Impact of exercise and leucine-enriched protein supplementation on physical function, body composition, and inflammation in pre-frail older adults: a quasi-experimental study.

Background: Exercise and a protein-enriched diet are essential for muscle protein synthesis, cellular growth, mitochondrial function, and immune function. The U.S. Food and Nutrition Board's current guideline on recommended dietary allowance for protein in older adults is 0.8 g/kg per day, which may not be sufficient in vulnerable pre-frail older adults. Aims: This study aimed to evaluate the impact of leucine-enriched protein supplementation with or without exercise over 3 months in pre-frail older adults who consumed ≤1 g/kg/day of protein on improving (i) physical function, (ii) body composition measures, and (iii) inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Methods: A non-randomized cluster quasi-experimental study guided by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist of 178 pre-frail older adults [112 control, 44 nutrition (Nu), and 22 in the nutrition with exercise (Nu+Ex) group] comparing the effect of Nu+Ex and Nu on physical function, body composition, and inflammation. At 0, 3, and 6 months, questionnaires on demographics, depression, perceived health, and cognition were administered. Physical function assessment (short physical performance battery [SPPB] test, gait speed, handgrip strength, 5× sit-to-stand [STS]) was conducted, and body composition analysis was performed using a bioelectrical impedance analysis machine. IL-6 and TNF-α were measured at 0 and 3 months. Results: At 3 months, there were significant improvements in gait speed, 5× STS, SPPB scores, depression, perceived health, fat-free mass, and appendicular skeletal muscle mass indices in the Nu+Ex group. Both Nu+Ex and Nu groups had improvements in body cell mass and reductions in IL-6 and TNF-α. The improvements were not sustained after 6 months. Conclusion: Our study results need to be validated in future longitudinal randomized studies with a larger sample size focusing on populations at risk.

Delirium is significantly associated with hospital frailty risk score derived from administrative data.

OBJECTIVES: Delirium is highly prevalent in hospitalised older adults, under-diagnosed and associated with poor outcomes. We aim to determine (i) association of frailty measured using Hospital Frailty Risk Score (HFRS) with delirium, (ii) impact of delirium on mortality, 30-days readmission, extended length of stay (eLOS) and cost (eCOST). METHODS: Retrospective cohort study was conducted on 902 older adults ≥75 years discharged from an academic tertiary hospital between March and September 2021. Data was obtained from hospital administrative database. RESULTS: Delirium was prevalent in 39.1%, 58.1% were female with mean age 85.3 ± 6.2 years. Patients with delirium were significantly older, had higher HFRS, pneumonia, urinary tract infection (UTI), E.coli and Klebsiella infection, constipation, dehydration, stroke and intracranial bleed, with comorbidities including dementia, diabetes, hypertension, hyperlipidaemia and chronic kidney disease. In-hospital mortality, 30-days mortality, 30-days readmission, median LOS and cost was significantly higher. Delirium was significantly associated with at least intermediate frailty (OR = 3.52; CI = 2.48-4.98), dementia (OR = 2.39; CI = 1.61-3.54), UTI (OR = 1.95; CI = 1.29-2.95), constipation (OR = 2.49; CI = 1.43-4.33), Klebsiella infection (OR = 3.06; CI = 1.28-7.30), dehydration (OR = 2.01; CI = 1.40 - 2.88), 30-day mortality (OR = 2.52; CI = 1.42-4.47), 30-day readmission (OR = 2.18; CI = 1.36-3.48), eLOS (OR = 1.80; CI = 1.30-2.49) and eCOST (OR = 1.67; CI = 1.20-2.35). CONCLUSIONS: Delirium was highly prevalent in older inpatients, and associated with dementia, frailty, increased cost, LOS, 30-day readmissions and mortality. Hospital Frailty Risk Score had robust association with delirium and can be auto-populated from electronic medical records. Prospective studies are needed on multicomponent delirium preventive measures in high-risk groups identified by HFRS in acute care settings.

Imaging Similarities Between Oral-Facial-Digital Syndrome Type 1 and Aicardi Syndrome: Prenatal and Postnatal Magnetic Resonance Imaging (MRI) Findings in 4 Patients.

