A Randomized Noninferiority Trial to Compare Enteral to Parenteral Phosphate Replacement on Biochemistry, Waste, and Environmental Impact and Healthcare Cost in Critically Ill Patients With Mild to Moderate Hypophosphatemia.

OBJECTIVES: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste. DESIGN: Prospective, randomized, parallel group, noninferiority clinical trial. SETTING: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022. PATIENTS: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L. INTERVENTIONS: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program. MEASUREMENT AND MAIN RESULTS: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents). CONCLUSIONS: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.

Community-acquired versus hospital-acquired acute kidney injury at a large Australian metropolitan quaternary referral centre: incidence, associations and outcomes.

BACKGROUND: There is increasing global incidence of acute kidney injury (AKI) and significant short- and long-term impacts on patients. AIMS: To determine incidence and outcomes of community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) among inpatients in the Australian healthcare setting using modern health information systems. METHODS: A retrospective cohort study of adult patients admitted to a quaternary hospital in Melbourne, Australia, between 1 January 2018 and 31 December 2019 utilising an electronic data warehouse. Participants included adult patients admitted for >24 h who had more than one serum creatinine level recorded during admission. Kidney transplant and maintenance dialysis patients were excluded. Main outcomes measured included AKI, as classified by the Kidney Disease Improving Global Outcomes (KDIGO) criteria, hospital length of stay and 30-day mortality. RESULTS: A total of 6477 AKI episodes was identified across 43 791 admissions. Of all AKI episodes, 77% (n = 5011), 15% (n = 947) and 8% (n = 519) were KDIGO stage 1, 2 and 3 respectively. HA-AKI accounted for 55.9% episodes. Patients required intensive care unit admission in 22.7% (n = 1100) of CA-AKI and 19.3% (n = 935) of HA-AKI, compared with 7.5% (n = 2815) of patients with no AKI (P = 0.001). Patients with AKI were older with more co-morbidities, particularly chronic kidney disease (CKD). Length of stay was longer in CA-AKI (8.8 days) and HA-AKI (11.8 days) compared with admissions without AKI (4.9 days; P < 0.001). Thirty-day mortality was increased with CA-AKI (10.2%) and HA-AKI (12.8%) compared with no AKI (3.7%; P < 0.001). CONCLUSION: The incidence of AKI detected by the electronic data warehouse was higher than previously reported. Patients who experienced AKI had greater morbidity and mortality. CKD was an important risk factor for AKI in hospitalised patients.

Hospital Acquired Infections in Surgical Patients: Impact of COVID-19-Related Infection Prevention Measures.

BACKGROUND: Hospital acquired infections are common, costly, and potentially preventable adverse events. This study aimed to determine the effect of the COVID-19 pandemic-related escalation in infection prevention and control measures on the incidence of hospital acquired infection in surgical patients in a low COVID-19 environment in Australia. METHOD: This was a retrospective cohort study in a tertiary institution. All patients undergoing a surgical procedure from 1 April 2020 to 30 June 2020 (COVID-19 pandemic period) were compared to patients pre-pandemic (1 April 2019-30 June 2019). The primary outcome investigated was odds of overall hospital acquired infection. The secondary outcome was patterns of involved microorganisms. Univariable and multivariable logistic regression analysis was performed to assess odds of hospital acquired infection. RESULTS: There were 5945 admission episodes included in this study, 224 (6.6%) episodes had hospital acquired infections in 2019 and 179 (7.1%) in 2020. Univariable logistic regression analysis demonstrated no evidence of change in odds of having a hospital acquired infection between cohorts (OR 1.08, 95% CI 0.88-1.33, P = 0.434). The multivariable regression analysis adjusting for potentially confounding co-variables also demonstrated no evidence of change in odds of hospital acquired infection (OR 0.93, 95% CI 0.74-1.16, P = 0.530). CONCLUSION: Increased infection prevention and control measures did not affect the incidence of hospital acquired infection in surgical patients in our institution, suggesting that there may be a plateau effect with these measures in a system with a pre-existing high baseline of practice.

eHealth Technologies for Screening, Diagnosis, and Management of Viral Hepatitis: A Systematic Review.

