The acute toxicity of water hemlock (Cicuta douglasii) in a goat model.

Water hemlock (Cicuta douglasii) is one of the most toxic plants to livestock and humans. Little is known regarding the amount of plant required to cause death. The objective of this study was to determine a lethal dose of water hemlock in a goat model. Plants were dosed to goats via oral gavage of freeze-dried ground plant material. The results from this study suggest that 1-2 fresh tubers would be lethal to goats.

Technical note: A comparison of alkali treatment methods to improve neutral detergent fiber digestibility of corn stover.

The objective of this study was to compare neutral detergent fiber (NDF) digestibility of corn stover that had been treated by 2 alkali treatment methods. Two experiments were conducted to test a sodium hydroxide (NaOH) treatment method that uses an ethanol/water co-solvent (NaOH/ethanol-H2O, United States Patent No. 20140220228) and a calcium hydroxide (CaOH) treatment method, which uses water as a solvent (CaOH/H2O). An in situ trial was conducted to compare NDF digestion kinetics between NaOH/ethanol-H2O-treated stover, CaOH/H2O-treated stover, untreated corn stover, and soy hulls. The digestion rate of potentially digestible NDF (kd) of NaOH/ethanol-H2O-treated corn stover (5.36%/h) was higher than CaOH/H2O-treated stover (2.27%/h), or untreated corn stover (1.76%/h) and similar to the kd of soy hulls (4.93%/h). The indigestible NDF (iNDF) fraction of untreated corn stover (35.1% of NDF) was reduced by CaOH/H2O treatment (27.3% of NDF) and by NaOH/ethanol-H2O treatment (2.8% of NDF). The iNDF fraction in soy hulls (3.6% of NDF) was similar to iNDF of NaOH/ethanol-H2O-treated stover. An in vivo digestibility trial was also conducted to compare fiber digestibility of diets supplemented with untreated corn stover, NaOH/ethanol-H2O-treated corn stover, or soy hulls. Total-tract apparent dry matter (DM) and NDF digestibility were measured with 8 lactating Holstein cows in a replicated 4 × 4 Latin square with four 21-d periods. Apparent DM digestibility (DMD) was improved when supplemental soy hulls were added to the base diet (60.0% DMD) compared with the base diet with no supplemental fiber (57.7% DMD). Apparent DM digestibility was reduced when diets were supplemented with untreated stover (52.4%). Dry matter digestibility of NaOH/ethanol-H2O-treated stover was similar (54.8% DMD) to all other treatments. Digestibility of NDF was lowest when cows were fed the diet with supplemented untreated stover (35.5% of NDF), and improved when soy hulls (40.6% of NDF) or NaOH/ethanol-H2O-treated stover (43.8% of NDF) were added to the diets. The NaOH/ethanol-H2O treatment process improves the DM and NDF digestibility of corn stover to values similar to those of soy hulls.

Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves.

Commercially available colostrum replacers (CR) are commonly used when maternal colostrum (MC) is unavailable, for managerial convenience, to ensure quality consistency at first feeding, or in disease control and eradication programs. The objective of this study was to determine the efficacy of feeding First Day Formula (Accelerated Genetics, Baraboo, WI) CR versus pooled MC on immunological status, growth, and health of preweaned dairy calves. A total of 1,220 Jersey and Jersey × Holstein calves born on a California Central Valley dairy farm were assigned after birth to receive either CR or MC following a systematic allocation procedure. Calves assigned to MC were tube fed 2.8 L of MC, and calves assigned to CR were tube fed a total of 500 g of CR (150 g of immunoglobulin G; IgG) mixed into 1.9 L of water at 1 h ± 5 min after the calf was born. A subset of calves was selected for passive transfer (n = 592) and growth (n = 268) analyses. Although both coliform count and total bacteria count were low for MC and CR fed to calves during the study, the predicted probability of calves receiving contaminated liquid feed (coliform count >10,000 cfu/mL) at first feeding was reduced for calves fed CR (1.5%) compared with calves fed MC (6.1%). The mean blood concentration of IgG was lower for calves fed CR than for calves fed MC (19.6 vs. 23.4 mg/mL). However, the apparent efficiency of absorption of IgG did not differ between treatments (34.4 and 35.9% for CR and MC, respectively). Total proteins were lower in calves fed CR compared with MC at 24 h (5.16 vs. 5.84 g/dL, respectively). Calves fed CR were 1.5 kg lighter at weaning and gained 0.03 kg less per day (0.30 vs. 0.33 kg/d, respectively) than calves fed MC before weaning. Height at weaning did not differ between the 2 treatment groups. Calves fed CR tended to have a higher predicted probability of not being treated for diarrhea than calves fed MC (0.142 vs. 0.110, respectively). However, when the disease was present, CR had a higher number of treatment days compared with MC (11.6 vs. 10.8 d, respectively). The hazard ratio of dying did not differ between MC and CR; however, CR calves had a numerically higher risk (hazard ratio = 1.347) of dying compared with calves that received MC. In conclusion, IgG absorption and serum concentration of calves were adequate when calves were fed either CR or MC. The CR-fed calves had a lower probability of receiving contaminated liquid feed and performed similar in terms of health compared with calves receiving high-quality MC, although they were slightly lighter at weaning. Therefore, the CR evaluated in this study is a valid alternative to high-quality (>50 mg of IgG/mL) MC.

