Statistical Considerations for the Design and Analysis of Pragmatic Trials in Aging Research.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

A cross sectional study assessing steatotic liver disease in patients with systemic lupus erythematosus.

Patients with immune-mediated inflammatory diseases are prone to steatotic liver disease (SLD), which has been observed in patients with psoriasis and hidradenitis suppurativa. We aimed to assess whether systemic lupus erythematosus (SLE) was associated with SLD and to define factors associated with SLD in SLE. This was a cross-sectional study, we included 106 consecutive patients with SLE who were seen in the rheumatology clinic between June 2021 and March 2022 and we chose two sex-paired controls for each SLE. All the participants underwent FibroScan and anthropometric assessments. SLD was defined as a controlled attenuation parameter ≥ 275dB/m. Prevalence of SLD was lower in patients with SLE (21.7% vs 41.5%, p < 0.001). Patients with SLE and SLD had a lower frequency of hydroxychloroquine use (65% vs 84%, p = 0.04), and higher C3 levels [123mg/dl (IQR 102-136) vs 99mg/dl (IQR 78-121), p = 0.004]. Factors associated with SLD in SLE were body mass index (BMI), waist circumference, glucose, and C3; hydroxychloroquine use was a protective factor. On univariate analysis, SLE was associated with a reduced risk of SLD (OR 0.39, 95%CI 0.23-0.67); however, after adjusting for age, BMI, waist, glucose, triglycerides, high-density cholesterol, low-density cholesterol, leukocytes, and hydroxychloroquine, it was no longer associated (OR 0.43, 95%CI 0.10-1.91). In conclusion, the prevalence of SLD in patients with SLE was not higher than that in the general population, and SLE was not associated with SLD. The factors associated with SLD were anthropometric data, glucose, hydroxychloroquine, and C3 levels.

Role of Renal Venous Oxygen Pressure for Renal Function Monitoring After Related Living-Donor Kidney Transplantation: Cohort Study.

BACKGROUND: Monitoring of renal function after kidney transplantation (KT) is performed by measuring serum creatinine (SCr), urine volumes (UV), and glomerular filtration rate (GFR). Other methods based on oxygen metabolism, such as the renal venous oxygen pressure (PrvO2), may be useful. The aim of this study was to explore the correlation between PrvO2 and SCr, UV, and GFR 5 days after KT (SCr5, UV5, and GFR5, respectively). METHODS: We conducted a prospective cohort study in adults scheduled for living donor KT. A venous blood sample was taken from the renal vein after declamping the renal artery, and blood gas determinations were made. Correlation analyses between PrvO2 and SCr5, UV5, and GFR5 were done by calculating Spearman's correlation coefficient with generalized linear models (GLM). A Spearman's correlation analysis was performed between the percentage decrease in SCr (%ΔSCr) and PrvO2. A GLM was also performed to determine the association of PrvO2 with slow graft function (SGF). RESULTS: The study included 42 patients, of whom 67% were men. The median age was 31 years (IQR, 27-43.5). PrvO2 was negatively correlated with SCr5 (ρ = -0.53, P = .003), and positively correlated with GFR5 (ρ = 0.49, P = .001) and %ΔSCr (ρ = 0.47, P = .002). A higher PrvO2 was associated with an increase in GFR in univariable (ß = 1.24, 95% CI, 0.56-1.93, P = .001) and multivariable (ß = 1.24, 95% CI, 0.53-1.94, P = .001) analyses. No association was found between PrvO2 and SGF. CONCLUSION: PrvO2 could be used to monitor renal function in the first 5 days after related living-donor KT, given its good correlation with SCr and GFR.

Estimation of vaccination coverage and associated factors in older Mexican adults.

