Subjective assessment underestimates surgical risk: On the potential benefits of cardiopulmonary exercise testing for open thoracoabdominal repair

BACKGROUND: Initial clinical evaluation (ICE) is traditionally considered a useful screening tool to identify frail patients during the preoperative assessment. However, emerging evidence supports the more objective assessment of cardiorespiratory fitness (CRF) via cardiopulmonary exercise testing (CPET) to improve surgical risk stratification. Herein, we compared both subjective and objective assessment approaches to highlight the interpretive idiosyncrasies. METHODS: As part of routine preoperative patient contact, patients scheduled for major surgery were prospectively “eyeballed” (ICE) by two experienced clinicians before more detailed history taking that also included the American Society of Anesthesiologists score classification. Each patient was subjectively judged to be either “frail” or “not frail” by ICE and “fit” or “unfit” from a thorough review of the medical notes. Subjective data were compared against the more objective validated assessment of postoperative outcomes using established CPET “cut‐off” metrics incorporating peak pulmonary oxygen uptake, V̇O(2PEAK) at the anaerobic threshold (V̇O(2)‐AT), and ventilatory equivalent for carbon dioxide that collectively informed risk stratification. These data were retrospectively extracted from a single‐center prospective National Health Service database. Data were analyzed using the Chi‐square automatic interaction detection decision tree method. RESULTS: A total of 127 patients were examined that comprised 58% male and 42% female patients aged 69 ± 10 years with a body mass index of 29 ± 7 kg/m(2). Patients were poorly conditioned with a V̇O(2PEAK) almost 20% lower than predicted for age, sex‐matched healthy controls with 35% exhibiting a V̇O(2)‐AT < 11 ml/kg/min. Disagreement existed between the subjective assessments of risk with ∼34% of patients classified as not frail on ICE were considered unfit by notes review (p < .0001). Furthermore, ∼35% of patients considered not frail on ICE and ∼31% of patients considered fit by notes review exhibited a V̇O(2)‐AT < 11 ml/kg/min, and of these, ∼28% and ∼19% were classified as intermediate to high risk. CONCLUSIONS: These findings highlight the interpretive limitations associated with the subjective assessment of patient frailty with surgical risk classification underestimated in up to a third of patients compared to the validated assessment of CRF. They reinforce the benefits of a more objective and integrated approach offered by CPET that may help us to improve perioperative risk assessment and better direct critical care provision in patients scheduled for “high‐stakes” surgery including open thoracoabdominal aortic aneurysm repair

Patient Outcomes at Twelve Months after Early Decompressive Craniectomy for Diffuse Traumatic Brain Injury in the Randomized DECRA Clinical Trial

Functional outcomes at 12 months were a secondary outcome of the randomized DECRA trial of early decompressive craniectomy for severe diffuse traumatic brain injury (TBI) and refractory intracranial hypertension. In the DECRA trial, patients were randomly allocated 1:1 to either early decompressive craniectomy or intensive medical therapies (standard care). We conducted planned secondary analyses of the DECRA trial outcomes at 6 and 12 months, including all 155 patients. We measured functional outcome using the Glasgow Outcome Scale-Extended (GOS-E). We used ordered logistic regression, and dichotomized the GOS-E using logistic regression, to assess outcomes in patients overall and in survivors. We adjusted analyses for injury severity using the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. At 12 months, the odds ratio (OR) for worse functional outcomes in the craniectomy group (OR 1.68; 95% confidence interval [CI]: 0.96-2.93; p = 0.07) was no longer significant. Unfavorable functional outcomes after craniectomy were 11% higher (59% compared with 48%), but were not significantly different from standard care (OR 1.58; 95% CI: 0.84-2.99; p = 0.16). Among survivors after craniectomy, there were fewer good (OR 0.33; 95% CI: 0.12-0.91; p = 0.03) and more vegetative (OR 5.12; 95% CI: 1.04-25.2; p = 0.04) outcomes. Similar outcomes in survivors were found at 6 months after injury. Vegetative (OR 5.85; 95% CI: 1.21-28.30; p = 0.03) and severely disabled outcomes (OR 2.49; 95% CI: 1.21-5.11; p = 0.01) were increased. Twelve months after severe diffuse TBI and early refractory intracranial hypertension, decompressive craniectomy did not improve outcomes and increased vegetative survivors

Hot Gauge Theories and ZNZ_{N} Phases

In this paper the several aspects of the $Z_{N}$ symmetry in gauge theories at high temperatures are discussed. The metastable $Z_{N}$ bubbles in the $SU(N)$ gauge theories with fermions may have, generically, unacceptable thermodynamic behavior. Their free energy $F \propto T^4$ with a positive proportionality constant. This leads not only to negative pressure but also to negative specific heat and, more seriously, to negative entropy. We argue that although such domains are important in the Euclidean theory, they cannot be interpreted as physical domains in Minkowski space. The related problem is connected with the analysis of the high-temperature limit of the confining phase. Using the two-dimensional QCD with adjoint fermions as a toy model we shall demonstrate that in the light fermion limit in this theory there is no breaking of the $Z_{N}$ symmetry in the high-temperature limit and thus there are no $Z_{N}$ bubbles.Comment: preprint PUPT-1415, 21