The effects of calcium hydroxide-treated whole-plant and fractionated corn silage on intake, digestion, and lactation performance in dairy cows.

The objective of this trial was to evaluate, in dairy cattle, the effects of calcium hydroxide treatment of whole-plant corn and a treatment applied to the bottom stalk fraction of the corn plant, achieved by harvesting corn in 2 crop streams. The treatments were calcium hydroxide-treated corn silage (TRTCS), toplage supplemented with calcium hydroxide-treated stalklage (TPL), a positive control of brown midrib corn silage (BMR), and a negative control of conventional whole-plant corn silage (WPCS). The toplage was harvested at a height of 82 cm with 2 of the 6 rows set as ear-snapping to incorporate higher tissues into the stalklage. Stalklage was harvested at 12 cm, and other corn silages were harvested at 27 cm. Sixteen pens, each with 8 Holstein cows averaging 70±25 d in milk and 46±11 kg of milk d(-1), were assigned 4 per treatment in a completely randomized design. The diet was approximately 40% corn silage, 20% alfalfa silage, and 40% concentrate on a dry matter basis. A 2-wk covariate period with conventional corn silage was followed by an 8-wk treatment period in which the 4 corn silage treatments were the only effective difference in diets. Cows fed TPL and TRTCS consumed more (1.9 and 1.4 kg of organic matter d(-1), respectively) than did cows fed WPCS. Milk yield was greater for cows fed BMR, TPL, and TRTCS. Cows fed BMR and TPL produced 2.9 and 2.7 kg d(-1), respectively, more energy-corrected milk (ECM) than cows fed WPCS, and cows fed TRTCS had the greatest ECM production (4.8 kg of ECM d(-1) greater than cows fed WPCS). No differences in body weight or body condition scored were observed. Milk fat concentration was similar among treatments and milk protein concentration was reduced for TRTCS. Starch and neutral detergent fiber digestibility were greater for cows fed TRTCS.

Selenium in commercial beer and losses in the brewing process from wheat to beer.

There is increasing interest in enhancing the micronutrient composition of cereals through fertilization. The aims of this study were (1) to determine the Se concentration of commercial beers retailing in the UK, and (2) to test if the transfer of Se, from biofortified grain to final beer product, is <10% under UK cultivation conditions, as seen previously under Mediterranean conditions. The Se concentration of 128 commercial beers was measured, using inductively coupled plasma-mass spectrometry (ICP-MS). The selenium content of commercial beers varied 6.5-fold, with beers originating from America having higher Se concentrations than those from Europe. Laboratory-scale brewing trials with isotopically-enriched (77)Se wheat, sampled from UK field-sites, showed that most (77)Se losses in the brewing process occurred during mashing (54%), with fermented beer containing ∼ 10% of the (77)Se initially present in the wheat grain. Total N values in wort and malt were positively correlated with the (77)Se content of the wheat grain.

Economic impact from unrestricted spread of potato cyst nematodes in australia.

