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.

Identifying delays in the outpatient interventional radiology department: a quality improvement study.

INTRODUCTION: In the post-COVID 19 environment, it has become increasingly important for healthcare services to optimise service delivery for the benefit of both patients and staff. The project purpose was to quantify and determine causes of throughput delays in a newly established outpatient angiography service in a public hospital setting. METHODS: This single-centre study obtained quantitative and qualitative data for 81 consecutive outpatient interventional radiology (IR) examinations over a 3-month period via survey and retrospective analysis of electronic medical records. Staff participating in data collection were able to record multiple causes for delay in a single case and were also able to include comments, allowing for more detailed descriptions of the delays that occurred. RESULTS: A total of 93 delay factors were identified in 73 of the 81 outpatient interventional examinations and grouped into six categories via thematic analysis. Availability of the IR room (40%), availability of the radiologist (28%) and insufficient documentation (18%) were identified as the most frequent causes for delay. Linear regression analysis showed that documentation (P = 0.0002) and room unavailability (P = 0.022) were independently associated with procedural starting delay. CONCLUSION: Delays to the IR procedural start time occurred in 90% of cases (73/81). This study identified the causes for delays in outpatient interventional procedures. This information can be used to improve service delivery in IR departments.

Nutrition delivery across hospitalisation in critically ill patients with COVID-19: An observational study of the Australian experience.

BACKGROUND: Data on nutrition delivery over the whole hospital admission in critically ill patients with COVID-19 are scarce, particularly in the Australian setting. OBJECTIVES: The objective of this study was to describe nutrition delivery in critically ill patients admitted to Australian intensive care units (ICUs) with coronavirus disease 2019 (COVID-19), with a focus on post-ICU nutrition practices. METHODS: A multicentre observational study conducted at nine sites included adult patients with a positive COVID-19 diagnosis admitted to the ICU for >24 h and discharged to an acute ward over a 12-month recruitment period from 1 March 2020. Data were extracted on baseline characteristics and clinical outcomes. Nutrition practice data from the ICU and weekly in the post-ICU ward (up to week four) included route of feeding, presence of nutrition-impacting symptoms, and nutrition support received. RESULTS: A total of 103 patients were included (71% male, age: 58 ± 14 years, body mass index: 30±7 kg/m2), of whom 41.7% (n = 43) received mechanical ventilation within 14 days of ICU admission. While oral nutrition was received by more patients at any time point in the ICU (n = 93, 91.2% of patients) than enteral nutrition (EN) (n = 43, 42.2%) or parenteral nutrition (PN) (n = 2, 2.0%), EN was delivered for a greater duration of time (69.6% feeding days) than oral and PN (29.7% and 0.7%, respectively). More patients received oral intake than the other modes in the post-ICU ward (n = 95, 95.0%), and 40.0% (n = 38/95) of patients were receiving oral nutrition supplements. In the week after ICU discharge, 51.0% of patients (n = 51) had at least one nutrition-impacting symptom, most commonly a reduced appetite (n = 25; 24.5%) or dysphagia (n = 16; 15.7%). CONCLUSION: Critically ill patients during the COVID-19 pandemic in Australia were more likely to receive oral nutrition than artificial nutrition support at any time point both in the ICU and in the post-ICU ward, whereas EN was provided for a greater duration when it was prescribed. Nutrition-impacting symptoms were common.

Nutrition provision in Australian and New Zealand PICUs: A prospective observational cohort study (ePICUre).

OBJECTIVES: The main aim of this study was to describe nutrition provision in Australian and New Zealand (ANZ) pediatric intensive care units (PICUs), including mode of nutrition and adequacy of enteral nutrition (EN) to PICU day 28. Secondary aims were to determine the proportion of children undergoing dietetics assessment, the average time to this intervention, and the methods for estimation of energy and protein requirements. METHODS: This observational study was conducted in all ANZ tertiary-affiliated specialist PICUs. All children ≤18 y of age admitted to the PICU over a 2-wk period and remaining for ≥48 h were included. Data were collected on days 1 to 7, 14, 21, and 28 (unless discharged prior). Data points included oral intake, EN and parenteral nutrition support, estimated energy and protein adequacy, and dietetics assessment details. RESULTS: We enrolled 141 children, of which 79 were boys (56%) and 84 were <2 y of age (60%). Thirty children (73%) received solely EN on day 7 with documented energy and protein targets for 22 (73%). Of these children, 14 (64%) received <75% of their estimated requirements. A dietetics assessment was provided to 80 children (57%), and was significantly higher in those remaining in the PICU beyond the median length of stay (41% in patients staying ≤4.6 d versus 72% in those staying >4.6 d; P < 0.001). CONCLUSIONS: This prospective study of nutrition provision across ANZ PICUs identified important areas for improvement, particularly in EN adequacy and nutrition assessment. Further research to optimize nutrition provision in this setting is urgently needed.

