Pneumonia incidence trends in UK primary care from 2002 to 2017:population-based cohort study

Increasing hospital admissions for pneumonia have been reported recently but it is not known whether pneumonia incidence rates have increased in the community. To determine whether incidence rates of pneumonia increased in primary care in the United Kingdom from 2002 to 2017, an open cohort study was conducted using electronic health records from the UK Clinical Practice Research Datalink. Clinically diagnosed pneumonia, influenza pneumonia, pleural infection and clinically suspected pneumonia, defined as chest infection treated with antibiotics, were evaluated. Age-standardised and age-specific rates were estimated. Joinpoint regression models were fitted and annual percentage changes (APC) were estimated. There were 70.7 million person-years of follow-up with 120 662 episodes of clinically diagnosed pneumonia, 1 831 005 of clinically suspected pneumonia, 23 814 episodes of influenza pneumonia and 2644 pleural infections over 16 years. The incidence of clinically diagnosed pneumonia increased from 1.50 per 1000 person-years in 2002 to 2.22 per 1000 in 2017. From 2010 to 2017, the APC in age-standardised incidence was 5.1% (95% confidence interval 3.4-6.9) compared with 0.3% (-0.6 to 1.2%) before 2010. Clinically suspected pneumonia incidence rates increased from 2002 to 2008 with an APC 3.8% (0.8-6.9) but decreased with an APC -4.9% (-6.7 to -3.1) from 2009 to 2017. Influenza pneumonia increased in the epidemic year of 2009. There was no overall trend in pleural infection. The results show that clinically diagnosed pneumonia has increased in primary care but there was a contemporaneous decline in recording of clinically suspected pneumonia or 'chest infection'. Changes in disease labelling practice might partly account for these trends.</p

Evaluation of the reported data linkage process and associated quality issues for linked routinely collected healthcare data in multimorbidity research: a systematic methodology review

Objective The objective of this systematic review was to examine how the record linkage process is reported in multimorbidity research. Methods A systematic search was conducted in Medline, Web of Science and Embase using predefined search terms, and inclusion and exclusion criteria. Published studies from 2010 to 2020 using linked routinely collected data for multimorbidity research were included. Information was extracted on how the linkage process was reported, which conditions were studied together, which data sources were used, as well as challenges encountered during the linkage process or with the linked dataset. Results Twenty studies were included. Fourteen studies received the linked dataset from a trusted third party. Eight studies reported variables used for the data linkage, while only two studies reported conducting prelinkage checks. The quality of the linkage was only reported by three studies, where two reported linkage rate and one raw linkage figures. Only one study checked for bias by comparing patient characteristics of linked and non-linked records. Conclusions The linkage process was poorly reported in multimorbidity research, even though this might introduce bias and potentially lead to inaccurate inferences drawn from the results. There is therefore a need for increased awareness of linkage bias and transparency of the linkage processes, which could be achieved through better adherence to reporting guidelines. PROSPERO registration number CRD42021243188

Clinical prediction models for mortality and functional outcome following ischemic stroke:A systematic review and meta-analysis

ObjectiveWe aim to identify and critically appraise clinical prediction models of mortality and function following ischaemic stroke.MethodsElectronic databases, reference lists, citations were searched from inception to September 2015. Studies were selected for inclusion, according to pre-specified criteria and critically appraised by independent, blinded reviewers. The discrimination of the prediction models was measured by the area under the curve receiver operating characteristic curve or c-statistic in random effects meta-analysis. Heterogeneity was measured using I2. Appropriateappraisal tools and reporting guidelines were used in this review.Results31395 references were screened, of which 109 articles were included in the review. These articles described 66 different predictive risk models. Appraisal identified poor methodological quality and a high risk of bias for most models. However, all models precede the development of reporting guidelines for prediction modelling studies. Generalisability of models could be improved, less than half of the included models have been externally validated(n =27/66). 152 predictors of mortality and 192 predictors and functional outcome were identified. No studies assessing ability to improve patient outcome (model impact studies) were identified.ConclusionsFurther external validation and model impact studies to confirm the utility of existing models in supporting decision-making is required. Existing models have much potential. Those wishing to predict stroke outcome are advised to build on previous work, to update and adapt validated models to their specific contexts opposed to designing new ones

