A comparative study into the effects of venous and arterial blood on clot microstructure in critically unwell patients. Assessment of the diagnostic potential of a biomarker of haemostasis.

Blood for coagulation analysis can be sampled from the arterial or venous system in intensive care units (ICU). The determination of clot microstructure and strength by fractal analysis (df) gives valuable information in a range of vascular haemostatic disease and sepsis. We aimed to determine if df could be measured equally and comparatively in arterial or venous blood, and 45 critically ill patients in an ICU were recruited. df was found to be readily measured in arterial blood with results comparable to those in venous blood and that add value of df as a potential marker of haemostasis in these patients.

Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis.

BACKGROUND: Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events. OBJECTIVES: (1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta-analysis. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 19 August 2020. SELECTION CRITERIA: We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar time points using random-effects methods. We also performed a network meta-analysis using Bayesian methods. MAIN RESULTS: We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg (n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Mean ages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (MD) -0.92 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) points (range 0 to 70), 95% confidence interval (CI) -1.44 to -0.40; high-certainty evidence). Donepezil 10 mg (MD -2.21 ADAS-Cog points, 95% CI -3.07 to -1.35; moderate-certainty evidence) and galantamine 16 to 24 mg (MD -2.01 ADAS-Cog point, 95%CI -3.18 to -0.85; moderate-certainty evidence) probably also improve cognition, although the larger effect estimates still may not be clinically important. With low certainty, there may be little to no effect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS-Cog points, 95% CI -3.04 to 3.10; low-certainty evidence). Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The results showed that there was probably little to no difference between donepezil 5 mg and placebo in the number of adverse events (odds ratio (OR) 1.22, 95% CI 0.94 to 1.58; moderate-certainty evidence), but there were slightly more adverse events with donepezil 10 mg than with placebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The effect of rivastigmine 3 to 12 mg on adverse events was very uncertain (OR 3.21, 95% CI 0.36 to 28.88; very low-certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverse events over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate-certainty evidence). In the network meta-analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes. AUTHORS' CONCLUSIONS: We found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain. The data suggest that donepezil 10 mg has the greatest effect on cognition, but at the cost of adverse effects. The effect is modest, but in the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches.

Predictors of post-traumatic stress disorder following critical illness: A mixed methods study.

PURPOSE: Post-traumatic stress disorder has been reported in survivors of critical illness. The aim of this study was to investigate the predictors of post-traumatic stress disorder in survivors of critical illness. MATERIALS AND METHODS: Patients attending the intensive care unit (ICU) follow-up clinic completed the UK-Post-Traumatic Stress Syndrome 14-Questions Inventory and data was collected from their medical records. Predictors investigated included age, gender, Apache II score, ICU length of stay, pre-illness psychopathology; delirium and benzodiazepine administration during ICU stay and delusional memories of the ICU stay following discharge. RESULTS: A total of 198 patients participated, with 54 (27%) patients suffering with post-traumatic stress disorder. On multivariable logistic regression, the significant predictors of post-traumatic stress disorder were younger age, lower Apache II score, pre-illness psychopathology and delirium during the ICU stay. CONCLUSIONS: The predictors of post-traumatic stress disorder in this study concur with previous research however a lower Apache II score has not been previously reported.

Management of the anticoagulated trauma patient in the emergency department: a survey of current practice in England and Wales.

OBJECTIVE: The aim of this study was to investigate current management of the anticoagulated trauma patient in the emergency departments (EDs) in England and Wales. METHODS: A survey exploring management strategies for anticoagulated trauma patients presenting to the ED was developed with two patient scenarios concerning assessment of coagulation status, reversal of international normalised ratio (INR), management of hypotension and management strategies for each patient. Numerical data are presented as percentages of total respondents to that particular question. RESULTS: 106 respondents from 166 hospitals replied to the survey, with 24% of respondents working in a major trauma unit with a specialist neurosurgical unit. Variation was reported in the assessment and management strategies of the elderly anticoagulated poly-trauma patient described in scenario one. Variation was also evident in the responses between the neurosurgical and non-neurosurgical units for the head-injured, anticoagulated trauma patient in scenario two. CONCLUSION: The results of this study highlight the similarities and variation in the management strategies used in the EDs in England and Wales for the elderly, anticoagulated trauma patient. The variations in practice reported may be due to the differences evident in the available guidelines for these patients.

Predictors of mortality in patients with flail chest: a systematic review.

OBJECTIVE: To summarise the risk factors for mortality in patients with flail chest based on available evidence in the literature. METHODS: A systematic review was completed using articles from PubMed, EMBASE, the Centre for Review and Dissemination database and the Cochrane Library. Additional studies were identified by hand-searching bibliographies, and grey literature was sought by searching abstracts from all relevant Emergency Medicine Conferences. All published and unpublished observational studies were included if they investigated estimates of association between a risk factor and mortality for patients with flail chest. RESULTS: This review found seven studies that matched the inclusion criteria, with a total of 944 patients. Patient age of ≥65 years was reported as a predictor of mortality when controlling for injury severity score (ISS) (p<0.02, OR 2.1, 95% CI 1.0 to 4.6). An ISS of ≥31 was reported to be a predictor of mortality in two studies; however, neither controlled for patient age. Pulmonary contusion, bilateral flail chest and hospital length of stay were not consistently found to be associated with mortality. CONCLUSIONS: The main independent predictors of mortality in patients with flail chest were reported to be increased age and ISS. More data are needed regarding the association of hospital length of stay, presence of pulmonary contusion and bilateral flail chest.

The effect of preinjury warfarin use on mortality rates in trauma patients: a European multicentre study.

OBJECTIVE: To define the relationship between preinjury warfarin use and mortality in a large European sample of trauma patients. METHODS: A multicentred study was conducted using data collated from European (predominately English and Welsh) trauma receiving hospitals. Patient data from the Trauma Audit and Research Network database from 2009 to 2013 were analysed. Univariate and multivariate logistic regression was used to estimate OR for mortality associated with preinjury warfarin use in the whole adult trauma cohort and a matched sample of patients comparable in terms of age, gender, GCS, pre-existing medical conditions and injury severity. RESULTS: A total of 136 617 adult trauma patients (2009-2013) were included, with 499 patients reported to be using warfarin therapy at the time of trauma. Preinjury warfarin use was associated with a significantly higher mortality rate at 30 days postinjury compared with the non-users. Following adjustment of age, injury severity and GCS, preinjury warfarin use was associated with increased mortality in trauma patients (adjusted OR 2.14; 95% CI 1.66 to 2.76; p<0.001). In the matched subset, 22% of warfarinised trauma patients died compared with 16.3% of non-warfarinised trauma patients with comparable age, injury severity and GCS (adjusted OR 1.94; 95% CI 1.25 to 3.01; p=0.003). CONCLUSIONS: Preinjury warfarin use has been demonstrated to be an independent predictor of mortality in trauma patients. Clinicians managing major trauma patients on warfarin need to be aware of the vulnerability of this group.

Long term health-related quality of life in survivors of sepsis in South West Wales: an epidemiological study.

INTRODUCTION: Survivors of sepsis report persistent problems that can last years after hospital discharge. The main aim of this study was to investigate long-term health-related quality of life in survivors of SIRS and sepsis compared with Welsh normative data, controlling for age, length of stay and pre-existing conditions. The second aim was to investigate any differences in long-term health-related quality of life specifically with the patients categorised into three groups; SIRS, uncomplicated sepsis and severe sepsis/septic shock. METHODS: A prospective study design was used in order to investigate all sepsis patients either presenting to the Emergency Department or admitted to the Intensive Care Unit of a regional trauma centre. Baseline demographics, clinical characteristics and outcomes were collected and surviving patients were sent a SF-12v2 survey at between six months to two years post-hospital discharge. RESULTS: Quality of life was significantly reduced in all patients when compared to local normative data (all p<0.0001). Reductions in the physical components of health-related quality of life were more pronounced in severe sepsis/septic shock patients when compared to uncomplicated sepsis and SIRS patients, when controlling for age, pre-existing conditions, hospital and ICU length of stay. CONCLUSIONS: This is the first observational study to specifically focus on the different groups of SIRS and sepsis patients to assess long-term quality of life. Local population norms were used for comparison, rather than UK-wide norms that fail to reflect the intricacies of a country's population.

Chronic pain in survivors of critical illness: a retrospective analysis of incidence and risk factors.

INTRODUCTION: Chronic pain has been reported in survivors of critical illness for many years after discharge from hospital. This study investigates the incidence and site of chronic pain in survivors of critical illness between 6 months and 1 year after hospitalization, including ICU admission. A retrospective analysis of the risk factors for chronic pain in this patient group was also completed. METHODS: A questionnaire method was used to investigate the incidence of chronic pain and the specific body parts affected. A retrospective study and multivariable analysis were used to investigate the risk factors for chronic pain in this patient group. All survivors of a general intensive care unit (ICU) in South Wales in a 6-month period were included in this study. RESULTS: Chronic pain was reported in 44% of all respondents. The shoulder was the most commonly reported joint affected by pain (22%). Risk factors for chronic pain between 6 months and 1 year after ICU discharge were increasing patient age and severe sepsis. CONCLUSIONS: Chronic pain is a problem in survivors of critical illness, especially in the shoulder joint, and further studies are needed investigating therapeutic interventions that address this long-term problem.

Risk factors that predict mortality in patients with blunt chest wall trauma: a systematic review and meta-analysis.

BACKGROUND: The risk factors for mortality following blunt chest wall trauma have neither been well established or summarised. OBJECTIVE: To summarise the risk factors for mortality in blunt chest wall trauma patients based on available evidence in the literature. DATA SOURCES: A systematic review of English and non-English articles using MEDLINE, EMBASE and the Cochrane Library from their introduction until May 2010. Additional studies were identified by hand-searching bibliographies and contacting relevant clinical experts. Grey literature was sought by searching abstracts from all Emergency Medicine conferences. Broad search terms and inclusion criteria were used to reduce the number of missed studies. STUDY SELECTION: A two step study selection process was used. All published and unpublished observational studies were included if they investigated estimates of association between a risk factor and mortality for blunt chest wall trauma patients. DATA EXTRACTION: A two step data extraction process using pre-defined data fields, including study quality indicators. STUDY APPRAISAL AND SYNTHESIS: Each study was appraised using a previously designed quality assessment tool and the STROBE checklist. Where sufficient data were available, odds ratios with 95% confidence intervals were calculated using Mantel-Haenszel method for the risk factors investigated. The I(2) statistic was calculated for combined studies in order to assess heterogeneity. RESULTS: Age, number of rib fractures, presence of pre-existing disease and pneumonia were found to be related to mortality in 29 identified studies. Combined odds ratio of 1.98 (1.86-2.11, 95% CI), 2.02 (1.89-2.15, 95% CI), 2.43 (1.03-5.72, 95% CI) and 5.24 (3.51-7.82) for mortality were calculated for blunt chest wall trauma patients aged 65 years or more, with three or more rib fractures, pre-existing conditions and pneumonia respectively. CONCLUSIONS: The risk factors for mortality in patients sustaining blunt chest wall trauma were a patient age of 65 years or more, three or more rib fractures and the presence of pre-existing disease especially cardiopulmonary disease. The development of pneumonia post injury was also a significant risk factor for mortality. As a result of the variable quality in the studies, the results of the selected studies should be interpreted with caution.