Baseline characteristics of people experiencing homelessness with a recent drug overdose in the PHOENIx pilot randomised controlled trial.

BACKGROUND: Drug-related deaths in Scotland are the highest in Europe. Half of all deaths in people experiencing homelessness are drug related, yet we know little about the unmet health needs of people experiencing homelessness with recent non-fatal overdose, limiting a tailored practice and policy response to a public health crisis. METHODS: People experiencing homelessness with at least one non-fatal street drug overdose in the previous 6 months were recruited from 20 venues in Glasgow, Scotland, and randomised into PHOENIx plus usual care, or usual care. PHOENIx is a collaborative assertive outreach intervention by independent prescriber NHS Pharmacists and third sector homelessness workers, offering repeated integrated, holistic physical, mental and addictions health and social care support including prescribing. We describe comprehensive baseline characteristics of randomised participants. RESULTS: One hundred and twenty-eight participants had a mean age of 42 years (SD 8.4); 71% male, homelessness for a median of 24 years (IQR 12-30). One hundred and eighteen (92%) lived in large, congregate city centre temporary accommodation. A quarter (25%) were not registered with a General Practitioner. Participants had overdosed a mean of 3.2 (SD 3.2) times in the preceding 6 months, using a median of 3 (IQR 2-4) non-prescription drugs concurrently: 112 (87.5%) street valium (benzodiazepine-type new psychoactive substances); 77 (60%) heroin; and 76 (59%) cocaine. Half (50%) were injecting, 50% into their groins. 90% were receiving care from Alcohol and Drug Recovery Services (ADRS), and in addition to using street drugs, 90% received opioid substitution therapy (OST), 10% diazepam for street valium use and one participant received heroin-assisted treatment. Participants had a mean of 2.2 (SD 1.3) mental health problems and 5.4 (SD 2.5) physical health problems; 50% received treatment for physical or mental health problems. Ninety-one per cent had at least one mental health problem; 66% had no specialist mental health support. Participants were frail (70%) or pre-frail (28%), with maximal levels of psychological distress, 44% received one or no daily meal, and 58% had previously attempted suicide. CONCLUSIONS: People at high risk of drug-related death continue to overdose repeatedly despite receiving OST. High levels of frailty, multimorbidity, unsuitable accommodation and unmet mental and physical health care needs require a reorientation of services informed by evidence of effectiveness and cost-effectiveness. Trial registration UK Clinical Trials Registry identifier: ISRCTN 10585019.

The relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted to hospital with COVID-19.

BACKGROUND: Micronutrients have been associated with disease severity and poorer clinical outcomes in patients with COVID-19. However, there is a paucity of studies examining if the relationship with micronutrient status and clinical outcomes is independent of recognised prognostic factors, specifically frailty and the systemic inflammatory response (SIR). The aim of the present study was to examine the relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted with COVID-19. METHODS: Retrospective analysis of prospectively collected data was performed on patients with confirmed COVID-19, admitted to hospital between the 1st April 2020-6th July 2020. Clinicopathological characteristics, frailty assessment, biochemical and micronutrient laboratory results were recorded. Frailty status was determined using the Clinical Frailty scale. SIR was determined using serum CRP. Clinical outcomes of interest were oxygen requirement, ITU admission and 30-day mortality. Categorical variables were analysed using chi-square test and binary logistics regression analysis. Continuous variables were analysed using the Mann-Whitney U or Kruskal Wallis tests. RESULTS: 281 patients were included. 55% (n = 155) were aged ≥ 70 years and 39% (n = 109) were male. 49% (n = 138) of patients were frail (CFS > 3). 86% (n = 242) of patients had a serum CRP > 10 mg/L. On univariate analysis, frailty was significantly associated with thirty-day mortality (p < 0.001). On univariate analysis, serum CRP was found to be significantly associated with an oxygen requirement on admission in non-frail patients (p = 0.004). Over a third (36%) of non-frail patients had a low vitamin B1, despite having normal reference range values of red cell B2, B6 and selenium. Furthermore, serum CRP was found to be significantly associated with a lower median red cell vitamin B1 (p = 0.029). CONCLUSION: Vitamin B1 stores may be depleted in COVID-19 patients experiencing a significant SIR and providing rationale for thiamine supplementation. Further longitudinal studies are warranted to delineate the trend in thiamine status following COVID-19.

