A systematic review and diagnostic test accuracy meta-analysis of the validity of anion gap as a screening tool for hyperlactatemia

Objective This systematic review and meta-analysis seeks to determine the validity of the anion gap to screen for hyperlactatemia in critically ill patients. We have previously shown that the anion gap does not predict 31-day and in-hospital mortality in critically ill patients. The present review aims to add confirmatory evidence to identify whether the anion gap is a suitable tool for risk stratification in low-resource countries. Results Nine studies reporting on 4504 samples from 2111 patients were included. The anion gap failed to detect hyperlactatemia defined as lactate above 2.5 mmol/l but showed good discriminatory ability for the detection of severe hyperlactatemia defined as lactate over 4 mmol/l. At the 2.5 mmol/l threshold, the anion gap had high specificity but low sensitivity for the detection of hyperlactatemia. A meta-analysis of correlation coefficients yielded high statistical heterogeneity. Therefore, in keeping with our previous findings, the use of the anion gap for risk stratification as an alternative to lactate cannot be recommended. However, the strength of the evidence we have synthesised is adversely affected by the small number of studies included, inconsistency of effect measures and positivity thresholds reported, and selection bias within individual studies. PROSPERO Registration Number: CRD42015016470 (registered on the 4th February 2015)

Anion gap as a prognostic tool for risk stratification in critically ill patients – a systematic review and meta-analysis

Background Lactate concentration is a robust predictor of mortality but in many low resource settings facilities for its analysis are not available. Anion gap (AG), calculated from clinical chemistry results, is a marker of metabolic acidosis and may be more easily obtained in such settings. In this systematic review and meta-analysis we investigated whether the AG predicts mortality in adult patients admitted to critical care settings. Methods We searched Medline, Embase, Web of Science, Scopus, The Cochrane Library and regional electronic databases from inception until May 2016. Studies conducted in any clinical setting that related AG to in-hospital mortality, in-intensive care unit mortality, 31-day mortality or comparable outcome measures were eligible for inclusion. Methodological quality of included studies was assessed using the Quality in Prognostic Studies tool. Descriptive meta-analysis was performed and the I2 test was used to quantify heterogeneity. Subgroup analysis was undertaken to identify potential sources of heterogeneity between studies. Results Nineteen studies reporting findings in 12,497 patients were included. Overall, quality of studies was poor and most studies were rated as being at moderate or high risk of attrition bias and confounding. There was substantial diversity between studies with regards to clinical setting, age and mortality rates of patient cohorts. High statistical heterogeneity was found in the meta-analyses of area under the ROC curve (I2=99%) and mean difference (I2=97%) for the observed AG. Three studies reported good discriminatory power of the AG to predict mortality and were responsible for a large proportion of statistical heterogeneity. The remaining 16 studies reported poor to moderate ability of the AG to predict mortality. Subgroup analysis suggested that intravenous fluids affect the ability of the AG to predict mortality. Conclusion Based on the limited quality of available evidence, a single AG measurement cannot be recommended for risk stratification in critically ill patients. The probable influence of intravenous fluids on AG levels renders the AG an impractical tool in clinical practice. Future research should focus on increasing the availability of lactate monitoring in low resource settings.Publisher PDFPeer reviewe

Point-of-care lactate and creatinine analysis for sick obstetric patients at Queen Elizabeth Central Hospital in Blantyre, Malawi : a feasibility study

Background To achieve good outcomes in critically ill obstetric patients it is necessary to identify organ dysfunction rapidly so that life saving interventions can be appropriately commenced. However, timely access to clinical chemistry results is problematic even in referral institutions in the sub Saharan African region. Reliable point of care tests licensed for clinical use are now available for lactate and creatinine. Aim We aimed to assess whether implementation of point of care testing for lactate and creatinine is feasible in the obstetric unit at the Queen Elizabeth Central Hospital (QECH), Malawi, by obtaining the opinions of clinical staff on the use of these tests in practice. Methods During a two month evaluation period nurse-midwives, medical interns, clinical officers, registrars and consultants were given the opportunity to use StatStrip® and StatSensor® (Nova Biomedical) devices for lactate and creatinine estimation as part of their routine clinical practice in the obstetric unit. They were subsequently asked to complete a short questionnaire. Results 37 questionnaire responses were received, 22 from nurse-midwives and the remainder from clinicians. The mean satisfaction score for the devices was 7.6/10 amongst clinicians and 8.0/10 amongst nurse-midwives. The majority of participants stated that the obstetric high dependency unit (HDU) was the most suitable location for the devices. For lactate, 31 participants strongly agreed that testing should be continued and 24 strongly agreed that it would influence patient management. For creatinine, 29 strongly agreed that testing should be continued and 28 strongly agreed that it would influence their patient management. 20 participants strongly agreed that they trust point of care devices. Conclusion Point of care clinical chemistry testing is feasible, practical, well received by staff and was considered by staff to have a useful role to play in the clinical care of very sick obstetric patients at this referral centre.PostprintPeer reviewe

Prospective observational cohort study of factors influencing trial participation in people with motor neuron disease (FIT-participation-MND): a protocol

