What is Hiding in Medicine's Dark Matter? Learning with Missing Data in Medical Practices

Electronic patient records (EPRs) produce a wealth of data but contain significant missing information. Understanding and handling this missing data is an important part of clinical data analysis and if left unaddressed could result in bias in analysis and distortion in critical conclusions. Missing data may be linked to health care professional practice patterns and imputation of missing data can increase the validity of clinical decisions. This study focuses on statistical approaches for understanding and interpreting the missing data and machine learning based clinical data imputation using a single centre's paediatric emergency data and the data from UK's largest clinical audit for traumatic injury database (TARN). In the study of 56,961 data points related to initial vital signs and observations taken on children presenting to an Emergency Department, we have shown that missing data are likely to be non-random and how these are linked to health care professional practice patterns. We have then examined 79 TARN fields with missing values for 5,791 trauma cases. Singular Value Decomposition (SVD) and k-Nearest Neighbour (kNN) based missing data imputation methods are used and imputation results against the original dataset are compared and statistically tested. We have concluded that the 1NN imputer is the best imputation which indicates a usual pattern of clinical decision making: find the most similar patients and take their attributes as imputation.Comment: 8 page

Desmopressin for reversal of Antiplatelet drugs in Stroke due to Haemorrhage (DASH): protocol for a phase II double-blind randomised controlled feasibility trial

IntroductionIntracerebral haemorrhage can be devastating and is a common cause of death and disability worldwide. Pre-intracerebral haemorrhage antiplatelet drug use is associated with a 27% relative increase in one-month case fatality compared to patients not using antithrombotic drugs. We aim to assess the feasibility of conducting a randomised controlled testing the safety and efficacy of desmopressin for patients with antiplatelet-associated intracerebral haemorrhage.Methods and AnalysisWe aim to include 50 patients within 24 hours of spontaneous intracerebral haemorrhage onset, associated with oral antiplatelet drug(s) use in at least the preceding seven days. Patients will be randomised (1:1) to receive intravenous desmopressin 20μg in 50 mls sodium chloride 0.9% infused over 20 minutes or matching placebo. We will mask participants, relatives and outcome assessors to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, number of patients receiving allocated treatment, rate of recruitment, and adherence to treatment and follow up. Secondary outcomes include change in intracerebral haemorrhage volume at 24 hours; hyponatraemia at 24 hours, length of hospital stay, discharge destination, early death less than 28 days, death or dependency at day 90, death up to day 90, serious adverse events (including thromboembolic events) up to day 90; disability (Barthel index, day 90), quality of life (EuroQol 5D (EQ-5D], day 90), cognition (telephone mini-mental state examination day 90), and health economic assessment (EQ-5D).Ethics and disseminationThe DASH trial received ethical approval from the East Midlands - Nottingham 2 research ethics committee (18/EM/0184). The DASH trial is funded by NIHR RfPB grant: PB-PG-0816-20011. Trial results will be published in a peer reviewed academic journal and disseminated through academic conferences and through patient stroke support groups. Reporting will be in compliance with CONSORT recommendations

Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure

Aims: Recent trials have evaluated sodium–glucose co‐transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). Methods and results: Fragility index is defined as the minimum number of patients that must be moved from the ‘non‐event’ to the ‘event’ group to turn a statistically significant result to non‐significant. In addition to FI, fragility quotient [(FQ); FI divided by the sample size] was calculated to assess the proportion of events that must be moved to change the significance. For statistically non‐significant outcomes, reverse fragility index (RFI) and reverse fragility quotient (RFQ) were calculated. Robustness of findings after pooling data from all three trials was also assessed. A robust reduction in first HF hospitalization or cardiovascular mortality was seen with dapagliflozin (FI = 62 and FQ = 0.013), empagliflozin (FI = 50 and FQ = 0.013), and sotagliflozin (FI = 60 and FQ = 0.049). Dapagliflozin nominally improved all‐cause and cardiovascular mortality, with modest FI (n = 8 and 5) and FQ (0.002 and 0.001). Empagliflozin and sotagliflozin did not demonstrate statistically significant reductions in all‐cause mortality, with modest RFI (empagliflozin: RFI = 26 and RFQ = 0.007; sotagliflozin: RFI = 6 and RFQ = 0.005). A similar trend was seen with cardiovascular mortality (empagliflozin: RFI = 24 and RFQ = 0.006; sotagliflozin: RFI = 7 and RFQ = 0.006). Upon meta‐analysis, the result for first HF hospitalization or cardiovascular mortality was robust (FI = 95 and FQ = 0.010). The reductions in all‐cause (FI = 12 and FQ = 0.001) and cardiovascular mortality (FI = 9 and FQ = 0.001), while statistically significant, were fragile. Conclusion: Improvement in the composite outcome of first HF hospitalization or cardiovascular death was highly concordant and robust across sodium–glucose co‐transporter 2 inhibitor trials. In contrast, secondary endpoints of all‐cause and cardiovascular mortality were statistically fragile, underscoring the need to power trials for mortality to fully understand the benefit of therapies on fatal events

Multi-centre randomised controlled trial of a smartphone-based event recorder alongside standard care versus standard care for patients presenting to the Emergency Department with palpitations and pre-syncope: the IPED (Investigation of Palpitations in the ED) Study.

