BackgroundComplex interventions in obese pregnant women should be theoretically based, feasible and shown to demonstrate anticipated behavioural change prior to inception of large randomised controlled trials (RCTs). The aim was to determine if a) a complex intervention in obese pregnant women leads to anticipated changes in diet and physical activity behaviours, and b) to refine the intervention protocol through process evaluation of intervention fidelity.MethodsWe undertook a pilot RCT of a complex intervention in obese pregnant women, comparing routine antenatal care with an intervention to reduce dietary glycaemic load and saturated fat intake, and increase physical activity. Subjects included 183 obese pregnant women (mean BMI 36.3 kg/m2).Diet was assessed by repeated triple pass 24-hour dietary recall and physical activity by accelerometry and questionnaire, at 16+0 to 18+6 and at 27+0 to 28+6 weeks’ gestation in women in control and intervention arms. Attitudes to behaviour change and quality of life were assessed and a process evaluation undertaken. The full RCT protocol was undertaken to assess feasibility.ResultsCompared to women in the control arm, women in the intervention arm had a significant reduction in dietary glycaemic load (33 points, 95% CI −47 to −20), (p < 0.001) and saturated fat intake (−1.6% energy, 95% CI −2.8 to −0. 3) at 28 weeks’ gestation. Objectively measured physical activity did not change. Physical discomfort and sustained barriers to physical activity were common at 28 weeks’ gestation. Process evaluation identified barriers to recruitment, group attendance and compliance, leading to modification of intervention delivery.ConclusionsThis pilot trial of a complex intervention in obese pregnant women suggests greater potential for change in dietary intake than for change in physical activity, and through process evaluation illustrates the considerable advantage of performing an exploratory trial of a complex intervention in obese pregnant women before undertaking a large RCT.Trial registrationTrial Registration Number: ISRCTN89971375

The objective of this study was to determine the impact of pressure ulceration on health-related quality of life (HRQoL) and to undertake a pilot study for a future larger study. The study comprised two parts. First, data from a large UK prospective cohort study were analyzed and the HRQoL of 218 people with pressure ulcers was compared with that of 2,289 people without ulcers using the Short Form-36 (SF-36) questionnaire. After adjusting for age, sex, and comorbidities, patients with pressure ulceration had significantly lower scores for both the physical (coefficient=-3.12, p<0.001) and mental (coefficient=-1.50, p=0.04) component summary scores of the SF-36. Second, a small pilot study was conducted to explore use of other tools. HRQoL was assessed in six patients with and 16 patients without pressure ulcers using the SF-36, the EQ-5D and a pain visual analog scale. SF-36 scores indicated that patients with pressure ulcers had significantly poorer physical functioning (d=22.3, p=0.001), role limitations due to physical problems (d=12.9, p=0.02), and vitality (d=20.6, p=0.04) than those without. EQ-5D scores were also poorer for patients with pressure ulceration, for both the visual analog scale (d=19.2, p=0.02) and the index (d=0.29, p=0.08). Patients with pressure ulceration had more perceived pain than those without; however, this difference was of borderline significance (d=-23.9, p=0.06). Pressure ulceration therefore has an impact on HRQoL that is measurable and persists after adjusting for potential confounding.

BackgroundSmoking during pregnancy is the main preventable cause of poor birth outcomes. Improved methods are needed to help women to stop smoking during pregnancy. Pregnancy provides a compelling rationale for physical activity (PA) interventions as cessation medication is contraindicated or ineffective, and an effective PA intervention could be highly cost-effective.ObjectiveTo examine the effectiveness and cost-effectiveness of a PA intervention plus standard behavioural support for smoking cessation relative to behavioural support alone for achieving smoking cessation at the end of pregnancy.DesignMulticentre, two-group, pragmatic randomised controlled trial and economic evaluation with follow-up at the end of pregnancy and 6 months postnatally. Randomisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio.Setting13 hospitals offering antenatal care in the UK.ParticipantsWomen between 10 and 24 weeks’ gestation smoking five or more cigarettes a day before pregnancy and one or more during pregnancy.InterventionsParticipants were randomised to behavioural support for smoking cessation (control) or behavioural support plus a PA intervention consisting of supervised treadmill exercise plus PA consultations. Neither participants nor researchers were blinded to treatment allocation.Main outcome measuresThe primary outcome was self-reported, continuous smoking abstinence between a quit date and end of pregnancy, validated by expired carbon monoxide and/or salivary cotinine. Secondary outcomes were maternal weight, depression, birth outcomes, withdrawal symptoms and urges to smoke. The economic evaluation investigated the costs of the PA intervention compared with the control intervention.ResultsIn total, 789 women were randomised (n = 394 PA,n = 395 control). Four were excluded post randomisation (two had been enrolled twice in sequential pregnancies and two were ineligible and randomised erroneously). The intention-to-treat analysis comprised 785 participants (n = 392 PA,n = 393 control). There was no significant difference in the rate of abstinence at the end of pregnancy between the PA group (7.7%) and the control group (6.4%) [odds ratio for PA group abstinence 1.21, 95% confidence interval (CI) 0.70 to 2.10]. For the PA group compared with the control group, there was a 33% (95% CI 14% to 56%), 28% (95% CI 7% to 52%) and 36% (95% CI 12% to 65%) significantly greater increase in self-reported minutes of moderate- and vigorous-intensity PA from baseline to 1 week, 4 weeks and 6 weeks respectively. Accelerometer data showed that there was no significant difference in PA levels between the groups. There were no significant differences between the groups for change in maternal weight, depression, withdrawal symptoms or urges to smoke. Adverse events and birth outcomes were similar between the groups except for there being significantly more caesarean births in the control group than in the PA group (28.7% vs. 21.3%;p < 0.023). The PA intervention was less costly than the control intervention by £35 per participant. This was mainly attributable to increased health-care usage in the control group. However, there was considerable statistical uncertainty around this estimate.ConclusionsDuring pregnancy, offering an intervention combining supervised exercise and PA counselling does not add to the effectiveness of behavioural support for smoking cessation. Only 10% of participants had PA levels accessed by accelerometer and it is, therefore, unclear whether or not the lack of an effect on the primary outcome is the result of insufficient increases in PA. Research is needed to identify the smoking populations most suitable for PA interventions and methods for increasing PA adherence.Trial registrationCurrent Controlled Trials ISRCTN48600346.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 84. See the NIHR Journals Library website for further project information.

