The short-term cost of falls, poisonings and scalds occurring at home in children under 5†years old in England: multicentre longitudinal study.

BACKGROUND: Childhood falls, poisonings and scalds, occurring predominantly in the home, are an important public health problem, yet there is limited evidence on the costs of these injuries to individuals and society. OBJECTIVES: To estimate National Health Service (NHS) and child and family costs of falls, poisonings and scalds. METHODS: We undertook a multicentre longitudinal study of falls, poisonings and scalds in children under 5 years old, set in acute NHS Trusts across four UK study centres. Data from parental self-reported questionnaires on health service resource use, family costs and expenditure were combined with unit cost data from published sources to calculate average cost for participants and injury mechanism. RESULTS: 344 parents completed resource use questionnaires until their child recovered from their injury or until 12 months, whichever came soonest. Most injuries were minor, with >95% recovering within 2 weeks, and 99% within 1 month of the injury. 61% emergency department (ED) attendees were not admitted, 35% admitted for ≤1 day and 4% admitted for ≥2 days. The typical healthcare cost of an admission for ≥2 days was estimated at £2000-3000, for an admission for ≤1 day was £700-1000 and for an ED attendance without admission was £100-180. Family costs were considerable and varied across injury mechanisms. Of all injuries, scalds accrued highest healthcare and family costs. CONCLUSIONS: Falls, poisonings and scalds incur considerable short-term healthcare and family costs. These data can inform injury prevention policy and commissioning of preventive services.

The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades.

Neuroimaging shows brain-functional differences due to apolipoprotein E (APOE) polymorphisms may exist decades before the increased risk period for Alzheimer's disease, but little is known about their effect on cognition and brain function in children and young adults. This study assessed 415 healthy epsilon2 and epsilon4 carriers and matched epsilon3/epsilon3 controls, spanning ages 6-65, on a range of cognitive tests. Subjects were also compared on a new dynamical measure of EEG activity during a visual working memory task using alphabetical stimuli. epsilon4 subjects had better verbal fluency compared to epsilon3, an effect that was strongest in 51-65 year-olds. No epsilon4 deficits in cognition were found. In 6-15 year-olds, there were differences in total spatio-temporal wave activity between epsilon3 and epsilon4 subjects in the theta band, approximately 200ms post-stimulus. Differences in brain function in younger epsilon4 subjects and superior verbal fluency across the entire age range suggest that the APOE epsilon4 allele is an example of antagonistic pleiotropy.

Microwave-assisted activation and modulator removal in zirconium MOFs for buffer-free CWA hydrolysis.

A novel, facile and efficient method was developed for the activation of acetic acid modulated zirconium MOFs. The protocol involves briefly heating the material in water using microwave irradiation. MOF-808, DUT-84 and UiO-66 were all activated in this manner to remove the modulator and organic solvent from the framework post synthesis, with retention of MOF integrity post activation. The degree of activation was characterised by the use of TGA and NMR. The catalytic activity of the activated MOFs and their non-activated counterparts was investigated for chemical warfare agent (CWA) hydrolysis. Upon activation, an increase in the rate of hydrolysis was observed in the degradation of CWA simulant dimethyl 4-nitrophenyl phosphate (DMNP). MOF-808 and DUT-84 were also screened as catalysts for the hydrolysis of the V-series agent VM, with remarkable half-lives obtained for MOF-808 in the absence of any buffers. Currently employed MOF activation procedures involve the use of additional organic solvents post synthesis; we believe this method to be ideally efficacious for the organic desolvation of zirconium MOFs and removing modulator additives.

Neonatal screening for inborn errors of metabolism: cost, yield and outcome.