Effect of Continuous Renal Replacement Therapy on Outcome in Pediatric Acute Liver Failure

Objectives: To establish the effect of continuous renal replacement therapy on outcome in pediatric acute liver failure.Design: Retrospective cohort study.Setting: Sixteen-bed PICU in a university-affiliated tertiary care hospital and specialist liver centre.Patients: All children (0–18 yr) admitted to PICU with pediatric acute liver failure between January 2003 and December 2013.Interventions: Children with pediatric acute liver failure were managed according to a set protocol. The guidelines for continuous renal replacement therapy in pediatric acute liver failure were changed in 2011 following preliminary results to indicate the earlier use of continuous renal replacement therapy for both renaldysfunction and detoxification.Measurements and Main Results: Of 165 children admitted with pediatric acute liver failure, 136 met the inclusion criteria and 45 of these received continuous renal replacement therapy prior to transplantation or recovery. Of the children managed with continuous renal replacement therapy, 26 (58%) survived: 19 were successfully bridged to liver transplantation and 7 spontaneously recovered. Cox proportional hazards regression model clearly showed reducing hyperammonemia by 48 hours after initiating continuous renal replacement therapy significantly improved survival (HR, 1.04; 95% CI, 1.013-1.073; p = 0.004). On average, for every 10% decrease in ammonia from baseline at 48 hours, the likelihood of survival increased by 50%. Time to initiate continuous renal replacement therapy from PICU admission was lower in survivors compared to nonsurvivors (HR, 0.96; 95% CI, 0.916-1.007; p = 0.095). Change in practice to initiate early and high-dose continuous renal replacement therapy led to increased survival with maximum effect being visible in the first 14 days (HR, 3; 95% CI, 1.0-10.3; p = 0.063). Among children with pediatric acute liver failure who did not receive a liver transplant, use of continuous renal replacement therapy significantly improved survival (HR, 4; 95% CI, 1.5-11.6; p = 0.006).Conclusion: Continuous renal replacement therapy can be used successfully in critically ill children with pediatric acute liver failure to provide stability and bridge to transplantation. Inability to reduce ammonia by 48 hours confers poor prognosis. Continuous renal replacement therapy should be considered at an early stage to help prevent further deterioration and buy time for potential spontaneous recovery or bridge to liver transplantation

Long-Term Survival After Intravenous Thrombolysis for Ischemic Stroke:A Propensity Score-Matched Cohort With up to 10-Year Follow-Up

Background and Purpose: IV thrombolysis with alteplase is one of the few approved treatments for acute ischemic stroke; nevertheless, little is known about its long-term effects on survival and recovery since clinical trials follow-up times are limited.Methods: Patients registered between Jan-2005 and Dec-2015 to the population-based South London Stroke Register of first-ever strokes. Propensity score was employed to match thrombolyzed and control cases to a 1:2 ratio by demographical and clinical covariates. The primary outcome was survival up to 10 years using Kaplan-Meier estimates, Cox Proportional Hazards and Restricted Mean Survival Time. Secondary outcomes included stroke recurrence and functional status (Barthel Index and Frenchay Activities Index scores) at 5 years. Results: From 2,052 ischemic strokes, 246 treated patients were matched to 492 controls. Median follow-up time: 5.45 years (IQR 4.56). Survival was higher in the treatment group (median: 5.72 years) compared to control group (4.98 years, stratified log-rank test &lt;0.001). The Number Needed to Treat (NNT) to prevent 1 death at 5 years was 12, and 20 at 10 years. After cox regression analysis, thrombolysis reduced risk of mortality by 37% (HR 0.63, 95%CI 0.48-0.82) at 10 years; however, after introducing a multiplicative interaction term into the model, mortality risk reduction was 42% (HR 0.58 95%CI 0.40-0.82) at 10 years for those arriving within 3 hours to the hospital. On average, in a 10-year period, treated patients lived one year longer than controls. At 5 years, thrombolysis was associated with independence (BI ≥90, OR 3.76 95%CI 1.22-13.34) and increased odds of a higher FAI (proportional OR 2.37 95%CI 1.16-4.91). There was no difference in stroke recurrence.Conclusion: Thrombolysis with IV alteplase is associated with improved long-term survival and functional status after ischemic stroke

