bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the effectiveness and cost‐effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease
Authors: Miners A. H. , Sabin C. A. , Tolley K. H. , Lee C. A. 
Published: December 2004

Abstract. Miners AH, Sabin CA, Tolley KH, Lee CA (Royal Free Hospital School of Medicine, London; University Hospital Queen's Medical Centre, Nottingham; and Royal Free Hampstead NHS Trust, London, UK). Assessing the effectiveness and cost‐effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease. J Intern Med 1998; 244: 515–22.Objectives To assess the effectiveness and cost‐effectiveness of prophylaxis with clotting factor against bleeding in patients with severe haemophilia and von Willebrand's disease (vWD).Design Treatment details that related to 179 patients with severe (< 1 u dL−1) haemophilia A, B and vWD were retrospectively examined for the period 1980–95. A subgroup of these patients, 25 adults and 22 children, who had previously received treatment on demand and who had switched to treating with prophylaxis, were studied in order to examine the effects of the change. The cost‐effectiveness of prophylaxis was also analysed using another subgroup of 38 patients and by adjusting their treatment details by age and method of treatment.Setting Data were obtained on patients who were solely registered at the Royal Free Hospital Haemophilia Centre (RFHHC), London, UK.Outcome measure Bleeds.Results The median annual number of bleeds decreased from 23.5 (range 1–107) in 1980, to 14 (range 0–45) in 1995 (P < 0.0001). Switching from treating on demand to prophylaxis reduced bleeding frequency in 41 out of 47 patients within the period of 1 year. At the base scenario, switching to prophylaxis cost an additional £547 per averted bleed; however, this figure was highly sensitive to certain variables.Conclusion Prophylaxis can reduce bleeding frequency but requires more clotting factor than treatment on demand. More detailed proof of cost‐effectiveness is likely to require the use of modelling techniques.
Life events and neurocirculatory asthenia. A controlled study
Authors: Sonino N. , Fava G. A. , Fava G. A. , Boscaro M. , Fallo F. 
Published: December 2004

Sonino N, Fava GA, Boscaro M, Fallo F (University of Padova, Padova, University of Bologna, Bologna, Italy; and State University of New York at Buffalo, NY USA). Life events and neurocirculatory asthenia. A controlled study. J Intern Med 1998; 244: 523–8.Objectives : The purpose of this study was to assess the occurrence of stressful life events in the year before the onset of neurocirculatory asthenia.Design : Case‐control retrospective study.Setting : A university medical outpatient clinic.Subjects : A consecutive series of 50 patients with neurocirculatory asthenia and a control group of 50 healthy subjects, matched for sociodemographic variables, were studied.Main outcome measures : Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered to patients and controls.Results : Patients with neurocirculatory asthenia reported significantly more stressful life events than the control group (P < 0.05) and had significantly more of the following: exits (P < 0.05), undesirable (P < 0.05) and uncontrolled (P < 0.01) events. More events that had an objective negative impact (P < 0.001) and more independent events (P = 0.07) were also reported. Ratings of impact and independence were carried out by a blind rater who was unaware whether the event had occurred in patients or controls.Conclusions : The results are suggestive of a strong relationship between stressful life events and neurocirculatory asthenia. This is in agreement with a multifactorial model of pathogenesis in neurocirculatory asthenia and with current understanding of the extensive links of behavioral responses to stress with neurophysiological and biochemical processes.
Planning of clinical trials
Authors: Boissel J.‐P. 
Published: December 2004

Abstract.This article focuses on steps of planning clinical trials most relevant to the question the clinician asks and how this question is properly transformed in a design and a protocol. All steps are important for the data quality or the validity of the results. A clinical trial is an experiment aimed at testing an hypothesis regarding the efficacy of a given intervention on an event, symptom or impaired quality of life in patients with a defined condition and a particular profile. As such, it should meet the fundamentals of scientific discovery that guarantee causality between the observed difference and the intervention. All the planning components are thought according to these fundamentals.
Undertreatment and overtreatment with statins: the Oslo Health Study 2000–2001
Authors: Tonstad S. , Rosvold E. O. , Furu K. , Skurtveit S. 
Published: December 2004

