "proportion of population using an improved drinking water source". This raises the question of whether "safe" and "improved" can be used interchangeably. This paper tests this hypothesis by comparing microbiological water quality in 346 different water sources across the District of Amuria in Uganda to each other and to defined standards, including the WHO drinking water standard of zero TTC per 100 ml, and the Ugandan national standard of 50 TTC per 100 ml. The water sources were grouped into six different categories: boreholes, protected springs, covered hand dug wells, open hand dug wells, open water and roofwater harvesting. The paper concludes that the ranking from the highest to the lowest microbiological quality water was: boreholes, protected springs and roofwater harvesting, open and covered hand dug wells, open water. It also concludes that sanitary surveys cannot be used to predict water quality precisely; however they are an essential component of the monitoring of safe water supplies.

Ex vivo delineation of placental angioarchitecture with the microbubble contrast agent Levovist.

OBJECTIVE: The aim of this study was to delineate placental vasculature with the microbubble contrast agent Levovist (99.9% galactose and 0.1% palmitic acid; Schering AG, Berlin, Germany), with the ultimate goal of delineating placental vascular anatomy in utero. STUDY DESIGN: A placental lobule from each of 11 term human placentas was perfused on the fetal side of the circulation under physiologic conditions. Randomly assigned dose-concentration combinations of Levovist were administered through a chorionic artery into the corresponding placental lobule, and the resultant echoenhancement with power Doppler imaging was recorded for digital analysis. Interplacental variability was corrected for by averaging the results of three injections at each dose-concentration combination. RESULTS: Echoenhancement was seen at all dose-concentration combinations in the injected lobule but not in adjacent control lobules. The three dose-concentration combinations that achieved optimal maximal integrated intensity and duration of action for both chorionic vessel and villus enhancement were 100 microL/kg of 400-mg/mL Levovist, 200 microL/kg of 400-mg/mL Levovist, and 400 microL/kg of 200-mg/mL Levovist. CONCLUSION: Microbubble contrast injection into the fetal vasculature enabled power Doppler imaging echoenhancement both in chorionic vessels and within the villus tree. We speculate that fetal injection of contrast agent may be applied to the delineation of placental lesions or areas of interfetal transfusion, although its applicability will be hindered by the need for fetal blood sampling.

Is phase-specific, community-oriented treatment of early psychosis an economically viable method of improving outcome?

OBJECTIVE: The Early Psychosis Prevention and Intervention Centre (EPPIC) provides a comprehensive 'real-world' model of early intervention to young people experiencing an emerging psychotic disorder. A prospective study has already provided evidence of improved clinical outcome at 12 months after entry. The present study examined whether the service was also cost-effective. METHOD: A cost-effectiveness analysis compared EPPIC with its immediate precursor service, from the perspective of the government funding agency. Only direct costs were included. RESULTS: EPPIC proved to be more cost-effective. The weighted average cost per patient for the first 12 months was cheaper (by $AUD 7110 per patient), while treatment outcomes were superior. The savings were due to the marked reduction in in-patient costs outweighing substantial increases in the costs of community care. CONCLUSION: These results, while encouraging in terms of the further development of integrated, phase-specific intervention programmes for early psychosis, are not conclusive, and further research is required.

Risk factors for seizure-related motor vehicle crashes in patients with epilepsy.

OBJECTIVE: We identified clinical risk factors for seizure-related motor vehicle crashes in patients with epilepsy. BACKGROUND: Current US laws permit epilepsy patients with controlled seizures to drive. These laws attempt to balance the important economic and social value of driving with the risk to public safety from seizure-related crashes. Various clinical factors are considered in these laws, particularly the seizure-free interval. Driving restrictions range from 3 to 18 months, however, and studies have not established how these various seizure-free intervals and other clinical factors influence the risk for seizure-related motor vehicle crashes. METHODS: We performed a retrospective case-control study to determine the influence of clinical risk factors associated with seizure-related motor vehicle crashes. Both "case" and "control" patients had epilepsy, drove, and were from the same clinic, but the cases differed in having had seizure-related crashes. RESULTS: Fifty patients with epilepsy who crashed during seizures and 50 matched control patients were compared. Factors that significantly decreased the odds of patients with epilepsy having motor vehicle crashes due to seizures were: long seizure-free intervals, reliable auras, few prior nonseizure-related accidents, and having had their antiepileptic drugs (AEDs) reduced or switched. For example, patients who had seizure-free intervals > or = 12 months had a 93% reduced odds for crashing compared to patients with shorter intervals. Other findings were: 25% of patients had more than one seizure-related crash and 20% had missed an AED dose just prior to their crash. The majority (54%) of patients who crashed were driving illegally, with seizure-free intervals shorter than legally permitted. CONCLUSION: Seizure-free intervals, the presence of reliable auras, AED therapy modifications, and a history of nonseizure-induced crashes should be considered when counseling patients with epilepsy on driving and when formulating driving regulatory policy. Case control studies of crashes due to seizures can help in assessing and monitoring such risks.

Evaluation of a series of N-alkyl benzomorphans in cell lines expressing transfected delta- and mu-opioid receptors.

