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Biomedical subjects

Robert K Hills

Publications and source records attributed to Robert K Hills.

10 recordsLinked to original sources

Assessing new interventions in women's health.

One of the most frequent clichés in evidence-based medicine (EBM) is that 'without evidence there can be no evidence-based practice'. How best to assemble evidence on the effectiveness (or ineffectiveness) of a treatment is central to the entire concept of EBM. Particularly in women's health, where even small or moderate improvements in the individual well-being of one woman can lead to an enormous impact on the overall health of the nation, it is important to be able to detect or refute reliably small to moderate treatment effects. Evidence must come from studies where biases and random errors have been minimised, which requires large scale randomised controlled trials, the methodology of which is relatively familiar. However, the challenges peculiar to running trials in women's health have been less fully considered. This article draws on examples from the literature to illustrate many of the principles that need to be considered when running, or assessing, a trial of an intervention in women's health.

Bias↗

Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials.

Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience in the Medical Research Council (MRC) AML 10 and AML 12 trials, which enrolled 46 children with ML-DS from 1988 to 2002. Eight per cent of UK children with AML had DS, but DS children comprised only 5% of children registered in MRC trials. The unique clinical characteristics of ML-DS were confirmed. Overall survival (OS) of ML-DS at 5 years increased from 47% in UK children diagnosed from 1988 to 1995 to 75% in children diagnosed from 1996 to 2002. OS for DS children registered in AML 10 and AML 12 was 74% in 5 years and improved from AML 10 to AML 12 (56% vs. 83%) There was no significant difference in OS between DS and non-DS children (OS: 74% vs. 62%, P = 0.4) in the trials, but this result masked a significant increase in early death amongst DS children, with a significant reduction in mortality later on. Relapse was significantly reduced (3% vs. 39%, P = 0.0003), leading to the improved disease-free survival (83% vs. 56%, P = 0.02). Given the increased number of early treatment-related deaths, future treatment protocols should aim to reduce chemotherapy dosage or intensity whilst maintaining low rates of resistant and recurrent disease.

Adolescent↗

A randomised-controlled trial in England of a postnatal midwifery intervention on breast-feeding duration.

OBJECTIVE: To determine whether postnatal 'hands off' care by midwives on positioning and attachment of the newborn baby improves breast-feeding duration. DESIGN: Mothers were randomised at the first postnatal feed to receive either care by a midwife trained in the experimental protocol or by a control midwife undertaking routine care. SETTING: Eight wards in four English Midlands hospitals. PARTICIPANTS: 370 primiparous mothers with term babies who intended to breast feed, and could sit out of bed to do so. INTERVENTIONS: Experimental protocol of verbal-only advice on positioning and attachment, delivered at the first postnatal ward feed compared with routine care by a qualified midwife. MAIN OUTCOME MEASURES: Duration of breast feeding up to 17 weeks as assessed by diaries and interviews with mothers and protocol adherence from self-completed checklist by the midwife. The mothers' self-reported experience of care and support before, during and after delivery were assessed at 6 weeks, and feeding outcomes and employment status at 17 weeks. FINDINGS: Experimental group mothers more often held the baby across their lap and received 'hands off advice', but fewer babies in the experimental than control groups attached and fed: 59% (106/180) vs. 67% (118/175), p=0.1. No significant differences were found in the numbers of mothers breast feeding at 6 or 17 weeks in the experimental and control groups (stopped exclusive breast feeding: 76% (130/172) vs. 77% (126/163) at 6 weeks; 96% (167/174) vs. 96% (161/168) at 17 weeks; odds ratio 1.02, 95% CI 0.77 to 1.22; p=0.8; stopped any breast feeding: 35% (61/172) vs. 32% (53/167) at 6 weeks; 63% (109/173) vs. 60% (101/167) at 17 weeks; odds ratio 1.10, 0.84 to 1.45; p=0.5). There were no significant differences in the incidence of problems with breast feeding and care experienced by mothers before or during hospitalisation (other than at the first postnatal ward feed), nor after discharge home. CONCLUSIONS: No significant beneficial effect was found on breast-feeding duration of the verbal- only advice on positioning and attachment, perhaps because aspects of the intervention are already within routine UK practice. Other care practices at subsequent feeds may negate benefits of care at earlier feeds. 'Hands off' care at the first feed may be less important to subsequent feeding than achieving a first feed under supervision in the postnatal ward. IMPLICATIONS FOR PRACTICE: Midwives can be trained in a 4-hr workshop to achieve improved knowledge of 'hands off' positioning and attachment care, and these can be translated into clinical practice. Future studies should differentiate the elements of the care that are effective in achieving postnatal feeds, and apply this advice consistently at successive feeds.