Abstract.Objective.  We examined the prevalence and factors associated with use of cholesterol‐lowering statins in the population.Methods.  Demographic, medical, anthropometric and lifestyle data was obtained from 6233 men and 7521 women born in 1924/25, 1940/41, 1955 and 1960 that participated in the Oslo Health Study 2000–2001. A nonfasting blood sample was collected.Results.  Of subjects with a heart attack, angina, stroke or diabetes 45% of men and 35% of women were taking a statin (P < 0.001). Of subjects with cardiovascular disease (CVD) or diabetes taking statins 61% of men and 40% of women achieved total serum cholesterol levels ≤5 mmol L−1. The odds ratio for taking a statin was increased amongst subjects who also took antihypertensive drug(s) or acetylsalicylic acid, subjects with a family history of coronary heart disease (CHD) and women who had visited the general practitioner within the last year. Amongst presumed healthy subjects use of statins increased from about 1% in women aged 40–45 years, to 7% at age 60 and to 12% at age 75 whilst the corresponding figures for men were 3%, 8% and 9%, respectively. About 22% of men but <2% of women aged 60 who were not taking statins had a 10‐year Framingham CHD risk score >20%. Determinants of statin use were similar to those amongst subjects with CVD or diabetes.Conclusion.  People with CVD or diabetes remain undertreated with statins, women more so than men. Use of other preventive drugs, the family history and recent contact with the general practitioner were the most important determinants of statin use in primary and secondary prevention. Amongst healthy subjects aged 60 or 75 years women received statins disproportionately to their low CHD risk compared with men.
On the evolution of statistical methods as applied to clinical trials
Authors: Machin D. 
Published: December 2004

Abstract.This paper describes how statistical methods have evolved in parallel with activities associated with randomized control trials. In particular we emphasize the pivotal role of two papers published inBritish Journal of Cancer, and the paper describing the Cox proportional hazards model. In addition, the importance of early papers on estimating the sample size required for trials is highlighted. Later developments including the increasing roles for competing risks, multilevel modelling and Bayesian methodologies are described. The interplay between computer software and statistical methodological developments is stressed. Finally some future directions are indicated.
Prognostic value of biochemical markers, 12‐lead ECG and patient characteristics amongst patients calling for an ambulance due to a suspected acute coronary syndrome
Authors: Svensson L. , Axelsson C. , Nordlander R. , Herlitz J. 
Published: December 2004

Abstract.Objectives.  To evaluate whether a 12‐lead ECG, together with a multi‐marker strategy that used point‐of‐care measurements of myoglobin, creatine kinase (CK‐MB) and troponin I, was able to predict patients at short‐ and long‐term risk of death, when simultaneously considering age, gender, previous history, symptoms and clinical findings on arrival of the ambulance.Design.  Prospective observational study.Setting and subjects.  Consecutive patients (n=511) in ambulances in Stockholm and Göteborg in Sweden who called for an ambulance due to chest pain or other symptoms raising a suspicion of acute coronary syndrome.Intervention.  In almost all patients, a diagnostic ECG, patient baseline characteristics and measurements of CK‐MB, troponin I and myoglobin were recorded.Results.  In univariate analysis, the highest 30‐day mortality (17%) was found amongst patients with the combination of ECG signs of myocardial ischaemia and the elevation of any biochemical marker. The highest 1‐year mortality (20%) was found amongst patients with ECG signs of myocardial ischaemia and the elevation of any biochemical marker. Increasing age (RR 1.07; 95 CI 1.02–1.13) lack of symptoms of chest pain and a previous history of hypertension (3.02; 1.08–8.79) were independent predictors of 30‐day mortality. Myoglobin was the only biochemical marker independently associated with 30‐day mortality (6.66; 1.83–22.3). Increasing age (1.11; 1.06–1.16), previous history of diabetes (3.42; 1.41–8.25) heart failure (2.64; 1.26–5.52) and other symptoms than chest pain and dyspnoea (5.23; 2.14–12.76) were independent predictors of 1‐year mortality. In many of the variables the confidence limits were wide.Conclusion.  Amongst patients with a clinical suspicion of acute coronary syndrome, those with the combination of ECG signs of myocardial ischaemia and the elevation of any biochemical marker on arrival of the ambulance form a group with a particularly high risk of death. However, age as well as aspects of clinical history and type of symptoms independently contribute to prognostic information.
Cost‐effectiveness of clopidogrel in acute coronary syndromes in Sweden: a long‐term model based on the cure trial
Authors: Lindgren P. , Jönsson B. , Yusuf S. 
Published: December 2004

Abstract.Objectives.  The purpose of this study was to evaluate the long‐term cost‐effectiveness of clopidogrel on top of standard therapy (including ASA) in patients with acute coronary syndromes without ST‐segment elevation in Sweden.Methods and results.  Incremental cost‐effectiveness ratios (ICER) were assessed using a Markov model with transition probabilities estimated from the Swedish hospital discharge and cause of death registers. Patients were assumed to be treated for 1 year, with treatment effects (RR = 0.8) and costs taken from the Clopidogrel in Unstable Angina to prevent Recurrent ischaemic Events trial. Two scenarios were analysed: with patients similar to those in the trial and with patients similar to those from the register. In the first scenario, the predicted net direct cost was 160€ and the net total cost −54€, which with an incremental survival of 0.12 years give the ICER of 1365€ per life‐year gained from the health care payer perspective (including direct costs) and cost savings from the societal perspective (also including indirect costs). The net costs in the second scenario were 149€, giving an ICER of 1009€ for both perspectives.Conclusions.  Adding clopidogrel to standard therapy including ASA is cost‐effective in the studied setting and compares favourably with other cardiovascular treatment and prevention strategies.
Bayesian approaches for the analysis of population genetic structure: an example fromPlatanthera leucophaea(Orchidaceae)
Authors: Holsinger Kent E. , Wallace Lisa E. 
Published: December 2004