Transfection of individual opioid receptors in Chinese hamster ovary (CHO) cells provides a pure, homogeneous population of receptors for screening drug candidates, and an alternative to the use of selective ligands. To evaluate the potential of this system, we chose a series of (-)-5,9 alpha-dimethyl-2-hydroxy-N-substituted-6,7-benzomorphans, for which the receptor selectivity and in vivo activity had been characterized recently, and tested them in CHO cells stably transfected with either the rat delta-opioid receptor or the mouse mu-opioid receptor. [3H]Diprenorphine was used to measure opioid receptors in P2 membrane preparations. A Bmax of 7.58 +/- 0.8 pmol/mg protein and a Kd of 0.42 +/- 0.04 nM was obtained in the mu-opioid receptor expressing cell line used in these studies. In addition, [3H]naltrindole was used to confirm the delta-specificity of the cloned receptor. Both compounds gave a Bmax of 1.2 pmol/mg in the CHO cells expressing the rat delta-opioid receptor. Displacement assays were performed with eleven (-)-N-alkyl-benzomorphans in the absence and presence of 150 mM NaCl, as well as known delta- and mu-selective agonists. Sodium reduced agonist affinity in the transfected cell lines. The benzomorphan compounds displayed a range of affinities in the mu- and delta-opioid receptor expressing cell lines. Good correlations were found between their affinities at the cloned mu- and delta-opioid receptors and those in rat brain and monkey cortex (r2 from 0.73 to 0.89, P < 0.001). Comparative analysis of Ki values with in vivo potency in the mouse tail flick test indicated a high degree of correlation between antinociception and affinity in the mu-opioid receptor cell line (r2 = 0.83, p < 0.0001). Lesser correlations were found between antinociception in the mouse and affinity at the rat mu-opioid receptor (r2 = 0.6610) and at the monkey mu-opioid receptor (r2 = 0.695). In sum, these studies indicate that the cell lines expressing the cloned mu- and delta-opioid receptors are appropriate models for determining the binding affinities of this class of opioid compounds. The diminishing correlations found between species when comparing in vitro and in vivo activity suggest that caution should be taken when extrapolating binding data to pharmacological activity among species.

Performance Evaluation Tests for Environmental Research (PETER): evaluation of 114 measures.

The goal of the Performance Evaluation Tests for Environmental Research (PETER) Program was to identify a set of measures of human capabilities for use in the study of environmental and other time-course effects. 114 measures studied in the PETER Program were evaluated and categorized into four groups based upon task stability and task definition. The Recommended category contained 30 measures that clearly obtained total stabilization and had an acceptable level of reliability efficiency. The Acceptable-But-Redundant category contained 15 measures. The 37 measures in the Marginal category, which included an inordinate number of slope and other derived measures, usually had desirable features which were outweighed by faults. The 32 measures in the Unacceptable category had either differential instability or weak reliability efficiency. It is our opinion that the 30 measures in the Recommended category should be given first consideration for environmental research applications. Further, it is recommended that information pertaining to preexperimental practice requirements and stabilized reliabilities should be utilized in repeated-measures environmental studies.

Performance Evaluation Tests for Environmental Research (PETER): Moran and computer batteries.

This investigation was directed at evaluating nine cognitive ability tasks for repeated measures applications and inclusion in the Performance Evaluation Tests for Environmental Research (PETER) battery. In the first study, five tasks from the Moran Battery, which were adapted from the French kit of factor-referenced tests, were administered to 18 subjects daily for 13 workdays. In the second study, four tasks from the Carter and Sbisa Computer Generated Battery were administered daily to 17 subjects (12 in common with first study) for 15 workdays. Examination of the means, variances, and interday reliabilities, together with factor analysis of the cross-task correlations, led to the recommendation of four tasks. Tasks recommended for repeated measures applications were Vertical Addition, Perceptual Speed, Grammatical Reasoning, and Flexibility of Closure.

Visual search with color.

Three experiments were conducted to discover how rapidly people can find a particular target when they know the color of the target. The subjects searched for specific-colored three-digit numbers among other three-digit numbers on a circular display screen. Three factors had profound effects on search speed. Search time increased dramatically (and approximately linearly) as the number of display items of the target's color increased from one to all of the items on the display. Search time also increased with the number of items not of the target's color (background items), if the color of those background items was sufficiently similar to that of the target. If the color of those background items was dissimilar to that of the target, then the background items had no effect. An effect of patterned versus random placement of target-colored items was also demonstrated.

High-contrast sets of colors.

A method is presented for choosing high-contrast sets of colors for additive color mixers (e.g., CRT). The method is based on data about target-location performance of human observers and adapts the color sets to the gamut of the color processor in use. The method produces any specified number of colors spread as far from each other as possible in color space to maximize contrast. Applications of high-contrast sets of colors are indicated, illustrative results are presented and discussed, and variations of the method are suggested.

Color and conspicuousness.

The principle that things are easier to find if they contrast with their environment is expressed quantitatively. Two indices of conspicuousness, relative fixation rate and search time, are shown to be related to the color difference between the target and background objects. The color difference equations used are CIELAB, CIELUV, and the Judd modification of the index of fading. None of the equations is superior to the others. Furthermore, neither Judd's modification nor Semmelroth's adjustment accounts for effects of surround lightness. It is suggested that color difference be used as a tool for design and evaluation of visual displays, for construction of color codes to optimize search time, and as a generalization of chromatic contrast in psychophysical research.