Case study : a patient-clinician collaboration that identified and prioritized evidence gaps and stimulated research development

Copyright © 2013 Elsevier Inc. All rights reserved.Peer reviewedPostprin

The introduction of new interventional procedures in the British National Health Service : A qualitative study

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.Peer reviewedPostprin

New postnatal urinary incontinence: obstetric and other risk factors in primparae.

Objective To identify obstetric and other risk factors for urinary incontinence which occurs during pregnancy or after childbirth. Design Questionnaire survey of women. Setting Maternity units in Aberdeen (Scotland), Birmingham (England) and Dunedin (New Zealand). Population 3405 primiparous women with singleton births delivered during one year. Methods Questionnaire responses and obstetric casenote data were analysed using multivariate analysis to identify associations with urinary incontinence. Main outcome measures Urinary incontinence at three months after delivery first starting in pregnancy or after birth. Results The prevalence of urinary incontinence was 29%. New incontinence first beginning after delivery was associated with higher maternal age (oldest versus youngest group, odds ratio, OR 2.02, 95% CI 1.35 to 3.02); and method of delivery (caesarean section versus spontaneous vaginal delivery, OR 0.28, 95% CI 0.19 to 0.41). There were no significant associations with forceps delivery (OR 1.18, 95% CI 0.92 to 1.51) or vacuum delivery (OR 1.16, 95% CI 0.83 to 1.63). Incontinence first occurring during pregnancy and still present at three months was associated with higher maternal body mass index (BMI > 25, OR 1.68, 95% CI 1.16 to 2.43), and heavier babies (birthweight in top quartile, OR 1.56, 95% CI 1.12 to 2.19). In these women, caesarean section was associated with less incontinence (OR 0.39, 95% CI 0.27 to 0.58) but incontinence was not associated with age. Conclusions Women have less urinary incontinence after a first delivery by caesarean section whether or not that first starts during pregnancy. Older maternal age was associated with new postnatal incontinence, and higher body mass index and heavier babies with incontinence first starting during pregnancy. The effect of further deliveries may modify these findings

Assessment of the learning curve in health technologies: a systematic review

Objective: We reviewed and appraised the methods by which the issue of the learning curve has been addressed during health technology assessment in the past. Method: We performed a systematic review of papers in clinical databases (BIOSIS, CINAHL, Cochrane Library, EMBASE, HealthSTAR, MEDLINE, Science Citation Index, and Social Science Citation Index) using the search term "learning curve:" Results: The clinical search retrieved 4,571 abstracts for assessment, of which 559 (12%) published articles were eligible for review. Of these, 272 were judged to have formally assessed a learning curve. The procedures assessed were minimal access (51%), other surgical (41%), and diagnostic (8%). The majority of the studies were case series (95%). Some 47% of studies addressed only individual operator performance and 52% addressed institutional performance. The data were collected prospectively in 40%, retrospectively in 26%, and the method was unclear for 31%. The statistical methods used were simple graphs (44%), splitting the data chronologically and performing a t test or chi-squared test (60%), curve fitting (12%), and other model fitting (5%). Conclusions: Learning curves are rarely considered formally in health technology assessment. Where they are, the reporting of the studies and the statistical methods used are weak. As a minimum, reporting of learning should include the number and experience of the operators and a detailed description of data collection. Improved statistical methods would enhance the assessment of health technologies that require learning

Assessing the learning curve effect in health technologies: Lessons from the non-clinical literature

Introduction: Many health technologies exhibit some form of learning effect, and this represents a barrier to rigorous assessment. It has been shown that the statistical methods used are relatively crude. Methods to describe learning curves in fields outside medicine, for example, psychology and engineering, may be better. Methods: To systematically search non–health technology assessment literature (for example, PsycLit and Econlit databases) to identify novel statistical techniques applied to learning curves. Results: The search retrieved 9,431 abstracts for assessment, of which 18 used a statistical technique for analyzing learning effects that had not previously been identified in the clinical literature. The newly identified methods were combined with those previously used in health technology assessment, and categorized into four groups of increasing complexity: a) exploratory data analysis; b) simple data analysis; c) complex data analysis; and d) generic methods. All the complex structured data techniques for analyzing learning effects were identified in the nonclinical literature, and these emphasized the importance of estimating intra- and interindividual learning effects. Conclusion: A good dividend of more sophisticated methods was obtained by searching in nonclinical fields. These methods now require formal testing on health technology data sets

Subversion of allocation concealment in a randomised controlled trial : a historical case study