Arthritis Research UK.

Background: Doctors’ organisations in the UK have reported worrying levels of work-related stress and burnout in the general practitioner (GP) workforce for some time, and the COVID-19 pandemic has presented clear new challenges. Aims: To synthesise international evidence exploring the impact of COVID-19 on primary care doctors’ mental health and wellbeing and identify risk factors associated with their psychological wellbeing during this time. Design and setting: Mixed-methods systematic review. Method: We searched six bibliographic databases, Google Scholar and MedRxiv and conducted reference checking to identify studies of GP psychological wellbeing during the pandemic. Two reviewers selected studies, extracted data and assessed the quality of studies using standardised tools. Heterogeneity in outcomes, setting and design prohibited statistical pooling; we combined the studies using a convergent integrated thematic synthesis. Results: Thirty-one studies were included. Multiple sources of stress were identified, including changed working practices, risk, exposure and inadequate PPE, information overload, pandemic preparedness and cohesion across sectors. Studies demonstrated an impact on psychological wellbeing, with some GPs experiencing stress, burnout, anxiety, depression, fear of COVID, lower job satisfaction and physical symptoms. Studies described gender and age differences: women report poorer psychological outcomes across all domains and older GPs reported greater stress and burnout. Use of outcome measures and reporting practice varied greatly. Conclusion: Our review of international evidence demonstrates that the COVID-19 pandemic has adversely affected GPs’ wellbeing around the world. Further research could explore gender and age differences, identifying interventions targeted to these groups.

BackgroundSmoking during pregnancy causes many adverse pregnancy and birth outcomes. Nicotine replacement therapy (NRT) is effective for cessation outside pregnancy but efficacy and safety in pregnancy are unknown. We hypothesised that NRT would increase smoking cessation in pregnancy without adversely affecting infants.ObjectivesTo compare (1) at delivery, the clinical effectiveness and cost-effectiveness for achieving biochemically validated smoking cessation of NRT patches with placebo patches in pregnancy and (2) in infants at 2 years of age, the effects of maternal NRT patch use with placebo patch use in pregnancy on behaviour, development and disability.DesignRandomised, placebo-controlled, parallel-group trial and economic evaluation with follow-up at 4 weeks after randomisation, delivery and until infants were 2 years old. Randomisation was stratified by centre and a computer-generated sequence was used to allocate participants using a 1 : 1 ratio. Participants, site pharmacies and all study staff were blind to treatment allocation.SettingSeven antenatal hospitals in the Midlands and north-west England.ParticipantsWomen between 12 and 24 weeks’ gestation who smoked ≥ 10 cigarettes a day before and ≥ 5 during pregnancy, with an exhaled carbon monoxide (CO) reading of ≥ 8 parts per million (p.p.m.).InterventionsNRT patches (15 mg per 16 hours) or matched placebo as an 8-week course issued in two equal batches. A second batch was dispensed at 4 weeks to those abstinent from smoking.Main outcome measuresParticipants: self-reported, prolonged abstinence from smoking between a quit date and childbirth, validated at delivery by CO measurement and/or salivary cotinine (COT) (primary outcome). Infants, at 2 years: absence of impairment, defined as no disability or problems with behaviour and development. Economic: cost per ‘quitter’.ResultsOne thousand and fifty women enrolled (521 NRT, 529 placebo). There were 1010 live singleton births and 12 participants had live twins, while there were 14 fetal deaths and no birth data for 14 participants. Numbers of adverse pregnancy and birth outcomes were similar in trial groups, except for a greater number of caesarean deliveries in the NRT group. Smoking: all participants were included in the intention-to-treat (ITT) analyses; those lost to follow-up (7% for primary outcome) were assumed to be smoking. At 1 month after randomisation, the validated cessation rate was higher in the NRT group {21.3% vs. 11.7%, odds ratio [OR], [95% confidence interval (CI)] for cessation with NRT, 2.05 [1.46 to 2.88]}. At delivery, there was no difference between groups’ smoking cessation rates: 9.4% in the NRT and 7.6% in the placebo group [OR (95% CI), 1.26 (0.82 to 1.96)]. Infants: at 2 years, analyses were based on data from 888 out of 1010 (87.9%) singleton infants (including four postnatal infant deaths) [445/503 (88.5%) NRT, 443/507 (87.4%) placebo] and used multiple imputation. In the NRT group, 72.6% (323/445) had no impairment compared with 65.5% (290/443) in placebo (OR 1.40, 95% CI 1.05 to 1.86). The incremental cost-effectiveness ratio for NRT use was £4156 per quitter (£4926 including twins), but there was substantial uncertainty around these estimates.ConclusionsNicotine replacement therapy patches had no enduring, significant effect on smoking in pregnancy; however, 2-year-olds born to women who used NRT were more likely to have survived without any developmental impairment. Further studies should investigate the clinical effectiveness and safety of higher doses of NRT.Trial registrationCurrent Controlled Trials ISRCTN07249128.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 18, No. 54. See the NIHR Journals Library programme website for further project information.