BACKGROUND & AIMS: Chronic viral hepatitis is a leading cause of worldwide liver-related morbidity and mortality, despite the availability of effective treatments that reduce or prevent complications in most patients. Electronic-health (eHealth) technologies have potential to intervene along the whole cascade of care. We aimed to summarize available literature on eHealth interventions with respect to conventional screening, diagnostic and treatment outcomes in chronic hepatitis B (HBV) and hepatitis C (HCV). METHODS: We systematically reviewed MEDLINE, EMBASE, Cochrane Library and international conference abstracts, including studies published from 2009 - 2020. Overall 80 studies were included, covering electronic medical record (EMR) interventions (n=39), telemedicine (n=20), mHealth (n=5), devices (n=4), clinical decision support (n=3), web-based (n=5), social media (n=1) and electronic communication (n=3). RESULTS: Compared to standard care, EMR alerts increase screening rates in eligible populations including birth cohort screening in HCV, universal HCV screening in Emergency Departments, ethnic groups with high HBV prevalence, and HBV screening prior to immunosuppression. Direct messaging alerts to providers and automated testing may have a greater effect. No significant difference was found in sustained virological response outcomes between telemedicine and face-to-face management for community, rural and prison cohorts in HCV in the direct acting antiviral era of treatment, with higher patient satisfaction in telemedicine groups. CONCLUSIONS: EMR alerts significantly increase screening rates in eligible cohorts in both chronic HBV and HCV. Telemedicine is equally efficacious to face-to-face care in HCV treatment. Other eHealth technologies show promise; however rigorous studies are lacking.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

The impact of electric scooters in Melbourne: data from a major trauma service.

BACKGROUND: The proliferation of electric scooters globally has been associated with an increase in related injuries and consequent economic burden. This study aims to assess the injury patterns and the economic impact associated with electric scooter use in Melbourne, Australia. METHODS: A retrospective cohort study was conducted using hospital and registry data from January 2022 to January 2023. Data collected included demographic details, alcohol and helmet use, injury type and severity, operative treatment provided, and direct medical costs. The economic impact (in AUD) of the patient's emergency presentation and hospital admission was calculated. RESULTS: During the study period, 256 electric scooter related injuries were recorded, comprising 247 riders and nine pedestrians. The majority of patients were males (69%) with a median age of 29.5 (15-78). Alcohol use was reported by 34% and helmet use by 33%. Injuries most commonly affected the upper limb (53%) and head (50%), with abrasions (75%) and fractures (48%) being the most common type of injury sustained. The total hospital cost was $1 911 062, and the median cost was $1321.66 per patient (IQR: $479.37-$5096.65). CONCLUSION: Electric scooter usage, as observed through patient presentations to the Royal Melbourne Hospital, is associated with a considerable number of injuries, primarily among young males, and an ensuing substantial economic burden. The findings underscore the urgent need for improved safety measures to minimize electric scooter-related injuries and their clinical and economic repercussions.

The Canadian Hypoglycemia During Hospitalization Score Is Externally Valid in the Australian Diabetes IN-hospital: Glucose & Outcomes (DINGO) Cohort.

OBJECTIVES: The Hypoglycemia During Hospitalization (HyDHo) score predicts hypoglycemia in a population of Canadian inpatients by assigning various weightings to 5 key clinical criteria known at the time of admission, in particular age, recent presentation to an emergency department, insulin use, use of oral hypoglycemic agents, and chronic kidney disease. Our aim in this study was to externally validate the HyDHo score by applying this risk calculator to an Australian population of inpatients with diabetes. METHODS: This study was a retrospective data analysis of a subset of the Diabetes IN-hospital: Glucose & Outcomes (DINGO) cohort. The HyDHo score was applied based on clinical information known at the time of admission to stratify risk of inpatient hypoglycemia. RESULTS: The HyDHo score was applied to 1,015 patients, generating a receiver-operating characteristic c-statistic of 0.607. A threshold of ≥9, as per the original study, generated a sensitivity of 83% and specificity of 20%. A threshold of ≥10, to better suit this Australian population, generated a sensitivity of 90% and specificity of 34%. The HyDHo score has been externally valid in a geographically different population; in fact, it outperformed the original study after accounting for local hypoglycemia rates. CONCLUSIONS: Our findings support the external validity of the HyDHo score in a geographically different population. Application of this simple and accessible tool can serve as an adjunct to predict an inpatient's risk of hypoglycemia and guide more appropriate glucose monitoring and diabetes management.

