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Abstract Background Postoperative atrial fibrillation (POAF) is a common and potentially serious complication post cardiac surgery. Hypomagnesaemia is common after cardiac surgery and recent evidence indicates that supplementation of magnesium may prevent POAF. We aim to investigate the effectiveness of continuous intravenous magnesium sulphate administration in the perioperative period to prevent POAF as compared to placebo. Methods The (POMPAE) trial is a phase 2, single-center, double-blinded randomized superiority clinical study. It aims to assess the impact of perioperative continuous intravenous magnesium administration on the occurrence of cardiac surgery-related POAF. A total of 530 patients will be included. Eligible patients will be randomized in 1:1 ratio to the intervention or placebo group with stratification based on the presence of valvular surgery. The objective of the infusion is to maintain ionized magnesium levels between 1.5 and 2.0 mmol/L. Discussion The primary outcome measure is the incidence of de novo POAF within the first 7 days following surgery, with censoring at hospital discharge. This trial may generate crucial evidence for the prevention of POAF and reduce clinical adverse events in patients following cardiac surgery. Trial registration The POMPAE trial was registered at ClinicalTrials.gov under the following identifier NTC05669417, https://clinicaltrials.gov/ct2/show/NCT05669417 . Registered on December 30, 2022. Protocol version Version 3.3, dated 13–01-2023.

Background. Organ transplantation is a well-established intervention but is reliant on the donation of organs and tissues, mostly from deceased donors. The proportion of Australians proceeding to organ donation (OD) has increased, but the proportion of Indigenous Australians proceeding remains two-thirds that of non-Indigenous Australians. We sought to explore perceived barriers and enablers for the involvement of Indigenous peoples in the OD process. Methods. Qualitative methodology centered around focus groups was used to capture the experiences and perspectives of Indigenous people regarding OD. A purposively sampled group of Aboriginal Liaison Officers working within the Alice Springs Hospital Intensive Care Unit (ASH ICU) participated in up to 6 focus groups during 2021 with subsequent thematic analysis of the enablers and barriers to Indigenous participation in the OD process. The ASH ICU is the only ICU servicing Central Australia, and 70% of admissions are Indigenous patients. Results. Four primary themes emerged: OD is a new and culturally taboo topic; conversations related to OD are confronting; education is needed (both about OD and cultural education for clinicians); and lack of trust in the healthcare system. Conclusions. There are cultural barriers to engaging in the OD process and clinicians need more training on the delivery of culturally safe communication is needed. Despite this, there was a recognition that OD is important. Education about OD needs to be place based, culturally and linguistically appropriate, informed by local knowledge, delivered in community, and occur before a family member is admitted to ICU.

Abstract A growing number of social media studies in the U.S. rely on the characterization of the opinion of individual users, for example, as Democrat- or Republican-leaning, or in continuous scales ranging from most liberal to most conservative. Recent works have shown, however, that additional opinion dimensions, for instance measuring attitudes towards elites, institutions, or cultural change, are also relevant for understanding socio-informational phenomena on social platforms and in politics in general. The study of social networks in high-dimensional opinion spaces remains challenging in the US, both because of the relative dominance of a principal liberal-conservative dimension in observed phenomena, and because two-party political systems structure both the preferences of users and the tools to measure them. This article leverages graph embedding in multi-dimensional latent opinion spaces and text analysis to propose a method to identify additional opinion dimensions linked to cultural, policy, social, and ideological groups and preferences. Using Twitter social graph data we infer the political stance of nearly 2 million users connected to the political debate in the U.S. for several issue dimensions of public debate. We show that it is possible to identify several new dimensions structuring social graphs, non-aligned with the classic liberal-conservative dimension. We also show how the social graph is polarized to different degrees along these newfound dimensions, leveraging multi-modality measures in opinion space. These results shed a new light on ideal point estimation methods gaining attention in social media studies, showing that they cannot always assume to capture liberal-conservative divides in single-dimensional models.

Abstract Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference − 69%, 95% CI − 127% to − 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment. Trial registration: ACTRN12617000545369, registered 18th April 2017.

