Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process

BackgroundThe study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. MethodsThe study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. ResultsApplying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. ConclusionsClinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest. Note: The terms \u27adverse drug reaction\u27 and \u27adverse drug event\u27 have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term \u27adverse drug event\u27 (ADE). <br /

Combining qualitative and quantitative operational research methods to inform quality improvement in pathways that span multiple settings

BACKGROUND: Improving integration and continuity of care across sectors within resource constraints is a priority in many health systems. Qualitative operational research methods of problem structuring have been used to address quality improvement in services involving multiple sectors but not in combination with quantitative operational research methods that enable targeting of interventions according to patient risk. We aimed to combine these methods to augment and inform an improvement initiative concerning infants with congenital heart disease (CHD) whose complex care pathway spans multiple sectors. METHODS: Soft systems methodology was used to consider systematically changes to services from the perspectives of community, primary, secondary and tertiary care professionals and a patient group, incorporating relevant evidence. Classification and regression tree (CART) analysis of national audit datasets was conducted along with data visualisation designed to inform service improvement within the context of limited resources. RESULTS: A 'Rich Picture' was developed capturing the main features of services for infants with CHD pertinent to service improvement. This was used, along with a graphical summary of the CART analysis, to guide discussions about targeting interventions at specific patient risk groups. Agreement was reached across representatives of relevant health professions and patients on a coherent set of targeted recommendations for quality improvement. These fed into national decisions about service provision and commissioning. CONCLUSIONS: When tackling complex problems in service provision across multiple settings, it is important to acknowledge and work with multiple perspectives systematically and to consider targeting service improvements in response to confined resources. Our research demonstrates that applying a combination of qualitative and quantitative operational research methods is one approach to doing so that warrants further consideration

Identifying improvements to complex pathways: evidence synthesis and stakeholder engagement in infant congenital heart disease

OBJECTIVES: Many infants die in the year following discharge from hospital after surgical or catheter intervention for congenital heart disease (3–5% of discharged infants). There is considerable variability in the provision of care and support in this period, and some families experience barriers to care. We aimed to identify ways to improve discharge and postdischarge care for this patient group. DESIGN: A systematic evidence synthesis aligned with a process of eliciting the perspectives of families and professionals from community, primary, secondary and tertiary care. SETTING: UK. RESULTS: A set of evidence-informed recommendations for improving the discharge and postdischarge care of infants following intervention for congenital heart disease was produced. These address known challenges with current care processes and, recognising current resource constraints, are targeted at patient groups based on the number of patients affected and the level and nature of their risk of adverse 1-year outcome. The recommendations include: structured discharge documentation, discharging certain high-risk patients via their local hospital, enhanced surveillance for patients with certain (high-risk) cardiac diagnoses and an early warning tool for parents and community health professionals. CONCLUSIONS: Our recommendations set out a comprehensive, system-wide approach for improving discharge and postdischarge services. This approach could be used to address challenges in delivering care for other patient populations that can fall through gaps between sectors and organisations

Assessing the effectiveness of front of pack labels: Findings from an online randomised-controlled experiment in a representative British sample

Front of pack food labels (FOPLs) provide accessible nutritional information to guide consumer choice. Using an online experiment with a large representative British sample, we aimed to examine whether FOPLs improve participants’ ability to identify the healthiness of foods and drinks. The primary aim was to compare ability to rank between FOPL groups and a no label control. Adults (≥18 years), recruited from the NatCen panel, were randomised to one of five experimental groups (Multiple Traffic Light, MTL; Nutri-Score, N-S; Warning Label, WL; Positive Choice tick, PC; no label control). Stratification variables were year of recruitment to panel, sex, age, government office region, and household income. Packaging images were created for three versions, varying in healthiness, of six food and drink products (pizza, drinks, cakes, crisps, yoghurts, breakfast cereals). Participants were asked to rank the three product images in order of healthiness. Ranking was completed on a single occasion and comprised a baseline measure (with no FOPL), and a follow-up measure including the FOPL as per each participant’s experimental group. The primary outcome was the ability to accurately rank product healthiness (all products ranked correctly vs. any incorrect). In 2020, 4504 participants had complete data and were included in the analysis. The probability of correct ranking at follow-up, and improving between baseline and follow-up, was significantly greater across all products for the N-S, MTL and WL groups, compared to control. This was seen for only some of the products for the PC group. The largest effects were seen for N-S, followed by MTL. These analyses were adjusted for stratification variables, ethnicity, education, household composition, food shopping responsibility, and current FOPL use. Exploratory analyses showed a tendency for participants with higher compared to lower education to rank products more accurately. Conclusions: All FOPLs were effective at improving participants’ ability to correctly rank products according to healthiness in this large representative British sample, with the largest effects seen for N-S, followed by MTL

Death and Emergency Readmission of Infants Discharged After Interventions for Congenital Heart Disease: A National Study of 7643 Infants to Inform Service Improvement.

