Reporting and interpreting the numerical results of a vaccine trial: a practical guide for students and health care professionals

In one year, the COVID pandemic has changed the world. Universities, pharmaceutical companies, and many other organisations worldwide worked effortlessly to develop vaccines to ease the socioeconomic burden of the disease and improve global health care. Nowadays, vaccine efficacy is a very popular term; but do we know what it means and how to calculate it? This article provides information on reporting and interpreting the numerical results of a vaccine trial. It aims to be a practical guide for students and health care professionals. It gives a simple definition of the common terminology, the vaccine efficacy, how to calculate it, and how the confidence interval can be found (though formulae for the latter are not given here). Additionally, it provides two simple examples (A, B), including the formulae for calculating the vaccine efficacy explaining the differences of vaccine efficacy between the two examples simply and pragmatically

Vaccine efficacy: The implication of using odds ratio and relative risk for the calculation. Which one would you choose?

During the last 12 months, COVID-19 became a global problem. Universities and drug companies are working together for the development of treatments. Vaccines appear to be one of the most promising treatments, and trials are completed, and others are ongoing. All these studies tend to use a common comparator, the percentage of vaccine efficacy (VE%), calculated using the following formula VE=(1-RR) x100. A recent study published in a renowned medical journal presented large trial results using a different formula VE=(1-OR) x100. We compared the analysis using relative risk (RR) versus an odds ratio (OR), and we did not find any large difference in the results. Nevertheless, we would advise using RR instead of OR in the interests of accuracy, for best practice

Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms.

BACKGROUND: The CRASH-2 trial showed that tranexamic acid (TXA) administration reduces mortality in bleeding trauma patients. However, the effect appeared to depend on how soon after injury TXA treatment was started. Treatment within 3 h reduced bleeding deaths whereas treatment after 3 h increased the risk. We examine how patient characteristics vary by time to treatment and explore whether any such variations explain the time-dependent treatment effect. METHODS: Exploratory analysis were carried out, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo-controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examine how patient characteristics (age, type of injury, presence or absence of head injury, Glasgow coma scale (GCS), systolic blood pressure and capillary refill time) vary with time to treatment and use univariable (restriction) and multivariable methods to examine whether any such variations explain the time-dependent effect of TXA. If not explained by differences in patient characteristics, we planned to conduct separate prespecified subgroup analyses for the early benefit and late harm. RESULTS: There was no substantial variation in age or capillary refill by time to treatment. However, the proportion of patients with blunt trauma, the proportion with head injury and mean systolic blood pressure increased as time to treatment increased. Mean GCS decreased as time to treatment increased. Analyses restricted to patients with blunt trauma, those without head injury and those with a systolic blood pressure 89 mmHg); GCS (severe 3-8, moderate 9-12, mild 13-15); and type of injury (penetrating versus blunt) showed no significant heterogeneity. CONCLUSIONS: The time-dependent effect of TXA in bleeding trauma patients is not explained by the type of injury, the presence or absence of head injury or systolic blood pressure. When given within 3 h of injury, TXA reduces death due to bleeding regardless of type of injury, GCS or blood pressure. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00375258 . Registered on 11 September 2006

Glucocorticoid therapy in ANCA Vasculitis - using the Glucocorticoid Toxicity Index as an outcome measure