Hyperglycemia in hospital: an independent marker of infection, acute kidney injury & stroke for hospital inpatients.

CONTEXT: Hyperglycemia in hospital inpatients without pre-existing diabetes is associated with increased mortality. However, the independent contribution of hyperglycemia to healthcare-associated infection (HAI), acute kidney injury (AKI), and stroke is unclear. OBJECTIVE: To investigate the relationship between hyperglycemia and adverse clinical outcomes in hospital for patients with and without diabetes. DESIGN: Diabetes IN-hospital: Glucose and Outcomes (DINGO) was a 26-week (October 2019 - March 2020) prospective cohort study. Clinical and glucose data were collected up to the 14th day of admission. Primary stratification was by hyperglycemia, defined as ≥2 random capillary blood glucose (BG) measurements ≥11.1 mmol/L (≥200 mg/dL). Propensity weighting for nine clinical characteristics, was performed to allow interrogation of causality. To maintain the positivity assumption, patients with HbA1c > 12.0% were excluded and pre-hospital treatment not adjusted for. SETTING: The Royal Melbourne Hospital, a quaternary referral hospital in Melbourne, Australia. PATIENTS: Admissions with at least two capillary glucose values and length of stay >24 hours were eligible, with half randomly sampled. OUTCOME MEASURES: HAI, AKI, stroke, and mortality. RESULTS: Of 2,558 included admissions, 1,147 (45%) experienced hyperglycemia in hospital. Following propensity-weighting and adjustment, hyperglycemia in hospital was found to, independently of nine covariables, contribute an increased risk of in-hospital HAI (130 [11.3%] vs.100 [7.1%], adjusted odds ratio [aOR] 1.03, 95% confidence interval [95%CI] 1.01-1.05, p = 0.003), AKI (120 [10.5%] vs. 59 [4.2%], aOR 1.07, 95%CI 1.05-1.09, p < 0.001), and stroke (10 [0.9%] vs. 1 [0.1%], aOR 1.05, 95%CI 1.04-1.06, p < 0.001). CONCLUSIONS: In hospital inpatients (HbA1c ≤ 12.0%), irrespective of diabetes status and pre-hospital glycaemia, hyperglycemia increases the risk of in-hospital HAI, AKI, and stroke compared with those not experiencing hyperglycemia.

Feasibility of Embedding a Randomised Clinical Trial (RCT) into an Electronic Medical Record (EMR) for Patients Admitted to an Intensive Care Unit (ICU).

To establish the feasibility of embedding an RCT into EMR in the ICU, we evaluated the route of phosphate replacement. The EMR screened 207 patients who met the inclusion criteria from 20 April 2022 to 30 June 2022. 162 patients were randomised and 145 patients allocated to treatment. Our study showed that it was feasible to embed screening, randomisation, and treatment allocation for an RCT within an EMR in the ICU.

Pharmacodynamics, safety, tolerability and pharmacokinetics of a single oral dose of an engineered phenylalanine ammonia-lyase in patients with phenylketonuria.