Virtual Touch™ Quantification to Diagnose and Monitor Liver Fibrosis in Hepatitis B and Hepatitis C: A NICE Medical Technology Guidance

King’s Technology Evaluation Centre is funded by NICE to act as an External Assessment Centre for the Medical Technologies Evaluation Programme. The NHS has a financial interest in the guidance issued by NICE as a result of this work and two authors are NHS employees (Prof. Keevil and Dr. Lewis

The role of clinical decision support systems in preventing stroke in primary care: a systematic review.

Computerized clinical decision support systems (CDSS) are increasingly being used to facilitate the role of clinicians in complex decision-making processes. This systematic review evaluates evidence of the available CDSS developed and tested to support the decision-making process in primary healthcare for stroke prevention and barriers to practical implementations in primary care settings. A systematic search of Web of Science, Medline Ovid, Embase Ovid, and Cinahl was done. A total of five studies, experimental and observational, were synthesised in this review. This review found that CDSS facilitate decision-making processes in primary health care settings in stroke prevention options. However, barriers were identified in designing, implementing, and using the CDSS

The Impact of Sample Size Misestimations on the Interpretation of ARDS Trials:Systematic Review and Meta-analysis

Background: Indeterminate randomized controlled trials (RCTs) in ARDS may arise from sample size misspecification, leading to abandonment of efficacious therapies. Research Questions: If evidence exists for sample size misspecification in ARDS RCTs, has this led to rejection of potentially beneficial therapies? Does evidence exist for prognostic enrichment in RCTs using mortality as a primary outcome? Study Design and Methods: We identified 150 ARDS RCTs commencing recruitment after the 1994 American European Consensus Conference ARDS definition and published before October 31, 2020. We examined predicted-observed sample size, predicted-observed control event rate (CER), predicted-observed average treatment effect (ATE), and the relationship between observed CER and observed ATE for RCTs with mortality and nonmortality primary outcome measures. To quantify the strength of evidence, we used Bayesian-averaged meta-analysis, trial sequential analysis, and Bayes factors. Results: Only 84 of 150 RCTs (56.0%) reported sample size estimations. In RCTs with mortality as the primary outcome, CER was overestimated in 16 of 28 RCTs (57.1%). To achieve predicted ATE, interventions needed to prevent 40.8% of all deaths, compared with the original prediction of 29.3%. Absolute reduction in mortality ≥ 10% was observed in 5 of 28 RCTs (17.9%) but was predicted in 21 of 28 RCTs (75.0%). For RCTs with mortality as the primary outcome, no association was found between observed CER and observed ATE (pooled OR: β = –0.04; 95% credible interval, –0.18 to 0.09). We identified three interventions that are not currently standard of care with a Bayesian-averaged effect size of &gt; 0.20 and moderate strength of existing evidence: corticosteroids, airway pressure release ventilation, and noninvasive ventilation. Interpretation: Reporting of sample size estimations was inconsistent in ARDS RCTs, and misspecification of CER and ATE was common. Prognostic enrichment strategies in ARDS RCTs based on all-cause mortality are unlikely to be successful. Bayesian methods can be used to prioritize interventions for future effectiveness RCTs.</p

Evaluation of eLearning for the teaching of undergraduate ophthalmology at medical school:a randomised controlled crossover study