The development of color categories in two languages: a longitudinal study

This study unites investigations into the linguistic relativity of color categories with research on children's category acquisition. Naming, comprehension, and memory for colors were tracked in 2 populations over a 3-year period. Children from a seminomadic equatorial African culture, whose language contains 5 color terms, were compared with a group of English children. Despite differences in visual environment, language, and education, they showed similar patterns of term acquisition. Both groups acquired color vocabulary slowly and with great individual variation. Those knowing no color terms made recognition errors based on perceptual distance, and the influence of naming on memory increased with age. An initial perceptually driven color continuum appears to be progressively organized into sets appropriate to each culture and language

Measurement of Heart Rate Using the Polar OH1 and Fitbit Charge 3 Wearable Devices in Healthy Adults During Light, Moderate, Vigorous, and Sprint-Based Exercise: Validation Study

Background: Accurate, continuous heart rate measurements are important for health assessment, physical activity, and sporting performance, and the integration of heart rate measurements into wearable devices has extended its accessibility. Although the use of photoplethysmography technology is not new, the available data relating to the validity of measurement are limited, and the range of activities being performed is often restricted to one exercise domain and/or limited intensities.Objective: The primary objective of this study was to assess the validity of the Polar OH1 and Fitbit Charge 3 devices for measuring heart rate during rest, light, moderate, vigorous, and sprint-type exercise.Methods: A total of 20 healthy adults (9 female; height: mean 1.73 [SD 0.1] m; body mass: mean 71.6 [SD 11.0] kg; and age: mean 40 [SD 10] years) volunteered and provided written informed consent to participate in the study consisting of 2 trials. Trial 1 was split into 3 components: 15-minute sedentary activities, 10-minute cycling on a bicycle ergometer, and incremental exercise test to exhaustion on a motorized treadmill (18-42 minutes). Trial 2 was split into 2 components: 4 × 15-second maximal sprints on a cycle ergometer and 4 × 30- to 50-m sprints on a nonmotorized resistance treadmill. Data from the 3 devices were time-aligned, and the validity of Polar OH1 and Fitbit Charge 3 was assessed against Polar H10 (criterion device). Validity was evaluated using the Bland and Altman analysis, Pearson moment correlation coefficient, and mean absolute percentage error.Results: Overall, there was a very good correlation between the Polar OH1 and Polar H10 devices (r=0.95), with a mean bias of −1 beats·min-1 and limits of agreement of −20 to 19 beats·min-1. The Fitbit Charge 3 device underestimated heart rate by 7 beats·min-1 compared with Polar H10, with a limit of agreement of −46 to 33 beats·min-1 and poor correlation (r=0.8). The mean absolute percentage error for both devices was deemed acceptable

GWAS on family history of Alzheimer’s disease

Alzheimer’s disease (AD) is a public health priority for the 21st century. Risk reduction currently revolves around lifestyle changes with much research trying to elucidate the biological underpinnings. We show that self-report of parental history of Alzheimer’s dementia for case ascertainment in a genome-wide association study of 314,278 participants from UK Biobank (27,696 maternal cases, 14,338 paternal cases) is a valid proxy for an AD genetic study. After meta-analysing with published consortium data (n = 74,046 with 25,580 cases across the discovery and replication analyses), three new AD-associated loci (P &lt; 5 × 10−8) are identified. These contain genes relevant for AD and neurodegeneration: ADAM10, BCKDK/KAT8 and ACE. Novel gene-based loci include drug targets such as VKORC1 (warfarin dose). We report evidence that the association of SNPs in the TOMM40 gene with AD is potentially mediated by both gene expression and DNA methylation in the prefrontal cortex. However, it is likely that multiple variants are affecting the trait and gene methylation/expression. Our discovered loci may help to elucidate the biological mechanisms underlying AD and, as they contain genes that are drug targets for other diseases and disorders, warrant further exploration for potential precision medicine applications

Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

Background: The English National Health Service has made a major investment in nine partnerships between higher education institutions and local health services called Collaborations for Leadership in Applied Health Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and implement research through sustained interactions between academics and health services. CLAHRCs provide a natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery. This protocol describes an externally funded evaluation that focuses on implementation mechanisms and processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances. Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth comparative case studies of research implementation using multiple data collection methods including interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of data collection. We will test the wider applicability of emerging findings with a wider community using an interpretative forum. Discussion: The idea that collaboration between academics and services might lead to more applicable health research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g., Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts particularly with respect to integrated stakeholder involvement

DNA sequence level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes