A core outcome set for pre-eclampsia research:an international consensus development study

Objective: To develop a core outcome set for pre-eclampsia. Design: Consensus development study. Setting: International. Population: Two hundred and eight-one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. Methods: Modified Delphi method and Modified Nominal Group Technique. Results: A long-list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. Conclusions: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies. Tweetable abstract: 281 healthcare professionals, 41 researchers and 110 women have developed #preeclampsia core outcomes @HOPEoutcomes @jamesmnduffy. [Correction added on 29 June 2020, after first online publication: the order has been corrected.].</p

A descriptive cohort study of withdrawal from inhaled corticosteroids in COPD patients

Inhaled corticosteroid (ICS) therapy is widely prescribed without a history of exacerbations and consensus guidelines suggest withdrawal of ICS in these patients would reduce the risk of side effects and promote cost-effective prescribing. The study describes the prescribing behaviour in the United Kingdom (UK) in relation to ICS withdrawal and identifies clinical outcomes following withdrawal using primary and secondary care electronic health records between January 2012 and December 2017. Patients with a history ≥12 months’ exposure who withdrew ICS for ≥6 months were identified into two cohorts; those prescribed a long-acting bronchodilator maintenance therapy and those that were not prescribed any maintenance therapy. The duration of withdrawal, predictors of restarting ICS, and clinical outcomes were compared between both patient cohorts. Among 76,808 patients that had ≥1 prescription of ICS in the study period, 11,093 patients (14%) withdrew ICS therapy at least once during the study period. The median time without ICS was 9 months (IQR 7–14), with the majority (71%) receiving subsequent ICS prescriptions after withdrawal. Patients receiving maintenance therapy with a COPD review at withdrawal were 28% less likely to restart ICS (HR: 0.72, 95% CI 0.61, 0.85). Overall, 69% and 89% of patients that withdrew ICS had no recorded exacerbation event or COPD hospitalisation, respectively, during the withdrawal. This study provides evidence that most patients withdrawing from ICS do not experience COPD exacerbations and withdrawal success can be achieved by carefully planning routine COPD reviews whilst optimising the use of available maintenance therapies

Prescribing antibiotics to “at-risk” children with influenza-like illness in primary care: qualitative study

Objectives NICE guidelines recommend immediate antibiotic treatment of respiratory tract infections in “at-risk” individuals with co-morbidities. Observational evidence suggests that influenza particularly predisposes children to bacterial complications. This study investigates GPs’ accounts of factors influencing their decision-making about antibiotic prescribing in management of at-risk children with influenza-like illness (ILI). Design Qualitative interview study using a maximum variation sample with thematic analysis through constant comparison Setting Semi-structured telephone interviews with UK GPs using a case vignette of a child with co-morbidities presenting with ILI Participants 41 GPs (41.5% male; 40 from England, 1 from Northern Ireland) with a range of characteristics including length of time in practice, paediatrics experience, practice setting, and deprivation. Results There was considerable uncertainty and variation in the way GPs responded to the case, and difference of opinion about how long-term co-morbidities should affect their antibiotic prescribing. Factors influencing their decision included the child’s case history and clinical examination; the GP’s view of the parent’s ability to self-manage; the GP’s own confidence and experiences of managing sick children; and assessment of individual vs. abstract risk. GPs rarely mentioned potential influenza infection or asked about immunisation status. All said they would want to see the child; views about delayed prescribing varied in relation to local health service provision including options for follow-up and paediatric services. Conclusions The study demonstrates diagnostic uncertainty and wide variation in GP decision-making about prescribing antibiotics to children with co-morbidity. Future guidelines might encourage consideration of a specific diagnosis such as influenza and risk assessment tools could be developed to allow clinicians to quantify the levels of risk associated with different types of co-morbidity. However, the wide range of clinical and non-clinical factors involved in decision-making during these consultations should also be considered in future guidelines

Blood eosinophils to guide inhaled maintenance therapy in a primary care COPD population

Blood eosinophils are a potentially useful biomarker for guiding inhaled corticosteroid (ICS) treatment decisions in COPD. We investigated whether existing blood eosinophil counts predict benefit from initiation of ICS compared to bronchodilator therapy. We used routinely collected data from UK primary care in the Clinical Practice Research Datalink. Participants were aged ≥40 years with COPD, were ICS-naïve and starting a new inhaled maintenance medication (intervention group: ICS; comparator group: long-acting bronchodilator, non-ICS). Primary outcome was time to first exacerbation, compared between ICS and non-ICS groups, stratified by blood eosinophils (“high” ≥150 cells·µL(−1) and “low” <150 cells·µL(−1)). Out of 9475 eligible patients, 53.9% initiated ICS and 46.1% non-ICS treatment with no difference in eosinophils between treatment groups (p=0.71). Exacerbation risk was higher in patients prescribed ICS than those prescribed non-ICS treatment, but with a lower risk in those with high eosinophils (hazard ratio (HR) 1.04, 95% CI 0.98–1.10) than low eosinophils (HR 1.19, 95% CI 1.09–1.31) (p-value for interaction 0.01). Risk of pneumonia hospitalisation with ICS was greatest in those with low eosinophils (HR 1.26, 95% CI 1.05–1.50; p-value for interaction 0.04). Results were similar whether the most recent blood eosinophil count or the mean of blood eosinophil counts was used. In a primary care population, the most recent blood eosinophil count could be used to guide initiation of ICS in COPD patients. We suggest that ICS should be considered in those with higher eosinophils and avoided in those with lower eosinophils (<150 cells·µL(−1))

Is stratification testing for treatment of chronic obstructive pulmonary disease exacerbations cost-effective in primary care? an early cost-utility analysis

OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) who experience acute exacerbations usually require treatment with oral steroids or antibiotics, depending on the etiology of the exacerbation. Current management is based on clinician's assessment and judgement, which lacks diagnostic accuracy and results in overtreatment. A test to guide these decisions in primary care is in development. We developed an early decision model to evaluate the cost-effectiveness of this treatment stratification test in the primary care setting in the United Kingdom. METHODS: A combined decision tree and Markov model was developed of COPD progression and the exacerbation care pathway. Sensitivity analysis was carried out to guide technology development and inform evidence generation requirements. RESULTS: The base case test strategy cost GBP 423 (USD 542) less and resulted in a health gain of 0.15 quality-adjusted life-years per patient compared with not testing. Testing reduced antibiotic prescriptions by 30 percent, potentially lowering the risk of antimicrobial resistance developing. In sensitivity analysis, the result depended on the clinical effects of treating patients according to the test result, as opposed to treating according to clinical judgement alone, for which there is limited evidence. The results were less sensitive to the accuracy of the test. CONCLUSIONS: Testing may be cost-saving in primary care, but this requires robust evidence on whether test-guided treatment is effective. High quality evidence on the clinical utility of testing is required for early modeling of diagnostic tests generally.status: publishe