Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study.

OBJECTIVE: To determine if patients that develop lingering neurologic symptoms of fatigue and "brain fog" after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology. DESIGN: In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function. RESULTS: PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion. CONCLUSIONS: Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19. (www. CLINICALTRIALS: gov; NCT04860869).

The Pre-Adaptation of a Stroke-Specific Self-Management Program Among Older Adults.

Objectives: Managing multimorbidity as aging stroke patients is complex; standard self-management programs necessitate adaptations. We used visual analytics to examine complex relationships among aging stroke survivors' comorbidities. These findings informed pre-adaptation of a component of the Chronic Disease Self-Management Program. Methods: Secondary analysis of 2013-2014 Medicare claims with stroke as an index condition, hospital readmission within 90 days (n = 42,938), and 72 comorbidities. Visual analytics identified patient subgroups and co-occurring comorbidities. Guided by the framework for reporting adaptations and modifications to evidence-based interventions, an interdisciplinary team developed vignettes that highlighted multimorbidity to customize the self-management program. Results: There were five significant subgroups (z = 6.19, p < .001) of comorbidities such as obesity and cancer. We constructed 6 vignettes based on the 5 subgroups. Discussion: Aging stroke patients often face substantial disease-management hurdles. We used visual analytics to inform pre-adaptation of a self-management program to fit the needs of older adult stroke survivors.

Feasibility and Acceptability of an Active Video Game-Based Physical Activity Support Group (Pink Warrior) for Survivors of Breast Cancer: Randomized Controlled Pilot Trial.

BACKGROUND: Survivors of breast cancer with functional limitations have a 40% higher mortality rate than those without. Despite the known benefits of physical activity (PA), <40% of survivors of breast cancer meet the recommendations for PA. The combination of active video games (AVGs) and group-based PA counseling may hold potential for motivating PA adoption and improving physical function. However, this method has not been widely studied in survivors of breast cancer. OBJECTIVE: We aimed to determine the feasibility and acceptability of a group AVG-based multicomponent PA intervention and estimate its effect size and variability on PA and physical function in female survivors of breast cancer in a clinic setting. METHODS: Female survivors of breast cancer (N=60) were recruited through the clinic and randomly assigned to the intervention group (12 weekly sessions) or the control group (existing support group). The intervention group received game-based pedometers and participated in weekly group AVG sessions, PA behavioral coaching, and survivorship navigation discussions. A participant manual with weekly reflection worksheets was provided to reinforce the coaching lessons and promote self-led PA. The control group received conventional pedometers and participated in an existing breast cancer support group. Feasibility was assessed by enrollment rate (≥50%), retention rate (≥80%), group attendance rate (75% attending ≥9 sessions [intervention group]), and the number of technological issues and adverse events. Acceptability was measured by participants' attitudes (from strongly disagree=1 to strongly agree=5) toward the use of AVGs and the overall program. The outcomes included PA (accelerometers) and physical function (Short Physical Performance Battery and gait speed). Analysis of covariance was used to determine differences in PA and physical function between the groups. The Cohen d and its 95% CI determined the effect size and variability, respectively. All the analyses followed the intention-to-treat principle. RESULTS: Participants were an average of 57.4 (SD 10.5) years old, 70% (42/60) White, and 58% (35/60) off treatment. The enrollment rate was 55.9% (66/118). Despite substantial long-term hurricane-related disruptions, we achieved an 80% (48/60) retention. The intervention group's attendance rate was 78% (14/18), whereas the control group's attendance rate was 53% (9/17). Of the 26 game-based pedometers, 3 (12%) were damaged or lost. No study-related adverse events occurred. Acceptability items were highly rated. Steps (ß=1621.64; P=.01; d=0.72), Short Physical Performance Battery (ß=.47; P=.01; d=0.25), and gait speed (ß=.12; P=.004; d=0.48) had a significant intervention effect. CONCLUSIONS: The intervention was feasible and acceptable in this population despite the occurrence of a natural disaster. Pilot results indicate that group AVG sessions, PA coaching, and survivorship navigation produced moderate effects on PA and physical functioning. AVGs with PA counseling can potentially be used in existing breast cancer support groups to encourage PA and improve physical function. TRIAL REGISTRATION: ClinicalTrials.gov NCT02750241; https://clinicaltrials.gov/ct2/show/NCT02750241.