National vaccination programmes recommend the influenza vaccine for older adults, but this population group has the greatest morbidity and mortality from other preventable vaccine diseases. The aim of this article is to estimate the vaccine coverage in adults aged 65 years and older and to analyse the factors that could increase or decrease vaccination uptake probability for the three listed vaccines in the national vaccination programme (influenza, tetanus and diphtheria, and pneumococcus) and the full scheme in Mexico. We conducted an analytical cross-sectional study with 2012, 2018, and 2021 rounds from the National Health and Nutrition Survey, in which we calculated the vaccine coverage estimations and performed multivariable logistic regression models to analyse the factors related to vaccine uptake. Tetanus and diphtheria vaccines had the greatest coverage estimation in all years (59-71%), whereas the pneumococcus vaccine had the lowest (32-53%). Full scheme vaccine coverage decreased from 37.80% to 24.77% in 2012 and 2021, respectively. The National Health Card property, morbidity, being a beneficiary of any health system institution, and use of preventive services increased the probability of vaccine uptake. In conclusion, vaccine coverage in older Mexican adults decreased over time, and the Mexican health system plays a strategic role in immunisation.

Hemodynamic and respiratory support in pulmonary embolism: a narrative review.

Pulmonary embolism is a common and potentially fatal disease, with a significant burden on health and survival. Right ventricular dysfunction and hemodynamic instability are considered two key determinants of mortality in pulmonary embolism, which can reach up to 65% in severe cases. Therefore, timely diagnosis and management are of paramount importance to ensure the best quality of care. However, hemodynamic and respiratory support, both major constituents of management in pulmonary embolism, associated with cardiogenic shock or cardiac arrest, have been given little attention in recent years, in favor of other novel advances such as systemic thrombolysis or direct oral anticoagulants. Moreover, it has been implied that current recommendations regarding this supportive care lack enough robustness, further complicating the problem. In this review, we critically discuss and summarize the current literature concerning the hemodynamic and respiratory support in pulmonary embolism, including fluid therapy, diuretics, pharmacological support with vasopressors, inotropes and vasodilators, oxygen therapy and ventilation, and mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation and right ventricular assist devices, while also providing some insights into contemporary research gaps.

Weight Gain After 12 Months of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV Patients.

Recent studies suggest that the introduction of antiretroviral agents such as integrase strand transfer inhibitors (INSTI) may lead to weight gain in people living with HIV (PLHIV). In this retrospective observational study, we report the weight changes observed in virologically suppressed HIV patients after 12 months of switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) due to a national change in public policy in Mexico. Patients on prior regimens based on TDF/FTC or ABC/3TC plus non-nucleoside retrotranscriptase inhibitor, INSTI, or protease inhibitor were included. In the 399 patients analyzed, a significant weight increase was found, as well as an increase in body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol (LDL-C), glucose, creatinine, and CD4+ cells after 12 months of switching treatment (all p ≤ .001). Mean weight gain was 1.63 kg [confidence interval (95% CI): 1.14-2.11], whereas the average percentage of weight gained was 2.5% (95% CI: 1.83-3.17). After considering the confounding effect of baseline weight status, the change in weight and BMI did not present significant differences between any of the prior treatment schemes. In conclusion, PLHIV switching to BIC/F/TAF therapy experienced weight gain after the first year of switching treatment. Although this weight gain could be due to the switch in treatment regimen, it cannot be excluded that it was caused by other factors since no comparable control group could be used for comparison.

Effectiveness of a nationwide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of national surveillance data.