ABSTRACT Potato cyst nematodes (PCN) (Globodera spp.) are quarantine pests with serious potential economic consequences. Recent new detections in Australia, Canada, and the United States have focussed attention on the consequences of spread and economic justifications for alternative responses. Here, a full assessment of the economic impact of PCN spread from a small initial incursion is presented. Models linking spread, population growth, and economic impact are combined to estimate costs of spread without restriction in Australia. Because the characteristics of the Australian PCN populations are currently unknown, the known ranges of parameters were used to obtain cost scenarios, an approach which makes the model predictions applicable generally. Our analysis indicates that mean annual costs associated with spread of PCN would increase rapidly initially, associated with increased testing. Costs would then increase more slowly to peak at over AUD$20 million per year approximately 10 years into the future. Afterward, this annual cost would decrease slightly due to discounting factors. Mean annual costs over 20 years were $18.7 million, with a 90% confidence interval between AUD$11.9 million and AUD$27.0 million. Thus, cumulative losses to Australian agriculture over 20 years may exceed $370 million without action to prevent spread of PCN and entry to new areas.

Investigation of the susceptibility of various strains of mice to methyllycaconitine toxicosis.

Although the mechanism of action for larkspur alkaloids has been described, little information is available on the variation of the physiological response of individual animals to larkspur alkaloids. Anecdotal observations and pilot studies in cattle indicate that there is animal-to-animal variation in response to a debilitating dose of larkspur alkaloids. The objective of this study was to determine whether there is variation in susceptibility of different strains of mice to larkspur alkaloid toxicosis and to identify factors responsible for the variation that could then be used as a model for studies in cattle. The acute toxicity of methyllycaconitine (MLA) in 9 different inbred strains of mice was compared. The rank order, from most to least susceptible, was A/J>B10>FVB>BALB/c>C57Bl/6>NZW>C3H>DBA>129. The calculated LD(50) ranged from 3.3+/-0.2 to 5.8+/-0.8 mg/kg of BW. The toxicokinetic profiles of MLA in the susceptible A/J strain and the more resistant 129 strain were compared to determine whether their differences in susceptibility were due to differences in their ability to eliminate MLA. The differences in toxicokinetic variables observed did not explain the differences in susceptibility. The protein expression of various nicotinic acetylcholine receptor (nAChR) subunits was also compared between the more resistant 129 strain and the susceptible A/J strain. The 129 strain of mice had twice the amount of alpha7 nAChR subunit expression as the A/J strain, which was in direct proportion to the approximately 2-fold difference in LD(50). There was also a significant difference (P<0.05) in expression of the alpha3 and alpha5 nAChR subunits between the 129 and A/J strains, with the 129 strain having a greater expression in each case. These data suggest that the increased susceptibility of the A/J mice could be due to a reduced expression of nAChR subunits. Similar analyses need to be made in cattle to determine whether there is a difference between breeds in susceptibility to larkspur poisoning and to identify the factors that regulate their susceptibility to larkspur poisoning. This information would be useful for livestock producers in their breeding, culling, and grazing management programs to reduce or prevent larkspur poisoning on rangelands.

Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever.

BACKGROUND: It has been hypothesized that early-life exposure to vaccinations, infections or antibacterials influence allergic disease development. Concurrent exposure to grass pollens may alter any effect. OBJECTIVE: To test the hypothesis that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections during the first grass pollen seasons of life influences the risk of hayfever more than at any other time of the year. METHODS: Nested case-control studies were based on birth cohorts within two large databases of computerized patient records from UK general practices: the General Practice Research Database (GPRD) and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever cases, diagnosed after age 2, were matched to controls for practice, age, sex and follow-up of control to case ascertainment date. Conditional logistic regression was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the grass pollen season (May, June, July). Odds ratios (ORs) were pooled across databases. RESULTS: There were no associations in either database between MMR during vs. outside the grass pollen season and later hayfever. Of 23 infections studied, none were statistically significant; although analyses for the less common conditions were limited by low statistical power. The pooled OR for hayfever comparing exposure to antibacterials only in the grass pollen season with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI 0.72-0.98). CONCLUSION: Although an interaction between early exposure to microbial agents and concurrent grass pollen exposure on hayfever risk seemed plausible, there was little evidence to support it across a range of analyses. However, the effect of DTP though weak deserves further study.

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory.