Prenatal identification by magnetic resonance imaging (MRI) of callosal anomalies, particularly with accompanying intracranial abnormalities, poses a challenge for accurate prognostication and fetal counseling as outcome can vary widely depending on underlying etiology. In female patients, Aicardi syndrome is an important consideration, and prompt postnatal ophthalmologic assessment to identify ocular stigmata of Aicardi syndrome can aid with anticipatory guidance and greater vigilance for seizures. We present a case of a female with fetal and postnatal MRI findings of agenesis of corpus callosum and type 2b interhemispheric cysts, characteristically found in Aicardi syndrome, but was found to have oral-facial-digital syndrome type 1 (OFD1). We also present 3 other companion cases with pre- and postnatal imaging of patients with Aicardi syndrome. These cases highlight the importance of widening the differential diagnosis to also include OFD1 for female patients with callosal anomalies.

Frailty, length of stay and cost in hip fracture patients.

A hip fracture causes high morbidity and mortality. Frailty is associated with adverse outcomes and increased costs. Frailty measured using the Hospital Frailty Risk Score (HFRS) is associated with higher costs and adverse outcomes. HFRS is useful as a fuss-free frailty measurement in the management of older adults with hip fractures. INTRODUCTION: Hip fractures account for an increasing number of hospital admissions around the world and are associated with high rates of morbidity and mortality. Frailty is increasingly recognized to be associated with adverse outcomes and increased costs. The purpose of this study is to determine the association of the Hospital Frailty Risk Score (HFRS) with the healthcare cost and outcomes in older adults who present with a hip fracture. METHODS: A retrospective analysis was performed on 1014 patients ≥ 60 years who presented with a hip fracture between January 2016 to June 2020. Each patient was classified into HFRS low, intermediate or high frailty cohorts. Demographics, hip fracture type, comorbidities, Charlson Comorbidity Index (CCI), American Society of Anesthesiologist score (ASA), costs, length of stay, time to surgery, complications, readmission rate and mortality were compared between the cohorts. RESULTS: Median total hospitalization costs were significantly higher in the highest HFRS (SGD$22,432) patients as compared to intermediate (SGD$18,759) and low HFRS (SGD$15,671) patients. The difference between the high and low groups remains significant after adjusting for covariates using quantile regression. Similar results were shown for median length of stay (14 vs 10 vs 8 days), total number of complications (2 vs 1 vs 0) and adjusted time to surgery (p < 0.05). HFRS was not associated with 30-day readmission or 30-day or 1-year mortality. CONCLUSION: Frailty is associated with a marked increase in total costs in hip fracture patients. HFRS proved useful in estimating LOS and outcomes for older patients with hip fractures.

Prenatal phenotyping of fetal tubulinopathies: A multicenter retrospective case series.

OBJECTIVE: Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging. METHODS: A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy. RESULTS: Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings were cerebral ventriculomegaly (15/19), cerebellar hypoplasia (13/19), absence of the cavum septum pellucidum (6/19), abnormalities of the corpus callosum (6/19), and microcephaly (3/19). Fetal MRI identified additional central nervous system features that were not appreciated on neurosonogram in eight cases. Single gene variants were reported in TUBA1A (13), TUBB (1), TUBB2A (1), TUBB2B (2), and TUBB3 (2). CONCLUSION: The presence of ventriculomegaly with cerebellar abnormalities in conjunction with additional prenatal neurosonographic findings warrants additional evaluation for a tubulinopathy. Conclusive diagnosis can be achieved by molecular sequencing, which may assist in coordination, prognostication, and reproductive planning.

Outcomes of Care by Geriatricians and Non-geriatricians in an Academic Hospital.