Background and objectivesProgesterone is essential to maintain a healthy pregnancy. Guidance from the Royal College of Obstetricians and Gynaecologists and a Cochrane review called for a definitive trial to test whether or not progesterone therapy in the first trimester could reduce the risk of miscarriage in women with a history of unexplained recurrent miscarriage (RM). The PROMISE trial was conducted to answer this question. A concurrent cost-effectiveness analysis was conducted.Design and settingA randomised, double-blind, placebo-controlled, international multicentre study, with economic evaluation, conducted in hospital settings across the UK (36 sites) and in the Netherlands (nine sites).Participants and interventionsWomen with unexplained RM (three or more first-trimester losses), aged between 18 and 39 years at randomisation, conceiving naturally and giving informed consent, received either micronised progesterone (Utrogestan®, Besins Healthcare) at a dose of 400 mg (two vaginal capsules of 200 mg) or placebo vaginal capsules twice daily, administered vaginally from soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) until 12 completed weeks of gestation (or earlier if the pregnancy ended before 12 weeks).Main outcome measuresLive birth beyond 24 completed weeks of gestation (primary outcome), clinical pregnancy at 6–8 weeks, ongoing pregnancy at 12 weeks, miscarriage, gestation at delivery, neonatal survival at 28 days of life, congenital abnormalities and resource use.MethodsParticipants were randomised after confirmation of pregnancy. Randomisation was performed online via a secure internet facility. Data were collected on four occasions of outcome assessment after randomisation, up to 28 days after birth.ResultsA total of 1568 participants were screened for eligibility. Of the 836 women randomised between 2010 and 2013, 404 received progesterone and 432 received placebo. The baseline data (age, body mass index, maternal ethnicity, smoking status and parity) of the participants were comparable in the two arms of the trial. The follow-up rate to primary outcome was 826 out of 836 (98.8%). The live birth rate in the progesterone group was 65.8% (262/398) and in the placebo group it was 63.3% (271/428), giving a relative risk of 1.04 (95% confidence interval 0.94 to 1.15;p = 0.45). There was no evidence of a significant difference between the groups for any of the secondary outcomes. Economic analysis suggested a favourable incremental cost-effectiveness ratio for decision-making but wide confidence intervals indicated a high level of uncertainty in the health benefits. Additional sensitivity analysis suggested the probability that progesterone would fall within the National Institute for Health and Care Excellence’s threshold of £20,000–30,000 per quality-adjusted life-year as between 0.7145 and 0.7341.ConclusionsThere is no evidence that first-trimester progesterone therapy improves outcomes in women with a history of unexplained RM.LimitationsThis study did not explore the effect of treatment with other progesterone preparations or treatment during the luteal phase of the menstrual cycle.Future workFuture research could explore the efficacy of progesterone supplementation administered during the luteal phase of the menstrual cycle in women attempting natural conception despite a history of RM.Trial registrationCurrent Controlled Trials ISRCTN92644181; EudraCT 2009-011208-42; Research Ethics Committee 09/H1208/44.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 41. See the NIHR Journals Library website for further project information.

Our results suggest that the three-option EQ-5D may not be an optimal primary end point for measuring clinical and cost-effectiveness in randomised controlled trials of interventions among hazardous and harmful alcohol users, although further testing of the sensitivity of the tool in these populations is needed.