Study protocol for a Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent–shunt in Acute Variceal Bleeding (REACT-AVB trial)

Introduction: In liver cirrhosis, acute variceal bleeding (AVB) is associated with a 1-year mortality rate of up to 40%. Data on early or pre-emptive transjugular intrahepatic portosystemic stent–shunt (TIPSS) in AVB is inconclusive and may not reflect current management strategies. Randomised controlled trial of EArly transjugular intrahepatiC porTosystemic stent–shunt in AVB (REACT-AVB) aims to investigate the clinical and cost-effectiveness of early TIPSS in patients with cirrhosis and AVB after initial bleeding control.Methods and analysis: REACT-AVB is a multicentre, randomised controlled, open-label, superiority, two-arm, parallel-group trial with an internal pilot. The two interventions allocated randomly 1:1 are early TIPSS within 4 days of diagnostic endoscopy or secondary prophylaxis with endoscopic therapy in combination with non-selective beta blockers. Patients aged ≥18 years with cirrhosis and Child-Pugh Score 7–13 presenting with AVB with endoscopic haemostasis are eligible for inclusion. The primary outcome is transplant-free survival at 1 year post randomisation. Secondary endpoints include transplant-free survival at 6 weeks, rebleeding, serious adverse events, other complications of cirrhosis, Child-Pugh and Model For End-Stage Liver Disease (MELD) scores at 6 and 12 months, health-related quality of life, use of healthcare resources, cost-effectiveness and use of cross-over therapies. The sample size is 294 patients over a 4-year recruitment period, across 30 hospitals in the UK.Ethics and dissemination: Research ethics committee of National Health Service has approved REACT-AVB (reference number: 23/WM/0085). The results will be submitted for publication in a peer-reviewed journal. A lay summary will also be emailed or posted to participants before publication.Trial registration number: ISRCTN85274829; protocol version 3.0, 1 July 2023

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The impact of obstructive sleep apnoea treatment on pain in patients with type 2 diabetes:Results from a 2-year feasibility RCT

Background: Obstructive Sleep Apnoea (OSA) is associated with an increased risk of pain in patients with Type 2 diabetes (T2D). Hence, it is plausible that continuous positive airway pressure (CPAP) might reduce pain in T2D. Method: We conducted an open-label multicentre (13 centres) feasibility randomised control trial (RCT) in which patients with T2D and OSA (apnoea hypopnea index AHI ≥ 10 events/hour) were randomised to CPAP vs no CPAP over 2 years. Participants with a resting oxygen saturation &lt;90%, a central apnoea index &gt;15/hrs or Epworth Sleepiness Score (ESS) &gt;= 11 were excluded. The primary outcomes of this trial were related to feasibility. In this abstract, we report on the secondary outcome related to pain which was assessed using the short firm Mcgail pain questionnaire SFMPQ.Results: Eighty-three patients were randomised to CPAP vs no CPAP (43 vs 40) with a median [IQR] follow-up of 645 [545,861] days. The study population mean (SD) age was 62.5 (10.9) years, and diabetes duration was 12.2(7.9) years. 89.1 % (n=74) were white European ethnicity, 71.1% (n=59) were men, 77.7% (n=59) had obesity, and 48.2% (n=40) were prescribed insulin. The intention-to-treat analysis is summarised in Table 1.Conclusion: CPAP might have a favourable impact on reducing pain. However, an adequately powered RCT is needed to test this.<br/

The impact of obstructive sleep apnoea treatment on pain in patients with type 2 diabetes:Results from a 2-year feasibility RCT