Introduction: While hospitalist and internist inpatient care models dominate the landscape in many countries, geriatricians and internists are at the frontlines managing hospitalized older adults in countries such as Singapore and the United Kingdom. The primary aim of this study was to determine outcomes for older patients cared for by geriatricians compared with non-geriatrician-led care teams. Materials and Methods: A retrospective cohort study of 1,486 Internal Medicine patients aged ≥75 years admitted between April and September 2021 was conducted. They were either under geriatrician or non-geriatrician (internists or specialty physicians) care. Data on demographics, primary diagnosis, comorbidities, mortality, readmission rate, Hospital Frailty Risk Score (HFRS), Age-adjusted Charlson Comorbidity Index, Length of Stay (LOS), and cost of hospital stay were obtained from the hospital database and analyzed. Results: The mean age of patients was 84.0 ± 6.3 years, 860 (57.9%) females, 1,183 (79.6%) of Chinese ethnicity, and 902 (60.7%) under the care of geriatricians. Patients under geriatrician were significantly older and had a higher prevalence of frailty, dementia, and stroke, whereas patients under non-geriatrician had a higher prevalence of diabetes and hypertension. Delirium as the primary diagnosis was significantly higher among patients under geriatrician care. Geriatrician-led care model was associated with shorter LOS, lower cost, similar inpatient mortality, and 30-day readmission rates. LOS and cost were lower for patients under geriatrician care regardless of frailty status but significant only for low and intermediate frailty groups. Geriatrician-led care was associated with significantly lower extended hospital stay (OR 0.73; 95% CI 0.56-0.95) and extended cost (OR 0.69; 95% CI 0.54-0.95). Conclusion: Geriatrician-led care model showed shorter LOS, lower cost, and was associated with lower odds of extended LOS and cost.

Factors impacting surgical decision making between prenatal and postnatal repair for myelomeningocele.

OBJECTIVES: To determine factors influencing patients to choose prenatal or postnatal repair of their child's myelomeningocele (MMC) when both treatment options are offered. METHODS: We distributed a retrospective survey via email and social media to parents of children with MMC who were offered both prenatal and postnatal surgery as intervention options. RESULTS: A total of 127 surveys met all inclusion criteria. The majority of responders considered partner's opinion (85%), maternal risks of prenatal surgery (71%), and risk for preterm labor (76%) as influencers. Financially, the costs of childcare (39.4% postnatal, 13.8% prenatal, p = 0.002), relocation (57.6% postnatal, 36.2% prenatal, p = 0.019), and travel (51.5% postnatal, 33% prenatal, p = 0.033) were more influential for the postnatal group while insurance coverage (36.4% postnatal, 68.1% prenatal, p = 0.003) was more influential to the prenatal group. Of the medical factors, the consideration of maternal risk for transfusion was different between surgical groups (39.4% postnatal, 18.1% prenatal, p = 0.015). The open responses suggest that both surgical groups found the quality of life for the baby to be significant to their decision-making. CONCLUSIONS: These findings should guide providers to tailor counseling to patient's needs. Comprehensive counseling should include information on financial resources, referral to financial counselors, and psychosocial support services.

Motoric cognitive risk syndrome, physio-cognitive decline syndrome, cognitive frailty and reversibility with dual-task exercise.

INTRODUCTION: Cognitive frailty (CF) is associated with dementia and disability. It was initially proposed in 2013 by the International Institute of Nutrition and Aging and the International Geriatrics Association. Over the years, there have been many emerging definitions e.g., Motoric Cognitive Risk Syndrome (MCR), Physio-cognitive Decline Syndrome (PCDS), reversible CF and potentially reversible CF. OBJECTIVE: Our objective was to determine the demographics including physical, functional, and psychosocial factors for the four CF definitions amongst community-dwelling older adults. In addition, the effect of dual-task exercise on the reversibility of different definitions of CF was also studied. METHODS: Participants were community-dwelling older adults aged ≥60 years recruited between August 2017 and December 2019. Older adults screened to be frail, prefrail or have cognitive impairment were invited to participate in dual-task exercise program called HAPPY (Healthy Ageing Promotion Program for You). Improvement in cognition, frailty, and physical performance after a 3-month dual-task exercise intervention program was compared with controls. RESULTS: The prevalence of CF depending on definition ranged from 8.8% to 28.7% with minimal overlap. The cognitive scores were significantly lower in all the groups predominantly affecting non-memory domains except for reversible CF. Frailty was three to seven times more prevalent in CF. MCR group had higher prevalence of functional limitation, pain and depression. All four groups had significant increase in global cognition scores especially in the attention domain where the control group declined, and reduction in the prevalence of frailty post intervention. MCR and reversible CF were significantly associated with increased odds of cognitive improvement after 3 months of intervention compared with control. CONCLUSION: CF is a novel concept and regardless of the definitions, is a target for reversing frailty, functional limitation and cognitive impairment through dual-task exercise. Long-term prospective studies are needed to evaluate the effectiveness of dual-task interventions in delaying the conversion to dementia and reduction of disability.