Lactate dehydrogenase: relationship with the diagnostic GLIM criterion for cachexia in patients with advanced cancer.

BACKGROUND: Although suggestive of dysregulated metabolism, the relationship between serum LDH level, phenotypic/aetiologic diagnostic Global Leadership Initiative on Malnutrition (GLIM) criteria and survival in patients with advanced cancer has yet to examined. METHODS: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011-2016, was retrospectively analysed. LDH values were grouped as <250/250-500/>500 Units/L. Relationships were examined using χ2 test for linear-by-linear association and binary logistics regression analysis. RESULTS: A total of 436 patients met the inclusion criteria. 46% (n = 200) were male and 59% (n = 259) were ≥65 years of age. The median serum LDH was 394 Units/L and 33.5% (n = 146) had an LDH > 500 Units/L. LDH was significantly associated with ECOG-PS (p < 0.001), NLR (p < 0.05), mGPS (p < 0.05) and 3-month survival (p < 0.001). LDH was significantly associated with 3-month survival independent of weight loss (p < 0.01), BMI (p < 0.05), skeletal muscle mass (p < 0.01), metastatic disease (p < 0.05), NLR (p < 0.05) and mGPS (p < 0.01). DISCUSSION: LDH was associated with performance status, systemic inflammation and survival in patients with advanced cancer. LDH measurement may be considered as an aetiologic criteria and become a potential therapeutic target in the treatment of cancer cachexia.

Pharmacist and Homeless Outreach Engagement and Non-medical Independent prescribing Rx (PHOENIx): a study protocol for a pilot randomised controlled trial.

INTRODUCTION: The number of people experiencing homelessness (PEH) is increasing worldwide. Systematic reviews show high levels of multimorbidity and mortality. Integrated health and social care outreach interventions may improve outcomes. No previous studies have targeted PEH with recent drug overdose despite high levels of drug-related deaths and few data describe their health/social care problems. Feasibility work suggests a collaborative health and social care intervention (Pharmacist and Homeless Outreach Engagement and Non-medical Independent prescribing Rx, PHOENIx) is potentially beneficial. We describe the methods of a pilot randomised controlled trial (RCT) with parallel process and economic evaluation of PEH with recent overdose. METHODS AND ANALYSIS: Detailed health and social care information will be collected before randomisation to care-as-usual plus visits from a pharmacist and a homeless outreach worker (PHOENIx) for 6-9 months or to care-as-usual. The outcomes are the rates of presentations to emergency department for overdose or other causes and whether to progress to a definitive RCT: recruitment of ≥100 participants within 4 months, ≥60% of patients remaining in the study at 6 and 9 months, ≥60% of patients receiving the intervention, and ≥80% of patients with data collected. The secondary outcomes include health-related quality of life, hospitalisations, treatment uptake and patient-reported measures. Semistructured interviews will explore the future implementation of PHOENIx, the reasons for overdose and protective factors. We will assess the feasibility of conducting a cost-effectiveness analysis. ETHICS AND DISSEMINATION: The study was approved by South East Scotland National Health Service Research Ethics Committee 01. Results will be made available to PEH, the study funders and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN10585019.

A comparison of CT-body composition measurements in non-cancer and cancer patients from a single UK centre.

Objectives: Establish the prevalence of low skeletal muscle index and density in our population, by comparing age and sex matched cohorts of patients with and without cancer, using standardized methodology for CT-Body composition (CT-BC). Methods: A retrospective analysis of prospectively collected data. Patients admitted to our institution between 17th March 2020 - 1st May 2020, with confirmed coronavirus disease and imaging suitable for CT-BC (n=52), were age and sex matched with patients undergoing resection for colorectal cancer (n=52). Results: 104 patients were included in the final analysis. 43% (n=45) were male, 77% (n=80) were aged 65 years or older, 50% (n=50) were overweight (BMI ≥25) and 53% (n=55) were systemically inflamed (mGPS ≥1). The prevalence of a low SMI (56% vs. 65%) and low SMD (83% vs. 67%) was similar between cohorts. A low SMI and SMD were both associated with age (p<0.05 and p<0.01, respectively) on univariate analysis. On multivariate analysis, a low SMD was independently associated with age (OR 2.38 (1.34-4.22), p=0.003) and mGPS (OR 2.10 (1.20-3.68), p=0.01). Conclusions: In conclusion, the prevalence of a low SMI and low SMD was similar in non-cancer and cancer cohorts in our institution.

Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores.

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275-675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms.ClinicalTrials.gov: NCT03466528.

High-sensitivity cardiac troponin and the diagnosis of myocardial infarction in patients with kidney impairment.

The benefit and utility of high-sensitivity cardiac troponin (hs-cTn) in the diagnosis of myocardial infarction in patients with kidney impairment is unclear. Here, we describe implementation of hs-cTnI testing on the diagnosis, management, and outcomes of myocardial infarction in patients with and without kidney impairment. Consecutive patients with suspected acute coronary syndrome enrolled in a stepped-wedge, cluster-randomized controlled trial were included in this pre-specified secondary analysis. Kidney impairment was defined as an eGFR under 60mL/min/1.73m2. The index diagnosis and primary outcome of type 1 and type 4b myocardial infarction or cardiovascular death at one year were compared in patients with and without kidney impairment following implementation of hs-cTnI assay with 99th centile sex-specific diagnostic thresholds. Serum creatinine concentrations were available in 46,927 patients (mean age 61 years; 47% women), of whom 9,080 (19%) had kidney impairment. hs-cTnIs were over 99th centile in 46% and 16% of patients with and without kidney impairment. Implementation increased the diagnosis of type 1 infarction from 12.4% to 17.8%, and from 7.5% to 9.4% in patients with and without kidney impairment (both significant). Patients with kidney impairment and type 1 myocardial infarction were less likely to undergo coronary revascularization (26% versus 53%) or receive dual anti-platelets (40% versus 68%) than those without kidney impairment, and this did not change post-implementation. In patients with hs-cTnI above the 99th centile, the primary outcome occurred twice as often in those with kidney impairment compared to those without (24% versus 12%, hazard ratio 1.53, 95% confidence interval 1.31 to 1.78). Thus, hs-cTnI testing increased the identification of myocardial injury and infarction but failed to address disparities in management and outcomes between those with and without kidney impairment.

The relationship between frailty, nutritional status, co-morbidity, CT-body composition and systemic inflammation in patients with COVID-19.

BACKGROUND: Frailty, determined by the Canadian Study of Health and Aging-Clinical Frailty Scale (CFS), is strongly associated with clinical outcomes including mortality in patients with COVID-19. However, the relationship between frailty and other recognised prognostic factors including age, nutritional status, obesity, sarcopenia and systemic inflammation is poorly understood. Therefore, the aim of this study was to examine the relationship between frailty and other prognostic domains, in patients admitted with COVID-19. METHODS: Patients who presented to our institutions between 1st April 2020-6th July 2020 with confirmed COVID-19 were assessed for inclusion. Data collected included general demographic details, clinicopathological variables, CFS admission assessment, Malnutrition Universal Screening Tool (MUST), CT-BC measurements and markers of systemic inflammation. RESULTS: 106 patients met the study inclusion criteria. The majority of patients were aged ≥ 70 years (67%), male (53%) and frail (scoring > 3 on the CFS, 72%). The majority of patients were not malnourished (MUST 0, 58%), had ≥ 1 co-morbidity (87%), were sarcopenic (low SMI, 80%) and had systemic inflammation (mGPS ≥ 1, 81%, NLR > 5, 55%). On multivariate binary logistics regression analysis, age (p < 0.01), COPD (p < 0.05) and NLR (p < 0.05) remained independently associated with frailty. On univariate binary logistics regression, NLR (p < 0.05) was significantly associated with 30-day mortality. CONCLUSION: Frailty was independently associated with age, co-morbidity, and systemic inflammation. The basis of the relationship between frailty and clinical outcomes in COVID-19 requires further study. Trial registration Registered with clinicaltrials.gov (NCT04484545).

Clinical and radiological characteristics of acute pulmonary embolus in relation to 28-day and 6-month mortality.

BACKGROUND: Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood. OBJECTIVES: To investigate the prognostic value of clinical, laboratory and radiological information that is available within routine tests undertaken for patients with acute PE. METHODS: Electronic patient records (EPR) of patients who underwent Computed Tomography Pulmonary Angiogram (CTPA) scan for the investigation of acute PE during 6-month period (01.01.2016-30.06.2016) were examined. Data was gathered from EPR for patients that met inclusion criteria and all CTPA scans were re-evaluated. Biochemical thresholds of low-grade and high-grade inflammation, serum CRP >10mg/L and >150mg/L and serum albumin concentrations <35g/L and <25 g/L, were combined in the Glasgow Prognostic Score (GPS) and peri-operative Glasgow Prognostic Score (poGPS) respectively. Neutrophil Lymphocyte ratio (NLR) was also calculated. Pulmonary Embolus Severity Index score was calculated. RESULTS: Of the total CTPA reports (n = 2129) examined, 245 patients were eligible for inclusion. Of these, 20 (8%) patients had died at 28-days and 43 (18%) at 6-months. Of the 197 non-cancer related presentations, 28-day and 6-month mortality were 3% and 8% respectively. Of the 48 cancer related presentations, 28-day and 6-month mortality were 29% and 58% respectively. On univariate analysis, age ≥65 years (p<0.01), PESI score ≥100(p = <0.001), NLR ≥3(p<0.001) and Coronary Artery Calcification (CAC) score ≥ 6 (p<0.001) were associated with higher 28-day and 6-month mortality. PESI score ≥100 (OR 5.2, 95% CI: 1.1, 24.2, P <0.05), poGPS ≥1 (OR 2.5, 95% CI: 1.2-5.0, P = 0.01) and NLR ≥3 (OR 3.7, 95% CI: 1.0-3.4, P <0.05) remained independently associated with 28-day mortality. On multivariate binary logistic regression analysis of factors associated with 6-month mortality, PESI score ≥100 (OR 6.2, 95% CI: 2.3-17.0, p<0.001) and coronary artery calcification score ≥6 (OR 2.3, 95% CI: 1.1-4.8, p = 0.030) remained independently associated with death at 6-months. When patients who had an underlying cancer diagnosis were excluded from the analysis only GPS≥1 remained independently associated with 6-month mortality (OR 5.0, 95% CI 1.2-22.0, p<0.05). CONCLUSION: PESI score >100, poGPS≥1, NLR ≥3 and CAC score ≥6 were associated with 28-day and 6-month mortality. PESI score ≥100, poGPS≥1 and NLR ≥3 remained independently associated with 28-day mortality. PESI score ≥100 and CAC score ≥6 remained independently associated with 6-month mortality. When patients with underlying cancer were excluded from the analysis, GPS≥1 remained independently associated with 6-month mortality. The role of the systemic inflammatory response (SIR) in determining treatment and prognosis requires further study. Routine reporting of CAC scores in CTPA scans for acute PE may have a role in aiding clinical decision-making regarding treatment and prognosis.

Relation Between Body Composition, Systemic Inflammatory Response, and Clinical Outcomes in Patients Admitted to an Urban Teaching Hospital with COVID-19.

BACKGROUND: COVID-19 has been associated with cases of severe respiratory illness, admissions to intensive therapy units (ITUs), and high mortality rates. OBJECTIVES: The aim of the present study was to examine the relation between computed tomography- body composition (CT-BC) measurements, systemic inflammation, and clinical outcomes in those with COVID-19. METHODS: Patients who presented to our institution between March 17 and May 1, 2020, with a positive PCR test for COVID-19 or characteristic radiological changes, were assessed for inclusion. Data collected included general demographic details, clinicopathological variables, poGPS, NLR , CT-BC measurements, and clinical outcomes including ITU admission and 30-d mortality, of those admitted. RESULTS: Sixty-three patients met the study inclusion criteria. Forty-two patients (67%) were aged ≥70 y, 30 (47.6%) were male and 34.9% ( n = 22) had a poGPS ≥1. ITU admission was significantly associated with a high VFA ( P < 0.05). Thirty-day mortality was associated with high VFA (P < 0.05) and low SMI (P < 0.05). CONCLUSIONS: Sarcopenia in the presence of obesity was associated with clinical outcomes including greater 30-d mortality.

The systemic inflammatory response and clinicopathological characteristics in patients admitted to hospital with COVID-19 infection: Comparison of 2 consecutive cohorts.

BACKGROUND: In order to manage the COVID-19 systemic inflammatory response, it is important to identify clinicopathological characteristics across multiple cohorts. METHODS: The aim of the present study was to compare the 4C mortality score, other measures of the systemic inflammatory response and clinicopathological characteristics in two consecutive cohorts of patients on admission with COVID-19. Electronic patient records for 2 consecutive cohorts of patients admitted to two urban teaching hospitals with COVID-19 during two 7-week periods of the COVID-19 pandemic in Glasgow, U.K. (cohort 1: 17/3/2020-1/5/2020) and (cohort 2: 18/5/2020-6/7/2020) were examined for routine clinical, laboratory and clinical outcome data. RESULTS: Compared with cohort 1, cohort 2 were older (p<0.001), more likely to be female (p<0.05) and have less independent living circumstances (p<0.001). More patients in cohort 2 were PCR positive, CXR negative (both p<0.001) and had low serum albumin concentrations (p<0.001). 30-day mortality was similar between both cohorts (23% and 22%). In cohort 2, age >70 (p<0.05), male gender (p<0.05), COPD (p<0.05), cognitive impairment (p<0.05), frailty (p<0.001), delirium (p = 0.001), CRP>150mg/L (p<0.05), albumin <30 g/L (p<0.01), elevated perioperative Glasgow Prognostic Score (p<0.05), elevated neutrophil-lymphocyte ratio (p<0.001), low haematocrit (p<0.01), elevated PT (p<0.05), sodium <133 mmol/L (p<0.01) elevated urea (p<0.001), creatinine (p<0.001), glucose (p<0.05) and lactate (p<0.001) and the 4C score (p<0.001) were associated with 30-day mortality. In multivariate analysis, greater frailty (CFS>3) (OR 11.3, 95% C.I. 2.3-96.7, p<0.05), low albumin (<30g/L) (OR 2.5, 95% C.I. 1.0-6.2, p<0.05), high NLR (≥3) (OR 2.2, 95% C.I. 1.5-4.5, p<0.05) and the 4C score (OR 2.4, 95% C.I. 1.0-5.6, p<0.05) remained independently associated with 30-day mortality. CONCLUSION: In addition to the 4C mortality score, frailty score and a low albumin were strongly independently associated with 30-day mortality in two consecutive cohorts of patients admitted to hospital with COVID-19. TRIAL REGISTRATION: clinicaltrials.gov: NCT04484545.

The relation between acute changes in the systemic inflammatory response and circulating thiamine and magnesium concentrations after elective knee arthroplasty.

Thiamine diphosphate (TDP) and magnesium are co-factors for key enzymes in human intermediary metabolism. However, their role in the systemic inflammatory response (SIR) is not clear. Therefore, the aim of the present study was to examine the relation between acute changes in the SIR and thiamine and magnesium dependent enzyme activity in patients undergoing elective knee arthroplasty (a standard reproducible surgical injury in apparently healthy individuals). Patients (n = 35) who underwent elective total knee arthroplasty had venous blood samples collected pre- and post-operatively for 3 days, for measurement of whole blood TDP, serum and erythrocyte magnesium, erythrocyte transketolase activity (ETKA), lactate dehydrogenase (LDH), glucose and lactate concentrations. Pre-operatively, TDP concentrations, erythrocyte magnesium concentrations, ETKA and plasma glucose were within normal limits for all patients. In contrast, 5 patients (14%) had low serum magnesium concentrations (< 0.75 mmol/L). On post-operative day1, both TDP concentrations (p < 0.001) and basal ETKA (p < 0.05) increased and serum magnesium concentrations decreased (p < 0.001). Erythrocyte magnesium concentrations correlated with serum magnesium concentrations (rs = 0.338, p < 0.05) and remained constant during SIR. Post-operatively 14 patients (40%) had low serum magnesium concentrations. On day1 serum magnesium concentrations were directly associated with LDH (p < 0.05), WCC (p < 0.05) and neutrophils (p < 0.01). Whole blood TDP and basal ETKA increased while serum magnesium concentrations decreased, indicating increased requirement for thiamine and magnesium dependent enzyme activity during SIR. Therefore, thiamine and magnesium represent potentially modifiable therapeutic targets that may modulate the host inflammatory response. Erythrocyte magnesium concentrations are likely to be reliable measures of status, whereas serum magnesium concentrations and whole blood TDP may not.ClinicalTrials.gov: NCT03554668.

