Conservative or liberal oxygen targets in patients on venoarterial extracorporeal membrane oxygenation.

PURPOSE: Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) frequently develop arterial hyperoxaemia, which may be harmful. However, lower oxygen saturation targets may also lead to harmful episodes of hypoxaemia. METHODS: In this registry-embedded, multicentre trial, we randomly assigned adult patients receiving VA-ECMO in an intensive care unit (ICU) to either a conservative (target SaO2 92-96%) or to a liberal oxygen strategy (target SaO2 97-100%) through controlled oxygen administration via the ventilator and ECMO gas blender. The primary outcome was the number of ICU-free days to day 28. Secondary outcomes included ICU-free days to day 60, mortality, ECMO and ventilation duration, ICU and hospital lengths of stay, and functional outcomes at 6 months. RESULTS: From September 2019 through June 2023, 934 patients who received VA-ECMO were reported to the EXCEL registry, of whom 300 (192 cardiogenic shock, 108 refractory cardiac arrest) were recruited. We randomised 149 to a conservative and 151 to a liberal oxygen strategy. The median number of ICU-free days to day 28 was similar in both groups (conservative: 0 days [interquartile range (IQR) 0-13.7] versus liberal: 0 days [IQR 0-13.7], median treatment effect: 0 days [95% confidence interval (CI) - 3.1 to 3.1]). Mortality at day 28 (59/159 [39.6%] vs 59/151 [39.1%]) and at day 60 (64/149 [43%] vs 62/151 [41.1%] were similar in conservative and liberal groups, as were all other secondary outcomes and adverse events. The conservative group experienced 44 (29.5%) major protocol deviations compared to 2 (1.3%) in the liberal oxygen group (P < 0.001). CONCLUSIONS: In adults receiving VA-ECMO in ICU, a conservative compared to a liberal oxygen strategy, did not affect the number of ICU-free days to day 28.

Impact of rosuvastatin on pulse-wave velocity in men with HIV at moderate cardiovascular risk.

This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96 weeks of rosuvastatin on pulse wave velocity (PWV) in men (n = 55, 54 years) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54 m/s standard error of difference (SED) 0.26] and placebo [0.50 m/s (SED 0.26), P = 0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40 m/s (SE 0.31); placebo 9.21 m/s (SE0.31), P = 0.676].

What Happens to Frailty in the First Year After Lung Transplantation?

BACKGROUND: Frailty is prevalent in lung transplant (LTx) candidates, but the impact and subsequent frailty trajectory is unclear. This study aimed to investigate frailty over the first year after LTx. METHOD: Post-LTx recipients completed a thrice weekly 12-week directly supervised exercise rehabilitation program. Edmonton Frail Scale (EFS) was used to assess frailty. Primary outcome was 6-Minute Walk Distance (6MWD) measured at pre-LTx, prerehabilitation, postrehabilitation, and 1 year post-LTx. RESULTS: 106 of 139 recruited participants underwent LTx: mean age 58 years, 48% male, 52% with chronic obstructive pulmonary disease. Mean (± SD) frailty scores pre-LTx and 1 year post-LTx were 5.54 ± 2.4 and 3.28 ±1.5. Mean 6MWD improved significantly for all: prerehabilitation 326 m (SD 116), versus postrehabilitation 523 m (SD 101) (p < 0.001) versus 1 year 512 m (SD 120) (p < 0.001). There were significant differences between an EFS > 7 (frail) and EFS ≤ 7 (not frail) for 6MWD, grip strength (GS), anxiety, and depression. Postrehabilitation, there were no significant differences in 6MWD, GS, anxiety, or depression while comparing EFS > 7 versus ≤ 7. At 1 year, there was a significant difference in depression but not 6MWD, GS, or anxiety between those EFS ≤ 7 and > 7 (p = 0.017). CONCLUSION: Participants in a structured post-LTx rehabilitation program improved in functional exercise capacity (6MWD), GS, depression, and anxiety. For frail participants exercise capacity, depression, anxiety, and GS were well managed in rehabilitation with no significant differences between those who were not frail. Pre-LTx frailty may be reversible post-LTx and should not be an absolute contraindication to LTx.

Characteristics of enteral and oral nutrition support among infants and young children in the pediatric intensive care unit: A descriptive cohort study.

