13 research outputs found

    Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT

    Get PDF
    BACKGROUND: Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. OBJECTIVES: The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. DESIGN: Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. SETTING: The randomised controlled trial was conducted in 18 neonatal intensive care units in England. PARTICIPANTS: Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). INTERVENTIONS: The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. MAIN OUTCOME MEASURE: Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. RESULTS: Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. LIMITATIONS: The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. CONCLUSIONS: No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81931394. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information

    Using electronic patient records to assess the effect of a complex antenatal intervention in a cluster randomised controlled trial-data management experience from the DESiGN Trial team.

    Get PDF
    BACKGROUND: The use of electronic patient records for assessing outcomes in clinical trials is a methodological strategy intended to drive faster and more cost-efficient acquisition of results. The aim of this manuscript was to outline the data collection and management considerations of a maternity and perinatal clinical trial using data from electronic patient records, exemplifying the DESiGN Trial as a case study. METHODS: The DESiGN Trial is a cluster randomised control trial assessing the effect of a complex intervention versus standard care for identifying small for gestational age foetuses. Data on maternal/perinatal characteristics and outcomes including infants admitted to neonatal care, parameters from foetal ultrasound and details of hospital activity for health-economic evaluation were collected at two time points from four types of electronic patient records held in 22 different electronic record systems at the 13 research clusters. Data were pseudonymised on site using a bespoke Microsoft Excel macro and securely transferred to the central data store. Data quality checks were undertaken. Rules for data harmonisation of the raw data were developed and a data dictionary produced, along with rules and assumptions for data linkage of the datasets. The dictionary included descriptions of the rationale and assumptions for data harmonisation and quality checks. RESULTS: Data were collected on 182,052 babies from 178,350 pregnancies in 165,397 unique women. Data availability and completeness varied across research sites; each of eight variables which were key to calculation of the primary outcome were completely missing in median 3 (range 1-4) clusters at the time of the first data download. This improved by the second data download following clarification of instructions to the research sites (each of the eight key variables were completely missing in median 1 (range 0-1) cluster at the second time point). Common data management challenges were harmonising a single variable from multiple sources and categorising free-text data, solutions were developed for this trial. CONCLUSIONS: Conduct of clinical trials which use electronic patient records for the assessment of outcomes can be time and cost-effective but still requires appropriate time and resources to maximise data quality. A difficulty for pregnancy and perinatal research in the UK is the wide variety of different systems used to collect patient data across maternity units. In this manuscript, we describe how we managed this and provide a detailed data dictionary covering the harmonisation of variable names and values that will be helpful for other researchers working with these data. TRIAL REGISTRATION: Primary registry and trial identifying number: ISRCTN 67698474 . Registered on 02/11/16

    Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

    Get PDF
    BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. CONCLUSIONS: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, ISRCTN67698474

    The Problem Management Plus psychosocial intervention for distressed and functionally impaired asylum seekers and refugees: the PROSPER feasibility RCT