Background: Obstructive Sleep Apnoea (OSA) is associated with an increased risk of pain in patients with Type 2 diabetes (T2D). Hence, it is plausible that continuous positive airway pressure (CPAP) might reduce pain in T2D. Method: We conducted an open-label multicentre (13 centres) feasibility randomised control trial (RCT) in which patients with T2D and OSA (apnoea hypopnea index AHI ≥ 10 events/hour) were randomised to CPAP vs no CPAP over 2 years. Participants with a resting oxygen saturation &lt;90%, a central apnoea index &gt;15/hrs or Epworth Sleepiness Score (ESS) &gt;= 11 were excluded. The primary outcomes of this trial were related to feasibility. In this abstract, we report on the secondary outcome related to pain which was assessed using the short firm Mcgail pain questionnaire SFMPQ.Results: Eighty-three patients were randomised to CPAP vs no CPAP (43 vs 40) with a median [IQR] follow-up of 645 [545,861] days. The study population mean (SD) age was 62.5 (10.9) years, and diabetes duration was 12.2(7.9) years. 89.1 % (n=74) were white European ethnicity, 71.1% (n=59) were men, 77.7% (n=59) had obesity, and 48.2% (n=40) were prescribed insulin. The intention-to-treat analysis is summarised in Table 1.Conclusion: CPAP might have a favourable impact on reducing pain. However, an adequately powered RCT is needed to test this.<br/

A randomized trial of synthetic osmotic cervical dilator for induction of labor vs dinoprostone vaginal insert

BACKGROUND: Induction of labor is a commonly performed obstetrical intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are slower in achieving cervical ripening but have a lower risk of adverse effects. OBJECTIVE: This study aimed to compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with those of dinoprostone. STUDY DESIGN: This was an open-label superiority randomized controlled trial in 4 English hospitals. Eligible participants were women ≥16 years of age undergoing induction of labor for a singleton pregnancy at ≥37 weeks’ gestation with vertex presentation and intact membranes. The women were randomly assigned to receive either Dilapan-S or dinoprostone using a telephone randomization system minimized by hospital, parity, body mass index, and maternal age. The induction agent was replaced as required until the cervix was assessed as favorable for labor by the Bishop score. The primary outcome was failure to achieve vaginal delivery (ieor a cesarean delivery being performed). The secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to-treat, adjusting for design variables where possible. RESULTS: Between December 19, 2017 and January 26, 2021, 674 women were randomized (337 to Dilapan-S, and 337 to dinoprostone). The trial did not reach its planned sample size of 860 participants because of restrictions on research during the COVID-19 pandemic. The primary outcome was missing for 2 women in the dinoprostone group. Failure to achieve vaginal delivery (or a cesarean delivery being performed) occurred in 126 women (37.4%) allocated to Dilapan-S and in 115 (34.3%) women allocated to dinoprostone (adjusted risk difference, 0.02; 95% confidence interval, −0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups. CONCLUSION: Women undergoing induction of labor with Dilapan-S have similar rates of cesarean delivery and maternal and neonatal adverse events compared with dinoprostone

A randomized trial of synthetic osmotic cervical dilator for induction of labor vs dinoprostone vaginal insert

Background: Induction of labor is a commonly performed obstetric intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are slower to achieve cervical ripening but have a lower risk of adverse effects. Objective: To compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with dinoprostone. Study Design: This was an open-label, superiority randomized controlled trial in four English hospitals. Eligible participants were women ≥ 16 years of age undergoing induction of labor for a singleton pregnancy, ≥ 37 weeks’ gestation with vertex presentation and intact membranes. Women were randomly assigned to receive Dilapan-S or dinoprostone using a telephone randomization system minimized by hospital, parity, BMI and maternal age. The induction agent was replaced as required until the cervix was assessed as favorable for labor by Bishop score. The primary outcome was failure to achieve vaginal delivery (i.e. Cesarean delivery). Secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to-treat, adjusting for design variables where possible. Results: Between 19 December 2017 and 26 January 2021, 674 women were randomized (337 to Dilapan-S and 337 to dinoprostone). The trial did not reach its planned sample size of 860 due to restrictions on research during the Covid-19 pandemic. The primary outcome was missing for two women in the dinoprostone group. Failure to achieve vaginal delivery (Cesarean section) occurred in 126 women (37.4%) allocated to Dilapan-S, and 115 (34.3%) women allocated to dinoprostone (adjusted risk difference 0.02, 95% confidence interval -0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups. Conclusion: Women undergoing induction of labor with Dilapan-S have similar rates of caesarean section and maternal and neonatal adverse events compared to dinoprostone

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension:study protocol for a randomised controlled trial (Giant PANDA)

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020