BACKGROUND: If the randomisation process within a trial is subverted, this can lead to selection bias that may invalidate the trial's result. To avoid this problem, it is recommended that some form of concealment should be put into place. Despite ongoing anecdotal concerns about their susceptibility to subversion, a surprising number of trials (over 10%) still use sealed opaque envelopes as the randomisation method of choice. This is likely due in part to the paucity of empirical data quantifying the potential effects of subversion. In this study we report a historical before and after study that compares the use of the sealed envelope method with a more secure centralised telephone allocation approach in order to provide such empirical evidence of the effects of subversion. METHODS: This was an opportunistic before and after study set within a multi-centre surgical trial, which involved 654 patients from 28 clinicians from 23 centres in the UK and Ireland. Two methods of randomly allocating subjects to alternative treatments were adopted: (a) a sealed envelope system administered locally, and (b) a centralised telephone system administered by the trial co-ordination centre. Key prognostic variables were compared between randomisation methods: (a) age at trial entry, a key prognostic factor in the study, and (b) the order in which 'randomisation envelopes' were matched to subjects. RESULTS: The median age of patients allocated to the experimental group with the sealed envelope system, was significantly lower both overall (59 vs 63 years, p < 0.01) and in particular for three clinicians (57 vs 72, p < 0.01; 33 vs 69, p < 0.001; 47 vs 72, p = 0.03). No differences in median age were found between the allocation groups for the centralised system. CONCLUSIONS: Due to inadequate allocation concealment with the sealed envelope system, the randomisation process was corrupted for patients recruited from three clinicians. Centralised randomisation ensures that treatment allocation is not only secure but seen to be secure. Where this proves to be impossible, allocation should at least be performed by an independent third party. Unless it is an absolute requirement, the use of sealed envelopes should be discontinued forthwith

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of different knee prostheses : the Knee Arthroplasty Trial (KAT)

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Deficiency in the mouse mitochondrial adenine nucleotide translocator isoform 2 gene is associated with cardiac noncompaction.

The mouse fetal and adult hearts express two adenine nucleotide translocator (ANT) isoform genes. The predominant isoform is the heart-muscle-brain ANT-isoform gene 1 (Ant1) while the other is the systemic Ant2 gene. Genetic inactivation of the Ant1 gene does not impair fetal development but results in hypertrophic cardiomyopathy in postnatal mice. Using a knockin X-linked Ant2 allele in which exons 3 and 4 are flanked by loxP sites combined in males with a protamine 1 promoter driven Cre recombinase we created females heterozygous for a null Ant2 allele. Crossing the heterozygous females with the Ant2(fl), PrmCre(+) males resulted in male and female ANT2-null embryos. These fetuses proved to be embryonic lethal by day E14.5 in association with cardiac developmental failure, immature cardiomyocytes having swollen mitochondria, cardiomyocyte hyperproliferation, and cardiac failure due to hypertrabeculation/noncompaction. ANTs have two main functions, mitochondrial-cytosol ATP/ADP exchange and modulation of the mitochondrial permeability transition pore (mtPTP). Previous studies imply that ANT2 biases the mtPTP toward closed while ANT1 biases the mtPTP toward open. It has been reported that immature cardiomyocytes have a constitutively opened mtPTP, the closure of which signals the maturation of cardiomyocytes. Therefore, we hypothesize that the developmental toxicity of the Ant2 null mutation may be the result of biasing the cardiomyocyte mtPTP to remain open thus impairing cardiomyocyte maturation and resulting in cardiomyocyte hyperproliferation and failure of trabecular maturation. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi

Equilibrium partitioning and isotopic fractionation of nitrogen between biotite, plagioclase, and K-feldspar during magmatic differentiation

Funding: UK Natural Environment Research Council (NE/R012253/1, NE/V010824/1, NE/P012167/1)A significant portion of the continental crust is composed of plutonic igneous rocks. However, little is known about the geochemical behaviour of N between the different minerals during magmatic differentiation. To provide new constraints for the behaviour of N during crust formation, we have characterised the geochemistry of nitrogen (N) in the compositionally zoned calc-alkaline pluton at Loch Doon, SW Scotland. We present N concentration and N isotope values for whole-rock data alongside biotite, plagioclase and K-feldspar mineral separates and assess the degree to which these data preserve equilibrium partitioning during magmatic differentiation. We show that whole rock likely inherited its N contents and δ15N signatures from the initial source composition and that this signature is homogenous at a pluton scale. Whilst the whole-rock data are best explained as crust-derived N in the source, the degree of homogenisation across a pluton scale is inconsistent with empirical N diffusivities, ruling out syn-emplacement crustal assimilation as the source of N. Instead, our data suggest a crustal signature inherited from depth associated with the Iapetus subduction zone. At a mineral scale, we find that N preferentially partitions into the feldspars over mica in this system in the order K-feldspar > plagioclase ≈ biotite > quartz, with average mineral-mineral distribution coefficients of DNplagioclase-biotite = 1.3 ± 0.6 and DNKspar-biotite = 2.8 ± 0.6. Partitioning is accompanied by a large and near constant equilibrium isotope fractionation factor between biotite and both feldspars (averages are Δ15NPlag-Biotite = +7.8 ± 1.2 ‰ and Δ15NKspar-Biotite = +7.9 ± 1.0 ‰), whereas Δ15NKspar-Plagioclase closely approximates 0 ‰, where both minerals show δ15N overlapping with the bulk rock δ15N values. These results show that mica crystallisation generates in a large negative Δ15N resulting a 15N-depleted reservoir within plutonic rocks. Moreover, our dataset suggests that feldspars might be a more significant host of N in the igneous portion of Earth’s continental and oceanic crust than previous thought.Publisher PDFPeer reviewe

Marketing and clinical trials: a case study.

BACKGROUND: Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. METHODS: Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. RESULTS: The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. CONCLUSION: The performance of future clinical trials could be enhanced if trialists routinely considered these factors