Standard- or high-dose oxytocin for nulliparous women with confirmed delay in labour: quantitative and qualitative results from a pilot randomised controlled trial.

OBJECTIVE: Evidence suggests that a high dose of oxytocin for nulliparous women at 37-42 weeks of gestation with confirmed delay in labour increases spontaneous vaginal birth. We undertook a pilot study to test the feasibility of this treatment. DESIGN: Pilot double-blind randomised controlled trial. SETTING: Three teaching hospitals in the UK. POPULATION: A total of 94 consenting nulliparous women at term with confirmed delay in labour were recruited, and 18 were interviewed. METHODS: Women were assigned to either a standard (2 mU/min, increasing every 30 minutes to 32 mU/minute) or a high-dose regimen (4 mU/minute, increasing every 30 minutes to 64 mU/minutes) oxytocin by computer-generated randomisation. Simple descriptive statistics were used, as the sample size was insufficient to evaluate clinical outcomes. The constant comparative method was used to analyse the interviews. MAIN OUTCOMES MEASURES: The main outcome measures: number of women eligible; maternal and neonatal birth; safety; maternal psychological outcomes and experiences; health-related quality of life outcomes using validated tools and data on health service resource use; incidence of suspected delay of labour (cervical dilatation of <2 cm after 4 hours, once labour is established); and incidence of confirmed delay of labour (progress of <1 cm on repeat vaginal examination after a period of 2 hours). RESULTS: We successfully developed systems to recruit eligible women in labour and to collect data. Rates of spontaneous vaginal birth (10/47 versus 12/47, RR 1.2, 95% CI 0.6-2.5) and caesarean section (15/47 versus 17/47, RR 1.1, 95% CI 0.6-2.0) were increased, and rates of instrumental birth were reduced (21/47 versus 17/47, RR 0.8, 95% CI 0.5-1.3). No evidence of increased harm for either mother or baby was found. The incidences of suspected delay (14%) and confirmed delay (11%) in labour were less than anticipated. Of those who did not go on to have delayed labour confirmed, all except one woman gave birth vaginally. CONCLUSIONS: A pilot trial assessing the efficacy of high-dose oxytocin was feasible, but uncertainty remains, highlighting the need for a large definitive trial. The implementation of national guidance of suspected and confirmed delay in labour is likely to reduce intervention.

How will it work? A qualitative study of strategic stakeholders' accounts of a patient safety initiative.

OBJECTIVES: Implementation of quality improvement programmes may suffer if the stakeholders involved do not share a common understanding of the theory of change or do not accept it as legitimate. We aimed to identify how strategic stakeholders understood and responded to the first phase of the Health Foundation's Safer Patients Initiative, a programme aimed at making hospitals safer for patients in the UK. METHODS: Semistructured telephone interviews were conducted with 60 strategic-level hospital stakeholders and with five stakeholders involved in commissioning, designing and introducing the initiative. Analysis was based on the constant comparative method. RESULTS: The aims of the initiative were seen as legitimate and sound by most hospital stakeholders, and the theory of change was generally understood and accepted, but seven hospital stakeholders were unable to describe it. Although participants had specific doubts, particularly relating to feasibility of implementation and scientific legitimacy of some elements of the initiative, overall there was a broadly shared vision and commitment to the principles and practices associated with the theory of change, and considerable enthusiasm and optimism. Contestations about the legitimacy and relevance of the initiative among front-line staff, local resistance to changes that went against established norms, and resource and structural issues were, however, seen as potentially threatening to implementation. CONCLUSIONS: It is possible to get strategic-level individuals, even when widely dispersed, to understand and agree upon a theory of change that can be used in their organisations. These individuals are also able to recognise the contexts of negotiation in which programmes of change are enacted.

Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial.

The effect of fish oil on the course of ulcerative colitis was investigated in a randomised blinded controlled study. Eighty seven patients received supplements of 20 ml HiEPA fish oil as triglyceride (4.5 g of eicosapentaenoic acid) or olive oil placebo daily for one year. The oils were given in addition to standard drug therapy and trial entry was stratified for disease activity. Fish oil significantly increased the eicosapentaenoic acid content of rectal mucosa to 3.2% of total fatty acids at six months, compared with 0.63% for patients on olive oil. This was associated with increased synthesis of leukotriene B5, and 53% suppression of leukotriene B4 synthesis by ionophore--stimulated neutrophils. Leukotriene B4 suppression persisted for at least two months after treatment was stopped. Treatment with fish oil resulted in measurable, but only limited clinical benefit. For patients entering the trial in relapse (n = 53), there was a significant reduction in corticosteroid requirement after one and two months treatment. There was a trend towards achieving remission (off corticosteroids) faster in the patients on fish oil, although differences were not significant. For patients in remission at trial entry or during the trial (n = 69), there was no significant difference in the rate of relapse by log rank analysis. We conclude that fish oil supplementation produces a modest corticosteroid sparing effect in active disease, but there is no benefit in maintenance therapy.

Effect in man of aspirin, standard indomethacin, and sustained release indomethacin preparations on gastric bleeding.

1. We have compared acute gastric bleeding caused by a new slow release preparation of indomethacin (indomethacin Continus) with that caused by aspirin and other indomethacin preparations. 2. In a randomized crossover study, blood loss into timed gastric aspirates was determined in 20 healthy volunteers after receiving, over 96 h, either placebo, aspirin (600 mg four times daily; 17 doses) indomethacin BP (50 mg three times daily; 13 doses), Indocid-R (75 mg twice daily; 9 doses) or indomethacin Continus (75 mg twice daily; 9 doses). A venous blood sample was also taken during each treatment period for subsequent determination of alpha 1-glycoprotein, and for drug assay. 3. Gastric bleeding on placebo was 1.4 (0.7-2.8) microliters 10 min-1 (mean, 95% confidence interval). Both aspirin and the indomethacin preparations caused significantly more bleeding (P less than 0.05). Rates of bleeding after aspirin, indomethacin BP, Indocid-R, and indomethacin Continus were respectively 22.0 (10.7-47.2) microliters 10 min-1, 4.4 (2.2-9.1) microliters 10 min-1, 10.8 (5.3-22.3) microliters 10 min-1, and 5.1 (3.0-10.6) microliters 10 min-1. 4. Rates of bleeding after indomethacin BP and indomethacin Continus, but not Indocid-R, were significantly less than after aspirin (P less than 0.01). 5. Salicylate or indomethacin was detectable in the plasma of all subjects after the active treatment periods, except for one instance involving a subject allocated indomethacin BP. Indomethacin levels were significantly higher 2 h after Indocid-R than with indomethacin BP or indomethacin Continus. 6. alpha 1-acid glycoprotein levels were not significantly affected by prior treatment with aspirin or indomethacin.

The role of lactoferrin released by phagocytosing neutrophils in the regulation of colony-stimulating activity production by human mononuclear cells.

There remains a controversy about the alleged inhibitory effect of lactoferrin on production of colony-stimulating activity (C.S.A.) by mononuclear cells. We confirm the inhibitory action of both lactoferrin purified from human breast milk and that released from phagocytosing neutrophils. To show the inhibitory effect, it is necessary to plot the dose-response curve of medium conditioned by mononuclear cells with and without lactoferrin. Crowding cells to promote contact is essential for the fraction of C.S.A. production inhibitable by lactoferrin. Saturation of purified lactoferrin by addition of iron salts in vitro may introduce an artifact, as this lactoferrin retained its inhibitory activity at much greater dilutions than lactoferrin released from phagocytosing neutrophils.