Delayed health consequences of COVID-19 lockdown in an older adult.

We report a case of a retired school teacher who presented with rapid cognitive and functional decline following the COVID-19 lockdown period that was diagnosed as worsening depression by referring physician. This highlights the potentially life-threatening consequences of delayed diagnosis and management of delirium, an often reversible syndrome, due to lockdown restrictions. As the pandemic outlives its initial projections, its downstream impact on an already vulnerable population continues to emerge.

Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes.

PURPOSE: Previous studies have reported that prenatal exome sequencing (pES) can detect monogenic diseases in fetuses with congenital anomalies with diagnostic yields ranging from 6% to 81%, but there are few reports of its clinical utility. METHODS: We conducted a retrospective chart review of patients who had pES to determine whether results led to clinical management changes. RESULTS: Of 20 patients, 8 (40%) received a definitive diagnosis. Seven patients (35%) had medical management changes based on the pES results, including alterations to their delivery plan and neonatal management (such as use of targeted medications, subspecialty referrals, additional imaging and/or procedures). All patients who received a definitive diagnosis and one who received a likely pathogenic variant (n = 9; 45%) received specific counseling about recurrence risk and the medical/developmental prognosis for the baby. In five (25%) cases, the result facilitated a diagnosis in parents and/or siblings. CONCLUSION: pES results can have significant impacts on clinical management, some of which would not be possible if testing is deferred until after birth. To maximize the clinical utility, pES should be prioritized in cases where multiple care options are available and the imaging findings alone are not sufficient to guide parental decision-making, or where postnatal testing will not be feasible.

Relationship of Fat Mass Index and Fat Free Mass Index With Body Mass Index and Association With Function, Cognition and Sarcopenia in Pre-Frail Older Adults.

Background: Body mass index (BMI) is an inadequate marker of obesity, and cannot distinguish between fat mass, fat free mass and distribution of adipose tissue. The purpose of this study was twofold. First, to assess cross-sectional relationship of BMI with fat mass index (FMI), fat free mass index (FFMI) and ratio of fat mass to fat free mass (FM/FFM). Second, to study the association of FMI, FFMI and FM/FFM with physical function including sarcopenia, and cognition in pre-frail older adults. Methods: Cross-sectional study of 191 pre-frail participants ≥ 65 years, 57.1% females. Data was collected on demographics, cognition [Montreal Cognitive Assessment (MoCA)], function, frailty, calf circumference, handgrip strength (HGS), short physical performance battery (SPPB) and gait speed. Body composition was measured using InBody S10. FMI, FFMI and FM/FFM were classified into tertiles (T1, T2, T3) with T1 classified as lowest and T3 highest tertile respectively and stratified by BMI. Results: Higher FFMI and lower FM/FFM in the high BMI group were associated with better functional outcomes. Prevalence of low muscle mass was higher in the normal BMI group. FMI and FM/FFM were significantly higher in females and FFMI in males with significant gender differences except for FFMI in ≥ 80 years old. Small calf circumference was significantly less prevalent in the highest tertile of FMI, FM/FMI and FFMI. Prevalence of sarcopenic obesity and low physical function (HGS, gait speed and SPPB scores) were significantly higher in the highest FMI and FM/FFM tertile. Highest FFMI tertile group had higher physical function, higher MoCA scores, lower prevalence of sarcopenic obesity and sarcopenia, After adjustment, highest tertile of FFMI was associated with lower odds of sarcopenia especially in the high BMI group. Highest tertile of FM/FFM was associated with higher odds of sarcopenia. Higher BMI was associated with lower odds of sarcopenia. Conclusion: FFMI and FM/FFM may be a better predictor of functional outcomes in pre-frail older adults than BMI. Cut-off values for healthy BMI values and role of calf circumference as a screening tool for sarcopenia need to be validated in larger population. Health promotion intervention should focus on FFMI increment.

Relationship Between Fear of Falling, Fear-Related Activity Restriction, Frailty, and Sarcopenia.