OBJECTIVES: Vaccination has been effective in ameliorating the impact of COVID-19. Here, we report vaccine effectiveness (VE) of the nationally available COVID-19 vaccines in Mexico. METHODS: Retrospective analysis of a COVID-19 surveillance system to assess the VE of the BNT162b2, messenger RNA (mRNA)-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1, and CoronaVac vaccines against SARS-CoV-2 infection, COVID-19 hospitalization, and death in Mexico. The VE was estimated using time-varying Cox proportional hazard models in vaccinated and unvaccinated adults, adjusted for age, sex, and comorbidities. VE was also estimated for adults with diabetes, aged ≥60 years, and comparing the predominance of SARS-CoV-2 variants B.1.1.519 and B.1.617.2. RESULTS: We assessed 793,487 vaccinated and 4,792,338 unvaccinated adults between December 24, 2020 and September 27, 2021. The VE against SARS-CoV-2 infection was the highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95% confidence interval [CI] 90.3-92.4) and Ad26.COV2.S (82.2%, 95% CI 81.4-82.9); for COVID-19 hospitalization, BNT162b2 (84.3%, 95% CI 83.6-84.9) and Gam-COVID-Vac (81.4% 95% CI 79.5-83.1), and for mortality, BNT162b2 (89.8%, 95% CI 89.2-90.2) and mRNA-12732 (93.5%, 95% CI 86.0-97.0). The VE decreased for all vaccines in adults aged ≥60 years, people with diabetes, and periods of Delta variant predominance. CONCLUSION: All the vaccines implemented in Mexico were effective against SARS-CoV-2 infection, COVID-19 hospitalization, and death. Mass vaccination with multiple vaccines is useful to maximize vaccination coverage.

Association of loneliness and social isolation with all-cause mortality among older Mexican adults in the Mexican health and aging study: a retrospective observational study.

BACKGROUND: Plenty of evidence shows how social isolation and loneliness are associated with increased risk for numerous diseases and mortality. But findings about their interactive or combined effects on health outcomes and mortality remains inconclusive. OBJECTIVE: Analyze the longitudinal association of loneliness, social isolation and their interactions, with the all-cause mortality among older adults in Mexico. METHODS: A retrospective observational study was conducted. Mexican adults older than 50 years were included. Data from the Mexican Health and Aging Study (MHAS) in the 2015 and 2018 waves were used. The subjects were classified according to their level of loneliness and the presence of social isolation. Multivariate logistic regression analyzes were performed to determine the degree of association between loneliness and social isolation with all-cause mortality at a 3-year follow-up. RESULTS: From the total sample of 11,713 adults aged 50 years or over, 707 (6%) did not survive, 42% presented loneliness, and 53% were classified as socially isolated. After multivariate adjustment only social isolation (OR = 1.30, 95%CI:1.03-1.64) was associated with all-cause mortality, loneliness (Mild: OR = 0.83, 95%CI:0.59-1.16; Severe: OR = 1.03, 95%CI:0.71-1.64), and the interaction between loneliness and social isolation were not associated with all-cause mortality. CONCLUSION: Social isolation, but not loneliness or their interaction, was associated with all-cause mortality in Mexican adults older than 50 years. This finding may help direct possible future interventions that help improve mental health in older adults from a highly collectivistic country.

Regional moderate hyperthermia for mild-to-moderate COVID-19 (TherMoCoV study): a randomized controlled trial.

Background: To prevent COVID-19 progression, low-cost alternatives that are available to all patients are needed. Diverse forms of thermotherapy have been proposed to prevent progression to severe/critical COVID-19. Objective: The aim of this study is to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Methods: A multicenter, open-label, parallel-group, randomized, adaptive trial is used to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Eligible hospitalized adult patients with symptoms of COVID-19 with ≤5 days from symptom onset, meeting criteria for mild or moderate COVID-19, were randomly assigned to the intervention consisting of local thermotherapy via an electric heat pad in the thorax (target temperature range 39.5­42°C) continuously for 90 min, twice daily, for 5 days, or standard care. The main outcome was the proportion of patients who progressed to severe-to-critical COVID-19 or death. Patients were randomized in a 1:1 ratio through a centralized computer-generated sequence of minimization with a random component of 20%. Participants and medical staff were not blinded to the intervention. Results: One-hundred and five participants (thermotherapy n = 54, control n = 51) with a median age of 53 (IQR: 41­64) years were included for analysis after the early cessation of recruitment due to the closure of all temporal COVID-19 units (target sample size = 274). The primary outcome of disease progression occurred in 31.4% (16/51) of patients in the control group vs. 25.9% (14/54) of those receiving thermotherapy (risk difference = 5.5%; 95%CI: −11.8­22.7, p = 0.54). Thermotherapy was well tolerated with a median total duration of thermotherapy of 900 (IQR: 877.5­900) min. Seven (13.7%) patients in the control group and seven (12.9%) in the thermotherapy group had at least one AE (p = 0.9), none of which were causally attributed to the intervention. No statistically significant differences in serum cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17, and IFN-γ) were observed between day 5 and baseline among groups. Conclusion: Local thermotherapy was safe and well-tolerated. A non-statistically significant lower proportion of patients who experienced disease progression was found in the thermotherapy group compared to standard care. Local thermotherapy could be further studied as a strategy to prevent disease progression in ambulatory settings.Clinical Trial registration: www.clinicaltrials.gov, identifier: NCT04363541.