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT). We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for. Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99). Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

Evaluation of total phosphorus and total nitrogen methods in pulp mill effluents.

Under the Clean Water Action Plan, the US Environmental Protection Agency is requiring states to establish numeric criteria for phosphorus and nitrogen. In preparation for the development of nutrient criteria NCASI undertook a research project to conduct a comparative study of methods for the determination of total phosphorus and total nitrogen in pulp and paper mill matrices. This paper presents results of a single laboratory method evaluation and comparative study of digestion techniques and analytical methods for the determination of total phosphorus (TP) and total nitrogen (TN) in pulp and paper mill secondary treated effluents. Analytical methods included EPA Methods 365.2 and 365.4 for TP. TN and total kjeldahl nitrogen (TKN) methods included EPA Methods 351.2, 351.4, and 353.2. Examinations of sample preservation and storage stability were conducted. Substitution of mercuric sulfate with copper sulfate during block digestion resulted in higher blank levels and method detection limits. TP measurements using EPA Method 365.4 (autoanalyzer) were found to be accurate with a positive bias as determined using matrix spike experiments. Sample digestion by acidic persulfate oxidation or mercuric sulfate block digestion in conjunction with EPA Method 365.4 yielded low blank levels (averages of 0.01 and 0.02 mg/L, respectively), precision of 2.1 and 2.4% relative standard deviations, respectively, and accuracy expressed as an average recovery (%R) of 117% for both. EPA Method 351.2 (autoanalyzer) was more precise than EPA Method 351.4 (ammonia probe). Accuracy (%R) for EPA Method 351.2 ranged from 81 to 95%, depending on the digestion technique applied, and was 55% when EPA Method 351.4 was utilized. Investigation of a method utilizing basic to acidic persulfate oxidation for the simultaneous determination of TN and TP using only two analytical techniques was found to be effective at concentrations above 1 mg/L in pulp mill effluents.

Effect of dietary copper source (cupric citrate and cupric sulfate) and concentration on growth performance and fecal copper excretion in weanling pigs.

In each of two experiments, 924 pigs (4.99 kg BW; 16 to 18 d of age) were assigned to 1 of 42 pens based on BW and gender. Pens were allotted randomly to dietary copper (Cu) treatments that consisted of control (10 ppm Cu as cupric sulfate, CuSO4 x 5H2O) and supplemental dietary Cu concentrations of 15, 31, 62, or 125 ppm as cupric citrate (CuCit), or 62 (Exp. 2 only), 125 (Exp. 1 only), or 250 ppm as CuSO4. Live animal performance was determined at the end of the 45-d nursery phase in each experiment. On d 40 of Exp. 2, blood and fecal samples were collected from two randomly selected pigs per pen for evaluation of plasma and fecal Cu concentrations and fecal odor characteristics. In Exp. 1, ADG, ADFI, and G:F were increased (P < 0.05), relative to controls, when pigs were fed diets containing 250 ppm Cu as CuSO4. Pigs fed diets containing 125 ppm Cu as CuCit had increased (P < 0.05) ADG compared with pigs fed diets supplemented with 15 or 62 ppm Cu as CuCit. The ADG, ADFI, and G:F did not differ among pigs fed diets containing 125 and 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. In Exp. 2, pigs fed diets containing 250 ppm Cu as CuSO4 had improved (P < 0.05) ADG, ADFI, and G:F compared with controls. In addition, ADG, ADFI, and G:F were similar when pigs were fed diets containing either 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. Pigs fed diets containing 62 ppm Cu as CuSO4 or CuCit had similar ADG, ADFI, and G:F. Plasma Cu concentrations were not affected by dietary Cu source or concentration, but fecal Cu concentrations were increased (P < 0.05) as the dietary concentration of Cu increased. Pigs consuming diets supplemented with 125 ppm Cu as CuCit had fecal Cu concentrations that were lower (P < 0.05) than pigs consuming diets supplemented with 250 ppm Cu as CuSO4. Fecal Cu did not differ in pigs receiving diets supplemented with 62 ppm Cu as CuSO4 or CuCit. Odor characteristics of feces were not affected by Cu supplementation or source. These data indicate that 125 and 250 ppm Cu gave similar responses in growth, and that CuCit and CuSO4 were equally effective at stimulating growth and improving G:F in weanling pigs. Fecal Cu excretion was decreased when 125 ppm Cu as CuCit was fed compared with 250 ppm Cu as CuSO4. Therefore, 125 ppm of dietary Cu, regardless of source, may provide an effective environmental alternative to 250 ppm Cu as CuSO4 in weanling pigs.