OBJECTIVES: To determine the prevalence of fear of falling (FOF) and fear-related activity restriction (FAR) and their association with frailty, sarcopenia, gait speed and grip strength, cognitive impairment, depression, social isolation, self-perceived health, and vision. DESIGN: Observational cross-sectional study. SETTING: Community. PARTICIPANTS: A total of 493 community-dwelling older adults, 60 years and older. MEASURES: FOF and FAR were assessed using validated single closed-ended questions. Questionnaire was administered to evaluate frailty (FRAIL scale - Fatigue, Resistance, Aerobic, Illness, and Loss of Weight), sarcopenia (SARC-F - lifting and carrying 10 pounds, walking across a room, transferring from bed/chair, climbing a flight of 10 stairs, and frequency of falls in the past 1 year), social isolation (six-item Lubben Social Network Scale), depression (Even Briefer Assessment Scale), cognition (Chinese Mini-Mental State Examination), and perceived general health and pain (The EuroQol-5 Dimension (EQ-5D)and EQ visual analogue scale (EQ VAS)) . Binary logistic regression was performed to determine the influence of sociodemographic, medical, functional, and cognitive variables on FOF with/without FAR. RESULTS: Prevalence of FOF was 69.2%, and among them, 38.4% had FAR. Prevalence of FOF with or without FAR in those with sarcopenia was 93.3% and in prefrail/frail was 76.6%. FOF was significantly associated with prefrail/frail (odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.26-3.73), depression (OR = 4.90; 95% CI = 1.06-22.67), number of medications (OR = 1.28; 95% CI = 1.03-1.59), and female sex (OR = 3.54; 95% CI = 1.82-6.90). FOF + FAR was associated with depression (OR = 5.17; 95% CI = 1.84-14.54) and sarcopenia (OR = 8.13; 95% CI = 1.52-43.41). CONCLUSION: FOF with/without FAR is highly prevalent among community-dwelling older adults, especially in those with sarcopenia, prefrailty, and frailty, with significant negative impact on function, quality of life, social network, and mental health. Further research is needed to investigate the value of population-level screening, causal relationship, and efficacy of comprehensive intervention strategies.

Lactobacillus garvieae endocarditis presenting with leg cramps.

An 85-year-old man with a history of aortic valve replacement presented with lower limb cramps. He was initially diagnosed with degenerative disc disease, but was found to have Lactococcus garvieae infective endocarditis with septic embolic strokes causing a central poststroke pain syndrome. Cardiothoracic surgery was deemed too high risk and the patient completed 6 weeks of intravenous antimicrobials as well as prolonged inpatient rehabilitation. Lactococcus garvieae is an aquaculture pathogen which typically affects elderly and immunocompromised patients. Atypical presentations of endocarditis in the elderly can lead to delays in diagnosis.

Genetic testing for Lynch syndrome in the province of Ontario.

BACKGROUND: In November 2001, genetic testing for Lynch syndrome (LS) was introduced by the Ministry of Health and Long-Term Care (MOH) in Ontario for individuals at high risk for LS cancers according to either tumor immunohistochemistry staining or their family history. This article describes the outcomes of the program and makes recommendations for improving it and informing other public health care programs. METHODS: Subjects were referred for molecular testing of the mismatch repair (MMR) genes MutL homolog 1, MutS homolog 2, and MutS homolog 6 if they met 1 of 7 MOH criteria. Testing was conducted from January 2001 to March 2015 at the Molecular Diagnostic Laboratory of Mount Sinai Hospital in Toronto. RESULTS: A total of 1452 subjects were tested. Of the 662 subjects referred for testing because their tumor was immunodeficient for 1 or more of the MMR genes, 251 (37.9%) carried a germline mutation. In addition, 597 subjects were tested for a known family mutation, and 298 (49.9%) were positive; 189 of these 298 subjects (63.4%) were affected with cancer at the time of testing. An additional 193 subjects were referred because of a family history of LS, and 34 of these (17.6%) had a mutation identified. CONCLUSIONS: These results indicate that the provincial criteria are useful in identifying LS carriers after an MMR-deficient tumor is identified. Placing greater emphasis on testing unaffected relatives in families with a known mutation may identify more unaffected carriers and facilitate primary prevention in those individuals. Cancer 2016;122:1672-9. © 2016 American Cancer Society.