OBJECTIVES. To systematically review the literature on inborn errors of metabolism, neonatal screening technology and screening programmes in order to analyse the costs and benefits of introducing screening based on tandem mass-spectrometry (tandem MS) for a wide range of disorders of amino acid and organic acid metabolism in the UK. To evaluate screening for cystic fibrosis, Duchenne muscular dystrophy and other disorders which are tested on an individual basis. HOW THE RESEARCH WAS CONDUCTED. Systematic searches were carried out of the literature on inborn errors of metabolism, neonatal screening programmes, tandem MS-based neonatal screening technology, economic evaluations of neonatal screening programmes and psychological aspects of neonatal screening. Background material on the biology of inherited metabolic disease, the basic philosophy, and the history and current status of the UK screening programme was also collected. Relevant papers in the grey literature and recent publications were identified by hand-searching. Each paper was graded. For each disease an aggregate grade for the state of knowledge in six key areas was awarded. Additional data were prospectively collected on activity and costs in UK neonatal screening laboratories, and expert clinical opinion on current treatment modalities and outcomes. These data were used to construct a decision-analysis model of neonatal screening technologies, comparing tandem MS with the existing phenylketonuria screening methods. This model determined the cost per additional case identified and, for each disease, the additional treatment costs per case, and the cost per life-year saved. All costs and benefits were discounted at 6% per annum. One-way sensitivity analysis was performed showing the effect of varying the discount rate, the incidence rate of each disorder, the number of neonates screened and the cost of tandem MS, on the cost per life-year gained. RESEARCH FINDINGS. The UK screening programmes for phenylketonuria and congenital hypothyroidism have largely achieved the expected objectives and are cost-effective. Current concerns are the difficulty of maintaining adequate coverage, perceived organisational weaknesses, and a lack of overview. For many of the organic acid disorders it was necessary to rely on data obtained from clinically-diagnosed cases. Many of these diseases can be treated very effectively and a sensitive screening test was available for most of the diseases. Except for cystic fibrosis, there have been no randomised controlled trials of the overall effectiveness of neonatal screening. Despite the anxiety generated by the screening process, there is strong parental support for screening. The effects of diagnosis through screening on subsequent reproductive behaviour is less clear. Conflicts exist between current concepts and the traditional principles of screening. The availability of effective treatment is not an absolute prerequisite: early diagnosis is of value to the family concerned and, to the extent that is leads to increased use of prenatal diagnosis, may help to reduce the overall burden of disease. Neonatal screening is also of value in diseases which present early but with non-specific symptoms. Indeed, almost all of the diseases considered could merit neonatal screening. The majority of economic evaluations failed to incorporate the health benefits from screening, and therefore failed to address the value of the information which the screening programmes provided to parents. The marginal cost of changing from present technology to tandem MS would be approximately 0.60 pounds per baby at a workload of 100,000 samples a year, and 0.87 pounds at 50,000 samples per year. The ability to screen for a wider range of diseases would lead to the identification of some 20 additional cases per 100,000 infants screened, giving a laboratory cost per additional diagnosis of 3000 pounds at an annual workload of 100,000 babies per year.(ABSTRACT TRUNCATED)

Decision analytical economic modelling within a Bayesian framework: application to prophylactic antibiotics use for caesarean section.

Economic evaluation of health care interventions based on decision analytic modelling can generate valuable information for health policy decision makers. However, the usefulness of the results obtained depends on the quality of the data input into the model; that is, the accuracy of the estimates for the costs, effectiveness, and transition probabilities between the different health states of the model. The aim of this paper is to review the use of Bayesian decision models in economic evaluation and to demonstrate how the individual components required for decision analytical modelling (i.e., systematic review incorporating meta-analyses, estimation of transition probabilities, evaluation of the model, and sensitivity analysis) may be addressed simultaneously in one coherent Bayesian model evaluated using Markov Chain Monte Carlo simulation implemented in the specialist Bayesian statistics software WinBUGS. To illustrate the method described, a simple probabilistic decision model is developed to evaluate the cost implications of using prophylactic antibiotics in caesarean section to reduce the incidence of wound infection. The advantages of using the Bayesian statistical approach outlined compared to the conventional classical approaches to decision analysis include the ability to: (i) perform all necessary analyses, including all intermediate analyses (e.g., meta-analyses) required to derive model parameters, in a single coherent model; (ii) incorporate expert opinion either directly or regarding the relative credibility of different data sources; (iii) use the actual posterior distributions for parameters of interest (opposed to making distributional assumptions necessary for the classical formulation); and (iv) incorporate uncertainty for all model parameters.