Background Anti-neutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV) is an autoimmune disease. Induction remission and maintenance treatment typically includes high dose, tapering glucocorticoids (GC) in addition to other immunosuppressive medication. The use of Glucocorticoid Toxicity Index (GTI), provides a global, quantifiable assessment tool in which clinicians can assess GC associated morbidity. Recent trials in AAV have exposed the need for systemic assessment of GC burden. In this small cohort study, we look to address these issues and the justification of newer GC sparing agents such as C5a inhibitors. Methods A retrospective cohort study of 43 patients with biopsy AAV was constructed from a single centre between 2012 to 2016 and followed up for 48 months. The GTI table made up of adverse features used to quantify patients GC toxicity. Electronic patient records were reviewed and scores calculated according to published methods. GTI scores were compared with cumulative steroid doses at separate intervals as well as incidences of adverse features in relation to the treatment timeline. Results The mean age was 65.9 (± 11.06) years and treatment regimens consisted of glucocorticoids alongside cyclophosphamide or rituximab. Our results showed statistical significance in the association of cumulative GC doses and GTI scores (p=0.008, 95% CI, 1.31 to 8.05). Adverse features relating to mood disturbance and GC induced psychosis occurred early, in contrast to adrenal insufficiency which typically presented later in the follow up. Infection related adverse events were consistent throughout. Conclusions We demonstrated that higher, cumulative doses of steroids in AAV lead to worse glucocorticoid related toxicity. Using the GTI creates potential to individualise and quantify the adverse effects patients experience as a result of GC treatment and permits more patient centred management. Whilst glucocorticoids remain the main adjunctive immunosuppression of AAV treatment, the narrow therapeutic window supports the need for GC-sparing treatments

Augmented renal clearance: a retrospective, cohort study of urinary creatinine clearance in critically ill patients in the United Kingdom

Objective: Augmented renal clearance (ARC) is associated with sub-therapeutic antibiotic, anti-epileptic, and anticoagulant serum concentrations leading to adverse patient outcomes. We aimed to describe the prevalence and associated risk factors for ARC development in a large, single-centre cohort in the United Kingdom. Methods: We conducted a retrospective observational study of critically unwell patients admitted to intensive care between 2014 and 2016. Urinary creatinine clearance was used to determine the ARC prevalence during the first 7 days of admission. Repeated measures logistic regression was used to determine risk factors for ARC development. Results: The ARC prevalence was 47.0% (95% confidence interval [95%CI]: 44.3%–49.7%). Age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and sepsis diagnosis were significantly associated with ARC. ARC was more prevalent in younger vs. older (odds ratio [OR] 0.95 [95%CI: 0.94–0.96]), male vs. female (OR 0.32 [95%CI: 0.26–0.40]) patients with lower vs. higher APACHE II scores (OR 0.94 [95%CI: 0.92–0.96]). Conclusions: This patient group probably remains unknown to many clinicians because measuring urinary creatinine clearance is not usually indicated in this group. Clinicians should be aware of the ARC risk in this group and consider measurement of urinary creatinine clearance

Returning to leisure activity post-stroke: barriers and facilitators to engagement

Objectives: To identify barriers and facilitators to engagement when returning to, or participating in, leisure activity post-stroke or TIA. Design: Sequential explanatory, mixed methods study Setting: 21 hospital sites across England, Wales and Northern Ireland Participants: Adults with a clinical diagnosis of first/recurrent stroke or TIA. Patients approaching end of life were excluded. Participants were recruited as in-patients or at first clinic appointment and a baseline questionnaire was completed. A 6-month follow-up questionnaire was sent to participants for self-completion. Open-text questions were asked about barriers and facilitators when returning to, or participating in, leisure activity. Responses were thematically analysed and explored by participant characteristics, including type of leisure activity undertaken. Characteristics also included measures of socioeconomic deprivation, mood, fatigue and disability. Results: 2000 participants returned a 6-month follow-up questionnaire (78% stroke, 22% TIA); 1045 participants responded to a question on barriers and 820 on facilitators. Twelve themes were identified and the proportion of responses were reported (%). Barriers: physical difficulties (69%), lower energy levels (17%), loss of independence (11%), psychological difficulties (10%), hidden disabilities (7%), and delay or lack of healthcare provision (3%). Facilitators: family support (35%), healthcare support (27%), well-being and fitness (22%), friendship support (20%), self-management (19%), and returning to normality (9%). ‘Physical difficulties’ was the most reported barrier across all participant characteristics and activity types. Family support was the most reported facilitator except for those with greater disability, where it was healthcare support and those without fatigue where it was well-being and exercise. Conclusions: Physical difficulties and lack of energy are problematic for stroke and TIA survivors who want to return to or participate in leisure activity. Healthcare support alone cannot overcome all practical and emotional issues related to leisure activity engagement. Family support and improving well-being are important facilitators and future research should explore these mechanisms further