AbstractWe describe four extensions to existing Bayesian methods for the analysis of genetic structure in populations: (i) use of beta distributions to approximate the posterior distribution offand θB; (ii) use of an entropy statistic to describe the amount of information about a parameter derived from the data; (iii) use of the Deviance Information Criterion (DIC) as a model choice criterion for determining whether there is evidence for inbreeding within populations or genetic differentiation among populations; and (iv) use of samples from the posterior distributions forfand θBderived from different data sets to determine whether the estimates are consistent with one another. We illustrate each of these extensions by applying them to data derived from previous alloyzme and random amplified polymorphic DNA surveys of an endangered orchid,Platanthera leucophaea, and we conclude that differences in θBfrom the two data sets may represent differences in the underlying mutational processes.
Effect of unsampled populations on the estimation of population sizes and migration rates between sampled populations
Authors: Beerli Peter 
Published: December 2004

AbstractCurrent estimators of gene flow come in two methods; those that estimate parameters assuming that the populations investigated are a small random sample of a large number of populations and those that assume that all populations were sampled. Maximum likelihood or Bayesian approaches that estimate the migration rates and population sizes directly using coalescent theory can easily accommodate datasets that contain a population that has no data, a so‐called ‘ghost’ population. This manipulation allows us to explore the effects of missing populations on the estimation of population sizes and migration rates between two specific populations. The biases of the inferred population parameters depend on the magnitude of the migration rate from the unknown populations. The effects on the population sizes are larger than the effects on the migration rates. The more immigrants from the unknown populations that are arriving in the sample populations the larger the estimated population sizes. Taking into account a ghost population improves or at least does not harm the estimation of population sizes. Estimates of the scaled migration rateM(migration rate per generation divided by the mutation rate per generation) are fairly robust as long as migration rates from the unknown populations are not huge. The inclusion of a ghost population does not improve the estimation of the migration rateM; when the migration rates are estimated as the number of immigrants Nm then a ghost population improves the estimates because of its effect on population size estimation. It seems that for ‘real world’ analyses one should carefully choose which populations to sample, but there is no need to sample every population in the neighbourhood of a population of interest.
Evaluating the performance of likelihood methods for detecting population structure and migration
Authors: Abdo ZAID , Crandall Keith A. , Joyce PAUL 
Published: December 2004

AbstractA plethora of statistical models have recently been developed to estimate components of population genetic history. Very few of these methods, however, have been adequately evaluated for their performance in accurately estimating population genetic parameters of interest. In this paper, we continue a research program of evaluation of population genetic methods through computer simulation. Specifically, we examine the software migratee‐n 1.6.8 and test the accuracy of this software to estimate genetic diversity (Θ), migration rates, and confidence intervals. We simulated nucleotide sequence data under a neutral coalescent model with lengths of 500 bp and 1000 bp, and with three different per site Θ values of (0.00025, 0.0025, 0.025) crossed with four different migration rates (0.0000025, 0.025, 0.25, 2.5) to construct 1000 evolutionary trees per‐combination per‐sequence‐length. We found that while migratee‐n 1.6.8 performs reasonably well in estimating genetic diversity (Θ), it does poorly at estimating migration rates and the confidence intervals associated with them. We recommend researchers use this software with caution under conditions similar to those used in this evaluation.
Microsatellite variation and population structure in a declining Australian HylidLitoria aurea
Authors: Burns Emma L. , Eldridge Mark D. B. , Houlden Bronwyn A. 
Published: December 2004

AbstractThe green and golden bell frog (Litoria aurea) was once a common Australian Hylid. Today, many populations are small and fragmented as a result of dramatic declines in distribution and abundance. We undertook a large‐scale assessment of genetic structure and diversity inL. aureausing four species‐specific microsatellite markers. Twenty‐one locations were sampled from throughout the species range covering 1000 km of the east coast of Australia. Levels of allelic diversity and heterozygosity were high (uncorrected mean alleles/locus andHEwere 4.8–8.8 and 0.43–0.8, respectively) compared to other amphibian species and significant differences among sampled sites were recorded. Despite recent population declines, no sites displayed a genetic signature indicative of a population bottleneck. Significant genetic structuring (overallFST0.172) was detected throughout the species range, but was relatively low compared to previous amphibian studies employing microsatellites. In addition we found that some areas sampled within continuous habitat showed evidence of weak genetic structuring (data subsetFST0.034). We conclude that maintaining areas of continuous habitat is critical to the conservation of the species and argue that population recovery and/or persistence in all areas sampled is possible if appropriate protection and management are afforded.
‘O father: where art thou?’— Paternity assessment in an open fission–fusion society of wild bottlenose dolphins (Tursiopssp.) in Shark Bay, Western Australia
Authors: Krützen Michael , Barré Lynne M. , Connor Richard C. , Mann Janet , Sherwin William B. 
Published: December 2004