Vitamin K deficiency and D-dimer levels in the intensive care unit: a prospective cohort study.

Patients in the intensive care unit (ICU) are at risk for the development of vitamin K deficiency. We sought to determine the frequency of this deficiency by performing a prospective cohort study in which patients were screened for vitamin K deficiency on ICU admission and every other day thereafter. Vitamin K deficiency was diagnosed by a functional coagulation factor II to Echis factor II ratio < 0.70. Activity of the coagulation cascade was measured by D-dimer. In total, 40 patients were enrolled into the study. Seven of the patients had ratios < 0.70 on the day of admission to the ICU, and three patients developed ratios < 0.70. Thus, 10 of 40 patients (25%; 95% confidence interval, 12-38%) had vitamin K deficiency. Two patients developed coagulopathy, as indicated by an International Normalized Ratio of more than 1.4. D-dimer levels were elevated in 86 of 111 samples. We conclude that vitamin K deficiency is common among critically ill patients, particularly on admission to the ICU. Our findings suggest that additional clinical research is warranted to determine whether vitamin K supplementation on admission to the ICU reduces the risk of ICU-acquired vitamin K deficiency and its attendant complications over the course of the ICU stay.

Trials of miscellaneous interventions to wean from mechanical ventilation.

We found eight randomized controlled trials (RCTs) of miscellaneous interventions that were designed to facilitate the process of weaning from mechanical ventilation. The two RCTs of high-fat/low-carbohydrate enteral nutrition found favorable physiologic effects on CO2 production and respiratory quotient, rendering this type of nutrition potentially useful in patients with impaired ventilatory reserve; however, no conclusions can be made about the outcomes of the duration of ventilation and weaning success. The two RCTs of postextubation use of noninvasive ventilation are conflicting, showing potential short-term physiologic benefit in one study, but no benefit in terms of reintubation rates or other morbidity. These RCTs are less promising than other applications of noninvasive ventilation such as those in patients with COPD exacerbations. One RCT showed no improvement in success of weaning with exogenous growth hormone administration. In the setting of very frequent baseline blood gas analyses, one RCT of oximetry and capnography was associated with significantly fewer blood gas analyses. Biofeedback to enhance safe and rapid weaning showed a dramatically lower duration of ventilation in one RCT that did not report the weaning methods used. One RCT of preextubation acupuncture showed lower rates of laryngospasm in the acupuncture group. Overall, these studies were underpowered for clinically important outcomes. Multidisciplinary, patient-centered, holistic, and non-pulmonary approaches to weaning may provide additional safe, effective adjunctive methods of hastening liberation from mechanical ventilation.

Neuronal apoptosis resulting from high doses of the isoflavone genistein: role for calcium and p42/44 mitogen-activated protein kinase.

Genistein is a potent plant-derived isoflavone displaying estrogenic activity at low (nanomolar) concentrations and antiproliferative and antiangiogenic properties at higher concentrations (above 10-50 microM). The antiproliferative potential of genistein has made it an interesting candidate for cancer chemotherapy at high concentrations; however, the potential for genistein toxicity in neurons at such concentrations has not been previously addressed. We show that genistein is toxic to rat primary cortical neurons at a concentration of 50 microM, whereas daidzein, a structural analog, shows no toxicity at similar concentrations. The dying cells display an apoptotic morphology that is characterized by fragmented nuclei, appearance of apoptotic bodies, DNA laddering, and caspase-dependent poly(ADP-ribose) polymerase cleavage. This cell death is partially dependent on caspase activity, independent of estrogen receptors, and does not result in a significant loss of Bcl-2 or Bcl-X(L) protein. Genistein exposure induces delayed and prolonged activation of p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK but not c-Jun NH2-terminal kinase. The specific p42/44 MAPK kinase inhibitor PD98059 (50 microM) partially blocks genistein-induced apoptosis, whereas the p38 MAPK inhibitor SB202190 (10 microM) has no effect. Genistein elevates intracellular calcium and both 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (1 microM) and dantrolene (10 microM) inhibit genistein-induced apoptosis, suggesting a link between genistein-induced intracellular calcium release and apoptosis. The combination of dantrolene and PD98059 block genistein-induced apoptosis in an additive manner compared with either compound alone. These findings provide evidence for a proapoptotic function of p42/44 MAPK and raise caution about potential side effects in the nervous system with genistein use as a high-dose therapeutic agent.