Abstract Background Identifying response markers is highly needed to guide the treatment strategy in patients with metastatic melanoma. Methods A retrospective study was carried out in patients with unresectable/metastatic melanoma (stage IIIb–IV), treated with anti-PD-1 in the first line setting, to better explore the role and the timing of neutrophil/lymphocyte ratio (NLR) as potential biomarker of response. The relationship of NLR with inflammation-immune mediators and the underlying negative effect of raising NLR during immunotherapy, have been investigated with transcriptomic gene analysis. Results The results confirmed previous findings that a high baseline NLR is associated with a poorer prognosis and with higher serum level of lactate dehydrogenase (LDH), regardless of the presence of brain metastases. The transcriptomic analysis showed that high baseline NLR is associated with a characteristic gene signature CCNA1, LDHA and IL18R1, which correlates with inflammation and tumorigenesis. Conversely, low baseline NLR is associated with the signature CD3, SH2D1A, ZAP70 and CD45RA, linked to the immune-activation. The genes positively associated with NLR (CD39 (ENTPD1), PTEN, MYD88, MMP9 and LDH) are involved in processes of immunosuppression, inflammation and tumor-promoting activity. Increased expression of CD39 correlated with TGFβ2, a marker of the N2 neutrophils with immunosuppressive activity. Conclusions These results suggest that increasing NLR is associated with an increased neutrophil population, with polarization to the N2 phenotype, and this process may be the basis for the negatively prognostic role of NLR.

Background: There is limited knowledge about the effect of liberal intraoperative oxygen on non-infectious complications and overall recovery from surgery. Methods: In this retrospective cohort study, we investigated associations between mean intraoperative fraction of inspired oxygen (FiO2), and outcome in adults undergoing elective surgery lasting more than 2 h at a large metropolitan New Zealand hospital from 2012 to 2020. Patients were divided into low, medium, and high oxygen groups (FiO2 ≤ 0.4, 0.41–0.59, ≥0.6). The primary outcome was days alive and out of hospital at 90 days (DAOH90). The secondary outcomes were post-operative complications and admission to the ICU. Results: We identified 15,449 patients who met the inclusion criteria. There was no association between FiO2 and DAOH90 when high FiO2 was analysed according to three groups. Using high FiO2 as the reference group there was an adjusted mean (95% confidence interval [CI]) difference of 0.09 (−0.06 to 0.25) days (P = 0.25) and 0.28 (−0.05 to 0.62) days (P = 0.2) in the intermediate and low oxygen groups, respectively. Low FiO2 was associated with increased surgical site infection: the adjusted odds ratio (OR) for low compared with high FiO2 was 1.53 (95% CI 1.12–2.10). Increasing FiO2 was associated with respiratory complications: the adjusted OR associated with each 10% point increase in FiO2 was 1.17 (95% CI 1.08–1.26) and the incidence of being admitted to an ICU had an adjusted OR of 1.1 (95% CI 1.03–1.18). Conclusions: We found potential benefits, and risks, associated with liberal intraoperative oxygen administration indicating that randomised controlled trials are warranted.

OBJECTIVES:. To determine the concordance between activated partial thromboplastin time (aPTT) and anti-factor-Xa (anti-Xa) in adults undergoing extracorporeal membrane oxygenation (ECMO) and to identify the factors associated with discordant paired aPTT/anti-Xa. DESIGN:. Pre-planned secondary analysis of the Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation pilot randomized unblinded, parallel-group controlled trial. SETTING:. Two ICUs in two university hospitals. PATIENTS:. Thirty-two critically ill patients who underwent ECMO and who had at least one paired aPTT and anti-Xa assay performed at the same time. INTERVENTIONS:. We analyzed the concordance between aPTT and anti-Xa and identified factors associated with discordant paired aPTT/anti-Xa based on their respective therapeutic ranges. We also compared biological parameters between heparin resistance episode and no heparin resistance. MEASUREMENTS AND MAIN RESULTS:. Of the 32 patients who were included in this study, 24 (75%) had at least one discordant paired aPTT/anti-Xa. Of the 581 paired aPTT/anti-Xa that were analyzed, 202 were discordant. The aPTT was relatively lower than anti-Xa in 66 cases (32.7%) or relatively higher than anti-Xa in 136 cases (67.3%). Thirty-three heparin resistance episodes were identified in six patients (19%). CONCLUSIONS:. In these critically ill patients undergoing ECMO, one third of paired aPTT/anti-Xa measures was discordant. Coagulopathy and heparin resistance might be the reasons for discordance. Our results support the potential importance of routinely monitoring both tests in this setting.