Life and Leisure Activities following Stroke or Transient Ischaemic Attack (TIA): An Observational, Multi-Centre, 6-Month Follow-Up Study

Objective: To examine changes in leisure participation following stroke/transient ischaemic attack (TIA) and explore its relationship to modifiable and non-modifiable participant characteristics. Design: An observational study design with self-report questionnaires collected at two time points (baseline and 6-months). Setting: The study was conducted across 21 hospital sites in England, Wales, and Northern Ireland. Participants: Participants were aged 18+ and had experienced a first or recurrent stroke or TIA and had a post-stroke/TIA modified Rankin score (mRS) of ≤3. Procedure: Research practitioners at each site approached potential participants. Individuals who agreed to participate completed a baseline questionnaire whilst an inpatient or at a first post-stroke/TIA clinic appointment. A follow-up questionnaire was posted to participants with a freepost return envelope. Two questionnaires were developed that collected demographic information, pre-stroke/TIA mRS, social circumstances (e.g., employment situation) and incorporated the shortened Nottingham Leisure Questionnaire (sNLQ). Results: The study recruited eligible participants (N = 3295); 2000 participants returned questionnaires at follow-up. Data showed three participant variables were significant predictors of engagement in leisure activities post-stroke/TIA: age, sex, and deprivation decile. There was an overall decline in the number and variety of leisure activities, with an average loss of 2.2 activities following stroke/TIA. Only one activity, “exercise/fitness” saw an increase in engagement from baseline to follow-up; watching TV remained stable, whilst participation in all other activities reduced between 10% and 40% with an average activity engagement reduction of 22%. Conclusions: Some groups experienced a greater reduction in activities than others—notably older participants, female participants, and those living in a low socioeconomic area. Registration: researchregistry4607. Strengths and limitations of this study: 1. This is the largest-ever study to survey life and leisure activity engagement following stroke/TIA. 2. Survey responses were self-reported retrospectively and, therefore, may have been misreported, or misremembered. 3. Despite the large cohort, there were few participants, and so respondents, from ethnic minority groups

Cancer incidence amongst UK firefighters

Firefighters suffer an increased risk of cancer from exposures to chemicals released from fires. Our earlier research has found that fire toxicants not only remain on firefighters’ PPE, but are also tracked back to fire stations. The UK Firefighter Contamination Survey assesses firefighters’ risk of developing cancer due to occupational exposure to fire toxins. Over 4% of surveyed firefighters were found to have a cancer diagnosis, with the age-specific cancer rate up to 323% higher (35–39 year olds) than that of the general population. Firefighters who had served ≥ 15 years were 1.7 times more likely to develop cancer than those who had served less time. Firefighters were at least twice as likely to be diagnosed with cancer if they noticed soot in their nose/throat (odds ratio (OR) = 2.0, 1.1–3.5), or remained in their PPE for more than four hours after attending a fire incident (OR = 2.3, 1.1–5.2). Also associated with an increased likelihood of cancer was: eating while wearing PPE (OR = 1.8, 1.2–2.7); failing to store clean/dirty PPE separately (OR = 1.3, 1.0–1.7); working in a station that smells of fire (OR = 1.3, 1.0–1.8) or not having designated (separated) clean and dirty areas (OR = 1.4, 1.1–1.7); using an on-site washing machine to launder fire hoods (OR = 1.3, 1.0–1.7); feeling that cleaning is not taken seriously at work (OR = 1.5, 1.2–2.0)

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

If it's normal, it's OK to be mean: Summarising data

� Continuous data can be summarised by their location and spread. � For symmetrical data, the location and spread are estimated by the mean and variance. � For non-symmetrical data, useful summaries are the median and interquartile range