Association between Sleep Quality and Mental Health among Patients at a Post-COVID-19 Recovery Clinic.

A growing body of research documents the persistence of physical and neuropsychiatric symptoms following the resolution of acute COVID-19 infection. To the best of our knowledge, no published study has examined the interaction between insomnia and mental health. Accordingly, we proposed to examine new diagnoses of insomnia, and referrals to pulmonary and sleep medicine clinics for treatment of sleep disorders, in patients presenting to one post-acute COVID-19 recovery clinic. Additionally, we aimed to examine the relationship between poor sleep quality, depression, anxiety, and post-traumatic stress. Patients presented to the clinic on average 2 months following COVID-19 infection; 51.9% (n = 41) were hospitalized, 11.4% (n = 9) were in the intensive care unit, 2.5% (n = 2) were on a mechanical ventilator, and 38.0% (n = 30) were discharged on oxygen. The most commonly reported symptom was fatigue (88%, n = 70), with worse sleep following a COVID-19 infection reported in 50.6% (n = 40). The mean PSQI score was 9.7 (82.3%, n = 65 with poor sleep quality). The mean GAD-7 score was 8.3 (22.8%, n = 14 with severe depression). The mean PHQ-9 was 10.1 (17.8%, n = 18 with severe anxiety). The mean IES-6 was 2.1 (54.4%, n = 43 with post-traumatic stress). Poor sleep quality was significantly associated with increased severity of depression, anxiety, and post-traumatic stress. Future work should follow patients longitudinally to examine if sleep, fatigue, and mental health symptoms improve over time.

Identifying who has long COVID in the USA: a machine learning approach using N3C data.

BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection, known as long COVID, have severely affected recovery from the COVID-19 pandemic for patients and society alike. Long COVID is characterised by evolving, heterogeneous symptoms, making it challenging to derive an unambiguous definition. Studies of electronic health records are a crucial element of the US National Institutes of Health's RECOVER Initiative, which is addressing the urgent need to understand long COVID, identify treatments, and accurately identify who has it-the latter is the aim of this study. METHODS: Using the National COVID Cohort Collaborative's (N3C) electronic health record repository, we developed XGBoost machine learning models to identify potential patients with long COVID. We defined our base population (n=1 793 604) as any non-deceased adult patient (age ≥18 years) with either an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) from an inpatient or emergency visit, or a positive SARS-CoV-2 PCR or antigen test, and for whom at least 90 days have passed since COVID-19 index date. We examined demographics, health-care utilisation, diagnoses, and medications for 97 995 adults with COVID-19. We used data on these features and 597 patients from a long COVID clinic to train three machine learning models to identify potential long COVID among all patients with COVID-19, patients hospitalised with COVID-19, and patients who had COVID-19 but were not hospitalised. Feature importance was determined via Shapley values. We further validated the models on data from a fourth site. FINDINGS: Our models identified, with high accuracy, patients who potentially have long COVID, achieving areas under the receiver operator characteristic curve of 0·92 (all patients), 0·90 (hospitalised), and 0·85 (non-hospitalised). Important features, as defined by Shapley values, include rate of health-care utilisation, patient age, dyspnoea, and other diagnosis and medication information available within the electronic health record. INTERPRETATION: Patients identified by our models as potentially having long COVID can be interpreted as patients warranting care at a specialty clinic for long COVID, which is an essential proxy for long COVID diagnosis as its definition continues to evolve. We also achieve the urgent goal of identifying potential long COVID in patients for clinical trials. As more data sources are identified, our models can be retrained and tuned based on the needs of individual studies. FUNDING: US National Institutes of Health and National Center for Advancing Translational Sciences through the RECOVER Initiative.

Impact of COVID-19 Infection and Persistent Lingering Symptoms on Patient Reported Indicators of Nutritional Risk and Malnutrition.