Bull selection and use in northern Australia. 5. Social behaviour and management.

Calf output of bulls was derived using DNA typing for paternity following multiple-sire mating at two sites in northern Australia. At Swan's Lagoon Beef Cattle Research Station, 12, mixed-age, Brahman cross bulls were continuously mated with an average of 325 females in a 22km2 open-savannah paddock. Water was available in two troughs. Behaviour of the bulls and location of cows were monitored. At Kamilaroi Station, 2- to 2.5-year-old Brahman bulls were introduced to the study. Twenty-four bulls (HIGH%) were mated in an 84km2 paddock for 3.5 months to 411 heifers in 1995/1995 and for 4.5 months to 350 heifers and 320 first-lactation cows in 1995/1996. A second group of 10 bulls (LOW%) selected on reproductive soundness was mated concurrently in a neighbouring 60km2 paddock to 411 heifers in 1995/1995 and to 350 heifers and 298 first-lactation cows in 1995/1996. In each paddock in both years, 300-350 females were expected to cycle during mating. Both paddocks were flat and semi-forested and water was available only at troughs. At both sites, detailed physical and reproductive examinations of all bulls were conducted prior to and post-mating.Calf output of individual bulls was highly variable but repeatable (r=0.6-0.7) between years. Up to 90% of the 270-380 calves resulting from each mating were sired by between 6 and 8 bulls. Reducing from 3.7 to 2.8% bulls:females at Swan's Lagoon did not delay conceptions. At Kamilaroi, reproductively sound bulls achieved an estimated 5-6 conceptions per week over the peak mating period when sufficient cycling females were available. Differences in pregnancy rates between paddocks appeared due to differences in nutrition and it appeared that conceptions were not delayed with LOW% vs. HIGH% bulls. Variance between bulls in calf output was substantially lower when fewer bulls were used. Bull attrition occurred each year in the HIGH% paddock but not in the LOW% paddock. Calf output was unrelated to body condition of bulls. Seven of the 12 bulls in one 2-year period at Swan's Lagoon appeared to restrict their movement range to 250-750ha for 90-100% of the time. These ranges expanded when the bull:female ratio was reduced. Only one of the nine bulls remained within a 500ha home range for at least 85% of the time during peak mating in 1998 at 2.8% bulls:females. In previous years with 3.7% bulls:females, up to eight of the 12 bulls had remained within a 500ha home range for 85% of the time. Bull behaviour related to high calf output included restricted movement range, grazing with females at a majority of observations, stable social behaviour, and social dominance. These observations demonstrate that multiple-sire mating of reproductively sound Brahman and Brahman-derived bulls at 2.5% of cycling females will not jeopardise herd fertility under extensive management in northern Australia.

Contraceptive efficacy of an intra-uterine device in Brahman cattle.