Adult↗

Measurement of beliefs about effectiveness of laparoscopic uterosacral nerve ablation.

To explore gynaecologists' 'prior' beliefs on effectiveness of laparoscopic uterosacral nerve ablation (LUNA), a structured survey was used to gather information on the distribution of their prior beliefs regarding the effects of LUNA on pelvic pain, both numerically [on a 10-point visual analogue scale] and by responses to a questionnaire. None of the 25 gynaecologists responding to the questionnaire stated that LUNA would increase pain, while two of the 25 gave numerical answers suggesting they believed that the intervention would worsen the pain. The most widely held 'prior belief', reflected in both questionnaire and numerical responses, was that LUNA would have a small beneficial effect on pain.

Attitude of Health Personnel↗

Genetic variation in XPD predicts treatment outcome and risk of acute myeloid leukemia following chemotherapy.

The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase that functions in nucleotide excision repair of chemotherapy-induced DNA damage, the efficiency of which is predicted to be affected by a lysine to glutamine variant at codon 751. We hypothesized that this constitutive genetic variant may modify clinical response to chemotherapy, and we have examined its association with outcome following chemotherapy for acute myeloid leukemia (AML) in 341 elderly patients entered into the United Kingdom Medical Research Council AML 11 trial, and with the risk of developing chemotherapy-related AML. Among subjects treated for AML, disease-free survival at one year was 44% for lysine homozygotes, compared with 36% for heterozygotes and 16% for glutamine homozygotes (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.01-1.70; P = .04). Similarly, overall survival at one year was 38% for lysine homozygotes, 35% for heterozygotes, and 23% for glutamine homozygotes (HR, 1.18; 95% CI, 0.99-1.41; P = .07). Furthermore, homozygosity for the XPD codon 751 glutamine variant was associated with a significantly increased risk of developing AML after chemotherapy (odds ratio, 2.22 for Gln/Gln vs Lys/Lys; 95% CI, 1.04-4.74). These data suggest that the XPD codon 751 glutamine variant protects against myeloid cell death after chemotherapy.

Adolescent↗

Continuous versus interrupted perineal repair with standard or rapidly absorbed sutures after spontaneous vaginal birth: a randomised controlled trial.

BACKGROUND: Trauma to the perineum is a serious and frequent problem after childbirth, with about 350000 women each year in the UK needing sutures for perineal injury after spontaneous vaginal delivery, and many millions more worldwide. We compared the continuous technique of perineal repair with the interrupted method, and the more rapidly absorbed polyglactin 910 suture material with the standard polyglactin 910 material. METHODS: 1542 women who had a spontaneous vaginal delivery with a second-degree perineal tear or episiotomy were randomly allocated to either the continuous (n=771) or interrupted (771) suturing method, and to either the more rapidly absorbed polyglactin 910 suture material (772) or standard polyglactin 910 material (770). Primary outcomes were pain 10 days after delivery and superficial dyspareunia 3 months postpartum. Analysis was by intention to treat. FINDINGS: At day 10, three women had dropped out of the study. Significantly fewer women reported pain at 10 days with the continuous technique than with the interrupted method (204/770 [26.5%] vs 338/769 [44.0%], odds ratio 0.47, 95% CI 0.38-0.58, p<0.0001). Occurrence of pain did not differ significantly between groups assigned the more rapidly absorbed material or standard material (256/769 [33.3%] vs 286/770 [37.1%], 0.84, 0.68-1.04, p=0.10). Women reported no difference in superficial dyspareunia at 3 months for the continuous vs the interrupted method (98/581 [16.9%] vs 102/593 [17.2%], 0.98, 0.72-1.33, p=0.88) or the more rapidly absorbed versus standard material (105/586 [17.9%] vs 95/588 [16.2%], 1.13, 0.84-1.54, p=0.42). Suture removal was done less with the more rapidly absorbed material than with standard suture material (22/769 [3%] vs 98/770 [13%], p<0.0001), and with the continuous versus interrupted method (24/770 [3%] vs 96/769 [12%], p<0.0001). INTERPRETATION: A simple and widely practicable continuous repair technique can prevent one woman in six from having pain at 10 days. Also, the more rapidly absorbed polyglactin 910 material obviates need for suture removal up to 3 months postpartum for one in ten women sutured.

Adult↗