    Get PDF
    Background The prevalence of psychological morbidity among asylum seekers and refugees is high, but these groups encounter extensive barriers to accessing health and social care. The aim of the PROSPER study was to assess the feasibility of conducting a randomised controlled trial in the UK of Problem Management Plus (PM+), an evidence-based psychosocial intervention delivered by lay therapists for distressed and functionally impaired asylum seekers and refugees. Design We undertook a feasibility study of PM+, which included a pilot study of the design features of a future definitive randomised controlled trial and economic evaluation. The feasibility study involved the adaptation of PM+ based on evidence drawn from literature synthesis and local stakeholder engagement, and a two-stage training procedure for lay therapists. These were followed by a pilot trial designed to assess the feasibility of conducting a three-arm randomised controlled trial of five 90-minute sessions of PM+, delivered individually or in groups, with 105 participants randomised 1 : 1 : 1 to individual PM+, group PM+ or a control intervention. Primary health outcomes were anxiety and depressive symptoms at 3 months; other outcomes included post-traumatic stress disorder symptoms, quality of life, progress with identified goals and service use. Findings We demonstrated that the form and content of PM+ could be adapted to meet the needs of asylum seekers and refugees. Twelve people with lived experience of the asylum process were successfully trained as lay therapists to deliver this targeted, low-intensity psychosocial intervention in local asylum seeker and refugee communities. The pilot trial was affected by governance issues. It began in December 2019 and was cut short by the COVID-19 pandemic. We were not able to complete recruitment and follow-up as planned; 11 out of 105 (10%) participants were recruited to the pilot trial (individual PM+, n = 4; group PM+, n = 3; control, n = 4); 8 out of 11 participants were followed up at 13 weeks and 7 out of 11 participants were followed up at 26 weeks. (Preliminary data were gathered on recruitment and retention, intervention fidelity and acceptability of study measures, including service use measures.) Limitations Protracted delays due to governance issues, followed by the COVID-19 pandemic, meant that we were unable to complete the pilot trial or to provide evidence regarding the feasibility of group PM+. The complexities of working with multiple languages and cultural groups were noted. There were mixed views on how successful PM+ might prove, and we had insufficient evidence to provide clear conclusions. Future work Future research could explore how technology can be used to improve the acceptability, feasibility, efficacy and potential cost-effectiveness of scalable mental health interventions and well-being support for distressed asylum seekers and refugees. The use of mobile phone and/or app-based forms of support may help to increase asylum seekers’ and refugees’ willingness to engage in research of this type. Conclusions Although it was not possible to specify the parameters for a full randomised controlled trial of PM+ for asylum seekers and refugees in the UK, our findings offer guidance on strategies that may be of value in future studies of this nature. Trial registration This trial is registered as ISRCTN15214107. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 10. See the NIHR Journals Library website for further project information

    Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

    Get PDF
    Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

    Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

    Get PDF
    Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

    Waterbirth: a national retrospective cohort study of factors associated with its use among women in England

    Get PDF
    open access articleBackground Waterbirth is widely available in English maternity settings for women who are not at increased risk of complications during labour. Immersion in water during labour is associated with a number of maternal benefits. However for birth in water the situation is less clear, with conclusive evidence on safety lacking and little known about the characteristics of women who give birth in water. This retrospective cohort study uses electronic data routinely collected in the course of maternity care in England in 2015–16 to describe the proportion of births recorded as having occurred in water, the characteristics of women who experienced waterbirth and the odds of key maternal and neonatal complications associated with giving birth in water. Methods Data were obtained from three population level electronic datasets linked together for the purposes of a national audit of maternity care. The study cohort included women who had no risk factors requiring them to give birth in an obstetric unit according to national guidelines. Multivariate logistic regression models were used to examine maternal (postpartum haemorrhage of 1500mls or more, obstetric anal sphincter injury (OASI)) and neonatal (Apgar score less than 7, neonatal unit admission) outcomes associated with waterbirth. Results 46,088 low and intermediate risk singleton term spontaneous vaginal births in 35 NHS Trusts in England were included in the analysis cohort. Of these 6264 (13.6%) were recorded as having occurred in water. Waterbirth was more likely in older women up to the age of 40 (adjusted odds ratio (adjOR) for age group 35–39 1.27, 95% confidence interval (1.15,1.41)) and less common in women under 25 (adjOR 18–24 0.76 (0.70, 0.82)), those of higher parity (parity ≥3 adjOR 0.56 (0.47,0.66)) or who were obese (BMI 30–34.9 adjOR 0.77 (0.70,0.85)). Waterbirth was also less likely in black (adjOR 0.42 (0.36, 0.51)) and Asian (adjOR 0.26 (0.23,0.30)) women and in those from areas of increased socioeconomic deprivation (most affluent versus least affluent areas adjOR 0.47 (0.43, 0.52)). There was no association between delivery in water and low Apgar score (adjOR 0.95 (0.66,1.36)) or incidence of OASI (adjOR 1.00 (0.86,1.16)). There was an association between waterbirth and reduced incidence of postpartum haemorrhage (adjOR 0.68 (0.51,0.90)) and neonatal unit admission (adjOR 0.65 (0.53,0.78)). Conclusions In this large observational cohort study, there was no association between waterbirth and specific adverse outcomes for either the mother or the baby. There was evidence that white women from higher socioeconomic backgrounds were more likely to be recorded as giving birth in water. Maternity services should focus on ensuring equitable access to waterbirth

    National Maternity and Perinatal Audit: Organisational Report 2017

    No full text
    Organisational report 2017 - A snapshot of NHS maternity and neonatal services in England, Scotland and Wales in January 201
    corecore