The effects of aging and frailty on inpatient glycemic control by continuous glucose monitoring in patients with type 2 diabetes.

BACKGROUND: Older adults with diabetes in the hospital are generally managed similarly to younger adults, however, it is unknown if the degree of frailty can affect glucose control among hospitalized patients. METHODS: We examined glycemic parameters derived from continuous glucose monitoring (CGM) in older adults with type 2 diabetes and frailty who were hospitalized in non-acute settings. Data was pooled from 3 prospective studies using CGM including 97 patients wearing Libre CGM sensors and 166 patients wearing Dexcom G6 CGM. Glycemic parameters (time in range (TIR) 70-180; time below range (TBR) <70 and 54 mg/dl) by CGM were compared between 103 older adults ≥60 years and 168 younger adults <60 years. Frailty was assessed using validated laboratory and vital signs frailty index FI-LAB (n = 85), and its effect on hypoglycemia risk was studied. RESULTS: Older adults, as compared to younger adults, had significantly lower admission HbA1c (8.76% ± 1.82 vs. 10.25% ± 2.29, p < 0.001), blood glucose (203.89 ± 88.65 vs. 247.86 ± 124.17 mg/dl, p = 0.003), mean daily BG (173.9 ± 41.3 vs. 183.6 ± 45.0 mg/dl, p = 0.07) and higher percent TIR 70-180 mg/dl (59.0 ± 25.6% vs. 51.0 ± 26.1%, p = 0.02) during hospital stay. There was no difference in hypoglycemia occurrence between older and younger adults. Higher FI-LAB score was associated with higher % CGM < 70 mg/dl (0.204) and % CGM < 54 mg/dl (0.217). CONCLUSION: Older adults with type 2 diabetes have better glycemic control prior to admission and during hospital stay compared to younger adults. Frailty is associated with longer presence of hypoglycemia in non-acute hospital settings.

Frailty Reduces Vaccine Effectiveness Against SARS-CoV-2 Infection: A Test-Negative Case Control Study Using National VA Data.

OBJECTIVES: To assess the variation of vaccine effectiveness against SARS-CoV-2 infection during the Delta wave according to frailty status among U.S. veterans. DESIGN: Test-negative case-control study of SARS-CoV-2 mRNA vaccine effectiveness. SETTING: Veterans Health Administration (VHA) medical centers. PARTICIPANTS: Veterans 19 years and older who had at least one COVID-19/Flu like symptoms and received a SARS-CoV-2 PCR or antigen test at VHA medical centers between July 25 to September 30, 2021. INTERVENTION: mRNA vaccination. MEASUREMENTS: New SARS-CoV-2 infection. Vaccine effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls, where cases were patients who had a COVID-19 test and tested positive for SARS-CoV-2, and controls were those who tested negative. Frailty was measured using the VA frailty index, categorized as robust (0-<0.1), pre-frail (≥0.1-<0.21) and frail (≥0.21). RESULTS: A total of 58,604 patients (age:58.9±17.0, median:61, IQR:45-72; 87.5%men; 68.1%white; 1.3%African American, 8.3%Hispanic) were included in the study. Of these, 27,733 (47.3%) were robust, 16,276 (27.8%) were prefrail, and 14,595 (24.9%) were frail. mRNA vaccine effectiveness against the Delta variant symptomatic infection was lower in patients with frailty, 62.8 %(95%CI:59.8-65.7), versus prefrail 73.9%(95%CI:72.0-75.7), and robust, 77.0 %(95%CI:75.7-78.3). CONCLUSIONS: This test-negative case control study showed that mRNA vaccine effectiveness against infection declined in veterans with frailty. Frailty status is a factor to consider when designing, developing, and evaluating COVID-19 vaccines.

Association between a Frailty Index from Common Laboratory Values and Vital Signs (FI-LAB) and Hospital and Post-Hospital Outcomes in Veterans with COVID-19 Infection.