Patients with palpitations and pre-syncope commonly present to Emergency Departments (EDs) but underlying rhythm diagnosis is often not possible during the initial presentation. This trial compares the symptomatic rhythm detection rate of a smartphone-based event recorder (AliveCor) alongside standard care versus standard care alone, for participants presenting to the ED with palpitations and pre-syncope with no obvious cause evident at initial consultation

Towards a conceptual framework demonstrating the effectiveness of audiovisual patient descriptions (patient video cases): a review of the current literature

Background: Technological advances have enabled the widespread use of video cases via web-streaming and online download as an educational medium. The use of real subjects to demonstrate acute pathology should aid the education of health care professionals. However, the methodology by which this effect may be tested is not clear. Methods: We undertook a literature review of major databases, found relevant articles relevant to using patient video cases as educational interventions, extracted the methodologies used and assessed these methods for internal and construct validity. Results: A review of 2532 abstracts revealed 23 studies meeting the inclusion criteria and a final review of 18 of relevance. Medical students were the most commonly studied group (10 articles) with a spread of learner satisfaction, knowledge and behaviour tested. Only two of the studies fulfilled defined criteria on achieving internal and construct validity. The heterogeneity of articles meant it was not possible to perform any meta-analysis. Conclusions: Previous studies have not well classified which facet of training or educational outcome the study is aiming to explore and had poor internal and construct validity. Future research should aim to validate a particular outcome measure, preferably by reproducing previous work rather than adopting new methods. In particular cognitive processing enhancement, demonstrated in a number of the medical student studies, should be tested at a postgraduate level

Cessation of Smoking Trial in the Emergency Department (COSTED): a multi-centre, randomised controlled trial

Background: Supporting people to quit smoking is one of the most powerful interventions to improve health. The Emergency Department (ED) represents a potentially valuable opportunity to deliver a smoking cessation intervention if it is sufficiently resourced. The objective of this trial was to determine whether an opportunistic ED based smoking cessation intervention can help people to quit smoking.   Methods: In this multi-centre, parallel-group, randomised controlled superiority trial conducted between January and August 2022, adults who smoked daily and attended one of six UK EDs were randomised to intervention (brief advice, e-cigarette starter kit and referral to stop smoking services) or control (written information on stop smoking services). The primary outcome was biochemically validated abstinence at six months.   Results: An intention-to-treat analysis included 972 of 1443 people screened for inclusion (intervention= 484, control= 488). Of 975 participants randomised, 3 were subsequently excluded, 17 withdrew and 287 were lost to follow-up. The six month biochemically verified abstinence rate was 7.2% in the intervention group and 4.1% in the control group (relative risk, 1.76; 95% confidence interval [CI] 1.03 to 3.01; p=0.038]). Self-reported 7-day abstinence at 6 months was 23.3% in the intervention group and 12.9% in the control group (relative risk, 1.80; 95% CI 1.36 to 2.38; p<0.001]). No serious adverse events related to taking part in the trial were reported.   Conclusions: An opportunistic smoking cessation intervention comprising brief advice, an e-cigarette starter kit and referral to stop smoking services is effective for sustained smoking abstinence with few reported adverse events

Fluid therapy in the emergency department: an expert practice review.

Intravenous fluid therapy is one of the most common therapeutic interventions performed in the ED and is a long-established treatment. The potential benefits of fluid therapy were initially described by Dr W B O'Shaughnessy in 1831 and first administered to an elderly woman with cholera by Dr Thomas Latta in 1832, with a marked initial clinical response. However, it was not until the end of the 19th century that medicine had gained understanding of infection risk that practice became safer and that the practice gained acceptance. The majority of fluid research has been performed on patients with critical illness, most commonly sepsis as this accounts for around two-thirds of shocked patients treated in the ED. However, there are few data to guide clinicians on fluid therapy choices in the non-critically unwell, by far our largest patient group. In this paper, we will discuss the best evidence and controversies for fluid therapy in medically ill patients