The performance of risk prediction models for pre-eclampsia using routinely collected maternal characteristics and comparison with models that include specialised tests and with clinical guideline decision rules: a systematic review.

BACKGROUND: Risk prediction models may be valuable to identify women at risk of pre-eclampsia to guide aspirin prophylaxis in early pregnancy. OBJECTIVE: To assess the performance of 'simple' risk models for pre-eclampsia that use routinely collected maternal characteristics; compare with 'specialised' models that include specialised tests; and to guideline recommended decision rules. SEARCH STRATEGY: MEDLINE, Embase and PubMed were searched to June 2014. SELECTION CRITERIA: We included studies that developed or validated pre-eclampsia risk models using maternal characteristics with or without specialised tests and reported model performance. DATA COLLECTION AND ANALYSIS: We extracted data on study characteristics; model predictors, validation and performance including area under the curve (AUC), sensitivity and specificity. MAIN RESULTS: We identified 29 studies that developed 70 models including 22 simple models. Studies included 151-9149 women with a pre-eclampsia prevalence of 1.2-9.5%. No single predictor was included in all models. Four simple models were externally validated, with a model using parity, pre-eclampsia history, race, chronic hypertension and conception method to predict early-onset pre-eclampsia achieving the highest AUC (0.76, 95% CI 0.74-0.77). Nine studies comparing simple versus specialized models in the same population reported AUC favouring specialised models. A simple model achieved fewer false positives than a guideline recommended risk factor list, but sensitivity to classify risk for aspirin prophylaxis was not assessed. CONCLUSION: Validated simple pre-eclampsia risk models demonstrate good risk discrimination that can be improved with specialised tests. Further research is needed to determine their clinical value to guide aspirin prophylaxis compared with decision rules. TWEETABLE ABSTRACT: Pre-eclampsia risk models using maternal factors show good risk discrimination to guide aspirin prophylaxis.

Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

BACKGROUND: Cancer patients want access to reliable information about currently recruiting clinical trials. PATIENTS AND METHODS: Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. RESULTS: Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). CONCLUSIONS: Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

Quantifying the advantages of conducting a prospective meta-analysis (PMA): a case study of early childhood obesity prevention.

BACKGROUND: For prospective meta-analyses (PMAs), eligible studies are identified, and the PMA hypotheses, selection criteria, and analysis methods are pre-specified before the results of any of the studies are known. This reduces publication bias and selective outcome reporting and provides a unique opportunity for outcome standardisation/harmonisation. We conducted a world-first PMA of four trials investigating interventions to prevent early childhood obesity. The aims of this study were to quantitatively analyse the effects of prospective planning on variations across trials, outcome harmonisation, and the power to detect intervention effects, and to derive recommendations for future PMA. METHODS: We examined intervention design, participant characteristics, and outcomes collected across the four trials included in the EPOCH PMA using their registration records, protocol publications, and variable lists. The outcomes that trials planned to collect prior to inclusion in the PMA were compared to the outcomes that trials collected after PMA inclusion. We analysed the proportion of matching outcome definitions across trials, the number of outcomes per trial, and how collaboration increased the statistical power to detect intervention effects. RESULTS: The included trials varied in intervention design and participants, this improved external validity and the ability to perform subgroup analyses for the meta-analysis. While individual trials had limited power to detect the main intervention effect (BMI z-score), synthesising data substantially increased statistical power. Prospective planning led to an increase in the number of collected outcome categories (e.g. weight, child's diet, sleep), and greater outcome harmonisation. Prior to PMA inclusion, only 18% of outcome categories were included in all trials. After PMA inclusion, this increased to 91% of outcome categories. However, while trials mostly collected the same outcome categories after PMA inclusion, some inconsistencies in how the outcomes were measured remained (such as measuring physical activity by hours of outside play versus using an activity monitor). CONCLUSION: Prospective planning led to greater outcome harmonisation and greater power to detect intervention effects, while maintaining acceptable variation in trial designs and populations, which improved external validity. Recommendations for future PMA include more detailed harmonisation of outcome measures and careful pre-specification of analyses to avoid research waste by unnecessary over-collection of data.