OBJECTIVES: Determine the association of higher FI-LAB scores, derived from common laboratory values and vital signs, with hospital and post-hospital outcomes in Veterans hospitalized with COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter, cohort study of 7 Veterans Health Administration (VHA) medical centers in Florida and Puerto Rico. Patients aged 18 years and older hospitalized with COVID-19 and followed for up to 1 year post discharge or until death. Clinical Frailty Measure: FI-LAB. MAIN OUTCOMES AND MEASURES: Hospital and post-hospital outcomes. RESULTS: Of the 671 eligible patients, 615 (91.5%) patients were included (mean [SD] age, 66.1 [14.8] years; 577 men [93.8%]; median stay, 8 days [IQR:3-15]. There were sixty-one in-hospital deaths. Veterans in the moderate and high FI-LAB groups had a higher proportion of inpatient mortality (13.3% and 20.6%, respectively) than the low group (4.1%), p <0.001. Moderate and high FI-LAB scores were associated with greater inpatient mortality when compared to the low group, OR:3.22 (95%CI:1.59-6.54), p=.001 and 6.05 (95%CI:2.48-14.74), p<0.001, respectively. Compared with low FI-LAB scores, moderate and high scores were also associated with prolonged length of stay, intensive care unit (ICU) admission, and transfer. CONCLUSIONS AND RELEVANCE: In this study of patients admitted to 7 VHA Hospitals during the first surge of the pandemic, higher FI-LAB scores were associated with higher in-hospital mortality and other in-hospital outcomes; FI-LAB can serve as a validated, rapid, feasible, and objective frailty tool in hospitalized adults with COVID-19 that can aid clinical care.

Identifying Dementia Risk in Older Veterans Using A Mailing Survey.

Evidence suggests that dementia can be prevented. Patients with frailty may be particularly at risk for cognitive impairment (CI). The aim of this study was to determine dementia risk in older Veterans and whether the risk varies according to frailty status. We also evaluated the feasibility of mailed dementia risk screening. Participants were mailed a questionnaire and the Self-Administered Gerocognitive Examination (SAGE). High dementia risk was defined as having mild cognitive impairment (MCI) on SAGE or a CAIDE score ≥6. Out of 5,432 mailed surveys, we obtained a response rate of 19.75%. Most responders completed the questionnaire items. We identified a total of 689 (75.9%) subjects to be at high risk for dementia. Individuals with frailty were at a greater risk for dementia when compared to robust individuals OR:1.921 (95%CI:1.259-2.930), p=.002. The mailed screening represents a convenient, alternative and scalable approach to screen for dementia risk.

The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty.

BACKGROUND: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 ("mild") or 6 ("moderate"), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

The Association of Frailty with Hospitalizations and Mortality among Community Dwelling Older Adults with Diabetes.

BACKGROUND: Diabetes (DM) is associated with an accelerated aging that promotes frailty, a state of vulnerability to stressors, characterized by multisystem decline that results in diminished intrinsic reserve and is associated with morbidity, mortality and utilization. Research suggests a bidirectional relationship between frailty and diabetes. Frailty is associated with mortality in patients with diabetes, but its prevalence and impact on hospitalizations are not well known. OBJECTIVES: Determine the association of frailty with all-cause hospitalizations and mortality in older Veterans with diabetes. DESIGN: Retrospective cohort. SETTING: Outpatient. PARTICIPANTS: Veterans 65 years and older with diabetes who were identified as frail through calculation of a 44-item frailty index. MEASUREMENTS: The FI was constructed as a proportion of healthcare variables (demographics, comorbidities, medications, laboratory tests, and ADLs) at the time of the screening. At the end of follow up, data was aggregated on all-cause hospitalizations and mortality and compared non-frail (robust, FI≤ .10 and prefrail FI=>.10, <.21) and frail (FI≥.21) patients. After adjusting for age, race, ethnicity, median income, history of hospitalizations, comorbidities, duration of DM and glycemic control, the association of frailty with all-cause hospitalizations was carried out according to the Andersen-Gill model, accounting for repeated hospitalizations and the association with all-cause mortality using a multivariate Cox proportional hazards regression model. RESULTS: We identified 763 patients with diabetes, mean age 72.9 (SD=6.8) years, 50.5% were frail. After a median follow-up of 561 days (IQR=172), 37.0% they had 673 hospitalizations. After adjustment for covariates, frailty was associated with higher all-cause hospitalizations, hazard ratio (HR)=1.71 (95%CI:1.31-2.24), p<.0001, and greater mortality, HR=2.05 (95%CI:1.16-3.64), p=.014. CONCLUSIONS: Frailty was independently associated with all-cause hospitalizations and mortality in older Veterans with diabetes. Interventions to reduce the burden of frailty may be helpful to improve outcomes in older patients with diabetes.

