Knowing when someone is resilient: Development and validation of a measure of adaptive functioning among war-affected Sri Lankan Tamils

Current measures of adaptive functioning are typically validated using samples from Western populations, which limit their utility in non-Western populations. The present study examines the development and utility of a locally derived measure of adaptive functioning, the Penn/RESIST/Peradeniya Competencies (PRPC) Scale, among Tamil survivors of the Sri Lankan civil war. This scale—developed using data from 622 qualitative interviews of war-affected Sri Lankan Tamils—was administered to three samples of war survivors (N ​= ​539) and was shown to have a three-factor structure that overlapped with domains identified through coding of the qualitative data: religious faith, community respect, and family responsibility. These three domains predicted lower levels of impaired functioning in daily life, as well as lower levels of depression and anxiety as measured by culturally sensitive assessments. Additionally, these domains predicted subjective trajectories of life satisfaction indicative of an adaptive sense of personal identity. These results highlight the value of culturally sensitive measures of adaptive functioning

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Reliability and reproducibility of cardiac MRI quantification of peak exercise function with long-axis views.

The conventional approach to cardiac magnetic resonance (CMR) involving breath holds, electrocardiography-gating, and acquisition of a short-axis (SAX) image stack, introduces technical and logistical challenges for assessing exercise left ventricular (LV) function. Real-time, free-breathing CMR acquisition of long-axis (LAX) images overcomes these issues and also enables assessment of global longitudinal strain (GLS). We evaluated the reliability of a free-breathing LAX approach compared to the standard SAX approach and the reproducibility of free-breathing LAX. LV SAX (contiguous stack) and LAX (two-chamber and four-chamber) 3T CMR cine images were acquired four times within one scan in 32 women with cardiovascular risk factors (56±10 years, 28±4 kg/m2) as follows: 1) resting, gated-segmented, end-expiration breath-hold; 2) resting, real-time, free-breathing; 3) test-retest set of resting, real-time, free-breathing; 4) peak exercise (incremental-to-maximum, in-magnet, stepper test), real-time, free-breathing. A second scan was performed within one week in a subset (n = 5) to determine reproducibility of peak exercise measures. Reliability and agreement of the free-breathing LAX approach with the conventional SAX approach were assessed by intraclass correlation coefficient (ICC) and Bland-Altman plots, respectively. Normal control GLS reserve was also acquired in a separate set of 12 young, healthy control women (25±4 years, 22±2 kg/m2) for comparison. Comparisons of LV volumes and function among all techniques at rest had good-to-excellent reliability (ICC = 0.80-0.96), and excellent reliability between peak exercise free-breathing LAX and SAX evaluations (ICC = 0.92-0.96). Higher resting heart rates with free-breathing acquisitions compared to breath-hold (mean difference, limits of agreement: 5, 1-12 beats per minute) reduced reliability for cardiac output (ICC = 0.67-0.79). Reproducibility of the free-breathing LAX approach was good-to-excellent at rest and peak exercise (ICC = 0.74-0.99). GLS exercise reserve was impaired in older women at cardiovascular risk compared to young healthy women (-4.7±2.3% vs -7.4±2.1%, p = 0.001). Real-time, free-breathing CMR with LAX evaluation provides a reliable and reproducible method to assess rest and peak exercise cardiac function, including GLS

Calcium influx is sufficient to induce muscular dystrophy through a TRPC-dependent mechanism

Muscular dystrophy is a general term encompassing muscle disorders that cause weakness and wasting, typically leading to premature death. Membrane instability, as a result of a genetic disruption within the dystrophin-glycoprotein complex (DGC), is thought to induce myofiber degeneration, although the downstream mechanism whereby membrane fragility leads to disease remains controversial. One potential mechanism that has yet to be definitively proven in vivo is that unregulated calcium influx initiates disease in dystrophic myofibers. Here we demonstrate that calcium itself is sufficient to cause a dystrophic phenotype in skeletal muscle independent of membrane fragility. For example, overexpression of transient receptor potential canonical 3 (TRPC3) and the associated increase in calcium influx resulted in a phenotype of muscular dystrophy nearly identical to that observed in DGC-lacking dystrophic disease models, including a highly similar molecular signature of gene expression changes. Furthermore, transgene-mediated inhibition of TRPC channels in mice dramatically reduced calcium influx and dystrophic disease manifestations associated with the mdx mutation (dystrophin gene) and deletion of the δ-sarcoglycan (Scgd) gene. These results demonstrate that calcium itself is sufficient to induce muscular dystrophy in vivo, and that TRPC channels are key disease initiators downstream of the unstable membrane that characterizes many types of muscular dystrophy

Designing care bundle documentation to support the recognition and treatment of acute kidney injury: a route to quality improvement

The chapter describes development of care bundle documentation, through an iterative, user-centred design process, to support the recognition and treatment of acute kidney injury (AKI). The chapter details stages of user and stakeholder consultation, employed to develop a design response that was sensitive to user experience and need, culminating in simulation testing of a near final prototype. The development of supplementary awareness-raising materials, relating to the main care bundle tool is also discussed. This information design response to a complex clinical decision-making process is contrasted to other approaches to promoting AKI care. The need for different but related approaches to the working tool itself and the tool’s communication are discussed. More general recommendations are made for the development of communication tools to support complex clinical processes

Additional file 1 of Accuracy of heart failure ascertainment using routinely collected healthcare data: a systematic review and meta-analysis

Additional file 1: Supplemental methods. Table S1. Characteristics of studies ascertaining acute heart failure (ordered by country and number of gold standard events). Table S2. Characteristics of studies ascertaining prevalent heart failure (ordered by country and number of gold standard events). Table S3. QUADAS-2 study quality assessment. Table S4. Sources of routine and gold standard data by country or region. Table S5. Gold standard heart failure ascertainment methods used in the reviewed studies. Table S6. Guidelines used for gold standard adjudication. Table S7. ICD-9 coding algorithms used to define heart failure in the studies reviewed. Table S8. ICD-10 coding algorithms used to define heart failure in the studies reviewed. Table S9. List of ICD codes used across the studies and their definitions. Table S10. Summary diagnostic accuracy statistics for coding algorithms ascertaining acute heart failure according to subgroup. Supplemental Figure S1. Calculation of performance statistics. Supplemental Figure S2. Funnel plot for the meta-analysis of studies ascertaining acute and prevalent HF using effective sample size weighted regression tests of funnel plot asymmetry. Supplemental Figure S3. SROC plot for the diagnostic accuracy of coding algorithms in studies with > 200 gold standard (GS) heart failure (HF) events. Supplemental Figure S4. SROC plots for the diagnostics accuracy of RCD algorithms ascertaining acute heart failure according to coding position. Supplemental Figure S5. SROC plots for the diagnostics accuracy of RCD algorithms ascertaining prevalent heart failure according to coding position