Hypothermic oxygenated perfusion (HOPE) safely and effectively extends acceptable donor heart preservation times: Results of the Australian and New Zealand trial.

BACKGROUND: Cold static storage preservation of donor hearts for periods longer than 4 hours increases the risk of primary graft dysfunction (PGD). The aim of the study was to determine if hypothermic oxygenated perfusion (HOPE) could safely prolong the preservation time of donor hearts. METHODS: We conducted a nonrandomized, single arm, multicenter investigation of the effect of HOPE using the XVIVO Heart Preservation System on donor hearts with a projected preservation time of 6 to 8 hours on 30-day recipient survival and allograft function post-transplant. Each center completed 1 or 2 short preservation time followed by long preservation time cases. PGD was classified as occurring in the first 24 hours after transplantation or secondary graft dysfunction (SGD) occurring at any time with a clearly defined cause. Trial survival was compared with a comparator group based on data from the International Society of Heart and Lung Transplantation (ISHLT) Registry. RESULTS: We performed heart transplants using 7 short and 29 long preservation time donor hearts placed on the HOPE system. The mean preservation time for the long preservation time cases was 414 minutes, the longest being 8 hours and 47 minutes. There was 100% survival at 30 days. One long preservation time recipient developed PGD, and 1 developed SGD. One short preservation time patient developed SGD. Thirty day survival was superior to the ISHLT comparator group despite substantially longer preservation times in the trial patients. CONCLUSIONS: HOPE provides effective preservation out to preservation times of nearly 9 hours allowing retrieval from remote geographic locations.

Virtual Reality for IMMunisation (VRIMM) pain in young children: Results of a randomised controlled trial in general practice.

BACKGROUND AND OBJECTIVES: Virtual reality (VR) may be useful for reducing needle-based pain and distress. Our objective was to compare VR against standard care for children undergoing routine four-year-old immunisations. METHOD: This was a randomised controlled superiority trial conducted in a single suburban general practice, comparing a VR sequence of an interactive marine adventure to standard care (parental comfort, distraction of child). Our primary outcome was self-rated pain scores (Faces Pain Scale - Revised and the poker chip tool). Secondary outcomes included observational ratings (visual analogue scales) of pain and distress from caregivers and an observing healthcare provider, and overall enjoyment of the immunisation experience for the parent and child. RESULTS: In all, 42 children received VR and 45 received standard care. There was no difference in the primary outcome, with median interquartile range self-rated pain scores of 2 (0-8) in the standard care group and 2 (0-6) in the VR group. Observer ratings of pain and distress, as well as ratings of overall enjoyment, favoured VR. There were no significant adverse events. DISCUSSION: VR was not superior to standard care for self-rated pain and distress in children aged four years receiving routine immunisations. However, parent and observer ratings of pain and distress and overall ratings of enjoyment all favoured VR.

Long term outcome and prognostic indicators in Posner Schlossman syndrome.