[Sonographic evaluation of Achilles tendon healing in tenotomies for congenital clubfoot and Ponsetis treatment. A 12-week follow-up]. / Evaluación ultrasonográfica del tendón de Aquiles en niños con pie equino varo aducto congénito posterior a tenotomía de Aquiles con el método de Ponseti. Seguimiento a 12 semanas.

OBJECTIVE: The aim of this study was to determine the healing time of Achilles tendon in pediatric patients treated with Achilles tenotomy with the Ponseti method in Shriners Childrens Hospital of Mexico, AC. MATERIAL AND METHODS: Experimental, analytical, prospective, longitudinal study of patients with a diagnosis of idiopathic congenital clubfoot treated with the Ponseti method with serial static and dynamic evaluation by ultrasound in real time with a Siemens Diagnostic Ultrasound System Sonoline 650, linear transducer 10.5 MHz of Achilles tendon before tenotomy and at three, six, nine and 12 weeks after the surgical treatment. RESULTS: A sample of 23 patients, 16 male and seven female, 16 with unilateral and seven with bilateral pathology was obtained, for a total of 39 feet, 18 right and 21 left, with a mean age of 8.3 ± 2.3 months. Before tenotomy, the width was 2.7 ± 0.42 mm; in week three, the average was 3 ± 0.39 mm; at six weeks, 2.92 ± 0.36 mm; ultrasound at nine weeks reported an average of 0.38 ± 2.84 mm, and 2.82 ± 0.39 mm at twelve weeks. They were compared using Students t presurgical width and at twelve weeks, without finding difference p 0.03. CONCLUSIONS: Although there is integrity at three weeks after Achilles tenotomy, complete repair is achieved at 12 weeks.

OBJETIVO: Determinar el tiempo de curación del tendón de Aquiles en pacientes pediátricos tratados mediante tenotomía de Aquiles con método Ponseti en el Hospital Shriners para Niños de México, AC. MATERIAL Y MÉTODOS: Estudio experimental, analítico, prospectivo, longitudinal de pacientes con diagnóstico de pie equino varo aducto congénito idiopático en tratamiento con método Ponseti con evaluación estática y dinámica mediante ecógrafo en tiempo real Siemens Diagnostic Ultrasound System Sonoline 650 con transductor lineal de 10.5 mHz seriada del tendón de Aquiles previa a la tenotomía y a las tres, seis, nueve y 12 semanas tras el tratamiento quirúrgico. RESULTADOS: Se obtuvo una muestra de 23 pacientes, 16 masculinos y siete femeninos, 16 con patología bilateral y siete unilateral, para un total de 39 pies, 18 derechos y 21 izquierdos, con una media de edad de 8.3 ± 2.3 meses. Previamente a la tenotomía, la anchura en corte longitudinal ultrasonográfico media fue de 2.7 ± 0.42 mm; en la semana tres, la media fue 3 ± 0.39 mm; a las seis semanas, 2.92 ± 0.36 mm; el ultrasonido de las nueve semanas reportó media de 2.84 ± 0.38 mm y a las 12 semanas, 2.82 ± 0.39 mm. Se compararon mediante t de Student el ancho prequirúrgico y a las 12 semanas, sin encontrarse diferencia p 0.03. CONCLUSIONES: La valoración ecográfica muestra integridad a las tres semanas posteriores a la tenotomía de Aquiles. Sin embargo, la reparación completa se logra a las 12 semanas.

Breast milk composition in a cohort of pre-term infants' mothers followed in an ambulatory programme in Colombia.