Oral administration of resveratrol reduces oxidative stress generated in the hippocampus of Wistar rats in response to consumption of ethanol.

Introduction: Chronic ethanol intake has been found to favor hippocampal deterioration and alter neuronal morphological maturation; resveratrol has been suggested as an antioxidant that may counteract these effects. The objective of this study was to analyze the effect of resveratrol on oxidative stress markers, endogenous antioxidant system in the hippocampus, and the behavior of male Wistar rats administered different concentrations of ethanol. Methods: The animals, at 3 months old, were randomly distributed into 11 study groups (n = 6/group), orally administered (5 days on, 2 days off) with water (control), ethanol (10, 20, 30, 40 or 50%), or ethanol (10, 20, 30, 40 or 50%) plus resveratrol (10 mg/Kg/day) for 2 months. Subsequently, the production of nitrites, malondialdehyde, and 4-hydroxy-alkenal (HNE) and the enzymatic activity of catalase and superoxide dismutase (SOD) were quantified. Results: The levels of nitric oxide and lipid peroxidation products were significantly increased in each ethanol concentration and were statistically different compared to the control group; however, resveratrol significantly reduced oxidative stress caused by high ethanol concentration. The SOD and CAT did not present significant changes with respect to the controls in any of the study groups. In the different concentrations of ethanol used, GR increases significantly in the groups administered with resveratrol but not GPx. Resveratrol was shown to maintain the results similar to the control at most ethanol concentrations. Discussion: Our results suggest that resveratrol prevents oxidative stress induced by ethanol in the hippocampus by decreasing cellular lipid peroxidation, but does not prevent the activation of catalase or SOD enzymes; however, allows glutathione to be kept active and in adequate concentrations in its reduced form and avoids alterations in the locomotor system.

Simplified acute physiology score II and Mannheim peritonitis index are associated with in-hospital mortality in patients with abdominal sepsis admitted to ICU.

OBJECTIVE: The objective of this study was to assess the association and interaction of laboratory parameters, Simplified Acute Physiology Score II (SAPSII), Modified Shock Index (MSI), and Mannheim Peritonitis Index (MPI) with in-hospital mortality. MATERIAL AND METHODS: We conducted a single-center case-control study. Adult patients with abdominal sepsis were included from May 2015 to May 2020. Baseline characteristics, laboratory parameters, SAPSII, MSI, and MPI scores at admission were collected. A principal component (PC) analysis was applied to evaluate variable interactions. In-hospital mortality risk was determined through logistic regression models. RESULTS: One hundred and twenty-seven patients were identified, 60 of which were included for analyses. Non-survivors (48.4%) had a higher frequency of hypertension, lactate and MPI, and lower BE and alactic BE levels. Eight PCs were obtained, PC1 being a linear combination of pH, AG, cAG, alactic BE, bicarbonate, and BE. MPI (OR = 9.87, 95% CI: 3.07-36.61, p = 0.0002), SAPSII (OR = 1.07, 95% CI: 1.01-1.14, p = 0.01), and PC1 (OR = 2.13, 95% CI: 1.12-4.76, p = 0.04) were significantly associated with mortality in univariate analysis, while MPI (OR = 10.1, 95% CI: 3.03-40.06, p = 0.0003) and SAPSII (OR = 1.07, CI95%: 1.01-1.14, p = 0.02) remained significant after adjusting for age and sex. CONCLUSION: MPI and SAPSII were associated with mortality, although the interaction of laboratory parameters was not.

