F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected infection

Contains fulltext : 88623.pdf (publisher's version ) (Closed access)PURPOSE: To assess the value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with CT in critically ill patients suspected of having an infection. METHODS: FDG-PET CT scans requested for evaluation of a suspected infection or inflammatory process in critically ill, mechanically ventilated patients were analyzed (blinded for the final clinical diagnosis) and compared with clinical follow-up. RESULTS: Thirty-five FDG-PET/CT scans performed in 33 ICU patients (28 adults and 5 children), median age 58 years (range 1 month-72 years), were analyzed. Twenty-one FDG-PET/CT scans were true positive. Three FDG-PET/CT scans were considered false positive, in one case leading to additional diagnostic procedures (specificity 79%). Additionally, 11 true negatives were found (sensitivity 100%), leading to an overall accuracy of 91%. CONCLUSIONS: FDG-PET/CT scanning is of additional value in the evaluation of suspected infection in critically ill patients in whom conventional diagnostics did not lead to a diagnosis. Apart from the high accuracy, in this study it appeared that, in addition to conventional diagnostic techniques that were routinely performed, a normal FDG-PET/CT ruled out important infections requiring prolonged antibiotic therapy or drainage. Since sensitivity is lower in highly metabolic active tissues (e.g., endocarditis, meningitis), the FDG-PET/CT scan is not suited to detect infections in these tissues.01 maart 201

Quantitative assessment of cardiac load-responsiveness during extracorporeal life support: case and rationale

We describe a case of a patient assisted by extracorporeal life support, in which we obtained the dynamic filling index, a measure for venous volume during extracorporeal life support, and used this index to assess cardiac load-responsiveness during acute reloading. While reloading, the obtained findings on cardiac pump function by the dynamic filling index were supported by trans-esophageal echocardiography and standard pressure measurement. This suggests that the dynamic filling index can be used to assess cardiac load-responsiveness during extracorporeal life support

Reflections as a settler person doing research in collaboration with Indigenous peoples.

Objectives To reflect on my position as a settler person in Australia and ensure Indigenous voices are prioritised throughout my research, as part of a co-designed, Aboriginal-led study which aims to understand trends in the removal of Indigenous children born in Western Australia using data linkage and qualitative research. Approach As a non-Indigenous person, it is important to reflect on my cultural background and acknowledge my limited understanding of the cultural context of the Indigenous communities represented in the data. Listening to Indigenous voices and collaborating with Indigenous peoples at all stages of my research – from my PhD supervisor to investigators on the broader study, to members of the community and policy reference groups – will be key to improve my understanding of the data from a system and context I am unfamiliar with. Results Collaboration has been cyclical, with results from the qualitative research and discussion with the reference groups informing the initial quantitative research direction. Findings from this research were presented back to the groups, resulting in further questions and directions to explore. The journey so far has been one of learning and understanding the skills I have and the role they can play whilst acknowledging the limits of my own knowledge and the need for Indigenous voices to guide the research in order to be doing research with Indigenous peoples, rather than on them. Conclusion Co-design with Indigenous peoples is critical for doing research which affects them or uses data from their communities. Understanding my own cultural background and acknowledging the limitations of my experience continues to be important for honest and meaningful collaboration

Cumulative incidence of child protection system contacts among a cohort of Western Australian Aboriginal children born 2000 to 2013

Background: Reducing the over-representation of Aboriginal children in the child protection system is a key target for the Australian government. Objective: We aimed to provide more recent evidence on the population-level cumulative incidence of contacts for Aboriginal children with child protective services (CPS) in Western Australia (WA). Participants and Setting: Linked administrative data was provided for WA CPS between 2000 and 2015 for 33,709 Aboriginal children born in WA between 2000 and 2013. Methods: Descriptive summaries and cumulative incidence estimates were used to examine changes in CPS contact trends over time and within sibling groups. Results: There was an increase in early-childhood contacts for children born more recently, with 7.6 % and 2.3 % of children born in 2000–2001 having a notification and placement in out-of-home care by age one, respectively, compared to 15.1 % and 4.3 % of children born in 2012–2013. Among sibling groups where at least one sibling had a CPS contact, approximately half of children had their first contacts on the same date as another sibling. For children born after one of their siblings had been placed in out-of-home care, 31.9 % had themselves been placed in out-of-home care by age one. Conclusions: Multiple children tend to be placed into out-of-home care when at least one sibling is, which is likely to have a significant impact on families affected. The additional risk of placement also carries over to children born after the first removal in a sibling group, highlighting the need for further support to prevent future removals

Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia

Ceftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal asphyxia. We aimed to describe the population pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and propose a population-based rational dosing regimen with optimal PK/pharmacodynamic (PD) target attainment. Data were collected in the PharmaCool prospective observational multicenter study. A population PK model was constructed, and the probability of target attainment (PTA) was assessed during all phases of controlled TH using targets of 100% of the time that the concentration in the blood exceeds the MIC (T.MIC) (for efficacy purposes and 100% T.4×MIC and 100% T.5×MIC to prevent resistance). A total of 35 patients with 338 ceftazidime concentrations were included. An allometrically scaled one-compartment model with postnatal age and body temperature as covariates on clearance was constructed. For a typical patient receiving the current dose of 100 mg/kg of body weight/day in 2 doses and assuming a worst-case MIC of 8 mg/L for Pseudomonas aeruginosa, the PTA was 99.7% for 100% T.MIC during hypothermia (33.7°C; postnatal age [PNA] of 2 days). The PTA decreased to 87.7% for 100% T.MIC during normothermia (36.7°C; PNA of 5 days). Therefore, a dosing regimen of 100 mg/kg/day in 2 doses during hypothermia and rewarming and 150 mg/kg/day in 3 doses during the following normothermic phase is advised. Higher-dosing regimens (150 mg/kg/day in 3 doses during hypothermia and 200 mg/kg/day in 4 doses during normothermia) could be considered when achievements of 100% T.4×MIC and 100% T.5×MIC are desired.</p

Relationship between de novo lipogenesis and serum sex hormone binding globulin in humans

Objective Obesity and liver fat are associated with decreased levels of serum sex hormone binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans. Design A cross-sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex. Participants Healthy men (n = 34) and women (n = 21) were combined from two cross-sectional studies. Forty-two per cent of participants had hepatic steatosis, and the majority were overweight (62%) or obese (27%). Results DNL was inversely associated with SHBG in women (beta: -0.015, 95% CI: -0.030; 0.000), but not in men (beta: 0.007, 95% CI: -0.005; 0.019) (p for interaction = .068). Adjustment for study population, age and body mass index did not materially change these results, although statistical significance was lost after adjustment for serum insulin. Conclusions An inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women.Peer reviewe

Chronic disease IMPACT (chronic disease early detection and improved management in primary care project): an Australian stepped wedge cluster randomised trial

Background: Interrelated chronic vascular diseases (chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease (CVD)) are common with high morbidity and mortality. This study aimed to assess if an electronic-technology-based quality improvement intervention in primary care could improve detection and management of people with and at risk of these diseases. Methods: Stepped-wedge trial with practices randomised to commence intervention in one of five 16-week periods. Intervention included (1) electronic-technology tool extracting data from general practice electronic medical records and generating graphs and lists for audit; (2) education regarding chronic disease and the electronic-technology tool; (3) assistance with quality improvement audit plan development, benchmarking, monitoring and support. De-identified data analysis using R 3.5.1 conducted using Bayesian generalised linear mixed model with practice and time-specific random intercepts. Results: At baseline, eight included practices had 37,946 active patients (attending practice ≥3 times within 2 years) aged ≥18 years. Intervention was associated with increased OR (95% CI) for: kidney health checks (estimated glomerular filtration rate, urine albumin:creatinine ratio (uACR) and blood pressure) in those at risk 1.34 (1.26–1.42); coded diagnosis of CKD 1.18 (1.09–1.27); T2D diagnostic testing (fasting glucose or HbA1c) in those at risk 1.15 (1.08–1.23); uACR in patients with T2D 1.78 (1.56–2.05). Documented eye checks within recommended frequency in patients with T2D decreased 0.85 (0.77–0.96). There were no significant changes in other assessed variables. Conclusions: This electronic-technology-based intervention in primary care has potential to help translate guidelines into practice but requires further refining to achieve widespread improvements across the interrelated chronic vascular diseases

Aneurysmal disease is associated with lower carotid intima-media thickness than occlusive arterial disease

Objective: Patients with aneurysmal and occlusive arterial disease have overlapping cardiovascular risk profiles. The question remains how atherosclerosis is related to the formation of aortic aneurysms. Common carotid artery intima-media thickness (CIMT) is an easily accessible and objective marker of early atherosclerosis. The aim of the current study was to investigate whether there is a difference in atherosclerotic burden as measured by CIMT between patients with aneurysmal and those with occlusive arterial disease. Methods: From 2004 to 2011, the CIMT was measured using B-mode ultrasound scanning in patients undergoing vascular surgery for aortic aneurysmal or occlusive arterial disease at the Erasmus University Medical Center. Cardiovascular risk factors, comorbidities, and medication were recorded. Patients treated for combined aneurysmal and occlusive arterial disease and patients diagnosed with a genetic aneurysm syndrome were excluded. Univariable and multivariable analyses wer

Retrograde movements determine effective stem cell numbers in the intestine

The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts(1-3). Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated.Peer reviewe