The contraceptive efficacy of an intra-uterine device was evaluated using 218 heifers and 212 cows on three north Australian cattle stations. The heifers were aged approximately 2 years and weighed 250-378 kg; the cows were aged 3-16 years and weighed 256-540 kg. All cattle were non-pregnant, non-lactating Brahmans. At the end of the monsoon (wet) season (April-June 1997), the cattle were allocated by stratified randomisation to the three treatments which were untreated controls (n=59), surgical ovariectomy (n=105), or implantation with a bovine intra-uterine device (BIUD; n=266). All cattle grazed and were managed as one group within each station. They were exposed to bulls (4 per 100 females) from soon after treatment until slaughter approximately 12 months later. The BIUD could not be implanted in 25% of heifers and 8% of cows due to narrow or twisted cervices. Correct placement of the BIUDs appeared to be achieved in 57% of heifers and 72% of cows. At slaughter, the devices were incorrectly positioned in 73% of heifers and 49% of cows into which BIUDs had been inserted and that remained non-pregnant. Uterine perforations by the BIUD were observed in 35 and 45% of these heifers and cows, respectively; most perforations appeared to occur during implantation. Low-grade endometritis was observed at slaughter in most BIUD-implanted animals; 2% had pyometra.BIUD animals did not have significantly different growth to that of control or ovariectomised animals, other than when ovariectomy suppressed growth following surgery. Most animals implanted with BIUDs appeared to have normal ovarian function and animals were observed mating. All ovariectomised animals remained non-pregnant. Over 80% of controls were pregnant within 8 months of exposure to bulls, except heifers at one station where pregnancy rate was restricted to 25% as a result of severe nutritional conditions. Pregnancy was diagnosed in 21% of heifers and 33% of cows with implanted BIUDs. The device remained correctly positioned and with no pregnancy diagnosed in the year following implantation in only 2% of heifers and 14% of cows originally allocated. Because of the difficulties of implanting BIUDs, the high frequency of associated uterine injury, the high pregnancy rate in implanted animals, and that growth was unaffected by the presence of a BIUD, it was concluded that the device had poor contraception efficacy and no growth-promotant effect in Brahman cattle.

An evaluation of visual assessment for fertility in Brahman cross cows using the Bonsma technique.

A technique of visual assessment of cattle for reproductive efficiency, described by Professor Jan Bonsma of South Africa, was evaluated in two well-managed large herds of 1/2 to 3/4 Brahman cross heifers and cows located in the dry tropics of north Australia. Individual lifetime performance records were available for all animals. Experienced cattlemen carried out the assessments. Higher scores were previously claimed to indicate higher fertility. The technique had high repeatability (0.7) and was quickly learned by the assessors. Scores from visual assessment had no useful predictive value for either heifer or cow fertility or for growth rate up to 27 mo of age, although 2.5-yr-old heifers which were scored as subfertile matured into 4% smaller cows than heifers which had scored higher. Scores decreased as fatness increased (P < 0.05). Some biases in visual assessment occurred. Lactating cows scored higher than nonlactating cows (P < 0.05), independently of their reproductive record. Red and grey cows scored higher than brindle and black/brown cows (P < 0.05). Bonsma scores were not influenced by the percentage of Brahman in the genotype. Significant, but apparently random, age effects on scores also occurred. It was concluded that the visual assessment criteria described by Bonsma were of no practical value in assessing potential productivity of breeding animals in well-managed Brahman cross cattle in the dry tropics.

Trial introduction of the Willis dropped ovary technique for spaying cattle in northern Australia.

OBJECTIVE: To compare the Willis dropped ovary technique with traditional spaying methods in extensive beef cattle herds in northern Australia. PROCEDURE: Three field trials were conducted simultaneously at different sites in northern Australia in 1996-97. Brahman and Brahman-Shorthorn cross heifers (n = 219, 2 years, 250 to 378 kg) and cows (n = 211, 3 to 16 years, 256 to 540 kg) were allocated by stratified randomisation to three treatments: spaying using the Willis dropped ovary technique (WDOT); spaying using traditional paralumbar and vaginal methods; and unspayed. Following these procedures, these nonpregnant, nonlactating cattle were then exposed to bulls (4 per 100 females) under extensive rangeland conditions for 12 months during which time weight, body condition, pregnancy and ovarian function were monitored and compared. RESULTS: Pregnancy rates varied from 60 to 90% for entire heifers and 80 to 100% for entire cows depending on site. The traditional spay methods were 100% successful in preventing pregnancy; the WDOT was 92 to 97% effective, depending on operator experience. The number of deaths was the same or higher in Willis spayed animals than other groups. Weight changes were similar in all groups at the three sites over the trial period. The time taken to spay using the WDOT was similar to or less than that required for the traditional methods. Uterine abnormalities were not observed in animals spayed with the WDOT, there were however 30 (12.4%) animals where excision of the ovary was incomplete; the still-attached ovarian remnant presumably accounting for the three pregnant animals in this group. CONCLUSION: The WDOT suffers from requiring a high degree of skill in transrectal ovarian manipulation. There were more deaths and more pregnancies than with traditional spay methods. More experienced operators can be expected to achieve lower mortalities, better contraception and higher processing rates. Pregnancy will occur as a consequence of ovarian remnants unless care is taken to ensure removal of the entire ovary.