Persistent malnutrition after COVID-19 infection may worsen outcomes, including delayed recovery and increased risk of rehospitalization. This study aimed to determine dietary intakes and nutrient distribution patterns after acute COVID-19 illness. Findings were also compared to national standards for intake of energy, protein, fruit, and vegetables, as well as protein intake distribution recommendations. Participants (≥18 years old, n = 92) were enrolled after baseline visit at the Post-COVID Recovery Clinic. The broad screening battery included nutritional assessment and 24-h dietary recall. Participants were, on average, 53 years old, 63% female, 69% non-Hispanic White, and 59% obese/morbidly obese. Participants at risk for malnutrition (48%) experienced significantly greater symptoms, such as gastric intestinal issues, loss of smell, loss of taste, or shortness of breath; in addition, they consumed significantly fewer calories. Most participants did not meet recommendations for fruit or vegetables. Less than 39% met the 1.2 g/kg/day proposed optimal protein intake for recovery from illness. Protein distribution throughout the day was skewed; only 3% met the recommendation at all meals, while over 30% never met the threshold at any meal. Our findings highlight the need for nutritional education and support for patients to account for lingering symptoms and optimize recovery after COVID-19 infection.

Improvements in sleep quality and fatigue are associated with improvements in functional recovery following hospitalization in older adults.

Study objectives: Poor sleep quality, a frequent problem in older adults, has been shown to be associated with reduced physical function and wellbeing. However, little is known about the relationship between sleep quality and the recovery of physical function following hospitalization. Thus, we conducted this study to examine the association between sleep quality and functional recovery after an acute hospitalization in community dwelling older adults. Methods: Older adult patients (N = 23, mean age = 74 ± 9 years) were recruited during an acute hospitalization (average length of stay 3.9 days) with a cardiovascular (56%), pulmonary (22%), or metabolic (13%) admission diagnosis. Objective physical function was measured using the Short Physical Performance Battery (SPPB) and self-reported function was assessed with Katz Index of Independence in Activities of Daily Living (ADL) and Lawton Instrumental Activities of Daily Living Scale (IADL). Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) global score and Iowa Fatigue Score (IFS). Testing was performed prior to discharge (baseline) and 4-weeks post-discharge (follow-up). Results: Regression models showed PSQI Subjective Sleep Quality change scores from baseline to 4-week follow-up predicted a change in ADL (ß = -0.22); PSQI Use of Sleep Medications change scores predicted a change in SPPB Total (ß = 1.62) and SPPB Chair Stand (ß = 0.63); IFS change scores predicted SPPB Total (ß = -0.16) and SPPB Chair Stand performance (ß = -0.07) change scores. Conclusions: For older adults, changes in sleep medication use, daytime dysfunction, and fatigue were associated with improvements in functional recovery (including physical performance and independence) from acute hospitalization to 4-week follow-up. These results suggest that interventions focused on improving sleep quality, daytime consequences, and fatigue might help enhance physical functioning following hospitalization. Clinical trial registration: ClinicalTrials.gov, identifier: NCT02203656.

Dietary Intake Patterns of Community-Dwelling Older Adults After Acute Hospitalization.

BACKGROUND: Malnutrition and sarcopenia are a growing concern in community-dwelling older adults. Hospitalization increases the risk of malnutrition and leads to a decline in functional and nutritional status at discharge. Persistent malnutrition after hospital discharge may worsen posthospital outcomes, including readmissions. The aim of this study was to determine dietary intakes and nutrient distribution patterns of community-dwelling older adults after acute hospitalization. METHOD: Participants (65 years and older, n = 85) were enrolled during acute hospitalization and dietary 24-hour recalls were collected weekly for 1 month postdischarge. Analysis included change in dietary intake over recovery timeframe; daily intake of energy, protein, fruit, vegetables, and fluids; comparison of intake to recommendations; distribution of energy and protein across mealtimes; and analysis of most common food choices. RESULTS: Most participants did not meet current recommendations for energy, fruit, vegetables, or fluids. Average protein consumption was significantly higher than the current recommendation of 0.8 g/kg/d; however, only 55% of participants met this goal and less than 18% met the 1.2 g/kg/d proposed optimal protein intake for older adults. The protein distribution throughout the day was skewed and no one met the 0.4 g/meal protein recommendation at all meals. CONCLUSIONS: Our findings indicate that community-dwelling older adults did not meet their nutritional needs during recovery after hospitalization. These data highlight the need for better nutritional evaluation and support of geriatric patients recovering from hospitalization.