BACKGROUND: Children who are critically ill are often reliant on enteral and oral nutrition support. However, there is limited evidence to guide "what" to prescribe, and current practice is unknown. The primary objective of this study was to describe enteral nutrition prescription in children ≤2 years of age in the pediatric intensive care unit (PICU). The secondary objectives were to describe oral nutrition support practices and factors associated with the use of increased energy and protein density nutrition support. METHODS: Children ≤2 years of age admitted to participating PICUs over a 2-week period in June 2021 were enrolled. Data were collected on PICU admission days 1 to 7, 14, 21, and 28 on the mode of nutrition, enteral and oral nutrition support prescription, and dietitian intervention. RESULTS: Eighty-four children were included (49 [58%] male; 79 [94%] ≤1 year of age). Enteral nutrition was administered to 79 (94%) children (with expressed breast milk in 45 [57%]). Forty-three children received formula as enteral nutrition. Increased energy and protein density formulas were provided to 14 (33%) children enterally, with concentrated standard infant formula powder being the most common (5 [12%]). Among children offered oral intake (22; 26%), three (14%) received oral nutrition support. Children who received increased energy and protein density enteral nutrition were more likely to receive dietitian intervention (P = 0.002). CONCLUSION: In children ≤2 years of age admitted to PICU, expressed breast milk was provided to half of those requiring enteral nutrition and oral nutrition support prescription was infrequent. One third of children receiving formula via enteral nutrition received an increased energy and protein density feed, and this was strongly associated with dietitian intervention.

Varenicline and Nicotine Replacement Therapy for Smokers Admitted to Hospitals: A Randomized Clinical Trial.

Importance: Varenicline is the most effective sole pharmacotherapy for smoking cessation. If used in combination with nicotine replacement therapy (NRT), cessation rates may be further improved, but the efficacy and safety of the combination need to be evaluated. Objective: To examine whether hospitalized smokers treated with varenicline and NRT lozenges achieve higher prolonged smoking abstinence rates compared with those treated with varenicline alone. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted in adult medical or surgical inpatients of 5 Australian public hospitals with a history of smoking 10 cigarettes or more per day, interested in quitting, and available for 12-month follow-up between May 1, 2019, and May 1, 2021 (final 12-month data collection in May 2022). Data analysis was performed from June 1 to August 30, 2023. Interventions: A 12-week varenicline regimen was initiated during hospitalization at standard doses in all participants. Participants were randomized to additionally use NRT (2 mg) or placebo lozenges if there was an urge to smoke. Behavioral support (Quitline) was offered to all participants. Main Outcomes and Measures: The primary outcome was biochemically verified sustained abstinence at 6 months. Secondary outcomes included self-reported prolonged abstinence, 7-day point prevalence abstinence (3, 6, and 12 months), and medicine-related adverse events. Results: A total of 320 participants (mean [SD] age, 52.5 [12.1] years; 183 [57.2%] male) were randomized. The conduct of biochemical verification was affected by COVID-19 restrictions; consequently, the biochemically verified abstinence in the intervention vs control arms (18 [11.4%] vs 16 [10.1%]; odds ratio [OR], 1.14; 95% CI, 0.56-2.33) did not support the combination therapy. The secondary outcomes in the intervention vs control arms of 7-day point prevalence abstinence at 6 months (54 [34.2%] vs 37 [23.4%]; OR, 1.71; 95% CI, 1.04-2.80), prolonged abstinence at 12 months (47 [29.9%] vs 30 [19.1%]; OR, 1.77; 95% CI, 1.05-3.00), and 7-day point prevalence abstinence at 12-months (48 [30.6%] vs 31 [19.7%]; OR, 1.79; 95% CI, 1.07-2.99) significantly improved with the combination therapy. The self-reported 6-month prolonged abstinence (61 [38.6%] vs 47 [29.7%]; OR, 1.49; 95% CI, 0.93-2.39) favored the combination therapy but was not statistically significant. Medicine-related adverse events were similar in the 2 groups (102 [74.5%] in the intervention group vs 86 [68.3%] in the control group). Conclusions and Relevance: In this randomized clinical trial of the combination of varenicline and NRT lozenges in hospitalized adult daily smokers, the combination treatment improved self-reported abstinence compared with varenicline alone, without compromising safety, but it did not improve biochemically validated abstinence. Trial Registration: anzctr.org.au Identifier: ACTRN12618001792213.

Acute versus non-acute targeted muscle reinnervation for pain control following major limb amputation: A comparative study.