The cornerstone treatment of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) is a lifelong low-protein diet with phenylalanine (Phe) free L-amino acid supplements. However, the PKU diet has significant shortcomings, and there is a clinically unmet need for new therapeutics to improve patient outcomes. CDX-6114 is a modified phenylalanine ammonia-lyase (PAL) enzyme obtained by a mutation in the Anabaena variabilis PAL sequence. CodeEvolver® protein engineering technology has been applied to improve the degradation resistance of the enzyme. In our first phase I trial, 19 patients were given a single oral dose of CDX-6114 at 7.5 g, 2.5 g, 0.7 g, or placebo in a cross-over design. After an overnight fast, patients received a standardised breakfast of 20 g of protein, thus exceeding the dietary recommendations for a single meal in patients with PKU. Plasma levels of Phe and cinnamic acid (CA) were measured over a 5-h period following CDX-6114 dosing. During the development of CDX-6114, a stability assessment using reverse-phase high-performance liquid chromatography (HPLC) assay revealed two peaks. The second peak was identified as CA. It was not previously known that as part of the mechanism of action, the CA remained associated with the protein following the conversion of Phe. Thus, recalculating the historical PAL enzyme amounts in CDX-6114 bulk substance was necessary. An updated extinction coefficient was achieved by applying a correction factor of 0.771 to previously reported doses. Postprandial plasma levels of Phe increased in all dose cohorts over time between 10% and 30% from baseline, although the actual peak of Phe levels was not achieved within the 5-h observation. When accounting for the interquartile ranges, these concentrations were similar to the placebo. As plasma levels of Phe were no longer a reliable marker for pharmacodynamics, the consistently detectable amount of CA seen in all patients who received CDX-6114 provided proof of the enzymatic activity of CDX-6114 in metabolising gastrointestinal Phe. Peak levels of CA were seen shortly after CDX-6114 intake, with a rapid decline, and remained low compared with the plasma Phe levels. This pattern indicates a short half-life, possibly due to the liquid formulation or the inability to withstand the lower pH in the human stomach compared with animal models in earlier studies. This was the first trial in patients with PKU to establish the safety and tolerability of CDX-6114. A single dose of CDX-6114 was safe and well tolerated, with no serious adverse events or presence of anti-drug antibodies detected. Efficacy will be explored in future trials using an optimised formulation.

Aggression, violence and threatening behaviour during critical illness.

Objective: This article aims to quantify prevalence of patient aggression or threatened/actual violence during critical illness. Design: This is a retrospective cohort study. Setting: This study was conducted in single adult trauma intensive care unit (ICU). Participants: Patients aged 18 years or over, admitted between January 2015 and December 2020, who triggered a "Code Grey" response due to aggression or threatened/actual violence. Main outcome measure: The primary outcome was prevalence of Code Grey events. Secondary outcomes included unadjusted and adjusted (logistic mixed model) effects of patient demographics, diagnoses and severity of illness on Code Grey events. Results: There were 16175 ICU admissions relating to 14085 patients and 807 Code Grey events involving 379 (2.7%) patients. The observed count of events increased progressively from 2015 (n = 77) to 2020 (n = 204). For patients with a Code Grey, the median count of events was 3 (range 1-33). Independent predictors of at least one ICU Code Grey event included male sex (OR 2.5; 95% CI 1.8 to 3.4), young age (most elevated odds ratio in patients 20-30 years), admission from the emergency department (OR 2.8, 95% CI 2.1 to 3.6) and a trauma diagnosis (OR 1.4, 95% CI 1.1 to 1.9). Code Grey patients had longer admissions with a reduced risk of death. Conclusions: The prevalence of Code Grey events in ICU appears to be increasing. Patients may have repeated events. Younger male patients admitted to ICU via the emergency department with a trauma or medical diagnosis are at greatest risk of a Code Grey event.

'A Missed Therapeutic Opportunity? SGLT-2 Inhibitor Use in General Medicine Patients With Heart Failure: A Retrospective Audit of Admissions to a Tertiary Health Service'.