BACKGROUND: Posner Schlossman syndrome is a well-defined uveitis entity that is characterised by relapsing remitting unilateral anterior uveitis with markedly raised intraocular pressure. The aim of this study was to determine the risk factors for progression in patients with Posner Schlossman syndrome. METHODS: Ninety-eight patients were enrolled in a retrospective case series. Progression was defined as a composite endpoint of any of development of permanent glaucoma (in patients with no evidence of glaucomatous loss on presentation), corneal failure, or chronic inflammation. Relapse was defined as a resolving episode of inflammation not meeting the criteria for progression. RESULTS: Seventy seven percent of patients relapsed on average each 2.2 years. Forty percent of patients progressed. On univariate analysis, increased age at enrolment, immunocompromise at enrolment, the presence of glaucomatous optic neuropathy at enrolment, the performance of an anterior chamber tap and a positive anterior chamber tap were all associated with increased risk of progression. On multivariate analysis, age at enrolment, immunocompromise at enrolment, the performance of an anterior chamber tap, and the presence of glaucomatous optic neuropathy at enrolment were independently associated with increased risk of disease progression. CONCLUSIONS: Posner Schlossman syndrome is not a benign uveitis entity and risk of both relapse and progression are high. Older patients, immunocompromised patients, patients with glaucomatous optic neuropathy at enrolment and those with a positive anterior chamber tap are all at increased risk of progression.

Temporal validation and updating of a prediction model for the diagnosis of gestational diabetes mellitus.

OBJECTIVE: The original Monash gestational diabetes mellitus (GDM) risk prediction in early pregnancy model is internationally externally validated and clinically implemented. We temporally validate and update this model in a contemporary population with a universal screening context and revised diagnostic criteria and ethnicity categories, thereby improving model performance and generalizability. STUDY DESIGN AND SETTING: The updating dataset comprised of routinely collected health data for singleton pregnancies delivered in Melbourne, Australia from 2016 to 2018. Model predictors included age, body mass index, ethnicity, diabetes family history, GDM history, and poor obstetric outcome history. Model updating methods were recalibration-in-the-large (Model A), intercept and slope re-estimation (Model B), and coefficient revision using logistic regression (Model C1, original ethnicity categories; Model C2, revised ethnicity categories). Analysis included 10-fold cross-validation, assessment of performance measures (c-statistic, calibration-in-the-large, calibration slope, and expected-observed ratio), and a closed-loop testing procedure to compare models' log-likelihood and akaike information criterion scores. RESULTS: In 26,474 singleton pregnancies (4,756, 18% with GDM), the original model demonstrated reasonable temporal validation (c-statistic = 0.698) but suboptimal calibration (expected-observed ratio = 0.485). Updated model C2 was preferred, with a high c-statistic (0.732) and significantly better performance in closed testing. CONCLUSION: We demonstrated updating methods to sustain predictive performance in a contemporary population, highlighting the value and versatility of prediction models for guiding risk-stratified GDM care.

Evaluation of the safety and efficacy of extracorporeal carbon dioxide removal in the critically ill using the PrismaLung+ device.

BACKGROUND: Several extracorporeal carbon dioxide removal (ECCO2R) devices are currently in use with variable efficacy and safety profiles. PrismaLung+ is an ECCO2R device that was recently introduced into clinical practice. It is a minimally invasive, low flow device that provides partial respiratory support with or without renal replacement therapy. Our aim was to describe the clinical characteristics, efficacy, and safety of PrismaLung+ in patients with acute hypercapnic respiratory failure. METHODS: All adult patients who required ECCO2R with PrismaLung+ for hypercapnic respiratory failure in our intensive care unit (ICU) during a 6-month period between March and September 2022 were included. RESULTS: Ten patients were included. The median age was 55.5 (IQR 41-68) years, with 8 (80%) male patients. Six patients had acute respiratory distress syndrome (ARDS), and two patients each had exacerbations of asthma and chronic obstructive pulmonary disease (COPD). All patients were receiving invasive mechanical ventilation at the time of initiation of ECCO2R. The median duration of ECCO2R was 71 h (IQR 57-219). A significant improvement in pH and PaCO2 was noted within 30 min of initiation of ECCO2R. Nine patients (90%) survived to weaning of ECCO2R, eight (80%) survived to ICU discharge and seven (70%) survived to hospital discharge. The median duration of ICU and hospital stays were 14.5 (IQR 8-30) and 17 (IQR 11-38) days, respectively. There were no patient-related complications with the use of ECCO2R. A total of 18 circuits were used in ten patients (median 2 per patient; IQR 1-2). Circuit thrombosis was noted in five circuits (28%) prior to reaching the expected circuit life with no adverse clinical consequences. CONCLUSION(S): PrismaLung+ rapidly improved PaCO2 and pH with a good clinical safety profile. Circuit thrombosis was the only complication. This data provides insight into the safety and efficacy of PrismaLung+ that could be useful for centres aspiring to introduce ECCO2R into their clinical practice.