BACKGROUND: Targeted muscle reinnervation (TMR) has been shown to reduce phantom limb pain (PLP) and residual limb pain (RLP) after major limb amputation. However, the effect of the timing of surgery on pain control and quality of life outcomes is controversial. We conducted a retrospective study to compare the outcomes of acute TMR for pain prevention with non-acute TMR for the treatment of established pain. METHODS: All patients treated with TMR in our institution between January 2018 and December 2021 were evaluated at 6, 12, 18 and 24 months post-operatively. Pain intensity and quality of life outcomes were assessed using the Brief Pain Inventory (Pain Severity and Pain Interference scales) and Pain Catastrophizing Scale. Outcomes were compared between acute and non-acute TMR using the Wilcoxon ranked-sum test or Fisher's exact test as appropriate. Multilevel mixed-effects linear regression was used to account for repeat measures and potential pain confounders. RESULTS: Thirty-two patients with 38 major limb amputations were included. Acute TMR patients reported significantly lower RLP and PLP scores, pain interference and pain catastrophisation at all time points (p < 0.05). Acute TMR was significantly associated with lower pain severity and pain interference in a linear mixed-effects model accounting for patient age, gender, amputation indication, amputation site, time post-TMR and repeated surveys (p < 0.05). There was no significant difference in the complication rate (p = 0.51). CONCLUSION: Acute TMR was associated with clinically and statistically significant pain outcomes that were better than that in non-acute TMR. This suggests that TMR should be performed with preventative intent, when possible, as part of a multidisciplinary approach to pain management, rather than deferred until the development of chronic pain.

Multi-parametric magnetic resonance imaging of the prostate in Victoria, Australia; unintended consequences of changing Medicare Benefits Schedule access.

ObjectiveTo assess whether prostate biopsy rates have altered with the July 2018 change in Australian Medicare Benefits Schedule (MBS) rebates supporting multiparametric magnetic resonance imaging (mpMRI) for diagnosing prostate cancer.MethodsBiopsy data (both trans-rectal and trans-perineal) were obtained from the Victorian Agency for Health Information from July 2016 to June 2022. The data were stratified by financial year, age group and hospital type (public vs private). Comparison was made between rates pre and post the mpMRI MBS code change.ResultsThere was an 11.9% increase in the number of biopsies performed per year compared to the pre-MBS change period. There is a significant decreasing trend (P<0.001-4) in number of biopsies in the 40-49, 50-59 and 60-69-year-old age groups with a significant increasing trend (P<0.001) in the 70-79 and 80-89-year-old age groups. There was a 32.9% reduction in the mean number of biopsies performed per year in public hospitals, compared with an 18.3% increase in private.ConclusionContrary to expectations, and proposed funding, there has been an increase in the number of prostate biopsies since MRI became more easily available. This change will put increased pressure on the health budget and the large increase in biopsies in elderly patients was not anticipated when the changes were proposed. A review of the criteria is suggested.

Presentation, characteristics and management of obstructive intestinal conditions in cystic fibrosis.

Objective: Constipation and distal intestinal obstruction syndrome (DIOS) are common gastrointestinal manifestations of cystic fibrosis (CF). The primary aim was to describe the characteristics of constipation and DIOS hospitalisations in a paediatric and adult CF service over a 12-year period. The secondary aims were to determine the proportion of constipation and DIOS presentations which met the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) CF Working Group definitions and to describe management strategies of both conditions. Method: A retrospective study of children and adults with CF who were admitted with a primary diagnosis of constipation or DIOS between 1 January 2011 and 31 December 2022. ESPGHAN definitions for constipation and DIOS were retrospectively applied to all admissions to determine if the primary medical diagnosis met ESPGHAN criteria. Results: During the 12-year study period, 42 hospitalisations for constipation were recorded in 19 patients, and 33 hospitalisations for DIOS were recorded in 23 patients. 88.10% of constipation episodes met ESPGHAN definitions, compared with 3.0% of DIOS episodes. Constipation and DIOS were primarily treated with polyethylene glycol (PEG). The use of sodium amidotrizoate meglumine enemas was significantly higher in the DIOS group (p=0.045). Those admitted with DIOS were significantly less likely to be recommended a weaning dose of PEG (p=0.018). Conclusion: Children and adults with CF are more commonly admitted for the management of constipation than DIOS. There is considerable variation in diagnostic and therapeutic practice, and this study highlights the need to enhance the translation and adoption of existing best-practice guidelines.

Trends and determinants of mental illness in humanitarian migrants resettled in Australia: Analysis of longitudinal data.