The use of narrative in the development of critical thinking.

This paper describes an approach to assessment aimed at developing critical skills in the production of arguments concerning contemporary issues in health. It is demonstrated that, in teaching from a constructivist position of knowledge, students can be cautious in producing assignments because of the relativist characteristic of constructivism. It is proposed that students could be more open and flexible in their approach to assessment and the use of cooperative working through the creation of narratives. It is suggested that narratives can provide an accessible and heuristic process from which academic accounts may be built. The use of narratives in taking the students from their everyday thinking to academic accounts is presented in relation to four teaching sessions. The use of this approach is in turn evaluated by students' narratives of their learning experience. Of 30 narratives obtained from students, analysis demonstrated that 21 accounts expressed aspects associated with the development of critical thinking. Nine students voiced some dissatisfaction with the assessment process, and further work to remedy these problems is outlined.

An investigation of EEG, genetic and cognitive markers of treatment response to antidepressant medication in patients with major depressive disorder: a pilot study.

The aim of this study was to investigate if biomarkers in QEEG, genetic and neuropsychological measures are suitable for the prediction of antidepressant treatment outcome in depression. Twenty-five patients diagnosed with major depressive disorder were assessed twice, pretreatment and at 8-wk follow-up, on a variety of QEEG and neuropsychological tasks. Additionally, cheek swab samples were collected to assess genetic predictors of treatment outcome. The primary outcome measure was the absolute decrease on the HAM-D rating scale. Regression models were built in order to investigate which markers contribute most to the decrease in absolute HAM-D scores. Patients who had a better clinical outcome were characterized by a decrease in the amplitude of the Auditory Oddball N1 at baseline. The 'Met/Met' variant of the COMT gene was the best genetic predictor of treatment outcome. Impaired verbal memory performance was the best cognitive predictor. Raised frontal Theta power was the best EEG predictor of change in HAM-D scores. A tentative integrative model showed that a combination of N1 amplitude at Pz and verbal memory performance accounted for the largest part of the explained variance. These markers may serve as new biomarkers suitable for the prediction of antidepressant treatment outcome.

Chemical coding and central projections of gastric vagal afferent neurons.

Vagal afferents that innervate gastric muscle or mucosa transmit distinct sensory information from their endings to the nucleus of the tractus solitarius (NTS). While these afferent subtypes are functionally distinct, no neurochemical correlate has been described and it is unknown whether they terminate in different central locations. This study aimed to identify gastric vagal afferent subtypes in the nodose ganglion (NG) of ferrets, their terminal areas in NTS and neurochemistry for isolectin-B4 (IB4) and calcitonin gene-related peptide (CGRP). Vagal afferents were traced from gastric muscle or mucosa and IB4 and CGRP labelling assessed in NG and NTS. 7 +/- 1% and 6 +/- 1% of NG neurons were traced from gastric muscle or mucosa respectively; these were more likely to label for CGRP or for both CGRP and IB4 than other NG neurons (P < 0.01). Muscular afferents were also less likely than others to label with IB4 (P < 0.001). Less than 1% of NG neurons were traced from both muscle and mucosa. Central terminals of both afferent subtypes occurred in the subnucleus gelatinosus of the NTS, but did not overlap completely. This region also labelled for CGRP and IB4. We conclude that while vagal afferents from gastric muscle and mucosa differ little in their chemical coding for CGRP and IB4, they can be traced selectively from their peripheral endings to NG and to overlapping and distinct regions of NTS. Thus, there is an anatomical substrate for convergent NTS integration for both types of afferent input.

Mixed treatment comparison with multiple outcomes reported inconsistently across trials: evaluation of antivirals for treatment of influenza A and B.