Increased risk of psychiatric sequelae of COVID-19 is highest early in the clinical course.

Background: COVID-19 has been shown to increase the risk of adverse mental health consequences. A recent electronic health record (EHR)-based observational study showed an almost two-fold increased risk of new-onset mental illness in the first 90 days following a diagnosis of acute COVID-19. Methods: We used the National COVID Cohort Collaborative, a harmonized EHR repository with 2,965,506 COVID-19 positive patients, and compared cohorts of COVID-19 patients with comparable controls. Patients were propensity score-matched to control for confounding factors. We estimated the hazard ratio (COVID-19:control) for new-onset of mental illness for the first year following diagnosis. We additionally estimated the change in risk for new-onset mental illness between the periods of 21-120 and 121-365 days following infection. Findings: We find a significant increase in incidence of new-onset mental disorders in the period of 21-120 days following COVID-19 (3.8%, 3.6-4.0) compared to patients with respiratory tract infections (3%, 2.8-3.2). We further show that the risk for new-onset mental illness decreases over the first year following COVID-19 diagnosis compared to other respiratory tract infections and demonstrate a reduced (non-significant) hazard ratio over the period of 121-365 days following diagnosis. Similar findings are seen for new-onset anxiety disorders but not for mood disorders. Interpretation: Patients who have recovered from COVID-19 are at an increased risk for developing new-onset mental illness, especially anxiety disorders. This risk is most prominent in the first 120 days following infection. Funding: National Center for Advancing Translational Sciences (NCATS).

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FUNDING: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.

Effect of the lysosomotropic agent chloroquine on mTORC1 activation and protein synthesis in human skeletal muscle.

BACKGROUND: Previous work in HEK-293 cells demonstrated the importance of amino acid-induced mTORC1 translocation to the lysosomal surface for stimulating mTORC1 kinase activity and protein synthesis. This study tested the conservation of this amino acid sensing mechanism in human skeletal muscle by treating subjects with chloroquine-a lysosomotropic agent that induces in vitro and in vivo lysosome dysfunction. METHODS: mTORC1 signaling and muscle protein synthesis (MPS) were determined in vivo in a randomized controlled trial of 14 subjects (10 M, 4 F; 26 ± 4 year) that ingested 10 g of essential amino acids (EAA) after receiving 750 mg of chloroquine (CHQ, n = 7) or serving as controls (CON, n = 7; no chloroquine). Additionally, differentiated C2C12 cells were used to assess mTORC1 signaling and myotube protein synthesis (MyPS) in the presence and absence of leucine and the lysosomotropic agent chloroquine. RESULTS: mTORC1, S6K1, 4E-BP1 and rpS6 phosphorylation increased in both CON and CHQ 1 h post EAA ingestion (P < 0.05). MPS increased similarly in both groups (CON, P = 0.06; CHQ, P < 0.05). In contrast, in C2C12 cells, 1 mM leucine increased mTORC1 and S6K1 phosphorylation (P < 0.05), which was inhibited by 2 mg/ml chloroquine. Chloroquine (2 mg/ml) was sufficient to disrupt mTORC1 signaling, and MyPS. CONCLUSIONS: Chloroquine did not inhibit amino acid-induced activation of mTORC1 signaling and skeletal MPS in humans as it does in C2C12 muscle cells. Therefore, different in vivo experimental approaches are required for confirming the precise role of the lysosome and amino acid sensing in human skeletal muscle. Trial registration NCT00891696. Registered 29 April 2009.

Countering disuse atrophy in older adults with low-volume leucine supplementation.