Objective: Sodium-glucose co-transporter-2 inhibitors (SGLT2-I's) are novel oral hypoglycaemic agents, with proven decreased MACE and re-hospitalisation risk in type 2 diabetic patients with concomitant heart failure. This study aimed to assess the current practice in the use of SGLT2-I's in general medical units at a large metropolitan health service. Methods/Results: A retrospective audit was conducted of patients admitted to general medicine over a 12 month period (between April 2018 and 2019). Inclusion criteria included decompensated heart failure of any aetiology and ejection fraction, and type 2 diabetes mellitus with an HbA1c ⩾ 7 within 6 months of the admission period. A total of 150 admissions fulfilled criteria. Baseline demographics and comorbidities identified an older, more comorbid population than reference trials. These included age (75% over 75 years), smoking history (46%), hypertension (83%), chronic kidney disease grade IV or V (26%), previous myocardial infarction (57%), stroke (18%), atrial fibrillation (55%) and known left ventricular ejection fraction < 50% (38%). Co-prescribed medications included ACE-I/ARB (53%), beta-blocker (67%), loop diuretic (87%), thiazide (7%), MRA (31%), insulin (57%), metformin (47%), sulphonylurea (31%), DPP-4 Inhibitor (21%), GLP-1 analogue (6%) and 15% of patients had an HbA1c > 10. There was a significant difference between patients in our study eligible for and prescribed metformin (66/111) compared to SGLT-2 inhibitors (4/25) (P = .013). A total of 26 patients had readmissions within 28 days, of which one had been discharged on an SGLT2-I. Conclusion: The results of this study identified significant under prescribing of SGLT2-I's in eligible type 2 diabetic patients with heart failure admitted under general medicine.

Telehealth during the coronavirus disease 2019 pandemic: Rapid expansion of telehealth outpatient use during a pandemic is possible if the programme is previously established.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the health-care system both in Australia and internationally, and has rapidly transformed the delivery of health care in hospitals and the community. Implementation of social isolation and distancing measures to stop the spread of the disease and to reduce potential harm to patients has necessitated the use of alternate models of health-care delivery. Changes that would normally take months or years have occurred within days to weeks. METHODS: We conducted analysis of outpatient clinic data during the period of the pandemic and compared this to previous telehealth use. We also present the results of clinician and patient telehealth experience surveys. RESULTS: We describe a 2255% increase in the use of telehealth at a tertiary hospital within a period of six weeks, and a significant simultaneous reduction in the outpatient clinic failure-to-attend rate. The vast majority of patients and clinicians agreed that the standard of care provided by telehealth was the same as that provided by on-site appointments. DISCUSSION: Telehealth that previously had only limited utilisation has now become a main method for the delivery of outpatient care. Clinicians and patients agreed that consultations provided by telehealth were of the same standard as those provided on site. Health care in the post-pandemic period should embed the use of telehealth for outpatient care and consider the range of other clinical contexts where this can be utilised.

Quality of care was not compromised during the COVID-19 pandemic at a level 1 trauma centre.

BACKGROUND: The COVID-19 pandemic has had a profound effect on the presentation and management of trauma at the Royal Melbourne Hospital, a level 1 adult major trauma service and a designated COVID-19 hospital. This study compares the changes in epidemiology and trauma patient access to emergency imaging and surgery during the pandemic response. METHODS: The population of interest was all trauma patients captured in the hospital's trauma registry from 16 March 2016 to 10 September 2020. Regression modelling assessed changes in mechanism and severity of the injury, and mortality during two lockdowns compared with the proceeding 4 years. Cases were matched with hospital administrative databases to assess mean time from admission to emergency computed tomography (CT) scan, operating theatre, length of stay (LOS) and immediate surgery (OPSTAT). RESULTS: Throughout 2020, the hospital treated 525 COVID-19 patients. Compared with previous years, there was up to 34% reduction in major trauma and a 28% reduction in minor trauma admissions during the pandemic (p < 0.05). Intensive care unit admissions were almost half of predicted. Some of the largest reductions were seen in motor vehicle crashes (49%) and falls (28%) (p < 0.05). Time to CT, surgery and immediate surgery (OPSTAT) showed no change and having a suspected COVID-19 diagnosis did not prolong any of these times except for the LOS. Mortality was similar to previous years. CONCLUSION: The COVID-19 pandemic has had widespread societal changes, resulting in a substantial decrease in trauma presentations. Despite COVID's immense impact on the hospital's trauma service, the quality of care was not impaired.