Gradual versus abrupt discontinuation of oxygen in preterm or low birth weight infants.

BACKGROUND: The issue of whether to abruptly or gradually discontinue supplemental oxygen is a contentious one. There have been mixed results in studies of both humans and animal models on the effects of either method of oxygen cessation on important infant outcomes. OBJECTIVES: In preterm or low birth weight infants, does gradual versus abrupt discontinuation of supplemental oxygen influence mortality, retinopathy of prematurity, lung function, growth or development? SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. An additional literature search of the MEDLINE and CINAHL databases was conducted in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which gradual weaning was compared with abrupt discontinuation of supplemental oxygen in preterm or low birth weight infants, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The methodological quality of the eligible trial was assessed independently by each author for the degree selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Results were compared and differences resolved as required. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The results of the one small trial of 51 infants included in this systematic review indicate a significant reduction in vascular retrolental fibroplasia (i.e. severe ROP) for infants weaned gradually from high oxygen concentrations compared with abrupt discontinuation (RR 0.22, 95% CI 0.07-0.68). This finding was independent of the duration of oxygen therapy. REVIEWER'S CONCLUSIONS: The results of this systematic review provide additional evidence linking routine exposure to high ambient oxygen in the early neonatal period to the development of ROP in preterm/LBW infants. However, due to small numbers and historical oxygen monitoring techniques, they provide little assistance to clinicians with regard to the most appropriate method of oxygen weaning, gradual or abrupt, in modern neonatal care settings.

Early versus late discontinuation of oxygen in preterm or low birth weight infants.

BACKGROUND: It has been hypothesized that the duration of supplemental oxygen administration, independent of the oxygen concentration, gestational age and/or birth weight, is influential in the development of severe retinopathy of prematurity. Concern regarding the possible deleterious effects of prolonged oxygen supplementation has lead many clinicians to wean infants from oxygen therapy as early as possible in their neonatal course. However recent work in feline models has suggested that visual outcomes may be improved by continuing oxygen supplementation during the recovery phase of ROP. The effect of duration of oxygen supplementation on the long term growth and development of preterm or low birth weight infants remains unclear. OBJECTIVES: In preterm or low birth weight infants, does early versus late weaning from supplementary oxygen influence mortality, retinopathy of prematurity, lung function, growth or development? SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. An additional literature search of the MEDLINE and CINAHL databases was conducted in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which early weaning was compared with late discontinuation of supplemental oxygen in preterm or low birth weight infants, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The methodological quality of the one eligible trial was assessed independently by each author for the degree of selection, performance, attrition and detection bias. Data regarding clinical outcomes including mortality, retinopathy of prematurity, and long term growth and development were extracted and reviewed independently by each author. Results were compared and differences resolved as required. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: In the single eligible trial of 99 infants with birthweights less than 1650g, there were no significant differences in neonatal death rates or retrolental fibroplasia (any grade or severe) for all infants, or among infants with birth weights of less than 1000g. No other outcome measures specified a priori as clinically meaningful were reported in enough detail or with satisfactory follow-up rates to include in the analysis (early death; chronic lung disease; and long term growth, development, lung or visual function). REVIEWER'S CONCLUSIONS: The results of this systematic review do not provide strong evidence for either the benefits or harms of early oxygen weaning in preterm/LBW infants. Future research should be directed toward addressing the question of what are the most appropriate target levels of oxygenation, in both the early and late neonatal periods, rather than whether oxygen should be weaned early or late.

Restricted versus liberal oxygen exposure for preventing morbidity and mortality in preterm or low birth weight infants.