Older adults are at increased risk of being bedridden and experiencing negative health outcomes including the loss of muscle tissue and functional capacity. We hypothesized that supplementing daily meals with a small quantity (3-4 g/meal) of leucine would partially preserve lean leg mass and function of older adults during bed rest. During a 7-day bed rest protocol, followed by 5 days of inpatient rehabilitation, healthy older men and women (67.8 ± 1.1 yr, 14 men; 6 women) were randomized to receive isoenergetic meals supplemented with leucine (LEU, 0.06 g/kg/meal; n = 10) or an alanine control (CON, 0.06 g/kg/meal; n = 10). Outcomes were assessed at baseline, following bed rest, and after rehabilitation. Body composition was measured by dual-energy X-ray absorptiometry. Functional capacity was assessed by knee extensor isokinetic and isometric dynamometry, peak aerobic capacity, and the short physical performance battery. Muscle fiber type, cross-sectional area, signaling protein expression levels, and single fiber characteristics were determined from biopsies of the vastus lateralis. Leucine supplementation reduced the loss of leg lean mass during bed rest (LEU vs. CON: -423 vs. -1035 ± 143 g; P = 0.008) but had limited impact on strength or endurance-based functional outcomes. Similarly, leucine had no effect on markers of anabolic signaling and protein degradation during bed rest or rehabilitation. In conclusion, providing older adults with supplemental leucine has minimal impact on total energy or protein consumption and has the potential to partially counter some, but not all, of the negative effects of inactivity on muscle health.NEW & NOTEWORTHY Skeletal muscle morphology and function in older adults was significantly compromised by 7 days of disuse. Leucine supplementation partially countered the loss of lean leg mass but did not preserve muscle function or positively impact changes at the muscle fiber level associated with bed rest or rehabilitation. Of note, our data support a relationship between myonuclear content and adaptations to muscle atrophy at the whole limb and single fiber level.

Developing a screening tool for sarcopenia in hospitalized geriatric patients: Estimation of appendicular skeletal muscle mass using bioelectrical impedance.

BACKGROUND & AIMS: Sarcopenia is now a billable ICD-10 geriatric condition characterized by low appendicular skeletal muscle mass (ASMM) and low function. There is an increasing need for portable, provider-friendly, cost-effective methods for estimating ASMM. The overall goal of this project was to create and validate a regression model for obtaining ASMM from Bioelectrical Impedance Analysis (BIA) measurements using Dual-energy X-ray Absorptiometry (DXA) as the reference. METHODS: Geriatric patients (≥65 years of age) were enrolled during an acute hospitalization. Body composition measurements were obtained through DXA and BIA devices. The ASMM prediction model was derived using stepwise multiple regression modeling. The model was 10 fold validated and tested as a screening tool (sensitivity, specificity, positive and negative predictive values) using the Foundation for the NIH Sarcopenia Project (FNIH) definition. RESULTS: The following variables were selected by stepwise regression modeling: sex, body mass index, max grip strength, and fat mass derived by BIA. The model was internally validated with 10 fold cross validation. Using the FNIH definition, the model was found to have a sensitivity of 80%, a specificity of 91%, a positive predictive value of 73% and a negative predictive value of 93%. CONCLUSIONS: We have developed a screening tool that can be easily used in geriatric patients to screen for sarcopenia. Once validated with a larger sample, the developed prediction model can be used to estimate ASMM using provider-friendly measurements and can be easily implemented as a sensitive screening tool for identifying patients at risk for sarcopenia. Those identified at risk would undergo further functional testing for diagnosis and treatment of sarcopenia.

A Narrative Review on the Potential of Red Beetroot as an Adjuvant Strategy to Counter Fatigue in Children with Cancer.