OBJETIVO: Evaluar la asociación e interacción de los parámetros de laboratorio, SAPSII, MSI y MPI con la mortalidad intrahospitalaria. MATERIALES Y MÉTODOS: Nosotros realizamos un estudio de casos y controles de pacientes adultos con sepsis abdominal desde mayo 2015 a mayo 2020. Recolectamos las características basales, parámetros de laboratorio, SAPSII, MSI y MPI al ingreso. Se aplicó un Análisis de Componentes Principales. El riesgo de mortalidad intrahospitalaria se determinó mediante modelos de regresión logística. RESULTADOS: Identificamos 127 pacientes, 60 de los cuales se incluyeron. Los no supervivientes (48,4%) tuvieron mayor frecuencia de HAS, lactato y MPI, y menores niveles de EB y EB aláctico. Se obtuvieron ocho Componentes Principales (PC), siendo PC1 una combinación lineal de pH, AG, cAG, EB aláctico, bicarbonato y EB. MPI (OR = 9.87, IC95%: 3.07-36.61, p = 0.0002), SAPSII (OR = 1.07, IC95%: 1.01-1.14, p = 0.01) y PC1 (OR = 2.13, IC95%: 1.12-4.76, p = 0.04) se asociaron significativamente con la mortalidad en el análisis univariado, mientras que MPI (OR = 10.1, IC95%: 3.03-40.06, p = 0.0003) y SAPSII (OR = 1.07, IC 95%: 1.01-1.14, p = 0.02) permanecieron significativos después del ajuste por edad y sexo. CONCLUSIONES: MPI y SAPSII se asociaron con mortalidad, aunque la interacción de los parámetros de laboratorio no lo hizo.

Potential use of banana peel (Musa cavendish) as ingredient for pasta and bakery products.

The consumption of fruits and vegetables involves the disposal of the inedible parts, conveying challenges such as waste management and environment pollution. In recent years, there have been multiple studies aimed at finding alternatives that reduce the negative impact of food/agricultural waste. Since most studies done with by-products recommend their careful selection, the aim of this study was to verify if discarded banana peels could be disinfected until microbiologically safe and to determine if they could still provide nutrients to formulate food products with sensory characteristics acceptable to a consumer market after disinfection. Banana peels were collected from markets, restaurants, and greengrocers. They were disinfected, dried, and pulverized to obtain a flour which was subjected to microbiological and proximal analysis. Once its microbial safety was assured, this flour was incorporated into bakery and pasta products, replacing wheat flour with 5-20% banana peel flour (BPF). The sensory evaluation of the different products was carried out and, after verifying that the products were sensory acceptable, the proximal analysis was implemented. The formulated products were suitable for the addition of BPF up to 10%, in which the Acceptability Index was higher than 80% and significant increases in fiber and fat were achieved. We conclude that waste banana peel flour can be incorporated into bread and pasta products for human consumption to provide nutrients which might contribute to reduce this type of waste and to recover nutrients from otherwise disposed banana peels.

[Stress, anxiety, and depression in health workers during the COVID-19 pandemic]. / Estrés, ansiedad y depresión en trabajadores de salud durante la pandemia por COVID-19.

