The role of the hormone relaxin in human reproduction

The polypeptide hormone relaxin has only recently been confirmed to be present in the human and specific roles for it in the human have not been delineated. The main aim of this thesis is to examine possible roles for this hormone in the human specifically in the areas of implantation of the fertilised ovum, the maintenance of myometrial quiescence during pregnancy and the facilitation of cervical ripening at parturition. As human relaxin was not available at the beginning or during any of these studies, pure porcine relaxin and a porcine relaxin radioimmunoassay were used to investigate the likely role of relaxin in the human. These studies have involved newly developed methods to purify extensive amounts of pure porcine relaxin for laboratory and clinical trials and the development of a homologous porcine relaxin radioimmunoassay for its heterologous application in measuring relaxin-like immunoactivity in the human. Where ethically and practically possible the studies were designed to investigate the role of the hormone relaxin in the human using human samples or by conducting clinical trials. However, where this was not possible, ainimal or in vitro studies have been performed to further define relaxin's possible role in reproduction

Rationing of total knee replacement: a cost-effectiveness analysis on a large trial data set

PMID: 22290396 [PubMed] PMCID: PMC3269047 Free PMC ArticlePeer reviewedPublisher PD

Partial factorial trials : comparing methods for statistical analysis and economic evaluation

The KAT trial was funded by the National Institute Health for Research (NIHR) Health Technology Assessment Programme (project number 95/10/01) and has been published in full in Health Technology Assessment. The NIHR provided partial funding of the Health Economics Research Centre during the time this research was undertaken. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.Peer reviewedPublisher PD

Brain damage and maternal medication

Michael E. O’Callaghan, Alastair H. MacLenna

Seminars may increase recruitment to randomised controlled trials: lessons learned from WISDOM

Background: Recruiting patients to large randomised controlled trials (RCTs) in the primary care setting can be challenging. Research teams need to identify and utilise strategies that both maximise the efficiency of recruitment and minimise the burden on general practitioners. Purpose: To describe our methods for identifying, approaching and recruiting female patients aged 50–69 years to a long-term double-blind RCT of hormone therapy (HT) – the Women's International Study of long Duration Oestrogen after Menopause (WISDOM). The effectiveness of conducting group seminars with patients prior to one-to-one screening is discussed. Methods: Female patients aged between 50 and 69 years were sent letters from participating general practitioners in Adelaide inviting them to participate in WISDOM and attend an initial seminar providing information about HT and the trial prior to a screening interview with a trial nurse. Recruitment rates for those who did or did not attend group seminars were compared. Results: Women who attended a group seminar conducted by the research team were twice as likely to attend an initial screening visit and enrol to participate in WISDOM than women who did not attend a seminar (p < 0.001). In addition, it was estimated that the time required to randomise a woman in the trial, and the number and duration of telephone calls to screen out uninterested women, was reduced for the seminar group. Conclusion: Conducting group seminars with potential participants may be a useful strategy for maximising recruitment from general practice, by increasing patient information and reducing a research team's workload.Bronwen J. Paine, Nigel P. Stocks and Alastair H. MacLenna

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

Peer reviewedPublisher PD

The Knee Arthroplasty Trial (KAT) : design features, baseline characteristics and two-year functional outcomes after alternative approaches to knee replacement

Background: The aim of continued development of total knee replacement systems has been the further improvement of the quality of life and increasing the duration of prosthetic survival. Our goal was to evaluate the effects of several design features, including metal backing of the tibial component, patellar resurfacing, and a mobile bearing between the tibial and femoral components, on the function and survival of the implant. Methods: A pragmatic, multicenter, randomized, controlled trial involving 116 surgeons in thirty-four centers in the United Kingdom was performed; 2352 participants were randomly allocated to be treated with or without a metal backing of the tibial component (409), with or without patellar resurfacing (1715), and/or with or without a mobile bearing (539). Randomization to more than one comparison was allowed. The primary outcome measures were the Oxford Knee Score (OKS), Short Form-12, EuroQol-5D, and the need for additional surgery. The results up to two years postoperatively are reported. Results: Functional status and quality-of-life scores were low at baseline but improved markedly across all trial groups following knee replacement (mean overall OKS, 17.98 points at baseline and 34.82 points at two years). Most of the change was observed at three months after the surgery. Six percent of the patients had additional knee surgery within two years. There was no evidence of differences in clinical, functional, or quality-of-life measures between the randomized groups at two years. Conclusions: Patients have substantial improvement following total knee replacement. This is the first adequately powered randomized controlled trial, of which we are aware, in which the effects of metal backing, patellar resurfacing, and a mobile bearing were investigated. We found no evidence of an effect of these variants on the rate of early complications or on functional recovery up to two years after total knee replacement. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.NIHR Health Technology Assessment Programme (Project Number 95/10/01); Howmedica Osteonics; Zimmer; DePuy, a Johnson and Johnson company; Corin Medical; Smith and Nephew Healthcare. Biomet Merck; and Wright CremascoliPeer reviewe

The antenatal causes of cerebral palsy - Genetic and viral associations

Cerebral palsy is the most common neurological disorder in children. Epidemiological evidence suggests that antenatal origins are a major cause. Currently there is no antenatal test for cerebral palsy, no proven preventable measures in late pregnancy, and no known cure. Cerebral palsy affects not only the diagnosed child, but also their family and the community, requiring considerable social and financial resources to assist these children in their daily lives.Catherine S. Gibson, Alastair H. MacLennan, Paul N. Goldwater, and Gustaaf A. Dekker for The South Australian Cerebral Palsy Research Grou