Cancer-related fatigue (CRF) is a debilitating adverse effect among children with cancer and a significant barrier to physical activity (PA) participation. PA interventions are effective at reducing fatigue and improving both quality of life (QOL) and functional outcomes in children with cancer. However, 50-70% of children with cancer do not meet PA guidelines. Thus, adjuvant methods are needed to increase PA participation. Given the growing interest in the use of beetroot juice to reduce exercise-induced fatigue, our narrative review evaluated the potential use of beetroot to improve PA participation to counter CRF and improve QOL. Our review of 249 articles showed a lack of published clinical trials of beetroot in children and adults with cancer. Trials of beetroot use had been conducted in a noncancer population (n = 198), and anticancer studies were primarily in the preclinical phase (n = 40). Although results are promising, with beetroot juice shown to counter exercise-induced fatigue in a variety of athletic and patient populations, its use to counter CRF in children with cancer is inconclusive. Pilot and feasibility studies are needed to examine the potential benefits of beetroot to counter CRF, increase PA participation, and improve QOL in children with cancer.

A Phase I Randomized Clinical Trial of Evidence-Based, Pragmatic Interventions to Improve Functional Recovery After Hospitalization in Geriatric Patients.

BACKGROUND: Physical function declines during hospitalization in geriatric patients, increasing the risk of loss of independence. There is a need for evidence-based, pragmatic interventions to improve functional recovery of older adults following acute hospitalization. Here, we report the results of a Phase I randomized clinical trial designed to determine safety and effect size of protein supplementation, exercise, and testosterone interventions on 30-day post-discharge functional recovery and readmissions in geriatric patients. METHODS: A total of 100 patients admitted to the University of Texas Medical Branch hospital for an acute medical illness were randomized to one of five intervention groups: isocaloric placebo, whey protein supplement, in-home rehabilitation + placebo, in-home rehabilitation + whey protein, or testosterone. Primary outcome measure was the change from baseline in short physical performance battery score at 1 and 4 weeks post-discharge. Secondary outcomes were changes in body composition, activities of daily living, and 30-day readmissions. Comparisons were made across study groups and between placebo and all active intervention groups. RESULTS: Four weeks post-discharge, the short physical performance battery total score and balance score increased more in active intervention groups than placebo group (p < .05). There were no significant differences in change in body composition or activities of daily living across groups or between active intervention groups and placebo group. Readmission rates were highest in placebo (28%), followed by rehabilitation + placebo (15%), whey protein (12%), rehabilitation + whey protein (11%), and testosterone (5%). There was a trend for lower readmission rates in all active intervention groups (11%) versus placebo group (28%). CONCLUSIONS: Findings from this Phase I clinical trial suggest that pragmatic, evidence-based interventions may accelerate recovery from acute hospitalization in geriatric patients. These data provide essential information to design larger randomized controlled trials to test the effectiveness of these interventions.

Testosterone Replacement Therapy and Rehospitalization in Older Men With Testosterone Deficiency in a Postacute Care Setting.

OBJECTIVE: The aim of the study was to examine whether receipt of testosterone replacement therapy was associated with reduced 30-day rehospitalization after postacute care among older men with testosterone deficiency. DESIGN, PATIENTS, AND METHODS: We conducted a retrospective cohort study using a 5% national sample of Medicare beneficiaries. We identified 1290 nonsurgical inpatient postacute care discharges between January 1, 2007, and October 31, 2014, for male patients, 66 yrs or older, with a previous diagnosis of testosterone deficiency. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals for 30-day postacute care rehospitalization related to receipt of testosterone replacement therapy. RESULTS: In older men with testosterone deficiency, receipt of testosterone replacement therapy was not associated with rehospitalization (odds ratio = 0.87, 95% confidence interval, 0.59-1.29) in the 30 days after postacute care discharge. These findings persisted after adjustment for quintile of propensity scores (odds ratio = 0.90, 95% confidence interval = 0.62-1.30). CONCLUSION: Testosterone replacement therapy was not associated with reduced rehospitalization after postacute care discharge in older men with testosterone deficiency. Further research in this population should examine the effects of testosterone replacement therapy on functional recovery and community independence.

Effect of Aerobic Exercise Training and Essential Amino Acid Supplementation for 24 Weeks on Physical Function, Body Composition, and Muscle Metabolism in Healthy, Independent Older Adults: A Randomized Clinical Trial.