Abstract Background Sedative agents may variably impact the stress response. Dexmedetomidine is a sympatholytic alpha2-adrenergic agonist mainly used as a second-line sedative agent in mechanically ventilated patients. We hypothesised that early sedation with dexmedetomidine as the primary agent would result in a reduced stress response compared to usual sedatives in critically ill ventilated adults. Methods This was a prospective sub-study nested within a multi-centre randomised controlled trial of early sedation with dexmedetomidine versus usual care. The primary outcome was the mean group differences in plasma levels of stress response biomarkers measured over 5 days following randomisation. Other hormonal, biological and physiological parameters were collected. Subgroup analyses were planned for patients with proven or suspected sepsis. Results One hundred and three patients were included in the final analysis. Baseline illness severity (APACHE II score), the proportion of patients receiving propofol and the median dose of propofol received were comparable between groups. More of the usual-care patients received midazolam (57.7% vs 33.3%; p = 0.01) and at higher dose (median (95% interquartile range) 0.46 [0.20–0.93] vs 0.14 [0.08–0.38] mg/kg/day; p

Abstract Background Data on long-term outcomes after sepsis-associated critical illness have mostly come from small cohort studies, with no information about the incidence of new disability. We investigated whether sepsis-associated critical illness was independently associated with new disability at 6 months after ICU admission compared with other types of critical illness. Methods We conducted a secondary analysis of a multicenter, prospective cohort study in six metropolitan intensive care units in Australia. Adult patients were eligible if they had been admitted to the ICU and received more than 24 h of mechanical ventilation. There was no intervention. Results The primary outcome was new disability measured with the WHO Disability Assessment Schedule 2.0 (WHODAS) 12 level score compared between baseline and 6 months. Between enrollment and follow-up at 6 months, 222/888 (25%) patients died, 100 (35.5%) with sepsis and 122 (20.1%) without sepsis (P

Abstract Background There are currently no validated globally and freely available tools to estimate the modified frailty index (mFI). The widely available and non-proprietary International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding could be used as a surrogate for the mFI. We aimed to establish an appropriate set of the ICD-10 codes for comorbidities to be used to estimate the eleven-variable mFI. Methods A three-stage, web-based, Delphi consensus-building process among a panel of intensivists and geriatricians using iterative rounds of an online survey, was conducted between March and July 2021. The consensus was set a priori at 75% overall agreement. Additionally, we assessed if survey responses differed between intensivists and geriatricians. Finally, we ascertained the level of agreement. Results A total of 21 clinicians participated in all 3 Delphi surveys. Most (86%, 18/21) had more than 5-years’ experience as specialists. The agreement proportionately increased with every Delphi survey. After the third survey, the panel had reached 75% consensus in 87.5% (112/128) of ICD-10 codes. The initially included 128 ICD-10 variables were narrowed down to 54 at the end of the 3 surveys. The inter-rater agreements between intensivists and geriatricians were moderate for surveys 1 and 3 (κ = 0.728, κ = 0.780) respectively, and strong for survey 2 (κ = 0.811). Conclusions This quantitative Delphi survey of a panel of experienced intensivists and geriatricians achieved consensus for appropriate ICD-10 codes to estimate the mFI. Future studies should focus on validating the mFI estimated from these ICD-10 codes. Trial registration Not applicable.