Real-World Analysis of Clinical Characteristics and Survival Outcomes in Patients With Extensive-Stage SCLC Treated With First-Line Chemoimmunotherapy.

Introduction: There are no clinically validated prognostic biomarkers in the management of extensive-stage SCLC (ES-SCLC). We explored the association between clinical characteristics and survival outcomes in patients with ES-SCLC treated with chemoimmunotherapy. Methods: In this retrospective cohort study, patients with ES-SCLC treated with first-line platinum-etoposide chemotherapy and atezolizumab were identified from medical records. Pretreatment clinical characteristics, biochemical parameters, and tumor and treatment characteristics were collected. Univariate and multivariate Cox regression were used to evaluate treatment effect on progression-free survival (PFS) and overall survival (OS). Results: We evaluated 75 patients in total. The median PFS and OS were 6.1 months and 9.2 months, respectively. Statistically significant associations were found with lower lactate dehydrogenase and improved OS (hazard ratio [HR] = 1.0, 95% confidence interval [CI]: 1.0-1.01, p = 0.006), whereas higher age (HR = 0.94, 95% CI: 0.90-0.98, p = 0.006) and lower neutrophil-to-lymphocyte ratio (HR = 1.08, 95% CI: 1.02-1.14, p = 0.005) were associated with improved PFS. The number of chemotherapy cycles received were associated with both an improved PFS (HR = 0.57, 95% CI: 0.37-0.89, p = 0.011) and OS (HR = 0.5, 95% CI: 0.30-0.84, p = 0.008). Conclusions: This study highlights the important effect of chemotherapy on survival. Furthermore, the association between lactate dehydrogenase and neutrophil-to-lymphocyte ratio on survival further suggests that baseline tumor burden and optimizing sarcopenia are important factors for clinicians to consider as we seek to develop personalized treatment for this disease.

Smaller Return Cannula in Venoarterial Extracorporeal Membrane Oxygenation Does Not Increase Hemolysis: A Single-Center, Cohort Study.

The aim of this study was to explore the association between arterial return cannula diameter and hemolysis during peripheral VA ECMO. We identified 158 adult patients who received peripheral VA ECMO at our institution from the national ECMO database (EXCEL) between January 2019 and July 2021. We classified patients into a small cannula group (15 Fr diameter, n = 45) and a large cannula group (≥17 Fr diameter, n = 113), comparing incidences of clinical hemolysis and plasma free hemoglobin ( pf Hb). Moderate hemolysis is defined as having pf Hb 0.05-0.10 g/L and severe hemolysis as having pf Hb >0.10 g/L sustained for at least two consecutive readings or leading to a circuit change. There were no significant differences in rates of moderate hemolysis between small and large cannula groups (1 vs . 6; p = 0.39) and severe hemolysis (0 vs . 3; p = 0.27), nor was the pf Hb level significantly different at 4 hours (0.086 ± 0.096 vs . 0.112 ± 0.145 g/L; p = 0.58) and at 24 hours (0.042 ± 0.033 vs . 0.051 ± 0.069 g/L; p = 0.99). There were no increased rates of hemolysis when comparing small versus large arterial return cannula diameter in peripheral VA ECMO.

Real world outcomes of CFTR modulator therapy in Australian adults and children.

BACKGROUND: Recent advances in CFTR modulator therapy have the potential to change the face of cystic fibrosis (CF). This retrospective observational study describes real world experience of the four available CFTR modulators in adults and children with CF in a single centre in Melbourne, Australia. METHOD: Data were collected for all patients treated with CFTR modulators at MonashCF between May 2012 and September 2020. Primary outcomes included lung function, admission days and BMI/BMI centile over time. Adverse events and reasons for changing or ceasing medications were also analysed. RESULTS: 55% (74/133) adult and 46% (55/119) paediatric patients were treated with CFTR modulators. FEV1 increased in adults treated with ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) by 4.73% and 10.07% respectively, and BMI also improved in these groups. Nutrition improved in adults and children treated with lumacaftor/ivacaftor (LUM/IVA). There was no significant improvement in FEV1 or admission days with LUM/IVA or tezacaftor/ivacaftor (TEZ/IVA). 36% (31/85) ceased LUM/IVA, due to adverse effects in 81% (25/31). Of these, 92% (23/25) changed to TEZ/IVA, 78% (18/23) without significant adverse effects. CONCLUSIONS: Our findings for LUM/IVA and TEZ/IVA are less encouraging than those seen in clinical trials, with no significant improvement in lung function or admission days and a higher rate of adverse effects with LUM/IVA compared with phase 3 clinical trials. TEZ/IVA was generally well tolerated by those who experienced side effects with LUM/IVA. The small number of patients treated with ELX/TEZ/IVA had improvements in all parameters. These findings support ongoing use of IVA for individuals with gating mutations, and transition to ELX/TEZ/IVA once available for patients with at least one Phe508del mutation.