Improvements in hospital-based care have reduced early mortality in congenital heart disease. Later adverse outcomes may be reducible by focusing on care at or after discharge. We aimed to identify risk factors for such events within 1 year of discharge after intervention in infancy and, separately, to identify subgroups that might benefit from different forms of intervention.Cardiac procedures performed in infants between 2005 and 2010 in England and Wales from the UK National Congenital Heart Disease Audit were linked to intensive care records. Among 7976 infants, 333 (4.2%) died before discharge. Of 7643 infants discharged alive, 246 (3.2%) died outside the hospital or after an unplanned readmission to intensive care (risk factors were age, weight-for-age, cardiac procedure, cardiac diagnosis, congenital anomaly, preprocedural clinical deterioration, prematurity, ethnicity, and duration of initial admission; c-statistic 0.78 [0.75-0.82]). Of the 7643, 514 (6.7%) died outside the hospital or had an unplanned intensive care readmission (same risk factors but with neurodevelopmental condition and acquired cardiac diagnosis and without preprocedural deterioration; c-statistic 0.78 [0.75-0.80]). Classification and regression tree analysis were used to identify 6 subgroups stratified by the level (3-24%) and nature of risk for death outside the hospital or unplanned intensive care readmission based on neurodevelopmental condition, cardiac diagnosis, congenital anomaly, and duration of initial admission. An additional 115 patients died after planned intensive care admission (typically following elective surgery).Adverse outcomes in the year after discharge are of similar magnitude to in-hospital mortality, warrant service improvements, and are not confined to diagnostic groups currently targeted with enhanced monitoring

Geometric Exponents, SLE and Logarithmic Minimal Models

In statistical mechanics, observables are usually related to local degrees of freedom such as the Q < 4 distinct states of the Q-state Potts models or the heights of the restricted solid-on-solid models. In the continuum scaling limit, these models are described by rational conformal field theories, namely the minimal models M(p,p') for suitable p, p'. More generally, as in stochastic Loewner evolution (SLE_kappa), one can consider observables related to nonlocal degrees of freedom such as paths or boundaries of clusters. This leads to fractal dimensions or geometric exponents related to values of conformal dimensions not found among the finite sets of values allowed by the rational minimal models. Working in the context of a loop gas with loop fugacity beta = -2 cos(4 pi/kappa), we use Monte Carlo simulations to measure the fractal dimensions of various geometric objects such as paths and the generalizations of cluster mass, cluster hull, external perimeter and red bonds. Specializing to the case where the SLE parameter kappa = 4p'/p is rational with p < p', we argue that the geometric exponents are related to conformal dimensions found in the infinitely extended Kac tables of the logarithmic minimal models LM(p,p'). These theories describe lattice systems with nonlocal degrees of freedom. We present results for critical dense polymers LM(1,2), critical percolation LM(2,3), the logarithmic Ising model LM(3,4), the logarithmic tricritical Ising model LM(4,5) as well as LM(3,5). Our results are compared with rigourous results from SLE_kappa, with predictions from theoretical physics and with other numerical experiments. Throughout, we emphasize the relationships between SLE_kappa, geometric exponents and the conformal dimensions of the underlying CFTs.Comment: Added reference

Estimating snow depth over Arctic sea ice from calibrated dual-frequency radar freeboards

Snow depth on sea ice remains one of the largest uncertainties in sea ice thickness retrievals from satellite altimetry. Here we outline an approach for deriving snow depth that can be applied to any coincident freeboard measurements after calibration with independent observations of snow and ice freeboard. Freeboard estimates from CryoSat-2 (Ku band) and AltiKa (Ka band) are calibrated against data from NASA's Operation IceBridge (OIB) to align AltiKa with the snow surface and CryoSat-2 with the ice–snow interface. Snow depth is found as the difference between the two calibrated freeboards, with a correction added for the slower speed of light propagation through snow. We perform an initial evaluation of our derived snow depth product against OIB snow depth data by excluding successive years of OIB data from the analysis. We find a root-mean-square deviation of 7.7, 5.3, 5.9, and 6.7 cm between our snow thickness product and OIB data from the springs of 2013, 2014, 2015, and 2016 respectively. We further demonstrate the applicability of the method to ICESat and Envisat, offering promising potential for the application to CryoSat-2 and ICESat-2, which launched in September 2018