BACKGROUND: Essential amino acids (EAA) and aerobic exercise (AE) acutely and independently stimulate skeletal muscle protein anabolism in older adults. OBJECTIVE: In this Phase 1, double-blind, placebo-controlled, randomized clinical trial, we determined if chronic EAA supplementation, AE training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis. METHODS: We phone-screened 971, enrolled 109, and randomized 50 independent, low-active, nonfrail, and nondiabetic older adults (age 72 ± 1 years). We used a 2 × 2 factorial design. The interventions were: daily nutritional supplementation (15 g EAA or placebo) and physical activity (supervised AE training 3 days/week or monitored habitual activity) for 24 weeks. Muscle strength, physical function, body composition, and muscle protein synthesis were measured before and after the 24-week intervention. RESULTS: Forty-five subjects completed the 24-week intervention. VO2peak and walking speed increased (p < .05) in both AE groups, irrespective of supplementation type, but muscle strength increased only in the EAA + AE group (p < .05). EAA supplementation acutely increased (p < .05) muscle protein synthesis from basal both before and after the intervention, with a larger increase in the EAA + AE group after the intervention. Total and regional lean body mass did not change significantly with any intervention. CONCLUSIONS: In nonfrail, independent, healthy older adults AE training increased walking speed and aerobic fitness, and, when combined with EAA supplementation, it also increased muscle strength and EAA-stimulated muscle protein synthesis. These increases occurred without improvements in muscle mass.

Muscle Protein Anabolic Resistance to Essential Amino Acids Does Not Occur in Healthy Older Adults Before or After Resistance Exercise Training.

Background: The muscle protein anabolic response to contraction and feeding may be blunted in older adults. Acute bouts of exercise can improve the ability of amino acids to stimulate muscle protein synthesis (MPS) by activating mechanistic target of rapamycin complex 1 (mTORC1) signaling, but it is not known whether exercise training may improve muscle sensitivity to amino acid availability. Objective: The aim of this study was to determine if muscle protein anabolism is resistant to essential amino acids (EAAs) and whether resistance exercise training (RET) improves muscle sensitivity to EAA in healthy older adults. Methods: In a longitudinal study, 19 healthy older adults [mean ± SD age: 71 ± 4 y body mass index (kg/m2): 28 ± 3] were trained for 12 wk with a whole-body program of progressive RET (60-75% 1-repetition maximum). Body composition, strength, and metabolic health were measured pre- and posttraining. We also performed stable isotope infusion experiments with muscle biopsies pre- and posttraining to measure MPS and markers of amino acid sensing in the basal state and in response to 6.8 g of EAA ingestion. Results: RET increased muscle strength by 16%, lean mass by 2%, and muscle cross-sectional area by 27% in healthy older adults (P < 0.05). MPS and mTORC1 signaling (i.e., phosphorylation status of protein kinase B, 4E binding protein 1, 70-kDa S6 protein kinase, and ribosomal protein S6) increased after EAA ingestion (P < 0.05) pre- and posttraining. RET increased basal MPS by 36% (P < 0.05); however, RET did not affect the response of MPS and mTORC1 signaling to EAA ingestion. Conclusion: RET increases strength and basal MPS, promoting hypertrophy in healthy older adults. In these subjects, a small dose of EAAs stimulates muscle mTORC1 signaling and MPS, and this response to EAAs does not improve after RET. Our data indicate that anabolic resistance to amino acids may not be a problem in healthy older adults. This trial was registered at www.clinicaltrials.gov as NCT02999802.

Protein Requirements in Critically Ill Older Adults.

Critically ill elderly patients' nutritional needs are not well understood and vary with the phase of illness and recovery. Patients' nutritional needs should be assessed early in hospitalization and re-assessed throughout the stay with additional attention during the transitions from critical illness, to severe illness, to post-hospital rehabilitation. In this review, we summarize recent findings and highlight recommendations for protein supplementation in critically ill geriatric patients throughout the stages of recovery. Future research specifically focusing on protein dose, its relationship with caloric needs, and delivery modality must be conducted to provide more specific guidelines for clinical practice.