The wider implications of the COVID-19 pandemic: Assessing the impact of accident and emergency use for frequent attenders.

INTRODUCTION: Emergency departments have seen altered patterns of attendance since the beginning of the COVID-19 pandemic, with reductions in the number of attendances for non-COVID-19 - patients. We assessed the use of the emergency department by frequent attenders during the height of the COVID-19 pandemic and explored any changes in emergency department attendance by this group. METHODS: As part of ongoing improvement work, we utilised a cohort design to evaluate the difference in patterns of attendance for the frequent attender group in a single centre. We created a 2019 'top attender' cohort and a similar cohort for 2020. We compared admission patterns between the two time periods in order to understand the impact of the COVID-19 pandemic on this group. RESULTS: Both groups were predominately male. Mental health and substance misuse use problems were common across both cohorts. The majority of patients lived in a socio-economically deprived areas. The median number emergency department visits in 2019, for the top attender cohort was 6 (IQR: 4-9) vs 4 (IQR: 2-7) for the top attender cohort of 2020 (p < .0013). CONCLUSION: This single centre evaluation has shown a significant reduction in emergency department attendances for a frequent attender cohort in a single centre. Future work should investigate the longer-term impact which the COVID-19 pandemic has had on this patient group.

High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial.

BACKGROUND: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early rule-out pathway is safe and effective for patients with suspected acute coronary syndrome. METHODS: We performed a stepped-wedge cluster randomized controlled trial in the emergency departments of 7 acute care hospitals in Scotland. Consecutive patients presenting with suspected acute coronary syndrome between December 2014 and December 2016 were included. Sites were randomized to implement an early rule-out pathway where myocardial infarction was excluded if high-sensitivity cardiac troponin I concentrations were <5 ng/L at presentation. During a previous validation phase, myocardial infarction was ruled out when troponin concentrations were <99th percentile at 6 to 12 hours after symptom onset. The coprimary outcome was length of stay (efficacy) and myocardial infarction or cardiac death after discharge at 30 days (safety). Patients were followed for 1 year to evaluate safety and other secondary outcomes. RESULTS: We enrolled 31 492 patients (59±17 years of age [mean±SD]; 45% women) with troponin concentrations <99th percentile at presentation. Length of stay was reduced from 10.1±4.1 to 6.8±3.9 hours (adjusted geometric mean ratio, 0.78 [95% CI, 0.73-0.83]; P<0.001) after implementation and the proportion of patients discharged increased from 50% to 71% (adjusted odds ratio, 1.59 [95% CI, 1.45-1.75]). Noninferiority was not demonstrated for the 30-day safety outcome (upper limit of 1-sided 95% CI for adjusted risk difference, 0.70% [noninferiority margin 0.50%]; P=0.068), but the observed differences favored the early rule-out pathway (0.4% [57/14 700] versus 0.3% [56/16 792]). At 1 year, the safety outcome occurred in 2.7% (396/14 700) and 1.8% (307/16 792) of patients before and after implementation (adjusted odds ratio, 1.02 [95% CI, 0.74-1.40]; P=0.894), and there were no differences in hospital reattendance or all-cause mortality. CONCLUSIONS: Implementation of an early rule-out pathway for myocardial infarction reduced length of stay and hospital admission. Although noninferiority for the safety outcome was not demonstrated at 30 days, there was no increase in cardiac events at 1 year. Adoption of this pathway would have major benefits for patients and health care providers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03005158.

Pharmacist led homeless outreach engagement and non-medical independent prescribing (Rx) (PHOENIx) intervention for people experiencing homelessness: a non- randomised feasibility study.

BACKGROUND: Homelessness and associated mortality and multimorbidity rates are increasing. Systematic reviews have demonstrated a lack of complex interventions that decrease unscheduled emergency health services utilisation or increase scheduled care. Better evidence is needed to inform policy responses. We examined the feasibility of a complex intervention (PHOENIx: Pharmacist led Homeless Outreach Engagement Nonmedical Independent prescribing (Rx)) to inform a subsequent pilot randomised controlled trial (RCT). METHODS: Non-randomised trial with Usual Care (UC) comparator group set in Greater Glasgow and Clyde Health Board, Scotland. Participants were adult inpatients experiencing homelessness in a city centre Glasgow hospital, referred to the PHOENIx team at the point of hospital discharge, from 19th March 2018 until 6th April 2019. The follow up period for each patient started on the day the patient was first seen (Intervention group) or first referred (UC), until 24th August 2019, the censor date for all patients. All patients were offered and agreed to receive serial consultations with the PHOENIx team (NHS Pharmacist prescriber working with Simon Community Scotland (third sector homeless charity worker)). Patients who could not be reached by the PHOENIx team were allocated to the UC group. The PHOENIx intervention included assessment of physical/mental health, addictions, housing, benefits and social activities followed by pharmacist prescribing with referral to other health service specialities as necessary. All participants received primary (including specialist homelessness health service based general practitioner care, mental health and addictions services) and secondary care. Main outcome measures were rates of: recruitment; retention; uptake of the intervention; and completeness of collected data, from recruitment to censor date. RESULTS: Twenty four patients were offered and agreed to participate; 12 were reached and received the intervention as planned with a median 7.5 consultations (IQR3.0-14.2) per patient. The pharmacist prescribed a median of 2 new (IQR0.3-3.8) and 2 repeat (1.3-7.0) prescriptions per patient; 10(83%) received support for benefits, housing or advocacy. Twelve patients were not subsequently contactable after leaving hospital, despite agreeing to participate, and were assigned to UC. Two patients in the UC group died of drug/alcohol overdose during follow up; no patients in the Intervention group died. All 24 patients were retained in the intervention or UC group until death or censor date and all patient records were accessible at follow up: 11(92%) visited ED in both groups, with 11(92%) hospitalisations in intervention group, 9(75%) UC. Eight (67%) intervention group patients and 3(25%) UC patients attended scheduled out patient appointments. CONCLUSIONS: Feasibility testing of the PHOENIx intervention suggests merit in a subsequent pilot RCT.

Prognostic factors in patients admitted to an urban teaching hospital with COVID-19 infection.

BACKGROUND: Severe COVID-19 infection results in a systemic inflammatory response (SIRS). This SIRS response shares similarities to the changes observed during the peri-operative period that are recognised to be associated with the development of multiple organ failure. METHODS: Electronic patient records for patients who were admitted to an urban teaching hospital during the initial 7-week period of the COVID-19 pandemic in Glasgow, U.K. (17th March 2020-1st May 2020) were examined for routine clinical, laboratory and clinical outcome data. Age, sex, BMI and documented evidence of COVID-19 infection at time of discharge or death certification were considered minimal criteria for inclusion. RESULTS: Of the 224 patients who fulfilled the criteria for inclusion, 52 (23%) had died at 30-days following admission. COVID-19 related respiratory failure (75%) and multiorgan failure (12%) were the commonest causes of death recorded. Age ≥ 70 years (p < 0.001), past medical history of cognitive impairment (p ≤ 0.001), previous delirium (p < 0.001), clinical frailty score > 3 (p < 0.001), hypertension (p < 0.05), heart failure (p < 0.01), national early warning score (NEWS) > 4 (p < 0.01), positive CXR (p < 0.01), and subsequent positive COVID-19 swab (p ≤ 0.001) were associated with 30-day mortality. CRP > 80 mg/L (p < 0.05), albumin < 35 g/L (p < 0.05), peri-operative Glasgow Prognostic Score (poGPS) (p < 0.05), lymphocytes < 1.5 109/l (p < 0.05), neutrophil lymphocyte ratio (p ≤ 0.001), haematocrit (< 0.40 L/L (male)/ < 0.37 L/L (female)) (p ≤ 0.01), urea > 7.5 mmol/L (p < 0.001), creatinine > 130 mmol/L (p < 0.05) and elevated urea: albumin ratio (< 0.001) were also associated with 30-day mortality. On multivariate analysis, age ≥ 70 years (O.R. 3.9, 95% C.I. 1.4-8.2, p < 0.001), past medical history of heart failure (O.R. 3.3, 95% C.I. 1.2-19.3, p < 0.05), NEWS > 4 (O.R. 2.4, 95% C.I. 1.1-4.4, p < 0.05), positive initial CXR (O.R. 0.4, 95% C.I. 0.2-0.9, p < 0.05) and poGPS (O.R. 2.3, 95% C.I. 1.1-4.4, p < 0.05) remained independently associated with 30-day mortality. Among those patients who tested PCR COVID-19 positive (n = 122), age ≥ 70 years (O.R. 4.7, 95% C.I. 2.0-11.3, p < 0.001), past medical history of heart failure (O.R. 4.4, 95% C.I. 1.2-20.5, p < 0.05) and poGPS (O.R. 2.4, 95% C.I. 1.1-5.1, p < 0.05) remained independently associated with 30-days mortality. CONCLUSION: Age ≥ 70 years and severe systemic inflammation as measured by the peri-operative Glasgow Prognostic Score are independently associated with 30-day mortality among patients admitted to hospital with COVID-19 infection.

