Safety data in randomised real-world evidence studies: Salford Lung Study learnings.

Evidence to support clinical decision making must be based on safety data that have been captured, analysed and interpreted in a robust and reliable way. Randomised real-world evidence (RRWE) studies provide the opportunity to evaluate the use of medicines in patients and settings representative of routine clinical practice. However, elements that underpin the design of RRWE studies can have a significant impact upon the analysis, interpretation and implications of safety data. In this narrative review, we use data from the Salford Lung Study; two prospective, 12-month, open-label, parallel-group, phase III randomised controlled trials conducted in primary care in the UK; to highlight the importance of capturing treatment modifications when attempting to evaluate safety events according to actual treatment exposure. We demonstrate that analysing safety data by actual treatment received (i.e. accounting for the treatment modifications that occur routinely in the primary care setting) provides additional insight beyond analysing according to randomised treatment strategy only. It is therefore proposed that understanding of safety data from RRWE trials can be optimised by analysing both by randomised group and by actual treatment received.

Cervical priming before surgical abortion up to 13+6 weeks' gestation: a systematic review and metaanalyses for the National Institute for Health and Care Excellence-new clinical guidelines for England.

OBJECTIVE: This study aimed to determine the optimal cervical priming regimen before surgical abortion up to and including 13+6 weeks' gestation. DATA SOURCES: Embase, MEDLINE, and the Cochrane Library were searched for publications up to February 2020. Experts were consulted for any ongoing or missed trials. STUDY ELIGIBILITY CRITERIA: This study included randomized controlled trials published in English after 2000 that compared the following: (1) mifepristone and misoprostol against each other, placebo, or no priming; (2) different doses of mifepristone or misoprostol; (3) different intervals between priming and abortion; or (4) different routes of misoprostol administration. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias was assessed using the Cochrane Collaboration checklist for randomized controlled trials, and data were metaanalyzed in Review Manager 5.3. Dichotomous outcomes were analyzed as risk ratios using the Mantel-Haenszel method, and continuous outcomes were analyzed as mean differences using the inverse variance method. Fixed effects models were used when there was no substantial heterogeneity (I2<50%), random effects models were used for moderate heterogeneity (I2≤50% and <80%), and evidence was not pooled when there was high heterogeneity (I2≥80%). Subgroup analyses were undertaken based on parity where available. The overall quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: A total of 18 randomized controlled trials (n=8538) were included and showed the following: decreased incomplete abortion rate (risk ratio=0.44; 95% confidence interval, 0.21-0.9) and force required to dilate the cervix (mean difference= -7.08 N; 95% confidence interval, -11.67 to -2.49) and increased preoperative bleeding (risk ratio=5.90; 95% confidence interval, 5.08-6.86) with misoprostol compared with no priming; decreased preoperative bleeding when sublingual misoprostol was given 1 hour before abortion compared with 3 hours before (risk ratio=0.14; 95% confidence interval, 0.03-0.56); and increased force required to dilate the cervix (mean difference=14.3 N; 95% confidence interval, 2.13-26.47) when mifepristone was given 24 hours before abortion compared with 48 hours before. The quality of the evidence base was limited by low event rates and risk of bias in included studies. CONCLUSION: Cervical priming with misoprostol decreases the force needed to dilate the cervix for first trimester surgical abortion and reduces the risk of incomplete abortion. Considered alongside clinical expertise, this evidence supports the use of routine cervical priming before first trimester surgical abortion with 400 µg misoprostol or, if misoprostol cannot be used, 200 mg oral mifepristone.

A comparison of termination of pregnancy procedures: Patient choice, emotional impact and satisfaction with care.

OBJECTIVES: To investigate: (1) whether women self-report an ability to choose their preferred termination of pregnancy (TOP) procedure, (2) what factors influence this choice, and (3) what effect this choice has on emotional responses and satisfaction with care. STUDY DESIGN: A mixed-method prospective comparative study in which women requesting a TOP between five and eighteen weeks gestation for social reasons (as opposed to medical indications), were invited to complete a semi-structured pre-TOP interview and questionnaire, and a post-TOP questionnaire four weeks after the procedure. MAIN OUTCOME MEASURES: Quantitative data was collected using the Patient Health Questionnaire, Generalised Anxiety Disorder Scale, Positive and Negative Affect Scale, Impact of Event Scale - Revised, and Client Satisfaction Questionnaire. RESULTS: Pre-TOP emotion-based factors did not differ between groups. Most women felt that they were able to choose their preferred method of TOP. Their decisions were based on factors categorised as procedure-related, lifestyle or social circumstance-related, emotional, or other factors. When no choice was perceived, common reasons reported were that: (1) gestation was too far along for there to be another option, or (2) an appointment was not available within the required timeframe. When women felt that the method of TOP performed was not their choice they found the procedure more stressful. All women reported high satisfaction with care. CONCLUSION: A better understanding of the patient experience can inform service development, enabling staff to ensure that the services provided meet women's needs. The perception that one is able to choose their preferred TOP procedure is important for reducing procedure-related stress and ensuring high satisfaction with care.

Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice: an open-label, parallel group, randomised controlled trial.

BACKGROUND: Evidence for management of asthma comes from closely monitored efficacy trials done in highly selected patient groups. There is a need for randomised trials that are closer to usual clinical practice. METHODS: We did an open-label, randomised, controlled, two-arm effectiveness trial at 74 general practice clinics in Salford and South Manchester, UK. Patients aged 18 years or older with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy were randomly assigned to initiate treatment with a once-daily inhaled combination of either 100 µg or 200 µg fluticasone furoate with 25 µg vilanterol or optimised usual care and followed up for 12 months. The primary endpoint was the percentage of patients who achieved an asthma control test (ACT) score of 20 or greater or an increase in ACT score from baseline of 3 or greater at 24 weeks (termed responders), in patients with a baseline ACT score less than 20 (the primary effectiveness analysis population). All effectiveness analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01706198. FINDINGS: Between Nov 12, 2012, and Dec 16, 2016, 4725 patients were enrolled and 4233 randomly assigned to initiate treatment with fluticasone furoate and vilanterol (n=2114) or usual care (n=2119). 1207 patients (605 assigned to usual care, 602 to fluticasone furoate and vilanterol) had a baseline ACT score greater than or equal to 20 and were thus excluded from the primary effectiveness analysis population. At week 24, the odds of being a responder were higher for patients who initiated treatment with fluticasone furoate and vilanterol than for those on usual care (977 [71%] of 1373 in the fluticasone furoate and vilanterol group vs 784 [56%] of 1399 in the usual care group; odds ratio [OR] 2·00 [95% CI 1·70-2·34], p<0·0001). At week 24, the adjusted mean ACT score increased by 4·4 points from baseline in patients initiated with fluticasone furoate and vilanterol, compared with 2·8 points in the usual care group (difference 1·6 [95% CI 1·3-2·0], p<0·0001). This result was consistent for the duration of the study. Pneumonia was uncommon, with no differences between groups; there was no difference in other serious adverse events between the groups. INTERPRETATION: In patients with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy, initiation of a once-daily treatment regimen of combined fluticasone furoate and vilanterol improved asthma control without increasing the risk of serious adverse events when compared with optimised usual care. FUNDING: GlaxoSmithKline.

Vacuum aspiration for induced abortion could be safely and legally performed by nurses and midwives.

BACKGROUND: Some 40% of abortions carried out in England and Wales are done by vacuum aspiration. It is widely assumed that, in order to be lawful, these procedures must be performed by doctors. AIM AND DESIGN: This study aimed to provide a detailed reassessment of the relevant law and the clinical evidence that supports this assumption. CONCLUSIONS: A close reading of relevant law reveals that this assumption is unfounded. On the contrary, it would be lawful for appropriately trained nurses or midwives, acting as part of a multidisciplinary team, to carry out vacuum aspiration procedures. This interpretation of the law offers the potential for developing more streamlined, cost-effective abortion services, which would be both safe and highly acceptable to patients.

Latex allergy in women's health care.

Latex allergy in midwifery and women's health care is not a new concept, with numerous case reports documenting adverse reactions in pregnant women to natural rubber latex in the birthing room. The practising midwife, nurse and sonographer need to be aware of the signs and symptoms of latex allergy and the implications of a severe reaction to latex not only to the woman but also the unborn child.

Termination of pregnancy services: experiences of gynaecological nurses.

AIM: This paper is a report of a study to identify the experience of gynaecological nurses involved with termination of pregnancy. BACKGROUND: Staff involved with termination of pregnancy have been found to experience both positive and negative views. Varying processes and experiences for staff have been identified, from termination of pregnancy work being emotionally draining and stressful to there being a process of care that evolves with greater experience. METHODS: A purposive sample of seven gynaecological nurses currently working in a termination of pregnancy service was recruited. Data were collected between October 2007 and January 2008 using interviews and standardized questionnaires. Transcripts of the interviews were analysed using Interpretive Phenomenological Analysis. RESULTS: Eight superordinate themes emerged from the analysis: (1) Unconditional acceptance and understanding of termination of pregnancy, (2) Strategies for managing the demands and challenges, (3) What we do for patients and job satisfaction, (4) Challenges to unconditional acceptance, (5) Juggling the contrasting needs and demands of patients, (6) The most demanding aspects of the role, (7) The significance of personal experience and (8) The service context. Some of the experiences were interpreted as ways in which nurses justified their role. The themes were understood in terms of a balance between strains, coping and contextual influences. CONCLUSION: Providing a recognized supportive supervisory environment might allow for the acknowledgement of the unique challenges staff in termination of pregnancy services face, and might enhance a sense of validation within the organization and hence staff wellbeing.