OBJECTIVES: Describing preterm breast milk evolution and composition according to gestational age (GA) and postnatal age (PNA) in a cohort of mothers cared for in an ambulatory Kangaroo Mother Care Program (KMCP) in a developing country. METHODS: A cohort involving 113 mothers who delivered 'healthy' preterms adequate for GA was assembled. Mothers received intensive breastfeeding support before discharge. Samples of both fore- and hind milk were obtained at entry into KMCP and weekly thereafter, until term. Composition was described according to PNA and postconceptional age (PCA). RESULTS: Protein concentration varied inversely with both PCA and PNA. Fat concentration was consistently higher in hind milk than in fore milk samples of the same feed. Lactose increased steadily with PCA. Calcium/phosphorus ratios were stable, close to 2:1 and content of both was similar in samples of different PCA and PNA. CONCLUSION: Minerals concentration could be inadequate for preterms. Protein concentration decreases steadily to mature milk levels by the third week of PNA, regardless of birth GA. Therefore, from the third week of PNA onwards, protein content could be insufficient to satisfy needs of preterms born at 32 weeks or less. Feeding hind milk could increase caloric density and fat intake to better meet preterms' nutritional needs.

Predictional need for supplementing breastfeeding in preterm infants under Kangaroo Mother Care.

UNLABELLED: It has been estimated that 95% of low-birthweight infants are born in developing countries. Nevertheless, most of the globally available resources are invested in developed countries, both for sophisticated, expensive technological care and for research focused on solving problems in scenarios in which access to expensive resources is available. Very little research on scientifically sound, economically accessible interventions reaches internationally recognized scientific journals. For instance, one accepted scientific dogma is that all premature infants must receive breast-milk fortifiers. Thus, healthcare workers consider that not offering fortification or supplementation to all preterm infants under 2000 g is unethical, as it denies them the proven benefits of this intervention. This approach oversimplifies the problem by assuming that infants under 2000 g are a homogeneous population, with similar needs and risks. The largest proportion of preterm survivors in developing countries comprises infants weighing > 1200 g, and their nutritional needs differ from those weighing < 1200 g, who represent a significantly smaller proportion. In developing countries, fortification of breast milk is seldom a feasible option. Even supplementing breast milk with formula implies an expense that cannot always be covered. In addition, many preterm infants (particularly those weighing > 1200 g) can grow properly on exclusive breastfeeding. In our experience, about 45% of infants under ambulatory Kangaroo Mother Care (KMC) thrive properly. The choice between giving and withholding supplementation for all preterm infants is not an ethical issue, because there is no choice. This was the justification for conducting the study reported here, which attempts to answer the question of how to identify, as early as possible, those premature infants who survive the early neonatal period and have no obvious risk factors for inadequate growth other than prematurity, but who are less likely to thrive with exclusive breastfeeding. CONCLUSION: The answer to this question will allow us to use our meagre resources in the most reasonable way, as supplementing breast milk involves not only the direct cost of the formula but also that of training the mothers in techniques for feeding their infants without compromising breastfeeding or increasing the risk of infectious diseases.

Alkaloids from Delphinium staphisagria.

Three new diterpenoid alkaloids, isoazitine (1), 19-oxodihydroatisine (2), and 22-O-acetyl-19-oxodihydroatisine (3), and eight known alkaloids-azitine (4), dihydroatisine (5), delphinine, neoline, bullatine C (14-acetylneoline), chasmanine, 14-acetylchasmanine, and the quaternary base atisinium chloride (7)-were isolated from the aerial parts of Delphinium staphisagria. Structures of the new alkaloids were established mainly by 1D and 2D NMR spectroscopy, including (1)H COSY, HMQC, HMBC, and ROESY. The (1)H and (13)C NMR data for alkaloids 4 and 5 are also reported.

Clinical epidemiological principles in bedside teaching.

Medical education emphasises the transmission of large amounts of short-lived medical information. Strategies must be developed to generate in the students, attitudes towards the independent search for and critical appraisal of evidences. Two complementary strategies are particularly well suited to promote these types of attitudes: clinical epidemiology and evidence-based clinical practice. Clinical epidemiology (CE) has been defined as "the science of making predictions about individual patients by counting clinical events in similar patients, using strong methods for studies of groups of patients to ensure that the predictions are accurate. The purpose of CE is to develop and apply methods of clinical observation that will lead to valid conclusions by avoiding being misled by systematic error and chance". On the other hand, evidence based practice has been defined as "an approach to the practice of medicine in which the clinician is aware not only of the evidences which support clinical practice, but the strength and soundness of such evidences". The paper discusses the usefulness of clinical epidemiology and evidence-based health practice for rational decision making at the bedside, and also as tools for clinical teaching. An example involving evidence-based strategies for the management of a patient with bronchiolitis in the emergency room is discussed.