BACKGROUND: Whilst the use of supplemental oxygen has a long history in neonatal care, resulting in both significant health care benefits and harms, uncertainty remains as to the most appropriate range to target blood oxygen levels in preterm and low birth weight infants. Potential benefits of higher oxygen targeting include more stable sleep patterns and improved long term growth and development. However, there may be significant deleterious pulmonary effects and health service use implications resulting from such a policy. OBJECTIVES: In preterm or low birth weight infants, does targeting ambient oxygen concentration to achieve a lower versus higher blood oxygen range, or administering restricted versus liberal supplemental oxygen, influence mortality, retinopathy of prematurity, lung function, growth or development? SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. An additional literature search was conducted of the MEDLINE and CINAHL databases in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). SELECTION CRITERIA: All trials in preterm or low birth weight infants utilising random or quasi-random patient allocation, in which ambient oxygen concentrations were targeted to achieve a lower versus higher blood oxygen range, or restricted versus liberal oxygen was administered, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The methodological quality of the eligible trials was assessed independently by each author for the degree selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The restriction of oxygen significantly reduced the incidence and severity of retinopathy of prematurity without unduly increasing death rates in the meta-analysis of the five trials included in this review. The one trial that specifically addressed the question of lower versus higher PaO2 found no effect on death, but did not report (in sufficient detail to warrant inclusion) the effect of this intervention on eye or other outcomes. The effects of either of these oxygen administration policies on other clinically meaningful outcomes including chronic lung disease and long term growth, neurodevelopment, lung or visual function were not reported in any of the available trials. REVIEWER'S CONCLUSIONS: The results of this systematic review confirm the commonly held view of today's clinicians that a policy of unrestricted, unmonitored oxygen therapy has potential harms, without clear benefits. However, the question of what is the optimal target range for maintaining blood oxygen levels in preterm/LBW infants was not answered by the data available for inclusion in this review.

Gradual versus abrupt discontinuation of oxygen in preterm or low birth weight infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: In preterm or low birth weight infants, does gradual versus abrupt discontinuation of supplemental oxygen influence mortality, retinopathy of prematurity, lung function, growth or development? SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. An additional literature search of the MEDLINE, EMBASE, and CINAHL databases was conducted in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which gradual weaning was compared with abrupt discontinuation of supplemental oxygen in preterm or low birth weight infants, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The methodological quality of the eligible trial was assessed independently by each author for the degree selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Results were compared and differences resolved as required. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The results of the one small trial of 51 infants included in this systematic review indicate a significant reduction in vascular retrolental fibroplasia (i.e. severe ROP) for infants weaned gradually from high oxygen concentrations compared with abrupt discontinuation (RR 0.22, 95% CI 0.07-0.68). This finding was independent of the duration of oxygen therapy. REVIEWER'S CONCLUSIONS: The results of this systematic review provide additional evidence linking routine exposure to high ambient oxygen in the early neonatal period to the development of ROP in preterm/LBW infants. However, due to small numbers and historical oxygen monitoring techniques, they provide little assistance to clinicians with regard to the most appropriate method of oxygen weaning, gradual or abrupt, in modern neonatal care settings.

Early versus late discontinuation of oxygen in preterm or low birth weight infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: In preterm or low birth weight infants, does early versus late weaning from supplementary oxygen influence mortality, retinopathy of prematurity, lung function, growth or development? SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, MEDLINE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language. An additional literature search of the MEDLINE, EMBASE, and CINAHL databases was conducted in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which early weaning was compared with late discontinuation of supplemental oxygen in preterm or low birth weight infants, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The methodological quality of the one eligible trial was assessed independently by each author for the degree of selection, performance, attrition and detection bias. Data regarding clinical outcomes including mortality, retinopathy of prematurity, and long term growth and development were extracted and reviewed independently by each author. Results were compared and differences resolved as required. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: In the single eligible trial of 99 infants with birthweights less than 1650g, there were no significant differences in neonatal death rates or retrolental fibroplasia (any grade or severe) for all infants, or among infants with birth weights of less than 1000g. No other outcome measures specified a priori as clinically meaningful were reported in enough detail or with satisfactory follow-up rates to include in the analysis (early death; chronic lung disease; and long term growth, development, lung or visual function). REVIEWER'S CONCLUSIONS: The results of this systematic review do not provide strong evidence for either the benefits or harms of early oxygen weaning in preterm/LBW infants. Future research should be directed toward addressing the question of what are the most appropriate target levels of oxygenation, in both the early and late neonatal periods, rather than whether oxygen should be weaned early or late.