Introduction Motor neuron disease (MND) is a rapidly progressive and fatal neurodegenerative disorder with limited treatment options. The Motor Neuron Disease Systematic Multi-Arm Randomised Adaptive Trial (MND-SMART) is a multisite UK trial seeking to address the paucity in effective disease-modifying drugs for people with MND (pwMND). Historically, neurological trials have been plagued by suboptimal recruitment and high rates of attrition. Failure to recruit and/or retain participants can cause insufficiently representative samples, terminated trials or invalid conclusions. This study investigates patient-specific factors affecting recruitment and retention of pwMND to MND-SMART. Improved understanding of these factors may improve trial protocol design, optimise recruitment and retention.Methods and analysis PwMND on the Scottish MND Register, Clinical Audit Research and Evaluation of MND (CARE-MND), will be invited to participate in a prospective observational cohort study that investigates factors affecting trial participation and attrition. We hypothesise that patient-specific factors will significantly affect trial recruitment and retention. Participants will complete the Hospital Anxiety and Depression Scale, 9-Item Patient Health Questionnaire and State-Trait Anxiety Inventory-Form Y to evaluate neuropsychiatric symptoms, the ALS-Specific Quality of Life Questionnaire-Brief Form and Centre for Disease Control and Prevention-Health-Related Quality of Life for quality of life and a novel study-specific questionnaire on Attitudes towards Clinical Trial Participation (ACT-Q). Clinical data on phenotype, cognition (Edinburgh Cognitive and Behavioural ALS Screen) and physical functioning (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) will also be collated. Caregivers will complete the Brief Dimensional Apathy Scale. After 12 months, a data request to MND-SMART will evaluate recruitment and retention. Descriptive statistics will summarise and compare assessments and participants reaching impairment thresholds. Variable groupings: attitudes, quality of life, cognition, behaviour, physical functioning, neuropsychiatric and phenotype. Univariate and multivariable logistic regression will explore association with participation/withdrawal in MND-SMART; presented as ORs and 95% CIs.Ethics and dissemination Ethical approval was provided by the West of Scotland Research Ethics Committee 3 (20/WS/0067) on 12 May 2020. The results of this study will be published in a peer-reviewed journal, presented at academic conferences and disseminated to participants and the public

Systematic review of prediction models in relapsing remitting multiple sclerosis

The natural history of relapsing remitting multiple sclerosis (RRMS) is variable and prediction of individual prognosis challenging. The inability to reliably predict prognosis at diagnosis has important implications for informed decision making especially in relation to disease modifying therapies. We conducted a systematic review in order to collate, describe and assess the methodological quality of published prediction models in RRMS. We searched Medline, Embase and Web of Science. Two reviewers independently screened abstracts and full text for eligibility and assessed risk of bias. Studies reporting development or validation of prediction models for RRMS in adults were included. Data collection was guided by the checklist for critical appraisal and data extraction for systematic reviews (CHARMS) and applicability and methodological quality assessment by the prediction model risk of bias assessment tool (PROBAST). 30 studies were included in the review. Applicability was assessed as high risk of concern in 27 studies. Risk of bias was assessed as high for all studies. The single most frequently included predictor was baseline EDSS (n = 11). T2 Lesion volume or number and brain atrophy were each retained in seven studies. Five studies included external validation and none included impact analysis. Although a number of prediction models for RRMS have been reported, most are at high risk of bias and lack external validation and impact analysis, restricting their application to routine clinical practice

Non-motor symptoms in motor neuron disease:Prevalence, assessment and impact

People with motor neuron disease often experience non-motor symptoms that may occur secondary to, or distinct from, motor degeneration and that may significantly reduce quality of life, despite being under-recognized and evaluated in clinical practice. Non-motor symptoms explored in this population-based study include pain, fatigue, gastrointestinal issues, poor sleep, low mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction. People registered on the Clinical Audit Research and Evaluation of motor neuron disease platform, the Scottish Motor Neuron Disease Register, were invited to complete a questionnaire on non-motor symptoms and a self-reported Amyotrophic Lateral Sclerosis Functional Rating Scale. The questionnaire comprised a pre-defined list of 11 potential non-motor symptoms, with the opportunity to list additional symptoms. A total of 120 individuals participated in this cross-sectional study, a 39% response rate of those sent questionnaires (n = 311); 99% of participants recruited (n = 120) experienced at least one non-motor symptom, with 72% (n = 120) reporting five or more. The symptoms most often reported were pain and fatigue (reported by 76% of participants, respectively). The symptoms reported to be most impactful were gastrointestinal issues (reported as ‘severe’ by 54% of participants who experienced them), followed by pain and problematic saliva (51%, respectively). Lower Amyotrophic Lateral Sclerosis Functional Rating Scale scores, indicating more advanced disease and being a long survivor [diagnosed over 8 years ago; Black et al. (Genetic epidemiology of motor neuron disease-associated variants in the Scottish population. Neurobiol Aging. 2017;51:178.e11-178.e20.)], were significantly associated with reporting more symptoms; 73% of respondents were satisfied with the frequency that non-motor symptoms were discussed in clinical care; 80% of participants indicated they believe evaluation of non-motor symptom is important to include as outcomes in trials, independent of their personal experience of these symptoms. The preferred method of assessment was completing questionnaires, at home. The overwhelming majority of people with motor neuron disease report non-motor symptoms and these frequently co-occur. Pain, fatigue, gastrointestinal issues, sleep, mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction are prevalent. People with motor neuron disease who had worse physical function and those who were long survivors were more likely to report more symptoms. Where reported, these symptoms are frequent, impactful and a priority for people with motor neuron disease in clinical care and trial design