We present a mixed treatment meta-analysis of antivirals for treatment of influenza, where some trials report summary measures on at least one of the two outcomes: time to alleviation of fever and time to alleviation of symptoms. The synthesis is further complicated by the variety of summary measures reported: mean time, median time and proportion symptom free at the end of follow-up. We compare several models using the deviance information criteria and the contribution of different evidence sources to the residual deviance to aid model selection. A Weibull model with exchangeable treatment effects that are independent for each outcome but have a common random effect mean for the two outcomes gives the best fit according to these criteria. This model allows us to summarize treatment effect on two outcomes in a single summary measure and draw conclusions as to the most effective treatment. Amantadine and Oseltamivir were the most effective treatments, with the probability of being most effective of 0.56 and 0.37, respectively. Amantadine reduces the duration of symptoms by an estimated 2.8 days, and Oseltamivir 2.6 days, compared with placebo. The models provide flexible methods for synthesis of evidence on multiple treatments in the absence of head-to-head trial data, when different summary measures are used and either different clinical outcomes are reported or where the same outcomes are reported at different or multiple time points.

Use of evidence in economic decision models: practical issues and methodological challenges.

This paper outlines the current 'state of play' regarding the use of evidence in decision modelling and highlights both practical issues and methodological challenges related to identifying, combining and reporting evidence to inform decision model parameters and structure. Based on discussions at two MRC HSRC-funded workshops consisting of 37 experts from a range of disciplines (i.e. decision-makers, health economists, information specialists, operations researchers and statisticians), it aims to derive a multi-disciplinary standpoint on the appropriate use of evidence in economic decision models and, where applicable, offer some suggestions for good modelling practice. Gaps in the established methodology knowledge base are identified for future research.

Meta-analysis of mixed treatment comparisons at multiple follow-up times.

Mixed treatment comparisons (MTC) meta-analysis is a methodology for making inferences on relative treatment effects based on a synthesis of both direct and indirect evidence on multiple treatment contrasts. This is particularly useful in the context of cost-effectiveness analysis and medical decision making. Here, we extend these methods to a more complex situation where trials report results at one or more, different yet fixed, follow-up times. These methods are applied to an illustrative data set combining evidence on healing rates under six different treatments for gastro-esophageal reflux disease (GERD). A series of Bayesian hierarchical models based on piece-wise exponential hazards is developed that borrow strength across the MTC networks and also across time points. These include models for absolute and relative treatment effects, models with fixed or random effects over time, random walk models, and models with homogeneous or heterogeneous between-trials variation. The deviance information criterion (DIC) is used to guide model development and selection. Models for absolute treatment effects generate materially different rankings of the treatments than models that separate the trial-specific baselines from the relative treatment effects. The extent of between-trials heterogeneity in treatment effects depends on treatment contrast. In discussion we note that models of this type have a very wide potential application.

The impact of diabetes on current revascularisation practice and clinical outcome in patients with critical lower limb ischaemia.