Background: Mental health is an integral part of health. Having some psychiatric condition without treatment predisposes to a poor quality of life. These alterations have been found with an incidence of up to 50% in the general population. There are very few studies in Mexico on these conditions in health workers during the COVID-19 pandemic. Objective: To determine the prevalence of stress, anxiety, and depression during the COVID-19 pandemic in health workers. Material and methods: A descriptive, cross-sectional observational study was conducted on health workers in a tertiary hospital, through the application of randomized and self-completed surveys, in search of levels of stress, anxiety, and depression during the COVID-19 pandemic. Results: 44.7% of those surveyed showed depression, 83.1% anxiety, and 66.3% stress. The main groups affected were female staff, singles, and medical residents. Those with type 2 diabetes mellitus had higher anxiety and depression. Conclusion: The prevalence of stress, anxiety, and depression in health workers is similar to that of the general population in our study. Depression was the alteration most found. The scrutiny of alterations in mental health in health workers is of the utmost importance, with greater emphasis in the context of the aforementioned pandemic.

Introducción: la salud mental es parte integral de la salud. Tener algún padecimiento psiquiátrico sin tratamiento predispone a una mala calidad de vida. Estas alteraciones se han encontrado con una prevalencia de hasta 50% en la población general. En México hay muy pocos estudios acerca de la incidencia de dichos padecimientos en los trabajadores de la salud durante la pandemia por COVID-19. Objetivo: determinar la presencia de estrés, ansiedad y depresión durante la pandemia de COVID-19 en los trabajadores de la salud de un hospital de tercer nivel. Material y métodos: se realizó un estudio observacional transversal, descriptivo en los trabajadores de la salud de un hospital de tercer nivel, mediante la aplicación de encuestas aleatorizadas y autocomplementadas, en búsqueda de grado de estrés, ansiedad y depresión, durante la pandemia por COVID-19. Resultados: el 44.7% de los encuestados presentó depresión, 83.1% ansiedad y 66.3% estrés. Los principales grupos afectados fueron el personal femenino, solteros y médicos residentes. Aquellos con diabetes mellitus tipo 2 tuvieron mayor incidencia de ansiedad y depresión. Conclusión: la presencia de estrés, ansiedad y depresión en los trabajadores de la salud es similar a la de la población general en nuestro estudio. La depresión fue la alteración más encontrada. Es de suma importancia el escrutinio de alteraciones en la salud mental en los trabajadores de la salud, con mayor énfasis en el contexto de la pandemia mencionada.

Combined First Month Body Weight Loss and Development of Tolerance as Predictors of 6-Month Efficacy of Mazindol in Mild and Moderate Obese Subjects.

The weight loss response to anti-obesity drugs is highly variable and poorly understood, which does not allow us to know, in advance, in which subjects the drug will be effective and in which it will not. The objective of this study was to explore the body weight reduction in kilograms in the first month (1mo-BWRkg) and the development of tolerance as predictors of 6-month efficacy for treatment with 1 mg mazindol twice a day. One hundred ninety-six obese subjects were individually or jointly analyzed. Approximately 60% of subjects developed tolerance to mazindol and achieved increasing proportional levels of 6-month efficacy according to 1mo-BWRkg intervals (<1 kg, 1 to <2 kg, 2 to <4 kg and ≥4 kg). Both moT and 1mo-BWRkg were significantly correlated with the mean percentage body weight reduction (BWR%) after 6-months of treatment. The qualitative analysis of both predictors on the progressive efficacy of mazindol was used to classify patients according to expected efficacy (inefficient, slightly effective, partially effective, or fully effective), based on the mean percentage efficacy and the number of subjects reaching a BWR% of <5%, 5 to <10%, 10 to <15% or ≥15%. In conclusion, combined 1mo-BWRkg and moT were early predictors for the progressive efficacy of 6-month mazindol anti-obesity therapy. This finding represents progress in predictive, preventive, and personalized medicine which could serve for estimating the expectations of individual efficacy with the use of the drug. and highlights the basic principle of personalized medicine, "one size does not fit all".