Use of alternative medicines in a multi-ethnic population.

BACKGROUND: The prevalence and cost of regular use of non-prescribed alternative medicines are rising around the world, yet, little evidence is available that demonstrates the safety, efficacy, or effectiveness of specific alternative medicine interventions. It is of interest to understand how and why these practices have become so popular in different societies with different health care organizations and provisions, and which factors predict the regular use of alternative medicines. METHODS: We assessed the prevalence and the predictors of regular use of non-prescribed vitamin supplements, cod liver oil, primrose oil, and garlic in a cross-sectional population-based study in South London of 1,577 men and women, aged 40-59 years (883 women, 523 White, 549 of African origin and 505 of South Asian origin), when allowing for potential confounders. RESULTS: The prevalence of regular users of alternative medicines was 10.4% (164/1,577); 7.4% (116) made regular use of non-prescribed vitamin supplements, whereas 5.3% (84) used either cod liver oil, primrose oil, or garlic preparations. When adjusted for age, ethnicity and social class, women were more likely than men to use at least one alternative medicine (OR 2.09 [95% CI 1.45-3.00]). This was true both for vitamin supplements (1.98 [1.29-3.03]) and for oil or garlic supplements (1.91 [1.17-3.14]). The use of oil or garlic (P<.005) but not vitamin supplements (P=.32) varied by ethnic group. In particular, Black people of African origin were more likely to use alternative medicines than either Whites (1.78 [1.07-2.94]) or South Asians (1.66 [1.07-2.59]), the least common users. People in social classes IV and V were less likely to use alternative medicines (0.53 [0.31-0.90]) than those in social classes I and II, though this was due more to lesser use of non-prescribed vitamin supplements than of cod liver oil, primrose oil or garlic. These associations were not attenuated by further adjustment for body mass index, smoking, marital status and age at leaving full-time education. CONCLUSIONS: The regular users of alternative medicines in London are more likely to be women, of African origin, and of higher socioeconomic status. Given the lack of evidence of efficacy and safety of these alternative medicines, it is important to understand the cultural differences in values and beliefs about traditional medicine that may underlie these findings.

Noninvasive positive pressure ventilation in the setting of severe, acute exacerbations of chronic obstructive pulmonary disease: more effective and less expensive.

OBJECTIVE: The use of noninvasive ventilation for patients with acute respiratory failure has become increasingly popular over the last decade. Although the literature provides good evidence for the effectiveness of noninvasive ventilation in addition to standard therapy compared with standard therapy alone in patients with chronic obstructive pulmonary disease (avoiding intubation and improving hospital mortality), the associated costs have not been rigorously measured. Adding noninvasive positive pressure ventilation (NPPV) to standard therapy in the setting of a severe, acute exacerbation of chronic obstructive pulmonary disease (COPD) in patients with respiratory acidosis who are at high risk of requiring endotracheal intubation is both more effective and less expensive. DESIGN: Economic evaluation based on theoretical model. SETTING: This analysis base case was modeled for a tertiary care, teaching hospital. PATIENTS OR OTHER PARTICIPANTS: Carefully selected patients with severe exacerbations of COPD. INTERVENTION: The two alternative therapies compared were standard therapy (oxygen, bronchodilators, steroids, and antibiotics) and standard therapy plus NPPV. MEASUREMENTS AND MAIN RESULTS: As the hypothesis was dominance, the main outcomes modeled and calculated were costs, mortality rate, and rates of intubation between the two interventions. To determine clinical effectiveness, we used a meta-analysis of randomized trials evaluating the impact of NPPV on hospital survival. A decision tree was constructed and probabilities were applied at each chance node using research evidence and a comprehensive regional database. To provide data for this economic evaluation, MEDLINE literature searches were conducted. Bibliographies of relevant articles were reviewed, as were personal files. To estimate the costs of the alternative therapeutic approaches, eight types of hospitalization days were costed using the London Health Sciences Center costing data. Sensitivity analyses were performed, varying all assumptions made. The meta-analysis yielded an odds ratio for hospital mortality in the NPPV arm, compared with standard therapy, of 0.22 (95% confidence interval, 0.10-0.66). By using baseline case assumptions, we found a cost savings of $3,244 (1996, Canadian), per patient admission, if NPPV were adopted in favor of standard therapy. These findings present a scenario of clear dominance for treatment with NPPV. Sensitivity analyses did not alter the results appreciably. CONCLUSIONS: We conclude that from a hospital's perspective, NPPV and standard therapy for carefully selected patients with acute, severe exacerbations of COPD are more effective and less expensive than standard therapy alone.

Development, dissemination, implementation and evaluation of a clinical pathway for oxygen therapy.

BACKGROUND: Oxygen is commonly administered to patients in hospital, but prescribing and monitoring of such therapy may be suboptimal. The objective of this study was to develop, disseminate, implement and evaluate a multidisciplinary clinical pathway for the administration of oxygen. METHODS: The authors developed a clinical pathway for the ordering, titration and discontinuation of oxygen, which was disseminated through teaching sessions, in-service training sessions and information posters in a medical clinical teaching unit (CTU). Implementation of the pathway was ensured by means of reminders and patient-centred audit and feedback to CTU nurses and house staff. During a 3-month intervention phase, consecutive patients requiring supplemental oxygen were treated according to the pathway. During a 1-month "wash-out" phase followed by a 3-month non-intervention phase, patients were treated at the discretion of the CTU team. Clinical and economic data were collected in both phases. RESULTS: In the 2 phases, patient characteristics, the concentration and duration of oxygen prescribed, the frequency of oxygen saturation monitoring, the frequency of arterial blood gas testing and the clinical outcomes were similar. However, there were more discontinuation orders in the intervention phase (p < 0.001). In the intervention phase, costs were higher for monitoring of oxygen saturation ($44.95/patient v. $36.17/patient, p = 0.048) and for order transcription ($2.71/patient v. $1.28/patient, p < 0.001); total costs, including those for personnel, were also higher in the intervention phase ($76.93/patient v. $56.67/patient, p = 0.02). The cost of education about the oxygen pathway was $45.71/patient. When the education cost was included, the total cost of oxygen therapy during the intervention phase was $122.64/patient; this was significantly higher than the total cost of oxygen therapy during the non-intervention phase ($56.67/patient) (p < 0.001). INTERPRETATION: This multidisciplinary, multimethod oxygen pathway led to changes in oxygen-prescribing behaviour, consumed more resources than standard management and was not associated with changes in patient outcome. Appropriate management of oxygen prescribing and monitoring by physicians and nurses take time and costs money.

Plasma vitamin C levels in men and women from different ethnic backgrounds living in England.

BACKGROUND: People of South Asian origin living in the UK have higher death rates due to coronary heart disease than whites. The reasons for these differences are not fully understood. Previous attempts to relate diet to cardiovascular risk in South Asians have been inconclusive. METHODS: We compared the levels of plasma vitamin C in a cross-sectional population-based study of 1018 men and women aged 40-59 (455 men, 563 women, 328 South Asians, 355 of African descent, 335 whites) co-resident in a geographically defined area of South London, when allowing for potential confounders. RESULTS: Fasting plasma vitamin C levels were significantly higher in women, vegetarians, supplement takers and non-smokers. After adjustment for age, body mass index, current smoking, supplement use and vegetarianism the mean plasma vitamin C levels were 38.8 (SE 1.6) mumol/l in white men, 36.5 (1.6) mumol/l in men of African descent and 32.9 (1.5) mumol/l in South Asian men (P = 0.033 by analysis of co-variance). In women the adjusted mean plasma vitamin C levels were 52.4 (1.6) mumol/l in whites, 46.0 (1.4) mumol/l in women of African descent and 37.3 (1.8) mumol/l in South Asians (P < 0.0001 by analysis of covariance). South Asians had lower levels than whites in both men (difference 6.4 [95% CI: 1.5, 11.3] mumol/l) and women (16.8 [95% CI: 11.5, 22.1] mumol/l). South Asian women, but not men, also had lower levels than those of African descent (8.8 [95% CI: 4.5, 13.1] mumol/l). African women, but not men, had lower levels than white women (6.6 [95% CI: 2.3, 10.9] mumol/l). No significant differences were seen between Caribbeans and West Africans or between South Asian Hindus and Muslims. CONCLUSIONS: These data suggest that important dietary differences in vitamin C exist between different ethnic groups living in England. The larger differences in South Asians may contribute to their increased coronary risk.