Estimating snow depth over Arctic sea ice from calibrated dual-frequency radar freeboards

Snow depth on sea ice remains one of the largest uncertainties in sea ice thickness retrievals from satellite altimetry. Here we outline an approach for deriving snow depth that can be applied to any coincident freeboard measurements after calibration with independent observations of snow and ice freeboard. Freeboard estimates from CryoSat-2 (Ku band) and AltiKa (Ka band) are calibrated against data from NASA's Operation IceBridge (OIB) to align AltiKa with the snow surface and CryoSat-2 with the ice–snow interface. Snow depth is found as the difference between the two calibrated freeboards, with a correction added for the slower speed of light propagation through snow. We perform an initial evaluation of our derived snow depth product against OIB snow depth data by excluding successive years of OIB data from the analysis. We find a root-mean-square deviation of 7.7, 5.3, 5.9, and 6.7&thinsp;cm between our snow thickness product and OIB data from the springs of 2013, 2014, 2015, and 2016 respectively. We further demonstrate the applicability of the method to ICESat and Envisat, offering promising potential for the application to CryoSat-2 and ICESat-2, which launched in September 2018.</p

The genotype of barley cultivars influences multiple aspects of their associated microbiota via differential root exudate secretion

Plant-associated microbe play vital roles in promoting plant growth and health, with plants secreting root exudates into the rhizosphere to attract beneficial microbes. Exudate composition defines the nature of microbial recruitment, with different plant species attracting distinct microbiota to enable optimal adaptation to the soil environment. To more closely examine the relationship between plant genotype and microbial recruitment, we analysed the rhizosphere microbiomes of landrace (Chevallier) and modern (NFC Tipple) barley (Hordeum vulgare) cultivars. Distinct differences were observed between the plant associated microbiomes of the 2 cultivars, with the plant-growth promoting rhizobacterial genus Pseudomonas substantially more abundant in the Tipple rhizosphere. Striking differences were also observed between the phenotypes of recruited Pseudomonas populations, alongside distinct genotypic clustering by cultivar. Cultivar-driven Pseudomonas selection was driven by root exudate composition, with the greater abundance of hexose sugars secreted from Tipple roots attracting microbes better adapted to growth on these metabolites and vice versa. Cultivar-driven selection also operates at the molecular level, with both gene expression and the abundance of ecologically relevant loci differing between Tipple and Chevallier Pseudomonas isolates. Finally, cultivar-driven selection is important for plant health, with both cultivars showing a distinct preference for microbes selected by their genetic siblings in rhizosphere transplantation assay

Factors associated with unplanned reinterventions and their relation to early mortality after pediatric cardiac surgery

Objective: Unplanned reintervention (uRE) is used as an indicator of patient morbidity and quality of care in pediatric cardiac surgery. We investigated associated factors and early mortality after uREs. / Methods: Morbidity data were prospectively collected in 5 UK centers between 2015 and 2017; uRE included surgical cardiac, interventional transcatheter cardiac, permanent pacemaker, and diaphragm plication procedures. Mortality (30-day and 6-month) in uRE/no-uRE patients was reported before and after matching. Predicted 30-day mortality was calculated using the Partial Risk Adjustment in Surgery score. / Results: A total of 3090 procedures (2861 patients) were included (median age, 228 days). There were 146 uREs, resulting in an uRE rate of 4.7%. Partial Risk Adjustment in Surgery score, 30-day mortality and 6-month mortality in uRE and no-uRE groups were 2.4% versus 1.3%, 8.9% versus 1%, and 17.1% versus 2.4%, respectively. After matching, mortality at 6 months remained higher in uRE compared with no-uRE (12.2% vs 1.4%; P = .02; 74 pairs). In the uRE group, 21 out of 25 deaths at 6 months occurred when at least 1 additional postoperative complication was present. In multivariable analysis, neonatal age (P = .002), low weight (P = .009), univentricular heart (P < .001), and arterial shunt (P < .001) were associated with increased risk of uRE, but Partial Risk Adjustment in Surgery score was not (only in univariable analysis). / Conclusions: uREs are a relatively frequent complication after pediatric cardiac surgery and are associated with some patient characteristics, but not the Partial Risk Adjustment in Surgery risk score. Early mortality was higher after uRE, independent of preoperative factors, but linked to other postoperative complications