Abstract Background The Clinical Frailty Scale (CFS) is the most commonly used frailty measure in intensive care unit (ICU) patients. The hospital frailty risk score (HFRS) was recently proposed for the quantification of frailty. We aimed to compare the HFRS with the CFS in critically ill patients in predicting long-term survival up to one year following ICU admission. Methods In this retrospective multicentre cohort study from 16 public ICUs in the state of Victoria, Australia between 1st January 2017 and 30th June 2018, ICU admission episodes listed in the Australian and New Zealand Intensive Care Society Adult Patient Database registry with a documented CFS, which had been linked with the Victorian Admitted Episode Dataset and the Victorian Death Index were examined. The HFRS was calculated for each patient using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes that represented pre-existing conditions at the time of index hospital admission. Descriptive methods, Cox proportional hazards and area under the receiver operating characteristic (AUROC) were used to investigate the association between each frailty score and long-term survival up to 1 year, after adjusting for confounders including sex and baseline severity of illness on admission to ICU (Australia New Zealand risk-of-death, ANZROD). Results 7001 ICU patients with both frailty measures were analysed. The overall median (IQR) age was 63.7 (49.1–74.0) years; 59.5% (n = 4166) were male; the median (IQR) APACHE II score 14 (10–20). Almost half (46.7%, n = 3266) were mechanically ventilated. The hospital mortality was 9.5% (n = 642) and 1-year mortality was 14.4% (n = 1005). HFRS correlated weakly with CFS (Spearman’s rho 0.13 (95% CI 0.10–0.15) and had a poor agreement (kappa = 0.12, 95% CI 0.10–0.15). Both frailty measures predicted 1-year survival after adjusting for confounders, CFS (HR 1.26, 95% CI 1.21–1.31) and HFRS (HR 1.08, 95% CI 1.02–1.15). The CFS had better discrimination of 1-year mortality than HFRS (AUROC 0.66 vs 0.63 p

Objective To determine the effect of sex on sepsis-related ICU admission and survival for up to 3-years. Methods Retrospective cohort study of adults admitted to Australian ICUs between 2018 and 2020. Men and women with a primary diagnosis of sepsis were included. The primary outcome of time to death for up to 3-years was examined using Kaplan Meier plots. Secondary outcomes included the duration of ICU and hospital stay. Results Of 523,576 admissions, there were 63,039 (12·0%) sepsis-related ICU admissions. Of these, there were 50,956 patients (43·4% women) with 3-year survival data. Men were older (mean age 66·5 vs 63·6 years), more commonly received mechanical ventilation (27·4% vs 24·7%) and renal replacement therapy (8·2% vs 6·8%) and had worse survival (Hazard Ratio [HR] 1·11; 95% Confidence Interval [CI] 1·07 to 1·14, PConclusion Men are more likely to be admitted to ICU with sepsis and have worse survival for up to 3-years. Understanding causal mechanisms of sex differences may facilitate the development of targeted sepsis strategies.

Background Nivolumab is an anti-PD-1 antibody approved for treating metastatic melanoma (MM), for which still limited evidence is available on the correlation between drug exposure and patient outcomes.Methods In this observational retrospective study, we assessed whether nivolumab concentration is associated with treatment response in 88 patients with MM and if the patient’s genetic profile plays a role in this association.Results We observed a statistically significant correlation between nivolumab serum concentration and clinical outcomes, measured as overall and progression-free survival. Moreover, patients who achieved a clinical or partial response tended to have higher levels of nivolumab than those who reached stable disease or had disease progression. However, the difference was not statistically significant. In particular, patients who reached a clinical response had a significantly higher concentration of nivolumab and presented a distinct genetic signature, with more marked activation of ICOS and other genes involved in effector T-cells mediated proinflammatory pathways.Conclusions In conclusion, these preliminary results show that in patients with MM, nivolumab concentration correlates with clinical outcomes and is associated with an increased expression of ICOS and other genes involved in the activation of T effectors cells.

IMPORTANCE:. The Clinical Frailty Scale (CFS) is the most used frailty measure in intensive care unit (ICU) patients. Recently, the modified frailty index (mFI), derived from 11 comorbidities has also been used. It is unclear to what degree the mFI is a true measure of frailty rather than comorbidity. Furthermore, the mFI cannot be freely obtained outside of specific proprietary databases. OBJECTIVE:. To compare the performance of CFS and a recently developed International Classification of Diseases-10 (ICD-10) mFI (ICD-10mFI) as frailty-based predictors of long-term survival for up to 1 year. DESIGN:. A retrospective multicentric observational study. SETTING AND PARTICIPANTS:. All adult (≥16 yr) critically ill patients with documented CFS scores admitted to sixteen Australian ICUs in the state of Victoria between April 1, 2017 to June 30, 2018 were included. We used probabilistic methods to match de-identified ICU admission episodes listed in the Australia and New Zealand Intensive Care Society Adult Patient Database with the Victorian Admission Episode Dataset and the Victorian Death Index via the Victorian Data Linkage Centre. MAIN OUTCOMES AND MEASURES:. The primary outcome was the longest available survival following ICU admission. We compared CFS and ICD-10mFI as primary outcome predictors, after adjusting for key confounders. RESULTS:. The CFS and ICD-10mFI were compared in 7,001 ICU patients. The proportion of patients categorized as frail was greater with the CFS than with the ICD-10mFI (18.9% [n = 1,323] vs. 8.8% [n = 616]; p < 0.001). The median (IQR) follow-up time was 165 (82–276) days. The CFS predicted long-term survival up to 6 months after adjusting for confounders (hazard ratio [HR] = 1.26, 95% CI, 1.21–1.31), whereas ICD-10mFI did not (HR = 1.04, 95% CI, 0.98–1.10). The ICD-10mFI weakly correlated with the CFS (Spearman’s rho = 0.22) but had a poor agreement (kappa = 0.06). The ICD-10mFI more strongly correlated with the Charlson comorbidity index (Spearman’s rho 0.30) than CFS (Spearman’s rho = 0.25) (p < 0.001). CONCLUSIONS:. CFS, but not ICD-10mFI, predicted long-term survival in ICU patients. ICD-10mFI correlated with co-morbidities more than CFS. These findings suggest that CFS and ICD-10mFI are not equivalent. RELEVANCE:. CFS and ICD-10mFI are not equivalent in screening for frailty in critically ill patients and therefore ICD-10mFI in its current form should not be used.