AbstractSexually mature male bottlenose dolphins in Shark Bay cooperate by pursuing distinct alliance strategies to monopolize females in reproductive condition. We present the results of a comprehensive study in a wild cetacean population to test whether male alliance membership is a prerequisite for reproductive success. We compared two methods for inferring paternity: both calculate a likelihood ratio, called the paternity index, between two opposing hypotheses, but they differ in the way that significance is applied to the data. The first method, a Bayesian approach commonly used in human paternity testing, appeared to be overly conservative for our data set, but would be less susceptible to assumptions if a larger number of microsatellite loci had been used. Using the second approach, the computer programcervus2.0, we successfully assigned 11 paternities to nine males, and 17 paternities to 14 out of 139 sexually mature males at 95% and 80% confidence levels, respectively. It appears that being a member of a bottlenose dolphin alliance is not a prerequisite for paternity: two paternities were obtained by juvenile males (one at the 95%, the other at the 80% confidence level), suggesting that young males without alliance partners pursue different mating tactics to adults. Likelihood analyses showed that these two juvenile males were significantly more likely to be the true father of the offspring than to be their half‐sibling (P < 0.05). Using paternity data at an 80% confidence level, we could show that reproductive success was significantly skewed within at least some stable first‐order alliances (P < 0.01). Interestingly, there is powerful evidence that one mating was incestuous, with one calf apparently fathered by its mother's father (P < 0.01). Our study suggests that the reproductive success of both allied males, and of nonallied juveniles, needs to be incorporated into an adaptive framework that seeks to explain alliance formation in male bottlenose dolphins.
Very low genetic variability in the Indian queenless ant Diacamma indicum
Authors: Viginier B. , Peeters C. , Brazier L. , Doums C. 
Published: December 2004

AbstractWe developed microsatellite markers and combined them with mitochondrial markers to analyse the population genetic structure of the queenless ant Diacamma indicum. This species, lacking winged queens, is likely to have a restricted female dispersal but exhibits various life history traits suggesting higher dispersal abilities than the other Diacamma species. Only 4 of 11 microsatellites were polymorphic and only 1 had more than 4 alleles over 166 individuals originating from 7 populations from the south of India. Only one mitochondrial DNA (mtDNA) haplotype was detected throughout India (including one population in the north) and Sri Lanka. Such a level of polymorphism is particularly low compared with other Diacamma species having much smaller ranges in the south of India. A strong genetic differentiation was observed between populations separated by more than a few kilometres. We also analysed the genetic differentiation between the Indian populations and two populations from the Japanese island of Okinawa, which are morphologically similar and might belong to the same species. The genetic differentiation was high for both markers, suggesting an absence of ongoing gene flow between these populations.
Distribution of the bacterial symbiont Cardinium in arthropods
Authors: ZCHORI‐FEIN EINAT , PERLMAN STEVE J. 
Published: December 2004

Abstract‘Candidatus Cardinium’, a recently described bacterium from the Bacteroidetes group, is involved in diverse reproduction alterations of its arthropod hosts, including cytoplasmic incompatibility, parthenogenesis and feminization. To estimate the incidence rate of Cardinium and explore the limits of its host range, 99 insect and mite species were screened, using primers designed to amplify a portion of Cardinium 16S ribosomal DNA (rDNA). These arthropods were also screened for the presence of the better‐known reproductive manipulator, Wolbachia. Six per cent of the species screened tested positive for Cardinium, compared with 24% positive for Wolbachia. Of the 85 insects screened, Cardinium was found in four parasitic wasp species and one armoured scale insect. Of the 14 mite species examined, one predatory mite was found to carry the symbiont. A phylogenetic analysis of all known Cardinium 16S rDNA sequences shows that distantly related arthropods can harbour closely related symbionts, a pattern typical of horizontal transmission. However, closely related Cardinium were found to cluster among closely related hosts, suggesting host specialization and horizontal transmission among closely related hosts. Finally, the primers used revealed the presence of a second lineage of Bacteroidetes symbionts, not related to Cardinium, in two insect species. This second symbiont lineage is closely allied with other arthropod symbionts, such as Blattabacterium, the primary symbionts of cockroaches, and male‐killing symbionts of ladybird beetles. The combined data suggest the presence of a diverse assemblage of arthropod‐associated Bacteroidetes bacteria that are likely to strongly influence their hosts’ biology.