AIM: To compare ophthalmology teaching delivered by eLearning with traditional lectures, in terms of undergraduate performance and satisfaction.METHODS: Randomised controlled crossover study at King's College London Medical School with 245 third year medical students. The ophthalmology syllabus was divided into ten topics. Five topics were randomised to be taught by traditional lectures and five by electronic learning (eLearning). For the second rotation of students the topics were crossed over, so that those topics taught by traditional lectures were taught by eLearning and vice versa. At the end of each rotation the students sat an optional online mock examination containing 100 questions (ten on each topic). Students' examination performance was compared between the two teaching methods. Student satisfaction was assessed using an online satisfaction survey. Outcome measures were the mean percentage of correct answers across all ten topics, student satisfaction and self-assessed knowledge.RESULTS: The mean examination score for questions taught by eLearning was 58% (95% CI, 55.7-59.6), versus 55% (95% CI 53.1-56.8) for traditional lectures (P = 0.047). Across all topics students were more satisfied with eLearning than traditional lectures, with 87% (95% CI 84.5-88.4) rating eLearning as 'excellent' or 'good' versus 65% (95% CI 62.0-67.4) for lectures (p &lt; 0.0001). Overall 180 (75.6%) preferred eLearning compared to traditional lectures, with 166 (69.7%) rating eLearning 'much better' or 'better,' 61 (25.6%) 'neutral' and 11 (4.6%) 'worse' or 'much worse.'CONCLUSIONS: Student satisfaction and examination performance are both enhanced by ophthalmology eLearning. Similar eLearning modules may be suitable for other specialties and postgraduate learning.</p

A comparison of trends in stroke care and outcomes between in-hospital and community-onset stroke – The South London Stroke Register

Background Stroke care and outcomes have improved significantly over the past decades. It is unclear if patients who had a stroke in hospital (in-hospital stroke, IHS) experienced similar improvements to those who were admitted with stroke (community-onset stroke, COS). Methods Data from the South London Stroke Register were analysed to estimate trends in processes of care and outcomes across three cohorts (1995–2001, 2002–2008, 2009–2015). Kaplan-Meier survival curves were calculated for each cohort. Associations between patient location at stroke onset, processes of care, and outcomes were investigated using multiple logistic regression and Cox proportional hazards models. Results Of 5,119 patients admitted to hospital and registered between 1995 and 2015, 552(10.8%) had IHS. Brain imaging rates increased from 92.4%(COS) and 78.3%(IHS) in 1995–2001 to 100% for COS and IHS in 2009–2015. Rates of stroke unit admission rose but remained lower for IHS (1995–2001: 32.2%(COS) vs. 12.4%(IHS), 2002–2008: 77.1%(COS) vs. 50.0%(IHS), 2009–2015: 86.3%(COS) vs. 65.4%(IHS)). After adjusting for patient characteristics and case-mix, IHS was independently associated with lower rates of stroke unit admission in each cohort (1995–2001: OR 0.49, 95%CI 0.29–0.82, 2002–2008: 0.29, 0.18–0.45, 2009–2015: 0.22, 0.11–0.43). In 2009–2015, thrombolysis rates were lower for ischaemic IHS (17.8%(COS) vs. 13.8%(IHS)). Despite a decline, in-hospital mortality remained significantly higher after IHS in 2009–2015 (13.7%(COS) vs. 26.7%(IHS)). Five-year mortality rates declined for COS from 58.9%(1995–2001) to 35.2%(2009–2015) and for IHS from 80.8%(1995–2001) to 51.1%(2009–2015). In multivariable analysis, IHS was associated with higher mortality over five years post-stroke in each cohort (1995–2001: HR 1.27, 95% CI 1.03–1.57, 2002–2008: 1.24, 0.99–1.55, 2009–2016: 1.39, 0.95–2.04). Conclusions Despite significant improvements for IHS patients similar to those for COS patients, rates of stroke unit admission and thrombolysis remain lower, and short- and long-term outcomes poorer after IHS. Factors preventing IHS patients from entering evidence-based stroke-specific hospital pathways in a timely fashion need further investigation.</p