The influence of dietary and nondietary calcium supplementation on blood pressure: an updated metaanalysis of randomized controlled trials.

We updated our previous systematic review of the effect of supplemental calcium on blood pressure. We extended our previous searches on MEDLINE and EMBASE to May 1997 and examined citations from relevant articles. We contacted the authors of eligible trials to ensure the accuracy and completeness of data, and to identify unpublished trials. We included any study in which investigators randomized hypertensive or normotensive people to calcium supplementation or alternative therapy and measured blood pressure for at least 2 weeks. In addition to 32 trials included in the prior metaanalysis, 10 new trials contributed to this metaanalysis. Two pairs of independent reviewers abstracted data and assessed the validity of the study data according to six quality criteria. We calculated the differences in blood pressure change between the calcium supplementation and control groups and pooled the estimates with each trial weighted with the inverse of the variance using a random effects model. The predictors of blood pressure reduction that we examined included method of supplementation, baseline blood pressure, and the methodologic quality of the studies. The pooled analysis shows a reduction in systolic blood pressure of -1.44 mm Hg (95% confidence interval -2.20 to -0.68; P < .001) and in diastolic blood pressure of -0.84 mm Hg (95% confidence interval -1.44 to -0.24; P < .001). We found statistically significant heterogeneity of results across trials (P < or = .02), which persisted when we looked at the nondietary trials alone, but not when we restricted our analysis to dietary trials. Although there was a trend toward larger effects with dietary interventions, none of the possible mediators of blood pressure reduction explained differences in treatment effect. We conclude that calcium supplementation leads to a small reduction in systolic and diastolic blood pressure. The effect of supplemental calcium in the diet is at least as great as nondietary supplementation.

Photochemical inactivation of viruses and bacteria in platelet concentrates by use of a novel psoralen and long-wavelength ultraviolet light.

BACKGROUND: A photochemical treatment process has been developed for the inactivation of viruses and bacteria in platelet concentrates. This process is based on the photochemical reaction of a novel psoralen, S-59, with nucleic acids upon illumination with long-wavelength ultraviolet light (UVA, 320-400 nm). STUDY DESIGN AND METHODS: High levels of pathogens were added to single-donor platelet concentrates containing 3 to 5 x 10(11) platelets in 300 mL of 35-percent autologous plasma and 65-percent platelet additive solution. After treatment with S-59 (150 microM) and UVA (0-3 J/cm2), the infectivity of each pathogen was measured with established biologic assays. In vitro platelet function after photochemical treatment was evaluated during 7 days of storage by using a panel of 14 assays. The in vivo recovery and life span of photochemically treated platelets were evaluated after 24 hours of storage in a primate transfusion model. RESULTS: The following levels of pathogen inactivation were achieved: >10(6.7) plaque-forming units (PFU) per mL of cell-free human immunodeficiency virus (HIV), >10(6.6) PFU per mL of cell-associated HIV, >10(6.8) infectious dose (ID50) per mL of duck hepatitis B virus (a model for hepatitis B virus), >10(6.5) PFU per mL of bovine viral diarrhea virus (a model for hepatitis C virus), >10(6.6) colony-forming units of Staphylococcus epidermidis, and >10(5.6) colony-forming units of Klebsiella pneumoniae. Expression of integrated HIV was inhibited by 0.1 microM S-59 and 1 J per cm2 of UVA. In vitro and in vivo platelet function were adequately maintained after antiviral and antibacterial treatment. CONCLUSION: Photochemical treatment of platelet concentrates offers the potential for reducing transfusion-related viral and bacterial diseases.