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Objective: To characterise the assessment and management of delirium in patients admitted to intensive care units (ICUs) in Australia and New Zealand. Methods: We conducted a multicentre observational point prevalence study across 44 adult Australian and New Zealand ICUs. Data were extracted for all patients in the ICU in terms of assessment and treatment of delirium. ICU-level data were collected regarding the use of explicit protocols related to delirium. Results: We studied 627 patients, with 54% (336/627) having at least one delirium screening assessment performed. The Confusion Assessment Method for the ICU (CAM-ICU) was the most frequently used tool (88%, 296/336). Of patients assessed, 20% (68) were identified to have delirium. Eighteen per cent (111) of patients were administered a drug to manage delirium, with 41% (46) of those receiving a drug having no recorded assessment for delirium on that day. Of the drugs used to treat delirium, quetiapine was the most frequently administered. Physical restraints were applied to 8% (48/626) of patients, but only 17% (8/48) of such patients had been diagnosed with delirium. Most physically restrained patients either did not have delirium diagnosed (31%, 15/48) or had no formal assessment recorded (52%, 25/48) on that day. Conclusions: On the study day, more than 50% of patients had a delirium screening assessment performed, with 20% of screened patients deemed to have delirium. Drugs that are prescribed to treat delirium and physical restraints were frequently used in the absence of delirium or the formal assessment for its presence.

Contains fulltext : 220640.pdf (Publisher’s version ) (Closed access), BACKGROUND: Late initiation of HIV antiretroviral therapy (ART) in pregnancy is associated with not achieving viral suppression before giving birth and increased mother-to-child transmission of HIV. We aimed to investigate virological suppression before giving birth with dolutegravir compared with efavirenz, when initiated during the third trimester. METHODS: In this randomised, open-label trial, DolPHIN-2, we recruited pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating ART in third trimester. Participants were randomly assigned (1:1) to dolutegravir-based or efavirenz-based therapy. HIV viral load was measured 7 days and 28 days after antiretroviral initiation, at 36 weeks' gestation, and at the post-partum visit (0-14 days post partum). The primary efficacy outcome was a viral load of less than 50 copies per mL at the first post-partum visit, and the primary safety outcome was the occurrence of drug-related adverse events in mothers and infants until the post-partum visit. Longer-term follow-up of mothers and infants continues. This study is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23, and Aug 15, 2018, we randomly assigned 268 mothers to dolutegravir (135) or efavirenz (133). All mothers and their infants were included in the safety analysis, and 250 mothers (125 in the dolutegravir group, 125 in the efavirenz group) and their infants in efficacy analyses, by intention-to-treat analyses. The median duration of maternal therapy at birth was 55 days (IQR 33-77). 89 (74%) of 120 in the dolutegravir group had viral loads less than 50 copies per mL, compared with 50 (43%) of 117 in the efavirenz group (risk ratio 1·64, 95% CI 1·31-2·06). 30 (22%) of 137 mothers in the dolutegravir group reported serious adverse events compared with 14 (11%) of 131 in the efavirenz group (p=0·013), particularly surrounding pregnancy and pue

Fracture-controlled sodic-calcic epidote/actinolite/tourmaline alteration in the Highland Valley copper porphyry district forms a large footprint (34 km2) outside of the porphyry Cu centres. Multiple stages of sodic-calcic alteration both pre- and postdate Cu mineralisation at the porphyry centres. Analysis suggests that the mineralising fluid was Cl bearing, at near-neutral pH, oxidised, and with high activities of Na, Ca, and Mg relative to propylitic and fresh-rock assemblages. The fluid was probably thermally prograding in response to magmatic heating. Whole-rock isotopic values reflect residual magma values after degassing, while the range of hydrothermal minerals requires a mixed-fluid origin with a contribution of magmatic water and an external water source. The O-H isotope results favour seawater as the source but could also reflect the ingress of meteoric water. Modelling in strongly Na-Ca–altered rocks suggests the Sr is derived predominantly from a magmatic source, but the system may contain up to 3% seawater Sr. Boron isotope data supports the presence of a seawater-derived fluid entrained in the porphyry Cu systems. The results imply that seawater-derived fluids can infiltrate batholiths and porphyry systems at deep levels (4-5 km) and that sodic/calcic alteration may be more common in rocks peripheral to porphyry Cu systems hosted in island-arc terranes and submarine rocks than currently recognised., Fracture-controlled sodic-calcic epidote/actinolite/tourmaline alteration in the Highland Valley copper porphyry district forms a large footprint (34 km2) outside of the porphyry Cu centres. Multiple stages of sodic-calcic alteration both pre- and postdate Cu mineralisation at the porphyry centres. Analysis suggests that the mineralising fluid was Cl bearing, at near-neutral pH, oxidised, and with high activities of Na, Ca, and Mg relative to propylitic and fresh-rock assemblages. The fluid was probably thermally prograding in response to magmatic heating. Whole-rock isotopic values reflect residual magma values after degassing, while the range of hydrothermal minerals requires a mixed-fluid origin with a contribution of magmatic water and an external water source. The O-H isotope results favour seawater as the source but could also reflect the ingress of meteoric water. Modelling in strongly Na-Ca–altered rocks suggests the Sr is derived predominantly from a magmatic source, but the system may contain up to 3% seawater Sr. Boron isotope data supports the presence of a seawater-derived fluid entrained in the porphyry Cu systems. The results imply that seawater-derived fluids can infiltrate batholiths and porphyry systems at deep levels (4-5 km) and that sodic/calcic alteration may be more common in rocks peripheral to porphyry Cu systems hosted in island-arc terranes and submarine rocks than currently recognised.