Restricted versus liberal oxygen exposure for preventing morbidity and mortality in preterm or low birth weight infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: In preterm or low birth weight infants, does targeting ambient oxygen concentration to achieve a lower versus higher blood oxygen range, or administering restricted versus liberal supplemental oxygen, influence mortality, retinopathy of prematurity, lung function, growth or development? SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. An additional literature search was conducted of the MEDLINE, EMBASE, and CINAHL databases in order to locate any trials in addition to those provided by the Cochrane Controlled Trials Register (CENTRAL/CCTR). SELECTION CRITERIA: All trials in preterm or low birth weight infants utilising random or quasi-random patient allocation, in which ambient oxygen concentrations were targeted to achieve a lower versus higher blood oxygen range, or restricted versus liberal oxygen was administered, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The methodological quality of the eligible trials was assessed independently by each author for the degree selection, performance, attrition and detection bias. Data were extracted and reviewed independently by the each author. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The restriction of oxygen significantly reduced the incidence and severity of retinopathy of prematurity without unduly increasing death rates in the meta-analysis of the five trials included in this review. The one trial that specifically addressed the question of lower versus higher PaO2 found no effect on death, but did not report (in sufficient detail to warrant inclusion) the effect of this intervention on eye or other outcomes. The effects of either of these oxygen administration policies on other clinically meaningful outcomes including chronic lung disease and long term growth, neurodevelopment, lung or visual function were not reported in any of the available trials. REVIEWER'S CONCLUSIONS: The results of this meta-analysis confirm the commonly held view of today's clinicians that a policy of unrestricted, unmonitored oxygen therapy has potential harms, without clear benefits. However, the question of what is the optimal target range for maintaining blood oxygen levels in preterm/LBW infants was not answered by the data available for inclusion in this review.

Attitudes of neonatal clinicians towards resuscitation of the extremely premature infant: an exploratory survey.

OBJECTIVE: This study aims to explore the current attitudes of Australian neonatologists and nurses towards the resuscitation of extremely preterm infants. METHODOLOGY: An anonymous questionnaire regarding resuscitation of infants of less than 28 weeks gestation was sent to all neonatologists and three registered nurses in each perinatal centre in Australia. RESULTS: One hundred and thirty-three questionnaires were sent. A return rate of 93% and 73% was obtained from neonatologists and nurses, respectively. Twenty-two per cent of neonatologists would 'occasionally' resuscitate at 22 weeks while none of the nurses would. A considerable proportion of neonatologists (23%) but only a few nurses (6%) would 'quite often' resuscitate 23-week infants. The majority of neonatologists (85%) and nurses (88%) would 'almost always' resuscitate 24 week infants. More than half of the respondents would 'occasionally' resuscitate a 400-499 g infant and most would resuscitate infants weighing more than 500 g. Clinicians were not as optimistic of long-term outcome as they were for survival. Typically, only 52% of neonatologists and 38% of nurses thought babies of 25 weeks gestation had a greater than 50% chance of survival without major handicap. Parental wishes and the presence of congenital abnormalities were major influences on decision to resuscitate. Hypothetically, most respondents, more doctors than nurses, would consider initiating resuscitation without parental consent at a median gestation of 25 weeks. CONCLUSIONS: The majority of Australian clinicians would resuscitate at a gestation of 24 weeks or greater or at a birth weight of over 500 g despite conservative estimates of intact survival. This survey has brought to light the importance of communication with parents prior to extreme premature birth.