Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations

Background & Aims: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic demands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations. / Methods: This single-center prospective cohort study of 38 mechanically ventilated COVID-19 patients from April 1, 2020 to February 1, 2021. The Q-NRG® Metabolic Monitor was used to obtain IC data. The Harris-Benedict (HB), Mifflin St-Jeor (MSJ), Penn State University (PSU), and weight-based equations from the American Society of Parenteral and Enteral Nutrition – Society of Critical Care Medicine (ASPEN-SCCM) Clinical Guidelines were utilized to assess the accuracy of common pREE equations and their ability to predict hypo/hypermetabolism in COVID-19 ICU patients. / Results: The IC measures collected revealed a relatively normometabolic or minimally hypermetabolic mREE at 21.3 kcal/kg/d or 110% of predicted by the HB equation over the first week of mechanical ventilation (MV). This progressed to significant and uniquely prolonged hypermetabolism over successive weeks to 28.1 kcal/kg/d or 143% of HB predicted by MV week 3, with hypermetabolism persisting to MV week 7. Obese individuals displayed a more truncated response with significantly lower mREE versus non-obese patients in MV week 1 (19.5±1.0 kcal/kg/d vs 25.1±1.8 kcal/kg/d, respectively; p < 0.01), with little change in weeks 2-3 (19.5±1.5 kcal/kg/d vs 28.0±2.0 kcal/kg/d; p < 0.01). Both ASPEN-SCCM upper range and PSU pREE equations provided close approximations of mREE yet, like all pREE equations, occasionally over- and under-predicted energy needs and typically did not predict late hypermetabolism. / Conclusions: Study results show a truly unique metabolic response in COVID-19 ICU patients, characterized by significant and prolonged, progressive hypermetabolism peaking at 3 weeks’ post-intubation, persisting for up to 7 weeks in ICU. This pattern was more clearly demonstrated in non-obese versus obese patients. This response is unique and distinct from any previously described model of ICU stress response in its prolonged hypermetabolic nature. This data reaffirms the need for routine, longitudinal IC measures to provide accurate energy targets in COVID-19 ICU patients. The PSU and ASPEN-SCCM equations appear to yield the most reasonable estimation to IC-derived mREE in COVID-19 ICU patients, yet still often over-/under-predict energy needs. These findings provide a practical guide for caloric prescription in COVID-19 ICU patients in the absence of IC

Unexpected Consequences: Women’s experiences of a self-hypnosis intervention to help with pain relief during labour.

Background Self-hypnosis is becoming increasingly popular as a means of labour pain management. Previous studies have produced mixed results. There are very few data on women’s views and experiences of using hypnosis in this context. As part of a randomized controlled trial of self-hypnosis for intra-partum pain relief (the SHIP Trial) we conducted qualitative interviews with women randomized to the intervention arm to explore their views and experiences of using self-hypnosis during labour and birth. Methods Participants were randomly selected from the intervention arm of the study, which consisted of two antenatal self-hypnosis training sessions and a supporting CD that women were encouraged to listen to daily from 32 weeks gestation until the birth of their baby. Those who consented were interviewed in their own homes 8-12 weeks after birth. Following transcription, the interviews were analysed iteratively and emerging concepts were discussed amongst the authors to generate organizing themes. These were then used to develop a principal organizing metaphor or global theme, in a process known as thematic networks analysis. Results Of the 343 women in the intervention group, 48 were invited to interview, and 16 were interviewed over a 12 month period from February 2012 to January 2013. Coding of the data and subsequent analysis revealed a global theme of ‘unexpected consequences’, supported by 5 organising themes, ‘calmness in a climate of fear’, ‘from sceptic to believer’, ‘finding my space’, ‘delays and disappointments’ and ‘personal preferences’. Most respondents reported positive experiences of self-hypnosis and highlighted feelings of calmness, confidence and empowerment. They found the intervention to be beneficial and used a range of novel strategies to personalize their self-hypnosis practice. Occasionally women reported feeling frustrated or disappointed when their relaxed state was misinterpreted by midwives on admission or when their labour and birth experiences did not match their expectations. Conclusion The women in this study generally appreciated antenatal self-hypnosis training and found it to be beneficial during labour and birth. The state of focused relaxation experienced by women using the technique needs to be recognized by providers if the intervention is to be implemented into the maternity service

Using genetic variation and environmental risk factor data to identify individuals at high risk for age-related macular degeneration

A major goal of personalized medicine is to pre-symptomatically identify individuals at high risk for disease using knowledge of each individual's particular genetic profile and constellation of environmental risk factors. With the identification of several well-replicated risk factors for age-related macular degeneration (AMD), the leading cause of legal blindness in older adults, this previously unreachable goal is beginning to seem less elusive. However, recently developed algorithms have either been much less accurate than expected, given the strong effects of the identified risk factors, or have not been applied to independent datasets, leaving unknown how well they would perform in the population at large. We sought to increase accuracy by using novel modeling strategies, including multifactor dimensionality reduction (MDR) and grammatical evolution of neural networks (GENN), in addition to the traditional logistic regression approach. Furthermore, we rigorously designed and tested our models in three distinct datasets: a Vanderbilt-Miami (VM) clinic-based case-control dataset, a VM family dataset, and the population-based Age-related Maculopathy Ancillary (ARMA) Study cohort. Using a consensus approach to combine the results from logistic regression and GENN models, our algorithm was successful in differentiating between high- and low-risk groups (sensitivity 77.0%, specificity 74.1%). In the ARMA cohort, the positive and negative predictive values were 63.3% and 70.7%, respectively. We expect that future efforts to refine this algorithm by increasing the sample size available for model building, including novel susceptibility factors as they are discovered, and by calibrating the model for diverse populations will improve accuracy