A serendipitous journey to a promoter variant: The c.-106C>A variant and its role in late-onset ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder characterised by reduced or absent OTC enzyme activity, resulting in the accumulation of neurotoxic ammonia. Approximately 80%-90% of the causative variants are identified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA) of the OTC gene. A 23-year-old male with biochemical evidence of OTCD was referred for molecular analysis. Initial Sanger sequencing yielded no pathogenic variants. MLPA testing raised suspicion of a mosaic deletion of exon 1; however, high-resolution microarray did not identify a copy number variant on the X chromosome. Sequencing over the suspected breakpoint detected a hemizygous likely pathogenic promoter variant, c.-106C > A, which was located within the MLPA probe binding site. Subsequently, historical patients referred to our centre, without a molecular aetiology for their OTCD, were re-sequenced with these primers and this variant was also identified in two additional unrelated males. All three patients described in this case series have the late-onset disease. Two presented at 5 years of age with vomiting, whilst the other was managed from birth based on a family history of late-onset OTCD. One patient required liver transplantation due to recurrent decompensations; the other two are managed with a protein-restricted diet. All three patients have not sustained any significant neurological insults and are functioning well as adults. These cases support screening of the promoter region within the OTC gene, particularly if a molecular basis has not been elucidated by MLPA or sequencing of the coding regions.

Troponin least significant change (z-score) is associated with poor clinical outcomes in patients presenting to the emergency department.

BACKGROUND: A rise and/or fall in high sensitivity cardiac troponin (hs-Tn) is critical in defining acute myocardial injury and therefore the diagnosis of acute myocardial infarction. A significant rise in hs-Tn is not well defined in current guidelines. Calculation of a z-score for two consecutive hs-Tn measurements is a method-independent measure of dynamic troponin elevation. However, the association of hs-Tn z-score with outcomes for unselected emergency department admissions is unknown. Moreover, the association of non-dynamic troponin elevations, as defined by a normal z-score, with clinical outcomes remains to be assessed. METHODS: We retrospectively calculated z-scores for patients presenting to emergency department over 18 months who had serial troponin measurements with at least one result >99th percentile using the Abbott hs-TnI assay. We assessed the association of z-score with discharge diagnosis, cardiac interventions, inpatient mortality, length of stay and readmission rates. RESULTS: There were 2062 presentations for 1830 patients where a z-score was calculated. Z-score was elevated in 1080 presentations. Dynamic troponin elevation (z-score ≥ 2) was associated with acute myocardial infarction (OR = 9.1, P < 0.01), admission to an inpatient unit (95 vs. 88%, P < 0.01), increased inpatient length of stay (97 vs. 65 days, P < 0.01), inpatient coronary intervention (21 vs. 6%, P < 0.01) and mortality (4.4 vs. 2.4%, P < 0.05) compared with myocardial injury with a static troponin elevation. CONCLUSIONS: Z-score is an assay-independent tool to alert clinicians of significant, dynamic troponin elevation and acute myocardial injury. It is associated with poorer clinical outcomes.

Venous thromboembolism prophylaxis and related outcomes in patients with traumatic brain injury and prolonged intensive care unit stay.

Objective: Traumatic brain injury (TBI) patients with prolonged intensive care unit (ICU) stay are at risk of secondary intracranial haemorrhage (ICH) and venous thromboembolism (VTE). We aimed to study VTE prophylaxis, secondary ICH, and VTE prevalence and outcomes in this population. Design: Retrospective observational study. Setting: Level 1 trauma centre ICU. Patients: One hundred TBI patients receiving prolonged ICU treatment (≥ 7 days). Interventions: We collected data from medical records, pathology and radiology systems, and hospital and ICU admission databases. We analysed patient characteristics, interventions, episodes and types of secondary ICH and VTE, and timing and dosage of VTE prophylaxis. Results: Data from the 100 patients in our study showed that early use of compression stockings and pneumatic calf compression was common (75% and 91% in the first 3 days, respectively). VTE chemoprophylaxis, however, was only used in 14% of patients by Day 3 and > 50% by Day 10. We observed VTE in 12 patients (10 as pulmonary embolism), essentially all after Day 6. Radiologically confirmed secondary ICH occurred in 43% of patients despite normal coagulation. However, 72% of ICH events (42/58) were radiologically mild, and the median time of onset of ICH was Day 1, when only 3% of patients were on chemical prophylaxis. Moreover, 82% of secondary ICH events (48/58) occurred in the first 3 days, with no severe ICH thereafter. Conclusions: In TBI patients receiving prolonged ICU treatment, early chemical VTE prophylaxis was uncommon. Early secondary ICH was common and mostly radiologically mild, whereas later secondary ICH was essentially absent. In contrast, early VTE was essentially absent, whereas later VTE was relatively common. Earlier chemical VTE prophylaxis and/or ultrasound screening in this population appears logical.