Quantitative analysis of MR T2 relaxation times in neck muscles.

T2 relaxation times (T2 times) are different between resting and exercised muscles and between muscles of healthy subjects and subjects with muscle pathology. However, studies specifically focusing on neck muscles are lacking. Furthermore, normative neck muscle T2 times are not well defined and methodology used to analyse T2 times in neck muscles is not robust. We analysed T2 times in key neck muscles and explored factors affecting variability between muscles. 20 healthy subjects were recruited. Two circular regions of interest (ROIs) were drawn in two mutually exclusive regions within neck muscles on T2 weighted images and values averaged. ROI measurements were performed by a co-investigator, supervised by a neuro-radiologist. For the first ten subjects, measurements were done from C1-T1. For the remaining subjects, ROIs were drawn at two pre-determined levels. Two MRIs were repeated at 31 degrees acquisition to evaluate the effect of muscle fibre orientation. ROI values were translated into T2 times. Results showed semispinalis capitis had the longest T2 times (range 46.88-51.42 ms), followed by splenius capitis (range 47.37-48.33 ms), trapezius (range 45.27-47.46 ms), levator scapulae (range 43.17-45.63 ms) and sternocleidomastoid (range 38.45-42.91 ms). T2 times did not vary along length of muscles and were unaffected by muscle fibre orientation (P > 0.05). T2 times of splenius capitis correlated significantly with age at C2/C3 and C5/C6 levels and trapezius at C7/T1 level. Gender did not influence relaxation times (P > 0.05). In conclusion, results of normative neck muscle T2 time values and factors influencing the T2 times could serve as a reference for future MR analysis of neck muscles. The methodology used may also be useful for related studies of neck muscles.

Different Case Finding Approaches to Optimise COPD Diagnosis: Evidence from the RADICALS Trial.

Aim: Diagnosis of COPD in primary care is hindered by underuse of spirometry. Case finding using validated symptom and health status questionnaires, and simple handheld devices in high-risk populations may improve diagnosis. This study aimed to determine the best combination of measures to optimise COPD diagnosis in the primary care setting. Methods: We recruited 335 current or ex-smokers, including those with an established diagnosis of COPD from general practices. Participants' FEV1 and FEV6 were measured using a handheld spirometry device (COPD-6®). Each completed the COPD assessment test (CAT), a modified Medical Research Council (mMRC) dyspnoea scale, St George's Respiratory Questionnaire (SGRQ) and smoking history questionnaire. From these data we calculated the predictive validity for spirometry-confirmed diagnosis of COPD. Area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for each. Kappa coefficient was used to measure the agreement between the Fixed-Ratio (FR) and Lower Limit of Normal (LLN) spirometric criteria in diagnosing COPD. Results: FEV1/FEV6 <0.70 alone showed significant association (p<0.0001) with COPD diagnosis and good predictive accuracy (AUROC=0.725). However, no further improvement was found after combining SGRQ, CAT and mMRC with FEV1/FEV6. FEV1/FEV6 <0.70 using the COPD-6® handheld device had moderate sensitivity (65.7%) and high PPV (90.1%), high specificity (79.3%) and NPV (44.8%). There was good agreement between FR and LLN definitions (κ=0.70). Conclusion: Handheld micro-spirometers can facilitate case finding of COPD in smokers and ex-smokers attending general practice. The fixed ratio criterion currently recommended by COPD-X guidelines offers the simplest method for diagnosing COPD in Australian primary care.