Given the frequent exposure of humanitarian migrants to traumatic or stressful circumstances, there exists a potential predisposition to mental illness. Our objective was to pinpoint the trends and determinants of mental illness among humanitarian migrants resettled in Australia. This study considered five waves of longitudinal data involving humanitarian migrants resettled in Australia. Post-traumatic stress disorder (PTSD) and psychological distress were assessed using PTSD-8 and Kessler-6 screening tools. Through a Generalised Linear Mixed model (GLMM), variables displaying a 95% CI that excluded the value of 1.0 for the odds ratio were identified as associated factors for both PTSD and elevated psychological distress. The selection of multivariable covariates was guided by causal loop diagrams and least absolute shrinkage and selection operators methods. At baseline, there were 2399 humanitarian migrants with 1881 retained and at the fifth yearly wave; the response rate was 78.4%. PTSD prevalence decreased from 33.3% (95% CI: 31.4-35.3) at baseline to 28.3% (95% CI: 26.2-30.5) at year 5. Elevated psychological distress persisted across all waves: 17.1% (95% CI: 15.5-18.6) at baseline and 17.1% (95% CI: 15.3-18.9) at year 5. Across the five waves, 34.0% of humanitarian migrants met screening criteria for mental illness, either PTSD or elevated psychological distress. In the multivariate model, factors associated with PTSD were loneliness (AOR 1.5, 95% CI: 1.3-1.8), discrimination (AOR 1.6: 1.2-2.1), temporary housing contract (AOR 3.7: 2.1-6.7), financial hardship (AOR 2.2:1.4-3.6) and chronic health conditions (AOR 1.3: 1.1-1.5), whereas the associated factors for elevated psychological distress were loneliness (AOR 1.8: 1.5-2.2), discrimination (AOR 1.7: 1.3-2.2) and short-term lease housing (AOR 1.6: 1.0-1.7). The prevalence, persistence and consequential burden of mental illness within this demographic underscore the urgent need for targeted social and healthcare policies. These policies should aim to mitigate modifiable risk factors, thereby alleviating the significant impact of mental health challenges on this population.

Nutrition delivery and the relationship with changes in muscle mass in adult patients receiving extracorporeal membrane oxygenation: A retrospective observational study.

BACKGROUND: Adverse changes in muscle health (size and quality) are common in patients receiving extracorporeal membrane oxygenation (ECMO). Nutrition delivery may attenuate such changes, yet the relationship with muscle health remains poorly understood. This study explored the association between energy and protein delivery and changes in muscle health measured using ultrasound from baseline to day 10 and 20 in patients receiving ECMO. METHODS: A secondary analysis of data from a prospective study quantifying changes in muscle health using ultrasound in adults receiving ECMO was completed. Patients were eligible for inclusion if they were prescribed artificial nutrition within 3 days of enrolment and had >1 ultrasound measurement. The primary outcome was the association between protein delivery (grams delivered and percentage of targets received) and change in rectus femoris cross-sectional area (RF-CSA) till day 20. Secondary outcomes were the association between energy and protein delivery and change in RF-CSA till day 10, RF-echogenicity, and quadriceps muscle layer thickness to day 10 and 20. Associations were assessed using Spearman's rank correlation. RESULTS: Twenty-three patients (age: 48 [standard deviation {SD}: 14], 44% male) were included. Mean energy and protein delivery were 1633 kcal (SD: 374 kcal) and 70 g (SD: 17 g) equating to 79% (SD: 19%) of energy and 73% (SD: 17%) of protein targets. No association was observed between protein delivery (r = 0.167; p = 0.495) or the percentage of targets received (r = 0.096; p = 0.694) and change in RF-CSA till day 20. No other significant associations were found between energy or protein delivery and change in RF-CSA, echogenicity, or quadriceps muscle layer thickness at any time point. CONCLUSIONS: This exploratory study observed no association between nutrition delivery and changes in muscle health measured using ultrasound in patients receiving ECMO. Larger prospective studies are required to investigate the association between nutrition delivery and changes in muscle health in patients receiving ECMO.

Impact of postoperative hyperlactatemia in orthotopic heart transplantation.