The effect of improved dietary control on cognitive and psychiatric functioning in adults with phenylketonuria: the ReDAPT study.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inherited disorder characterised by a deficiency in phenylalanine hydroxylase. Untreated, PKU is associated with a wide range of cognitive and psychiatric sequelae. Contemporary management guidelines recommend lifetime dietary control of phenylalanine (Phe) levels, however many individuals who discontinue dietary control subsequently suffer symptoms of anxiety, depression and disturbances to cognition. We undertook a prospective cohort study of patients with early-treated phenylketonuria who had ceased dietary control to test the hypothesis that resumption of dietary control of PKU is associated with improvements in measures of psychiatric morbidity and cognitive functioning. METHODS: We re-initiated dietary control for early-treated patients with PKU and monitored cognitive and psychiatric outcomes over a twelve-month period. Assessments included objective cognitive function (measured by cognitive proficiency index (CPI)), anxiety and depression scales. General linear mixed model (GLMM) analyses were performed to assess change in psychometric variables from baseline over twelve months after resumption of dietary control. RESULTS: A total of nine patients were recruited. Mean age was 33 years (SD = 8.75), five were female. Mean time off dietary control was 19.1 years (SD = 11.3), and mean baseline phenylalanine (Phe) levels were 1108 µmol/L (SD = 293). GLMM analysis demonstrated a positive relationship between CPI and time on diet (b = 0.56 [95% CI = 0.17, 0.95]). Age, time off diet, Phe levels and depression scores were not associated with cognitive function. There was a negative relationship between time on diet and anxiety (b = - 0.88 95% CI = [- 1.26, - 0.50]) and depression ratings (b = - 0.61, 95% CI = [- 0.95, - 0.26]). CONCLUSIONS: This study demonstrated improvements in cognitive function, anxiety, and depression ratings associated with resumption of dietary control of PKU. Raw Phe levels were not strongly associated with psychiatric or cognitive scores in this cohort. These findings support the importance of lifelong treatment for PKU in improving the cognitive and psychiatric sequelae of the disease.

A microcosting analysis of ICU expenditure in the interval between brain death and organ donation.

Objective: The cost of providing care in an intensive care unit (ICU) after brain death to facilitate organ donation is unknown. The objective of this study was to estimate expenditure for the care delivered in the ICU between the diagnosis of brain death and subsequent organ donation. Design: Cohort study of direct and indirect costs using bottom-up and top-down microcosting techniques. Setting: Single adult ICU in Australia. Participants: All patients who met criteria for brain death and proceeded to organ donation during a 13-month period between 1 January 2018 and 31 January 2019. Main outcome measures: A comprehensive cost estimate for care provided in the ICU from determination of brain death to transfer to theatre for organ donation. Results: Forty-five patients with brain death became organ donors during the study period. The mean duration of postdeath care in the ICU was 37.9 hours (standard deviation [SD], 16.5) at a mean total cost of $7520 (SD, $3136) per donor. ICU staff salaries were the greatest contributor to total costs, accounting for a median proportion of 0.72 of total expenditure (interquartile range, 0.68-0.75). Conclusions: Substantial costs are incurred in ICU for the provision of patient care in the interval between brain death and organ donation.