OBJECTIVE: To compare current revascularisation practice and outcome in diabetic and non-diabetic patients presenting with critical limb ischaemia (CLI) to a single vascular surgeon. METHODS: Data for 113 patients presenting with CLI were collected prospectively over a 3-year period. Forty-four (39%) were diabetic. Treatment was classified as percutaneous angioplasty, arterial reconstruction, primary major amputation, and conservative therapy. Main outcome measures were 30-day mortality, major amputation, survival, and amputation-free survival. RESULTS: Diabetic patients were more likely to present with gangrene, give a history of angina, be treated with nitrates and statins, and have lower cholesterol levels. No significant differences were found in the initial treatment options between diabetics and non-diabetics: angioplasty 39 vs 26%, surgical revascularisation 34 vs 33%, primary major amputation 9% vs 17%, and conservative treatment 11 vs 19% (p = ns in all). There were eight deaths (7%) within 30-days. At follow-up (1-44 months, median 14 months), rates of major amputation and death for the entire population were 23 and 8%, respectively. The 12-month cumulative survival and amputation-free survival rates were 90 and 72%, respectively. When comparing diabetic to non-diabetic patients, there were no significant differences in the 30-day mortality (6.8 vs 7.2%, p = 0.4), cumulative survival (93 vs 89% at 12 months, log-rank test: 0.00, p = 0.9), amputation-free survival (71 vs 73% at 12 months, log-rank test: 0.00, p = 0.99), and major amputation rates (22.7 vs 23.1% at 12 months, p = 0.96). Similarly, there were no differences in limb salvage rates between diabetic and non-diabetic patients undergoing revascularisation procedures (78 vs 90% at 12 months, log-rank test: 2.04, p = 0.15). CONCLUSIONS: In current practice, an aggressive multidisciplinary approach in diabetic patients presenting with CLI leads to similar limb salvage, amputation-free survival, mortality, and major amputation rates to those seen in non-diabetic patients. The presence of diabetes should not deter clinicians from attempting revascularisation by means of angioplasty or surgical reconstruction.

The cost-effectiveness of influenza vaccination of healthy adults 50-64 years of age.

Influenza can cause significant morbidity and mortality. Influenza vaccination is an effective and safe strategy in the prevention of influenza. Currently the National Health Service (NHS) vaccinates 'at-risk' individuals only. This definition includes everyone over 65 years of age but excludes individuals 50-64 years of age unless they have an additional risk factor, such as underlying heart disease or lung disease. In order to examine the cost-effectiveness of an extension of the vaccination policy to include this age group we constructed an economic model to estimate the costs and benefits of vaccination from both a health service and a societal perspective. Data to populate the model was obtained from the literature and the outcome measure used was the quality adjusted life year (QALY). Influenza vaccination prevented an estimated 4508 cases (95% CI: 2431-7606) per 100,000 vaccinees per influenza season for a net cost to the NHS of pound653,221 (95% CI: 354,575-1,072,257). The net cost increased to pound1,139,069 (95% CI 27,052-2,030,473) when non-NHS costs were included and the estimated cost-per-QALY were pound6174 and pound10,766 for NHS and all costs respectively. Extension of the current immunisation policy has the potential to generate a significant health benefit at a comparatively low cost.

Economic burden of rheumatoid arthritis: a systematic review.

OBJECTIVE: To summarize the state of knowledge with regard to the economic impact of rheumatoid arthritis (RA) and to highlight any weaknesses in the work conducted to date, so as to inform future RA cost-of-illness studies. METHODS: Four computerized literature databases were searched to identify all the literature relevant to this review. Seven elements indicating a quality cost-of-illness study were established and used to appraise the literature identified critically. Where possible, costs reported by the different studies were converted to 1996 US dollars using the consumer price index for medical care. RESULTS: Total average medical costs were reported to range from US$5720 (UK pound3575) to US$5822 (UK pound3638). Medication constituted between 8 and 24% of total medical costs, physician visits between 8 and 21%, and in-patient stays between 17 and 88%. The average number of days absent from work due to a person's RA was reported to range from 2.7 to 30 days/year. CONCLUSION: The economic impact of RA in terms of cost was reported to be substantial by all studies reviewed. However, methodological problems meant that discrepancies in the average (per person) annual cost of RA existed across studies.

Biochemical catalysis involving coenzyme B-12: a rational stepwise mechanistic interpretation of vicinal interchange rearrangements.

A mechanism is proposed for the catalytic action of coenzyme B-12 which is consistent with current knowledge of organometallic reactions and with the experimental data now available from biochemical studies. A key feature of the proposal is an electrocyclic cleavage of the coenzyme that reduces cobalt and also leads to a 1,19-seco-corrin. The seco-corrin serves as a tridentate ligand about Co(I). This arrangement permits the metal to take part in the kinds of organometallic reactions that are ideal for coenzyme B-12 catalysis, including oxidative addition and its reverse, reductive elimination. It is further proposed that the rearrangement steps involve cobaltcarbene complexes.