BACKGROUND: Hyperlactatemia (HL) is a common phenomenon after cardiac surgery which is related to tissue hypoperfusion and hypoxia and associated with poor outcomes. It is also often seen in the postoperative period after orthotopic heart transplantation (OHTx), but the association between HL and outcomes after OHTx is not well known. We evaluated the incidence and outcome of HL after OHTx. METHODS: This was a retrospective study of 209 patients who underwent OHTx between January 2011 and December 2020. Patients were classified into 3 groups according to their peak lactate levels within the first 72 h postoperatively: group 1, normal to mild hyperlactatemia (<5 mmol/L, n = 42); group 2, moderate hyperlactatemia (5-10 mmol/L, n = 110); and group 3, severe hyperlactatemia (>10 mmol/L, n = 57). The primary composite endpoint was all-cause mortality or postoperative initiation of veno-arterial extracorporeal membrane oxygenation (VA ECMO) within 30 days. Secondary endpoints included duration of mechanical ventilation, intensive care unit length of stay, and hospital length of stay. RESULTS: Patients with higher postoperative peak lactate levels were more commonly transplanted from left ventricular assist device support (33.3 % vs 50.9 % vs 64.9, p < 0.01) and had longer cardiopulmonary bypass time [127 min (109-148) vs 141 min (116-186) vs 153 min (127-182), p = 0.02]. Composite primary endpoint was met in 18 patients (8.6 %) and was significantly more common in patients with higher postoperative peak lactate levels (0.0 % vs 6.4 % vs 19.3 %, p < 0.01). CONCLUSIONS: Severe hyperlactatemia following orthotopic heart transplant was associated with an increased risk of post-transplant VA ECMO initiation and mortality at 30 days.

Epidemiological trends of respiratory tract pathogens detected via mPCR in Australian adult patients before COVID-19.

BACKGROUND: Respiratory tract infections (RTIs) are a major global health burden due to their high morbidity and mortality. This retrospective study described the epidemiology of respiratory pathogens in adults over a 5-year period at an Australian tertiary healthcare network. METHODS: All multiplex reverse transcription polymerase chain reaction respiratory samples taken between the 1st of November 2014 and the 31st of October 2019 were included in this study. Overall prevalence and variations according to seasons, age groups and sex were analysed, as well as factors associated with prolonged hospital and intensive care length of stay. RESULTS: There were 12,453 pathogens detected amongst the 12,185 positive samples, with coinfection rates of 3.7%. Picornavirus (Rhinovirus), Influenza A and respiratory syncytial virus were the most commonly detected pathogens. Mycoplasma pneumoniae was the most commonly detected atypical bacteria. Significant differences in the prevalence of Chlamydia pneumoniae and Human metapneumovirus infections were found between sexes. Longest median length of intensive care and hospital stay was for Legionella species. Seasonal variations were evident for certain pathogens. CONCLUSIONS: The high rates of pathogen detection and hospitalisation in this real-world study highlights the significant burden of RTIs, and the urgent need for an improved understanding of the pathogenicity as well as preventative and treatment options of RTIs.

Prognostic value of high-sensitivity cardiac troponin in non-cardiac surgical patients in intensive care units.

Type II myocardial injury following surgical procedures is associated with adverse outcomes. The prognostic value of high-sensitivity cardiac troponin (hs-cTn) due to type II myocardial injury in surgical patients admitted to intensive care unit (ICU) remains unclear. The aim of this study was to assess prognostic value of hs-cTn in type II acute myocardial injury in non-cardiac surgical patients requiring post-operative ICU admission. Retrospective analysis of patients admitted to two level III ICUs following surgery and had hs-cTn measured on the day of ICU admission. Patients who had type I acute myocardial infarction (AMI) during their admission were excluded from the study. The primary outcome was hospital mortality. Secondary outcomes included ICU mortality, ICU length of stay (LOS) and hospital LOS. A total of 420 patients were included. On univariable analysis, higher hs-cTn was associated with increased hospital mortality (14.6% vs 6.3%, p = 0.008), ICU LOS (41.1 h, vs 25 h, p = 0.004) and hospital LOS (253 h vs 193 h, p = 0.02). On multivariable analysis, hs-cTn was not independently associated with increased risk of hospital mortality. However, in patients who had elective surgery, hs-cTn was associated with increased risk (OR 1.048; 95% CI 1.004-1.094; p = 0.031) of hospital mortality with area under the receiver operating characteristic curve of 0.753 (95% CI 0.598-0.908). In elective surgical patients, hs-cTn was associated with increased risk of mortality. Larger multicentre studies are required to confirm this association that may assist in risk stratification of elective surgical patients requiring ICU admission.