A locus at 19q13.31 significantly reduces the <em>ApoE</em> ε4 risk for Alzheimer\u27s Disease in African Ancestry

Copyright: \ua9 2022 Rajabli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. African descent populations have a lower Alzheimer disease risk from ApoE ε4 compared to other populations. Ancestry analysis showed that the difference in risk between African and European populations lies in the ancestral genomic background surrounding the ApoE locus (local ancestry). Identifying the mechanism(s) of this protection could lead to greater insight into the etiology of Alzheimer disease and more personalized therapeutic intervention. Our objective is to follow up the local ancestry finding and identify the genetic variants that drive this risk difference and result in a lower risk for developing Alzheimer disease in African ancestry populations. We performed association analyses using a logistic regression model with the ApoE ε4 allele as an interaction term and adjusted for genome-wide ancestry, age, and sex. Discovery analysis included imputed SNP data of 1,850 Alzheimer disease and 4,331 cognitively intact African American individuals. We performed replication analyses on 63 whole genome sequenced Alzheimer disease and 648 cognitively intact Ibadan individuals. Additionally, we reproduced results using whole-genome sequencing of 273 Alzheimer disease and 275 cognitively intact admixed Puerto Rican individuals. A further comparison was done with SNP imputation from an additional 8,463 Alzheimer disease and 11,365 cognitively intact non-Hispanic White individuals. We identified a significant interaction between the ApoE ε4 allele and the SNP rs10423769_A allele, (β = -0.54,SE = 0.12,p-value = 7.50x10-6) in the discovery data set, and replicated this finding in Ibadan (β = -1.32,SE = 0.52,p-value = 1.15x10-2) and Puerto Rican (β = -1.27,SE = 0.64,p-value = 4.91x10-2) individuals. The non-Hispanic Whites analyses showed an interaction trending in the “protective” direction but failing to pass a 0.05 significance threshold (β = -1.51,SE = 0.84,p-value = 7.26x10-2). The presence of the rs10423769_A allele reduces the odds ratio for Alzheimer disease risk from 7.2 for ApoE ε4/ε4 carriers lacking the A allele to 2.1 for ApoE ε4/ε4 carriers with at least one A allele. This locus is located approximately 2 mB upstream of the ApoE locus, in a large cluster of pregnancy specific beta-1 glycoproteins on chromosome 19 and lies within a long noncoding RNA, ENSG00000282943. This study identified a new African-ancestry specific locus that reduces the risk effect of ApoE ε4 for developing Alzheimer disease. The mechanism of the interaction with ApoEε4 is not known but suggests a novel mechanism for reducing the risk for ε4 carriers opening the possibility for potential ancestry-specific therapeutic intervention

Protocol for a randomised controlled trial of an outreach support program for family carers of older people discharged from hospital

Background: Presentations to hospital of older people receiving family care at home incur substantial costs for patients, families, and the health care system, yet there can be positive carer outcomes when systematically assessing/addressing their support needs, and reductions in older people's returns to hospital attributed to appropriate discharge planning. This study will trial the Further Enabling Care at Home program, a 2-week telephone outreach initiative for family carers of older people returning home from hospital. Hypotheses are that the program will (a) better prepare families to sustain their caregiving role and (b) reduce patients' re-presentations/readmissions to hospital, and/or their length of stay; also that reduced health system costs attributable to the program will outweigh costs of its implementation. Methods/Design: In this randomised controlled trial, family carers of older patients aged 70+ discharged from a Medical Assessment Unit in a Western Australian tertiary hospital, plus the patients themselves, will be recruited at discharge (N = 180 dyads). Carers will be randomly assigned (block allocation, assessors blinded) to receive usual care (control) or the new program (intervention). The primary outcome is the carer's self-reported preparedness for caregiving (Preparedness for Caregiving Scale administered within 4 days of discharge, 2-3 weeks post-discharge, 6 weeks post-discharge). To detect a clinically meaningful change of two points with 80 % power, 126 carers need to complete the study. Patients' returns to hospital and subsequent length of stay will be ascertained for a minimum of 3 months after the index admission. Regression analyses will be used to determine differences in carer and patient outcomes over time associated with the group (intervention or control). Data will be analysed using an Intention to Treat approach. A qualitative exploration will examine patients' and their family carers' experiences of the new program (interviews) and explore the hospital staff's perceptions (focus groups). Process evaluation will identify barriers to, and facilitators of, program implementation. A comprehensive economic evaluation will determine cost consequences. Discussion: This study investigates a novel approach to identifying and addressing family carers' needs following discharge from hospital of the older person receiving care. If successful, the program has potential to be incorporated into routine post-discharge support. Trial registration: Australian and New Zealand Clinical Trial Registry: ACTRN12614001174673

A Common Complement C3 Variant Is Associated with Protection against Wet Age-Related Macular Degeneration in a Japanese Population

博士（医学）神戸大