Here, using clinical samples and autopsy tissues, the authors combine fast-colorimetric test (LAMP) for SARS-CoV-2 infection and large-scale shotgun metatranscriptomics for host, viral, and microbial profiling and provide a map of the viral genetic features of the New York City outbreak and associate specific host responses and gene expression perturbations with SARS-CoV-2 infection.

Abstract Background Data from clinical registries may be linked to gain additional insights into disease processes, risk factors and outcomes. Identifying information varies from full names, addresses and unique identification codes to statistical linkage keys to no direct identifying information at all. A number of databases in Australia contain the statistical linkage key 581 (SLK-581). Our aim was to investigate the ability to link data using SLK-581 between two national databases, and to compare this linkage to that achieved with direct identifiers or other non-identifying variables. Methods The Australian and New Zealand Society of Cardiothoracic Surgeons database (ANZSCTS-CSD) contains fully identified data. The Australian and New Zealand Intensive Care Society database (ANZICS-APD) contains non-identified data together with SLK-581. Identifying data is removed at participating hospitals prior to central collation and storage. We used the local hospital ANZICS-APD data at a large single tertiary centre prior to deidentification and linked this to ANZSCTS-CSD data. We compared linkage using SLK-581 to linkage using non-identifying variables (dates of admission and discharge, age and sex) and linkage using a complete set of unique identifiers. We compared the rate of match, rate of mismatch and clinical characteristics between unmatched patients using the different methods. Results There were 1283 patients eligible for matching in the ANZSCTS-CSD. 1242 were matched using unique identifiers. Using non-identifying variables 1151/1242 (92.6%) patients were matched. Using SLK-581, 1202/1242 (96.7%) patients were matched. The addition of non-identifying data to SLK-581 provided few additional patients (1211/1242, 97.5%). Patients who did not match were younger, had a higher mortality risk and more non-standard procedures vs matched patients. The differences between unmatched patients using different matching strategies were small. Conclusion All strategies provided an acceptable linkage. SLK-581 improved the linkage compared to non-identifying variables, but was not as successful as direct identifiers. SLK-581 may be used to improve linkage between national registries where identifying information is not available or cannot be released.

Abstract Background Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting. Methods In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4). Results Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio. Conclusions In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP. Trial registration The SPICE III trial was registered at ClinicalTrials.gov ( NCT01728558 ).

Introduction It is plausible that a longer duration of nutrition intervention may have a greater impact on clinical and patient-centred outcomes. The Intensive Nutrition care Therapy comparEd to usual care iN criTically ill adults (INTENT) trial will determine if a whole hospital nutrition intervention is feasible and will deliver more total energy compared with usual care in critically ill patients with at least one organ system failure.Methods and analysis This study is a prospective, multicentre, unblinded, parallel-group, phase II randomised controlled trial (RCT) conducted in 23 hospitals in Australia and New Zealand. Mechanically ventilated critically ill adult patients with at least one organ failure who have been in intensive care unit (ICU) for 72–120 hours and meet all of the inclusion and none of the exclusion criteria will be randomised to receive either intensive or usual nutrition care. INTENT started recruitment in October 2018 and a sample size of 240 participants is anticipated to be recruited in 2022. The study period is from randomisation to hospital discharge or study day 28, whichever occurs first, and the primary outcome is daily energy delivery from nutrition therapy. Secondary outcomes include daily energy and protein delivery during ICU and in the post-ICU period, duration of ventilation, ventilator-free days, total bloodstream infection rate and length of hospital stay. All other outcomes are considered tertiary and results will be analysed on an intention-to-treat basis.Ethics and dissemination Ethics approval has been received in Australia (Alfred Hospital Ethics Committee (HREC/18/Alfred/101) and Human Research Ethics Committee of the Northern Territory Department of Health (2019-3372)) and New Zealand (Northern A Health and Disability Ethics Committee (18/NTA/222). Results will be disseminated in an international peer-reviewed journal(s), at scientific meetings and via social media.Trial registration number NCT03292237.

American shad (Alosa sapidissima) are native to the east coast of North America from the St. Johns River, Florida, to the St. Lawrence River region in Canada. Since the 1800s, dams have reduced access to spawning habitat. To assess the impact of dams, we estimated the historically accessed spawning habitat in coastal rivers (485,618 river segments with 21,113 current dams) based on (i) width, (ii) distance from seawater, and (iii) slope (to exclude natural barriers to migration) combined with local knowledge. Estimated habitat available prior to dam construction (2,752 km2) was 41% greater than current fully accessible habitat (1,639 km2). River-specific population models were developed using habitat estimates and latitudinally appropriate life history parameters (e.g., size at age, maturity, iteroparity). Estimated coast-wide annual production potential was 69.1 million spawners compared with a dammed scenario (41.8 million spawners). Even with optimistic fish passage performance assumed for all dams (even if passage is completely absent), the dam-imposed deficit was alleviated by fewer than 3 million spawners. We estimate that in rivers modeled without dams, 98,000 metric tons of marine sourced biomass and nutrients were annually delivered, 60% of which was retained through carcasses, gametes and metabolic waste. Damming is estimated to have reduced this by more than one third. Based on our results, dams represent a significant and acute constraint to the population and, with other human impacts, reduce the fishery potential and ecological services attributed to the species.

Abstract Background Hospital‐acquired acute kidney injury (AKI) in humans and dogs increases morbidity and nonsurvival. Azotemia at presentation has been associated with a poor outcome in horses; however, prevalence and consequences of hospital‐acquired AKI are unreported. Hypothesis/Objectives To evaluate the prevalence of AKI in hospitalized horses, risk factors associated with AKI, and the effect of AKI on short‐term survival. We hypothesized that the prevalence of AKI in horses is similar to that reported in other domestic mammalian species and would be associated with nonsurvival. Animals Adult horses hospitalized for >2 days from which a minimum of 2 measurements of serum creatinine concentration were available. Methods Retrospective cohort study. Clinical records were reviewed and horses grouped according to their baseline serum creatinine concentration and change in serum creatinine concentration from baseline. The associations between signalment, diagnosis, and treatment variables, and the presence of azotemia or AKI were assessed using multinomial logistic regression. The relationship between these conditions and survival to discharge was evaluated. Results Three hundred twenty‐five horses were included; 4.3% (14/325) had azotemia at baseline and 14.8% (48/325) developed AKI. There were no significant associations between investigated risk factors and development of AKI. The presence of azotemia and AKI did not significantly affect survival to discharge (P = .08 and .81, respectively). Conclusions and Clinical Importance The prevalence of AKI in this population of hospitalized horses is similar to that reported in dogs and humans; however, in this study population, there was less impact on morbidity and short‐term survival.

Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection correlates with antibody responses and is also associated with IFNγ+ TNFα+ double positive CD8+ T-cells. In this study, we compared single DNA vs. multiple DNA prime immunizations, and short vs. long time intervals between the DNA prime and the rAd5 boost to evaluate the impact of these different prime-boost strategies on vaccine-induced humoral and cellular responses in non-human primates. We demonstrated that DNA/rAd5 prime-boost strategies can be tailored to induce either CD4+ T-cell or CD8+ T-cell dominant responses while maintaining a high magnitude antibody response. Additionally, a single DNA prime immunization generated a stable memory response that could be boosted by rAd5 3 years later. These results suggest DNA/rAd5 prime-boost provides a flexible platform that can be fine-tuned to generate desirable T-cell memory responses.

Abstract Background Intravenous fluids may contribute to lower haemoglobin levels in patients with septic shock. We sought to determine the relationship between the changes in haemoglobin concentration and the volume of intravenous fluids administered during resuscitation from septic shock. Methods We performed a retrospective cohort study of patients enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial who were not transfused red blood cells (N = 1275). We determined the relationship between haemoglobin concentration, its change over time and volume of intravenous fluids administered over 6, 24 and 72 h using univariate and multivariate analysis. Results Median (IQR) haemoglobin concentration at baseline was 133 (118–146) g/L and decreased to 115 (102–127) g/L within the first 6 h of resuscitation (P

Purpose: This clinical focus article presents a modified user-centered design framework in order to facilitate the role of pediatric clinicians who treat feeding/ swallowing disorders in redesigning the clinical experience in order to improve outcomes. The article establishes a physiologically based design framework and presents a user-centered design tool that clinicians may utilize to view the patient interaction from a design mindset in their practice. Method: Two case studies are presented to demonstrate the clinical application of the user-centered design tool. Case 1 applies the tool to controlled flow drinking cups and includes a pilot study that explores prototype testing of a novel cup design and the resulting patient experience. Case 2 presents a unique pediatric patient and the application of the user-centered method to analyze a modified treatment experience. Conclusions: Clinicians who treat pediatric feeding and swallowing disorders can benefit from the utilization of a user-centered design approach to observe the patient experience from a design perspective. This approach provides a structure to guide individual clinicians to key insights that may lead to improved treatments. Furthermore, user-centered methods may facilitate the analysis of complex patient scenarios by clinician-led teams, which may result in novel solutions. [ABSTRACT FROM AUTHOR]

Abstract Background In the critically ill, energy delivery from enteral nutrition (EN) is often less than the estimated energy requirement. Parenteral nutrition (PN) as a supplement to EN may increase energy delivery. We aimed to determine if an individually titrated supplemental PN strategy commenced 48–72 hours following ICU admission and continued for up to 7 days would increase energy delivery to critically ill adults compared to usual care EN delivery. Methods This study was a prospective, parallel group, phase II pilot trial conducted in six intensive care units in Australia and New Zealand. Mechanically ventilated adults with at least one organ failure and EN delivery below 80% of estimated energy requirement in the previous 24 hours received either a supplemental PN strategy (intervention group) or usual care EN delivery. EN in the usual care group could be supplemented with PN if EN remained insufficient after usual methods to optimise delivery were attempted. Results There were 100 patients included in the study and 99 analysed. Overall, 71% of the study population were male, with a mean (SD) age of 59 (17) years, Acute Physiology and Chronic Health Evaluation II score of 18.2 (6.7) and body mass index of 29.6 (5.8) kg/m2. Significantly greater energy (mean (SD) 1712 (511) calories vs. 1130 (601) calories, p

Although sex disparity in immunological function and susceptibility to various inflammatory and infectious disease is recognized in adults, far less is known about the situation in young infants during immune development. We have used an outbred piglet model to explore potential early sex disparity underlying both mucosal immune development and systemic responses to novel antigen. Despite similarities in intestinal barrier function and therefore, presumably, antigen exposure, females had less CD172+ (Sirp-α) antigen presenting cells and expression of MHCIIDR at 28 days old compared to males, along with greater regulatory T-cell numbers. This suggests that, during infancy, females may have greater potential for local immune regulation than their male counterparts. However, females also presented with significantly greater systemic antibody responses to injected ovalbumin and dietary soya. Females also synthesized significantly more IgA in mesenteric lymph nodes, whereas males synthesized more in caecal mucosa, suggesting that plasma cells were retained within the MLN in females, but increased numbers of plasma cells circulated through to the mucosal tissue in males. Significant effects of inulin and Bifidobacterium lactis NCC2818 on the developing immune system were also sex-dependent. Our results may start to explain inconsistencies in outcomes of trials of functional foods in infants, as distinction between males and females is seldom made. Since later functionality of the immune system is highly dependent on appropriate development during infancy, stratifying nutritional interventions by sex may present a novel means of optimizing treatments and preventative strategies to reduce the risk of the development of immunological disorders in later life.