Alteration mineralogy data from the Highland Valley district (British Columbia, Canada) was linked to lithogeochemical data to test how sensitive whole-rock determinations are in detecting changes in mineralogy (and material transfer) in the porphyry footprint. It was found that the host-rock composition influences the alteration mineralogy, that material transfer occurred in the green rock outboard of mineralisation, and that feldspar staining can identify subtle alteration that cannot be determined from lithogeochemistry. The paragenetic origin of secondary calcite and how it contributes to the porphyry footprint was also studied. Results could be transferable to other porphyry systems and have implications for porphyry Cu exploration. Feldspar staining and shortwave infrared imaging highlight weak and cryptic alteration. Prehnite can be a key mineral phase in propylitic alteration related to porphyry genesis, and its presence can be predicted based on host-rock composition. Sodic-calcic alteration depletes the protolith in Fe (and magnetite) and will affect the petrophysical and geophysical characteristics of the system. Whole-rock loss on ignition and C and S analyses can be used to map enrichment in water and CO2 in altered rocks, and together these form a large porphyry footprint., Alteration mineralogy data from the Highland Valley district (British Columbia, Canada) was linked to lithogeochemical data to test how sensitive whole-rock determinations are in detecting changes in mineralogy (and material transfer) in the porphyry footprint. It was found that the host-rock composition influences the alteration mineralogy, that material transfer occurred in the green rock outboard of mineralisation, and that feldspar staining can identify subtle alteration that cannot be determined from lithogeochemistry. The paragenetic origin of secondary calcite and how it contributes to the porphyry footprint was also studied. Results could be transferable to other porphyry systems and have implications for porphyry Cu exploration. Feldspar staining and shortwave infrared imaging highlight weak and cryptic alteration. Prehnite can be a key mineral phase in propylitic alteration related to porphyry genesis, and its presence can be predicted based on host-rock composition. Sodic-calcic alteration depletes the protolith in Fe (and magnetite) and will affect the petrophysical and geophysical characteristics of the system. Whole-rock loss on ignition and C and S analyses can be used to map enrichment in water and CO2 in altered rocks, and together these form a large porphyry footprint.

OBJECTIVE: The impact of heart failure (HF) on perceived and objectively measured levels of physical activity (PA) can inform risk stratification and treatment recommendation. We aimed to compare self-reported and objectively measured PA levels in a large sample of participants with and without HF. METHODS: A validated PA questionnaire was used to estimate self-reported weekly PA among 1600 participants with HF and 387 580 participants without HF. Accelerometer data were studied in 596 participants with HF and 96 105 participants without HF for a period of 7 days. Using multivariable linear regression models, we compared the PA levels between participants with HF and without HF, focusing on both the average daily PA levels and the intensity of PAs throughout the day. RESULTS: PA levels were significantly lower in participants with HF using both self-report (excess metabolic equivalent of task hours per week of 26.5 (95% CI 24.7 to 28.4) vs 34.7 (95% CI 34.5 to 34.9), respectively (p<0.001)) and accelerometer measures (mean accelerations of 23.7 milligravity (95% CI 23.1 to 24.4) vs 28.1 milligravity (95% CI 28.0 to 28.1), respectively (p<0.001)). Findings were consistent across different PA intensities. Hour-by-hour comparisons showed that accelerometer-derived PA levels of patients with HF were reduced throughout the day. CONCLUSION: Perceived and objectively recorded PA levels of patients with chronic HF are significantly lower than those of individuals without HF. This difference is continuous throughout the different hours of the day, with individuals with HF being on average 16% less active than individuals without HF. In patients with HF, increases in everyday activity may be a potential alternative to structured exercise programmes.

BACKGROUND: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses. METHODS AND ANALYSIS: This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment. DISCUSSION: Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung

IMPORTANCE: It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock. OBJECTIVE: To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019. INTERVENTIONS: Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. MAIN OUTCOMES AND MEASURES: The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality. RESULTS: Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69