High-Sensitivity Cardiac Troponin and the Universal Definition of Myocardial Infarction.

BACKGROUND: The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin testing and classification of patients with myocardial injury based on pathogenesis, but the clinical implications of implementing this guideline are not well understood. METHODS: In a stepped-wedge cluster randomized, controlled trial, we implemented a high-sensitivity cardiac troponin assay and the recommendations of the Universal Definition in 48 282 consecutive patients with suspected acute coronary syndrome. In a prespecified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death and secondary outcome of noncardiovascular death at 1 year across diagnostic categories. RESULTS: Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4471), type 2 myocardial infarction by 22% (205/916), and acute and chronic myocardial injury by 36% (443/1233) and 43% (389/898), respectively. Compared with those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [HR] 5.64 [95% CI, 5.12-6.22]), but was similar across diagnostic categories, whereas noncardiovascular deaths were highest in those with acute myocardial injury (cause specific HR 2.65 [95% CI, 2.33-3.01]). Despite modest increases in antiplatelet therapy and coronary revascularization after implementation in patients with type 1 myocardial infarction, the primary outcome was unchanged (cause specific HR 1.00 [95% CI, 0.82-1.21]). Increased recognition of type 2 myocardial infarction and myocardial injury did not lead to changes in investigation, treatment or outcomes. CONCLUSIONS: Implementation of high-sensitivity cardiac troponin assays and the recommendations of the Universal Definition of Myocardial Infarction identified patients at high-risk of cardiovascular and noncardiovascular events but was not associated with consistent increases in treatment or improved outcomes. Trials of secondary prevention are urgently required to determine whether this risk is modifiable in patients without type 1 myocardial infarction. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

A prospective evaluation of thiamine and magnesium status in relation to clinicopathological characteristics and 1-year mortality in patients with alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is routinely treated with B-vitamins. However, the relationship between thiamine status and outcome is rarely examined. The aim of the present study was to examine the relationship between thiamine and magnesium status in patients with AWS. METHODS: Patients (n = 127) presenting to the Emergency Department with AWS were recruited to a prospective observational study. Blood samples were drawn to measure whole blood thiamine diphosphate (TDP) and serum magnesium concentrations. Routine biochemistry and haematology assays were also conducted. The Glasgow Modified Alcohol Withdrawal Score (GMAWS) measured severity of AWS. Seizure history and current medications were also recorded. RESULTS: The majority of patients (99%) had whole blood TDP concentration within/above the reference interval (275-675 ng/gHb) and had been prescribed thiamine (70%). In contrast, the majority of patients (60%) had low serum magnesium concentrations (< 0.75 mmol/L) and had not been prescribed magnesium (93%). The majority of patients (66%) had plasma lactate concentrations above 2.0 mmol/L. At 1 year, 13 patients with AWS had died giving a mortality rate of 11%. Male gender (p < 0.05), BMI < 20 kg/m2 (p < 0.01), GMAWS max ≥ 4 (p < 0.05), elevated plasma lactate (p < 0.01), low albumin (p < 0.05) and elevated serum CRP (p < 0.05) were associated with greater 1-year mortality. Also, low serum magnesium at time of recruitment to study and low serum magnesium at next admission were associated with higher 1-year mortality rates, (84% and 100% respectively; both p < 0.05). CONCLUSION: The prevalence of low circulating thiamine concentrations were rare and it was regularly prescribed in patients with AWS. In contrast, low serum magnesium concentrations were common and not prescribed. Low serum magnesium was associated more severe AWS and increased 1-year mortality.

Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome.

BACKGROUND: Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized. OBJECTIVES: The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome. METHODS: Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year. RESULTS: A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p < 0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01). CONCLUSIONS: Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]; NCT01852123).